Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by the aggregation of the mutant protein mHttn. HD progression occurs over many years and its symptoms progress at different rates for each patient. Researchers at UCI have developed a method for monitoring the severity of HD and its progression or remission in a subject. In addition, the invention provides further assays for the development of new therapeutic compounds for the treatment of HD.  There are currently no accurate and inexpensive tests for monitoring the severity and progression of HD; the development of effective treatments will be greatly accelerated by such an assay. (more...)

The Madou laboratory at the University of California, Irvine has developed a new amplification technique that allows for the electrochemical detection of the amplification of DNA sequences. Compared to currently available optical detection technologies used to detect DNA amplification, this amplification technique may be combined with portable and low cost electrodes to detect DNA amplification. This amplification technique may be implemented onto a handheld device and may provide genotyping information under 20 minutes. This technique may also implement a novel and highly sensitive interdigitated electrode array made of carbon developed by the same lab. (more...)

The majority of patients who die of cirrhosis die due to a complication of increased portal venous pressure. The hepatic vein pressure gradient (HVPG) is a prognostic indicator for long term survival in cirrhosis, and can also reflect progression of disease in the pre-cirrhotic stage. Patients that present with cirrhosis often hemorrhage after medical procedures. There is no test to determine whether patients have portal hypertension other than performing a screening esophogo-gastro-duodenoscopy (EGD), and patients undergoing this upper endoscopy do so at a cost of $3,000-$10,000 per procedure. A diagnostic test that can exclude patients at risk will eliminate the need for EGD in those patients. (more...)

Cancer is characterized by dynamic changes in the genome and a number of mutations and deletions are known to be associated with the onset and progression of specific primary cancers. However, the inherent complexity and variability of genomic signatures has compromised the ability to use such information to inform clinical practice. In addition, current methods for deletion mapping require extremely pure tumor samples – a problem that was tackled in an early version of this technology (Primer Associated Multiplex PCR or “PAMP”). However, “PAMP 1.0” required hundreds of oligonucleotides to capture the variability observed between different tumor samples. This approach has been applied for cancer monitoring by independent groups.By taking a slightly different approach and using dedicated software, inventors have developed an assay that has expanded the utility and relevance of methods used for PAMP. (more...)

Acute Myelogenous Leukemia (AML) is a cancer that typically presents with rapid and uncontrolled growth of immature cells of the myeloid lineage and represents the most common form of acute leukemia in adults. The disease is fatal is left untreated. Current therapies are largely ineffective, leading to relapse and death in the majority of patients. Roughly 35% of patients less than 60 years of age survive longer than 5 years. In the case of elderly patients, the survival rate is less than 10%. Due to the aggressive nature of the disease and the lack of successful treatment options, AML remains a challenging disease. (more...)

This novel companion diagnostic improves the treatment strategy and therapeutic efficacy of currently available therapies used to treat cancer, such as follicular lymphoma. (more...)

The diagnosis of psychiatric disorders, such as bipolar disorder, is currently dependent on the presentation of clinical or psychological symptoms over an extended period of time. Given that several psychiatric disorders are heritable, the identification of biomarkers for them would provide a major advance in early diagnosis. While some researchers have pursued gene-based biomarkers, such as mRNA expression levels, other investigators are discovering novel biomarkers using microarray analysis, such as the correlation between the increased expression of a specific protein in the blood and brain of patients with schizophrenia. (more...)

Late gadolinium enhancement (LGE) MRI is the clinical gold standard for in vivo myocardial tissue characterization and is useful for assessing tissue viability in patients with ischemic heart disease, myocarditis, cardiomyopathies, as well as other heart conditions. LGE MRI is also playing an increasing role in guiding catheter ablation treatments for arrhythmia. Cardiac pacemakers and implantable cardioverter defibrillators (ICDs), which are often implanted into patients with such heart conditions, impair the utility of LGE MRI by producing disruptive imaging artifacts. These artifacts manifest as bright contrast signals, image distortions, or signal voids. Combined, these artifacts drastically limit a physician’s ability to determine if scar tissue is present. Given that over 500,000 patients are implanted with ICDs or pacemakers every year in the U.S., the inability to have diagnostic LGE MRI imaging for these patients represents a significant hazard and unmet need. Thus, novel methods or approaches are needed to clarify LGE MRI images for these at-risk patient populations. (more...)

Chronic Lymphocytic Leukemia (CLL) is a cancer of white blood cells and bone marrow that is characterized by accumulation of B-cells, by uncontrolled proliferation and/or reduced cell death (apoptosis). CLL is typically an adult cancer and more commonly seen in patients over 65. CLL is a heterogeneous disease classified as: aggressive, which requires immediate treatment, or indolent, which is slow-growing and does not require treatment. Current approaches for staging CLL are primarily based on physical examination and blood counts. Improved methods of diagnosis and prognosis of CLL are needed, including biomarkers to stage the disease and predict the clinical course of individual patients. (more...)

Arterial spin labeling (ASL) is a useful tool for measuring local tissue perfusion with magnetic resonance imaging. However in pathologies where slow or collateral flow conditions exist, ASL methods may not provide robust measure of cerebral blood. ASL with Velocity-selective tags (VSASL) can potentially measure cerebral blood flow under slow and collateral flow conditions and avoid main error sources of conventional ASL techniques.VSASL tags spins on a basis of flow velocity, instead of the spatial distribution that is commonly used by conventional ASL techniques. Using a specific pulse train in combination with flow sensitive gradients, VSASL can potentially generate tags that are very close to the imaging plane and whereby avoid the main error source of conventional ASL technique. However, it had been demonstrated that eddy currents (EC) can erroneously tag the static tissue, resulting in overestimation of mean gray matter perfusion. One way to reduce this is to arrange the gradients pulses so that the eddy currents can be compensated. Recently a VSASL tagging module based on a asymmetric BIR-8 pulse train was introduced by Meakin and Jezzard. UCSD researchers design a gradient pulse that further improves EC compensation using symmetric BIR-8 pulse train. (more...)

Glaucoma is the second-leading cause of blindness internationally, with a prevalence projected to reach nearly 60 million by 2020. Anti-glaucoma products took in approximately $5.8bn in revenue in 2009, with industry analysts projecting this figure to rise to $6.6bn by 2014. Precisely and accurately assessing the stage of the disease is crucial to determining which of the many classes of medications would be most effective for a given patient. Currently, staging is done largely by combining structural, functional, and clinical data of the patient. However, the addition of a genomic profile, a rich source of patient-specific data, would empower physicians to perform evidence-based risk assessment, thereby greatly improving glaucoma staging and patient outcomes.  (more...)

Thiopurine drugs – including 6-thioguanine, 6-mercaptopurine, and azathioprine – are used to treat transplant rejection, hematological malignancies, as well as a number of chronic autoimmune inflammatory conditions.  In particular, thiopurine therapy has a long-standing, proven efficacy for the treatment of inflammatory bowel disease (IBD).  However, thiopurines have well-known toxic, adverse effects, which can become life threatening. These adverse effects include liver toxicity, pancreatitis, and myelosuppression, which may lead to dangerous infections.  Recent insight into the pharmacology and mechanisms of action of thiopurines has led to an emphasis on dosage optimization to improve therapeutic efficacy and mitigate the risk of adverse affects.  Although this approach may improve responsiveness in some patients, a significant proportion of patients that are refractory to thiopurine treatment will still be exposed to the drugs and receive little or no therapeutic benefit.  In addition, dose-independent toxic effects and wide interindividual variance in thiopurine tolerance should exclude some patients from continued therapy.  Thus, a major therapeutic challenge exists in identifying which individuals will benefit from thiopurine therapy prior to administration.  New tests to classify patients as candidates for 6-thiopurine therapy would improve patient safety and outcome as well as improve utilization of clinical resources.  (more...)

Functional MRI (fMRI) based on blood oxygenation level dependent (BOLD) signal changes has had an enormous impact on basic neuroscience studies but has had little impact on clinical practice. The problem is that the BOLD signal is a good indicator of where neural activity has changed in response to a stimulus but it is a poor indicator of how much it has changed in an absolute sense due to the complexity of the BOLD effect. Because the BOLD response can vary across subjects even if the underlying neural activity change is identical, we cannot establish the kind of normative data that is needed for clinical applications. For this reason, the only clinical applications of fMRI are in neurosurgery planning, because the critical question in that application is: where is the activity? There is a clear potential for much broader applications of fMRI in evaluating neurodegenerative disease, but these have not yet developed because the critical question is the harder one of: how much has activity changed? Arterial spin labeling (ASL) measures cerebral blood flow (CBF), a well-defined physiological variable and in particular a quantitative variable for which normative data can be acquired as a basis for clinical applications. However, the ASL measurement tends to be significantly noisier than the BOLD measurement. For this reason, most quantitative functional imaging studies with ASL are performed using long, simple stimuli such that measurements may be taken in an “active steady-state” and repeated to improve signal to noise ratio (SNR). This limits basic studies of brain dynamics during conditions that better approximate everyday human experience where a stimulus pattern is unknown, and also limits the complexity of neuropsychological tests that could be employed in clinical applications to assess brain function. Although the sensitivity of the ASL method can be improved with background suppression to remove tissue signal, this eliminates any information present in the BOLD signal. An important advantage of acquiring both ASL and BOLD signals is that the dynamics of the cerebral metabolic rate of oxygen (CMRO2) also can be measured. The primary challenge is then: how can we best derive quantitative measurements of CBF and CMRO2 dynamics when the driving stimulus is complex or even unknown? (more...)

Aging is a complex process that manifests different in different people. Chronological age does not accurately reflect the process of aging on a molecular level. Though fundamental processes underlying human aging are still not known, epigenetic changes such as nucleosome positioning, histone modifications, and genome wide DNA methylation patterns have been linked to the aging process. One of the challenges in studying these epigenetic effects is identifying biomarkers and precisely quantifying the actual rate of aging in an individual. There are reports available linking the methylation markers to the human aging, but no quantitative models have been established which can measure the actual rate of aging. (more...)

AIDS, the disease caused by the virus HIV, represents a devastating global pandemic. According to a United Nations report in 2010, HIV has killed nearly 30 million people worldwide, with over 2.5 million additional infections each year. Detecting HIV particles is critical not only to patient diagnosis, but also for basic and clinical research, the source of future therapies. Unfortunately, current methods are severely lacking. Phenotypic testing can take over a month to complete and only reports a single time point. Another system widely used for research employs cell lines that express CD4 and co-receptors at abnormally high levels, rendering results of questionable physiological relevance. Patients, physicians, and researchers alike would benefit greatly from a new method of detecting and characterizing HIV; one that is rapid, sensitive, adaptable, and most importantly, physiologically accurate.      (more...)

Most quantitative functional imaging studies of cerebral blood flow (CBF) are performed using long, simple stimuli such that measurements may be taken in an "active steady-state" and repeated to improve signal to noise ratio (SNR). It is thus highly desirable to have a technique that could permit quantitative study of cerebral metabolic and hemodynamic activity under conditions that better approximate everyday human experience where a stimulus pattern is unknown. (more...)

ImmunoPET is a powerful imaging tool that combines monoclonal antibodies (mAbs) with radiochemistry to illuminate biological processes in vivo.  Much like metabolic PET tracers, such as FDG, ImmunoPET tracers can distinguish areas of high and low expression or activity of a particular biological process.  By providing a snapshot of localization of a particular antigen within the body, ImmunoPET has vast utility as tool for diagnosing disease, monitoring treatment, and tailoring therapy.    CD20, a surface protein found on B cells, has been established as a biomarker for B cell lymphoid malignancies and a subset of autoimmune diseases.  CD20 is also widely used as a target for antibody therapies.  Anti-CD20 mAbs (Arzerra®, Rituxan®, Zevalin ®) have been developed for treating B cell neoplasms, autoimmune diseases, and have demonstrated some efficacy as anti-rejection therapies for transplant patients.  However, there is significant patient-to-patient variation in treatment responses to anti-CD20 therapy.  Given the large costs associated with antibody treatments and the genetic heterogeneity between patient tumors, there is need for reliable diagnostic imaging that can be used to personalize therapy.  Thus, new ImmunoPET tracers based on anti-CD20 antibodies have enormous potential as tools for diagnostics and therapy management. (more...)

The invention (software) relates to methods for estimating the strength of the hip (the proximal femur) for assessing osteoporosis and the risk of hip fracture. It can also be used for other applications for which the strength of the hip is important. In this context, the strength of the proximal femur is defined as the maximum force that can be applied to the femoral head before the bone will break and no longer be able to support the applied force. It has been demonstrated previously that proximal femoral strength can best be estimated by combining quantitative CT scan imaging, which provides the bone geometry and density at each point in the bone, with a structural engineering technique called finite element (FE) analysis. In essence, this numerical technique subdivides a structure into many smaller parts (finite elements) which, together, explicitly represent the complex material heterogeneity and 3-D bone geometry as a mathematical model. Force or displacement is then mathematically applied to represent a specific loading condition, e.g. single-limb stance or a particular type of fall onto the greater trochanter. When the FE model is analyzed, stress and strain throughout the bone structure are computed. This information is used in conjunction with material failure criteria in various ways to estimate the strength of the proximal femur under the particular loading condition. Collectively, this technique is called, “subject-specific CT scan-based finite element modeling for calculation of proximal femoral strength." This invention disclosure pertains to a specific improvement to techniques for patient-specific FE modeling for predicting the strength of the proximal femur for loading from a fall onto the greater trochanter (more...)

In optical coherence tomography (OCT), Axial and lateral resolutions are determined by the source coherence length and numerical aperture of the sampling lens, respectively. While axial resolution can be improved using a broadband light source, there is a trade-off between lateral resolution and focusing depth when conventional optical elements are used. The incorporation of an axicon lens into the sample arm of the interferometer overcomes this limitation. Using an axicon lens with a top angle of 160 degrees, 10 μm or better-lateral resolution is maintained over a focusing depth of at least 6 mm. In addition to high lateral resolution, the focusing spot intensity is approximately constant over a greater depth range. (more...)

Acute kidney injury (AKI) represents a complex disorder that occurs in a wide variety of clinical settings, with manifestations ranging from a minimal elevation in serum creatinine to anuric renal failure. AKI represents a common but under-recognized problem in clinical medicine, with devastating immediate and long-term consequences. The incidence of AKI varies from ~ 5% of hospitalized patients to > 30% of patients in intensive care units. Diagnosis involves a confounding evaluation of urine output, serum creatinine, and slope of creatinine levels. AKI can be prevented and/or treated by several maneuvers; however treatment largely depends on the experience of the physician. There is a paucity of biomarkers for diagnosis as well as monitoring the response of patients to AKI interventions. Currently, there is no single biomarker which has been established in a clinical setting to accurately monitor AKI recovery. (more...)

Hydrogen peroxide (H2O2) is a toxic byproduct of many physiologic and pathological reactions, and elevated in a variety of conditions in which free radicals have been implicated, such as inflammation, infection, cancer, diabetes, aging, and cardiovascular disease. Most conventional methods for H2O2 detection are limited to in vitro use. Being able to detect and image elevated H2O2 levels in vivo and in situ provides accurate and real time diagnosis and monitoring of many pathologies and body’s response to perturbation. (more...)

Treating blood loss with cell free oxygen carrier (artificial blood) is essential to maintain oxygen supply to the patient as well as prevent the collapse of capillaries. Effective substitution by artificial blood hinges on oxygen delivery, blood-gas and pH balance, and carbon dioxide removal. Therefore it is important to monitor the efficacy of the artificial blood or compare the efficacy of different types of them. (more...)

ANCCA as a marker and therapeutic target in breast cancer (more...)

More than 35% (73 million) of American adult and 17% (10.5 million) of America children were classified as obese in 2009-2010. Obesity increases risk of several health conditions including: type 2 diabetes, adverse lipid concentrations, reduced HDL cholesterol and hypertension. Collectively these conditions may be referred to a Metabolic Syndrome, which affects 25% of adults worldwide. People with Metabolic Syndrome are twice as likely to die from heart attack or stroke compared with unaffected individuals. Current diagnostic assessment of obesity-related metabolic complications may be variable and lack sensitivity and specificity to diagnose pre-diabetes and reliably identify patients who may be at risk to progress to diabetes. Adipose tissue inflammation may be central to mechanisms leading to pre-diabetes and diabetes, accordingly, assessing the health of adipose cells may provide valuable diagnostic and prognostic information in relation to obesity-related disorders. There is an unmet medical need for diagnostics and biomarkers for detection and assessment of adipose health. (more...)

   For in vitro measurements of ion channels, the ion channels typically are situated in lipid bilayers which are suspended at the interface between two chambers; ionic currents are measured when a bias voltage is applied between two chambers. In vivo studies of ion channels are typically performed with patch-clamp excision of membranes using micro-pipettes, a laborious, time-consuming process with low yield. In spite of this, these studies have yielded important information between structure and function of ion channels in biology. Although these naturally occurring biological nanopores are relatively weak in their structural durability and have a limited life-time, they are still intriguing candidates for sensing technology due to their sensitivity and specificity.    Researchers at the University of California, Irvine have developed a novel sensor device that allows for the interrogation of a single ion channel nanopore. The device integrates lipid bilayers on semiconducting carbon nanotube networks with ion channel nanopores    This new sensor device measures the current when a ligand binds to the ion channel nanopore. This technology is easier to implement than the patch clamp excision of membranes. In addition, the fabrication of these devices is in principle compatible with printed circuit technology. (more...)

University of California, Davis researchers have developed a computer algorithm that precisely measures the extent of brain atrophy on structural MRI images over successive time intervals.  The method achieves higher sensitivity and specificity than previous algorithms.  Due to the bias in images and in conventional algorithms, a penalty term reduces the algorithm sensitivity and localization, leading to an under-reporting of real change.  This algorithm restores sensitivity without losing specificity by also incorporating a priori tissue boundary information. (more...)

Conventional micro analytical systems typically involve integration of various material systems and device components: III-V photonic emitters, III-V or II-VI optical filters, polymer fluidic channels, silicon-based or III-V photodetectors and Si CMOS data processing units.  While the currently available large-scale systems have proven useful, miniaturization of these systems would greatly broaden the applications for this technology.In response to this challenge, investigators at University of California have developed a u-TAS fully integrated microspectrometer with a photon engine.  This u-TAS fully integrated microspectrometer is a ubiquitous optical microsystem platform which can perform point-of-care diagnostics, high throughput screening for diseases, bio-warfare agent detection, and environmental monitoring.  A miniaturizing system, usually called micro total analysis systems (u-TAS), is highly desirable for commercialization.  Miniaturization of these systems not only will reduce the physical size, which greatly improves the portability, but will also gain wide spread acceptance due to the significant reduction of reagent and sample consumption.  The investigators u-TAS fully integrated microspectrometer with a photon engine, in early trials has identified 3 different phosphor samples. (more...)

Rapid, efficient, and low cost detection and identification of microorganisms including pathogenic bacteria, viruses, and fungi is a challenge facing plant and animal health. Current technologies such as Q-PCR rely on multiple assays and amplification methods to identify bacteria and viruses. Traditional optical detection methods also require fluorescent markers. These multiple independent steps and tests increase the processing time and cost for detection and identification. Researchers at the University of California, Davis, have developed a technique that uses nanotechnology to electrically detect and identify bacterial and viral RNA sequences without the necessity of using enzymatic amplification methods or fluorescent markers. In cases where microbe densities are particularly low, the technique provides additional sensitivity that allows for the target molecules to be detected in small quantities. Furthermore, the technique may be scaled into large multiplexed arrays for high-throughput and rapid screening. The implementation is further able to differentiate closely related variants of a given bacterial or viral species or strain. This technique addresses the need for a quick, efficient, and inexpensive bacterial and viral detection and identification system. (more...)

Researchers at University of California, Davis have discovered a nanophotonic device that reduces limits of detection of an immunoassay by orders of magnitude. (more...)

University researchers have developed a microfluidic device to efficiently extract, capture, concentrate, and isolate DNAs and RNAs, including miRNAs, from bio-fluids. The device is high-throughput and suitable for clinical use, particularly for point-of-care applications. The invention provides a platform technology that can be applied to all types of miRNAs for the detection of a wide range of diseases. (more...)

As much as 15% of the adult population exhibits symptoms of irritable bowel syndrome (IBS), a disorder characterized by abdominal pain, diarrhea and/or constipation, bloating, and discomfort. Although IBS does not cause permanent harm, it can render sufferers unable to work, attend social events, or even travel short distances. IBS is also associated with significant health care costs and economic burden. Lacking well-defined and specific diagnostic criteria, physicians currently diagnose IBS on the basis of a complete medical history, physical examination, and other assays. These may include invasive procedures such as sigmoidoscopy or colonoscopy. As such, there is a need for a simple and reliable method to diagnose this condition, as well as a therapeutic target for drug development. (more...)

Because of significant improvements made in the treatment of primary cancers, distant organ metastases caused by hematogenous spread of tumor cells are now responsible for the majority of cancer related deaths in solid organ malignancies. Dissemination of tumor cells into the circulation is now considered an early disease event and a variety of studies have demonstrated that these cells can be detected in the blood of cancer patients even when the tumor appears localized. Furthermore, the presence or absence of these so called Circulating Tumor Cells (CTCs) has been demonstrated to have prognostic significance and is taken into consideration when staging a tumor. Other studies strongly suggest that the presence of CTCs may be able to predict disease recurrence in patients in remission. Because cancers generally become more difficult to control once they have spread beyond the primary tumor site, timely detection of CTCs holds significant value in charting disease progression and tailoring more appropriate interventions. Thus, numerous companies are actively developing technologies for sensitive and specific detection of CTCs in patients. To date, CellSearch™ System developed by Veridex (now part of Johnson & Johnson) is the only device which has received approval by the US Food and Drug Administration for this purpose. (more...)

Sinusitis is one of the most common health care challenges in the United States affecting an estimated 15% of the population resulting in direct health care costs of approximately $6 billion per year.  According to the American Academy of Otolaryngology, chronic sinusitis alone results in 18-22 million US physician office visits annually.  Decongestants, antibiotics and anti-inflammatory medication are the initial line of treatment before opting for surgery in chronic rhinosinusitis (CRS) patients who do not improve.  Approximately 200,000 U.S. adults undergo CRS surgery per year.  The diagnosis on the basis of symptoms is common but can be unreliable since bacterial pathogens isolated from CRS patients are also found in healthy sinuses.  Accurate diagnosis based on the local microbiota is greatly needed for effective treatment. (more...)

Leveraging some earlier findings in the study of pain, "Detection of Acute Pain During the Cold Pressor Test by Sparse Representation of Electrocardiographic Signals Using OverComplete Dictionaries" UCSD and Stanford researchers have developed a set of computational algorithms which can identify the early signs of cardiac arrhythmia, enabling potentially life-saving intervention.    (more...)

Acyl-COA: cholesterol acyl transferases or ACAT is an enzyme that catalyzes the esterification of cholesterol to form cholesteryl ester. Minimally, ACAT-mediated formation of cholesteryl ester from cholesterol prevents the toxic accumulation of excess cholesterol in a cell and maintains a free diffusion gradient across the cell membrane, particularly in the small intestine. In addition, the assembly and secretion of Apolipoprotein-B containing lipoproteins in the liver and intestines is thought to be dependent on the ACAT-mediated formation of cholesteryl esters from cholesterol. In steroidogenic tissue such as the adrenal glands, ACAT activity produces cytosolic droplets loaded with cholesteryl esters from which they can be mobilized as cholesterol substrates for the generations of steroids. Furthermore, macrophages that accumulate cholesteryl ester in cytosolic lipid droplets as a result of ACAT activity appear foamy and are a characteristic early indicator of atherosclerotic lesions. Animal models that completely lack ACAT protein are viable, albeit with tissue-specific reductions in cholesteryl ester, suggesting that another ACAT enzyme is present in these animals. (more...)

Currently, it is not clear what causes chest pain/heartburn. It is thought that acid reflux from the stomach to esophagus is the cause of these events. UCSD researchers have shown that contraction of the muscles of the esophagus that lasts more than 30 or 40 seconds is associated with chest pain. Their recent studies show that sustained contraction of the esophagus is also associated with significant reduction in blood to the esophageal wall. A device that is specially designed to measure blood flow while monitoring esophageal wall contraction and other physical signals can help differentiate various causes of chest pain/heartburn and provide guideline on the effective therapeutics. (more...)

Using a population-based prospective 15 year cardiovascular and stroke risk outcomes the researchers were able to demonstrate the clinical value of oxidation-specific biomarkers as predictors of cardiovascular events and stroke. Individually, one set of markers predicted a higher event rate, whereas another set of markers predicted a lower event rate. Since there are very few biomarkers for predicting stroke, laboratory assays with strong predictive value are certainly needed. The use of OxPL/apoB assay and other markers related to OxLDL to predict risk of stroke and TIA was previously not known. Oxidation specific epitopes have been shown here to predict CVD and stroke outcomes and provide clinical utility by reclassifying individuals into higher or lower risk categories. (more...)

Initial diagnoses of Chronic Myeloid Leukemia (CML) or Acute Myeloid Leukemia (AML) rely on a bevy of tests, which assay patient tissues by cytometric, immunohistochemical and cytogenetic techniques as well as gene expression and/or microarray analyses. However, these tests do not capture specific information on the critical sub-population of cancer stem cells (CSC), which are substantially predictive of outcomes in CML and AML. In current practice, CSC signatures comprise specific gene expression levels. However, state-of-the-art methods can provide a more complete and informative characterization of stem cell populations throughout treatment.  (more...)

Recent reports in the scientific literature have shown the ability of microneedle arrays to detect analytes via electrochemical methods. However, these technologies require the uptake of biological fluids via integrated microfluidic systems, thus complicating overall device design. Microneedle arrays for drug delivery have also been reported in the literature but these are not coupled with biosensing. (more...)

Bladder cancer, with around 70,000 new cases and 15,000 deaths per year, is the fifth most common cancer in the United States. The standard treatment consists of trans-urethral resection of the tumor followed by intravesical immunotherapy using Bacillus-Calemtte-Guerin (BCG). Although BCG eradicates residual tumor cells by inducing long-term inflammation, it is a living pathogen that often causes infections and complications. There is thus a need for an alternative immunotherapy that eradicates residual tumor cells without causing the complications associated with BCG. (more...)

Positron Emission Tomography (PET) is an imaging modality that yields physiological information necessary for clinical diagnoses based on altered tissue metabolism. Once a compound or radiopharmaceutical has distributed within the body according to the physiologic status of the patient, annihilation positrons emitted by the positron emitting radiopharmaceutical are detected by external imaging using PET. Neuroinflammation is a hallmark of major central nervous system (CNS) disorders. Arachidonic acid (AA) is found in high concentrations in brain phospholipids and is released as a second messenger during neurotransmission and much more so during pathological neuroinflammation and excitotoxicity. The use of C-14 AA in animal studies, and of C-11 AA in patients with Alzheimer's disease, has demonstrated on neuroimaging a relation between neuroinflammation-excitotoxicity and upregulated brain AA metabolism. However, use of C-11 AA in a clinical environment displays difficulties in maintaining a stable precursor, preparing C-11 fatty acid in special and less generally available cyclotron, and because of the short (20 minute) radioactive half-life of 11C in the body after injection. F-18 radiopharmaceuticals have proven to be of great utility in the measurement of metabolism in a wide variety of organs and disease states in humans. Because F-18 labeled tracers can be synthesized in most cyclotrons, the long 120 min radioactive half-life allows more quantitative imaging and transport from one center to the clinical positron emission tomography (PET) site, and allows much easier use. (more...)

Microfluidic devices are poised to revolutionize environmental, chemical, biological, medical and pharmaceutical detectors and diagnostics. The term “microfluidic devices” loosely describes the new generation of instruments that mix, react, count, fractionate, detect, and characterize samples in a micro-electro-mechanical system (MEMS) circuit manufactured through standard semiconductor lithography techniques. Although a wide array of microfluidic technologies are currently available, novel MEMS fluidic systems are needed as scientists continue to work with smaller sample volumes and desire devices with increased sensitivity and effectiveness. Researchers at the University of California, Irvine have developed a unique non-contact system for sorting monodisperse water-in-oil emulsion droplets in a microfluidic device. The technology can be coupled to other on-chip processes to increase device efficiency by sorting out un-reacted droplets. (more...)

Fluorescence tomography (FT) is a sensitive but intrinsically low spatial resolution imaging modality due to strong photon scattering in biological tissue. Recently, a temperature-responsive fluorescence contrast agent has been reported using ICG loaded pluronic nanocapsules. The temperature dependence of these contrast agents provides a major opportunity to overcome the spatial resolution of regular FT by using temperature modulation/tagging.Researchers at the University of California, Irvine have developed a new molecular optical imaging modality termed “temperature-modulated fluorescence tomography (TM-FT)” that can provide high resolution images without sacrificing the exceptional sensitivity of fluorescence-based detection. TM-FT is based on the temperature modulation of fluorescence quantum efficiency in a highly scattering medium. The medium is irradiated by both excitation light and a high intensity focused ultrasound (HIFU) wave. The crucial benefit of HIFU is that the temperature of the medium is modulated with a very high spatial resolution (~1.5 mm) due to the absorption of acoustic power in the ultrasound focal zone. When the temperature sensitive fluorescence agent presents within HIFU focal zone, the local temperature increases and in turn, changes the fluorescence quantum efficiency inside the focal zone. As a result, the emitted fluorescence light intensity and lifetime have detectable change only when the agent is present within the focal zone. In other words, it allows fluorescence reconstruction with high spatial resolution by scanning focused ultrasound column over the medium while detecting the change in fluorescence signal. Using a proper reconstruction algorithm, this technique can also provide quantitatively accurate fluorescence images. Finally, the temperature sensitive agents can be modified to target molecular pathways and processes associated with many diseases and hence, TM-FT technique can provide a suitable platform for true molecular in vivo imaging. (more...)

Researchers at UCLA have characterized the genome-wide expression profiles ofpostmortem brain tissue from several brain regions in ASD patients and controls. Theyidentified numerous genes showing consistent changes in expression level and employeda network-based approach to identify groups of functionally-related genes that areaberrantly expressed in the ASD brain. These analyses highlight genes that aredysregulated in ASD in the disease-relevant tissue, and define a set of co-expressed genesthat may serve as therapeutic candidates or potential biomarkers for the disease. Some ofthe identified genes also change in peripheral blood lymphocytes, suggesting that thesegenes may serve as diagnostic biomarkers in peripheral tissue samples. The molecularentities identified herein can be utilized as a genetic diagnostic test for ASD, or exploitedfor the discovery and development of ASD therapeutics.  (more...)

To date, acne and associated morbidity represent an unmet clinical need. While the production of acne products has been prolific, the standard of treating acne with antibiotics and retinoid has not changed. Both antibiotic and retinoid-based treatments have varying efficacy and side effects between acne patients, driving continued research for the $3B acne market. Propionibacterium acnes, the bacterium implicated in causing acne, is the intended target of most antimicrobial-based acne treatments. However, those treatments do not consider the genetic diversity between P. acnes strains nor their distribution within pores of the skin, which undoubtedly differs between individual patients. Thus, employing the principles of personalized medicine to treat acne will potentially improve treatment and diminish the social and psychological impacts of the disease. (more...)

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose, with only ~10% positive-finding rate when using conventional neuroimaging methods of CT and MRI. Diffusion tensor imaging (DTI), which is still under development, has a positive-finding rate of ~20-30% in mild TBI patients. (more...)

A novel hydrolytically degradable polyethylene glycol derivative for use in pharmaceutical and cosmetic formulations. (more...)

Superhydrophobic surfaces have attracted tremendous attention due to their self-cleaning, anti-contamination, and anti-sticking properties. Conventional methods used to create superhydrophobic surfaces include creating a rough structure on a hydrophobic surface or modifying a rough surface by materials with low surface free energy. In many instances, these conventional methods utilize expensive materials or time-consuming procedures to obtain the desired surface properties. Newer, less expensive methods to generate superhydrophobic surfaces will allow this unique property to be more accessible for a multitude of applications. Researchers at the University of California, Irvine have developed a new process to create superhydrophobic surfaces. The method uses only an inexpensive bench-top plasma etcher common to most microfluidic laboratories and achieved superhydrophobic surfaces in PDMS without any chemical modifications. By using this technique, the inventors were able to fabricate a micro droplet array for easy manipulation of liquids. (more...)

UCLA researchers have identified mutually exclusive mechanisms of acquired resistance to B-RAF inhibitors. By utilizing resistant melanoma sub-lines, patient-derived biopsies and short-term cultures they determined that a subset exhibit a mutation in N-RAS, a component of the MAPK signaling pathway. Another subset exhibits activation of PDGFRβ, a receptor tyrosine kinase involved in additional cell proliferation and survival pathways. Knockdown of N-RAS or PDGFRβ significantly reduced the growth of the resistant melanomas. Importantly, the acquired resistance develops not from secondary B-RAF mutations, but through reactivation of MAPK signaling or activation of alternate survival pathways. These findings offer assays to stratify patients for sequential treatment strategies. (more...)

A personalized approach to medical diagnostics and treatment is required due to heterogeneity within the human population and within diseased tissues. To that end, functional assays at the single-cell level can contribute to uncovering heterogeneity and ultimately assist in improved treatment decisions based on the presence of outlier cells. Single-cell fluorescent microscopy provides a high level of intracellular resolution and dynamics of molecular events. However, the process is slow and manual. Flow cytometry on the other hand, has a high throughput but provides no intracellular resolution or dynamics of molecular events. An automated fluorescent microscopy using a scanning microscope provides a higher throughput and intracellular resolution but there are increased costs and complexity due to the optical requirements. (more...)

Centrifugal microfluidic devices find extensive use for in vitro diagnostics. One of the most important considerations in developing a microfluidic device is determining how the liquids will be transferred in a controlled manner. The discovery of new methods for controlled release of liquids is an area of significant importance in the future development of microfluidic technologies. Researchers at the University of California, Irvine have developed a method for controlled release of liquids on a centrifugal platform. This invention has the ability to store liquid on a centrifugal microfluidic platform and, when needed, is able to transfer this liquid to any location on the platform independent of its proximity to the center of rotation. The invention is a non-contact method, uses stable materials, and would be easy to assemble in a mass manufacturing setting. (more...)

The study of microbiomes can offer new insight into the origins of environmental changes, disease, immunological functions, and host physiological functions.  With as many as 1030 microbial genomes globally, characterizing the microbial composition of these assemblages is a challenge for current approaches.  Standard culturing techniques are successful in identifying only a small fraction of the microogranisms in nature.  A more direct profiling approach, such as sequencing, presents a complex problem for an already laborious task due to the sheer number of different species in a given sample and the degree of biomarker sequence homology between microbial members.  Confidently identifying the thousands of taxa present in a given sample and relating their relative abundance and distribution in these consortia to disease states is a significant challenge to current methods of detection.  Improved methods for designing nucleic acids, proteins, or other markers that can recognize specific organisms, or taxa are needed.  Also, improved methods for data analyses that allow detection and quantification of the members of microbial community at high confidence levels are also needed. (more...)

The Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate marker that could be used to target any HIV-infected cell regardless of its mutational status, enabling eradication of the virus. In this regard, scientists at UCSF have recently begun to take a closer look at Human Endogenous Retroviruses (HERVs) that are present in all human cells.  HERVs are a family of retroviruses found in the human genome and are thought to have originated from an ancient retrovirus that become permanently integrated with the DNA of its host's germ cells.  HERV viruses are inactive in normal cells but one type of HERV, HERV-K, is activated in HIV-infected cells.  The HERV-K proteins are presented on the surface of HIV-infected cells.  Because HERV-K is expressed in all HIV-infected cells, it is thought HERV-K antigens presented on the surface could be a good candidate to generally target any HIV+ cell. (more...)

Interstitial lung disease (ILD) is a common manifestation of systemic autoimmune diseases such as rheumatoid arthritis (RA), lupus and scleroderma, which can lead to inflammation and scarring of the lung and, consequently, to hypoxemia, pulmonary hypertension and death.  It is estimated that ILD occurs in approximately 15 percent of patients with RA.  Very little is known about how ILD disorders arise and what role loss of immune tolerance plays in ILD development.  Presently, there are no validated lung-specific autoantigens for diagnosis of autoimmune-mediated lung disease.  Current options for ILD treatment are limited to powerful immunosuppressive medications with significant side effects.  Identification of novel pulmonary biomarkers is sorely needed to develop better diagnostic methods and therapies for ILD. (more...)

Immunoassays have a tremendous range of uses in the diagnosis of diseases, pharmaceutical drug development studies, and therapeutic drug monitoring.They are highly popular due to their high specificity and sensitivity for a variety of analytes in biological samples.However, immunoassays can be labor intensive, time consuming, and require expensive reagents.An immunoassay method that is rapid, inexpensive, and highly effective would be practical and may have widespread use.Researchers at the University of California, Irvine have developed a fluoroimmunoassay chip that can be used for improving the detection of low concentration (approx. 1 nM) biological agents.The method is rapid, inexpensive, and provides a fluorescence enhancement that is approximately 30-fold greater than glass.In addition, this method does not use the principle of metal enhanced fluorescence to enhance the signal, so the fluorophore is not distance dependent in order to achieve enhancements. (more...)

The kinesin superfamily is an extended family of related microtubule motor proteins, encompasssing a number of families that exhibit a variety of microtubule motor functions, e.g., vesicle and organelle transport, mitotic spindle function, and meiotic spindle function. These proteins typically work as monomers, are ATP dependent, and have plus end-directed microtubule motor activity involved in fast anterograde organelle transport in neurons. (more...)

The ability to study the microstructural and physiological properties of biological tissue in vivo has benefited greatly from the exquisite sensitivity of water diffusion magnetic resonance imaging (MRI). However, the ability to effectively and non-invasively probe biological tissue microstructures requires that one resolve both scale and orientation information. While current approaches (such as diffusion spectrum imaging (DSI) and high angular resolution diffusion imaging (HARDI)) are designed to capture either parameter separately, these methods do not allow simultaneous estimation of both scale and orientation. (more...)

A crucial limitation to our understanding of Alzheimer's disease (AD) is the inability to test hypotheses on live, patient-specific neurons. Patient autopsies are limited in supply and only reveal endpoints of disease. Rodent models harboring familial AD mutations lack important pathologies, and animal models have not been useful in modeling the sporadic form of AD because of complex genetics. The recent development of induced pluripotent stem cells (iPSCs) provides a method to create live, patient-specific models of disease and to investigate disease phenotypes in vitro. A proper understanding of the initiating events of AD and the existence of live disease models that accurately recapitulate the pathogenesis would lead to a much better informed therapeutic development effort. (more...)

Cyanide is a highly toxic and rapidly acting poison that is infamous due to its use in murders, suicides, wars and attempted genocide.In the present day, cyanide may be responsible for up to 10,000 deaths annually in the United States due to smoke inhalation.Cyanide may also be used as a terrorist weapon. Prior methods to measure cyanide in the blood have involved acidifying the blood after lysis of red blood cells.However, this method is time consuming (takes at least a few hours) and tedious, and thus, inadequate for rapid detection of cyanide toxicity in field or hospital settings.Field or laboratory devices capable of rapidly measuring cyanide levels in blood or body fluids are not currently available, however such field or laboratory devices would be highly useful. Researchers at the University of California, Irvine have developed a method to rapidly measure cyanide in biological samples, which can be carried out in field settings.This method is based on measuring cyanide based on spectral changes that occur when cyanide binds to the reagent.Advantages of this method are its ease of use, stability, and applicability across a wide range of cyanide concentrations and may be used with ease in the field or on laboratory devices. (more...)

Tachycardia is a type of abnormally fast heart beating arrhythmia-a heart rate greater than 100 beats per minute at rest, whose symptoms include palpitations, dizziness, angina, heart failure, or ultimately a heart attack. One of the commonly used non-surgical methods to treat this disease is Radiofrequency Ablation (RFA). Physicians guide a catheter with an electrode at the tip to the area of the heart muscle where there is an accessory extra pathway where heart cells give off the electrical signals that stimulate the abnormal heart rhythm. A radiofrequency energy is transmitted to the pathway and destroys carefully selected cells in a very small area. By doing so, the area stops conducting the extra impulses that cause the tachycardia. Researchers at the University of California, Irvine have developed a novel therapy modality, which combines optical coherence tomography and ultrasound with a electrophysiology catheter for real-time monitoring of the RFA treated area of the heart. The invention will provide images with high resolution and high penetration depth. (more...)

The ability to optically apply input signals and reconfigure existing gene circuit connections would be transformative for engineering functional gene circuits in complex, naturally occurring living systems. To date, current optical methods to interface living cells have so far relied on genomic modifications to permanently encode living cells with light responsive genes, thus limiting dynamic circuit reconfiguration. On-demand optical circuit reconfiguration can be enabled by resonant optical nanoantennas (herein referred to as biomolecular nanoantennas) functioning as selectively addressable optical receivers and biomolecular emitters of small interfering RNA (siRNA). Researchers at the University of California, Berkeley have for the first time reported the design and implementation of photonic gene circuits constructed using biomolecular nanoantennas as optical inputs to existing circuit connections of living cells. They show that photonic gene circuits are modular, enabling sub-circuits to be combined to form large-scale circuit configurations. (more...)

An estimated 5.3 million Americans have AD, the most common form of dementia. For decades, diagnosis of AD has relied on the evaluation of cognitive impairment by neuropsychological tests. However, most medical experts now agree that AD actually begins long before patients exhibit clinical symptoms. Beta-amyloid (A-beta) plaques and neurofibrillary tangles, the pathological hallmarks of the disease, actually appear in the brain much earlier. Recent efforts to identify these brain lesions early, including by positron emission tomography (PET) imaging or by cerebral spinal fluid (CSF) testing, have met with some success. Additional methods for early AD diagnosis may yield new progress in the development of therapeutics that can slow or stop the disease. (more...)

There is a broad interest in targeting kinases for drug discovery and patient diagnosis. For example, kinases are important biomarkers in cancer diagnostics and treatment, or their activity can be monitored to determine the state of a cell (e.g. via PET imaging). This interest led to the development of numerous kinase assay technologies. Generally, radiometric assays are adopted as the primary technology used by companies that provide kinase profiling services. However, they suffer from several limitations. The input amounts required for these assays make it difficult to study kinase activity on a small level. Also, these assays are labor-intensive, expensive, and are potentially hazardous to those handling the radioactive materials. Further, regulations that control the levels of a specific radioisotope that can be used may limit the desired work pace. (more...)

Immune rejection is a major barrier to successful transplantation in patients. Transplantation of the kidney, liver, heart, or lungs for example, require rigorous monitoring of organ function as well as immunosuppressive drug regimens. The nature of immune rejection of a given transplanted organ is distinct but can be generally characterized as either cellular (T-cell-mediated) or humoral (B-cell/antibody-mediated) rejection. Defining the type of rejection is critical to matching an appropriate immunosuppressive therapy and preserving transplant function. Currently, the definitive test for immune rejection is biopsy followed by pathological analysis, which is both expensive and invasive. Therefore, a reliable blood plasma test for immune rejection would be extraordinarily more desirable to improve post-transplantation care in patients. (more...)

In conventional vessel encoded ASL (VEASL), pseudo-continuous ASL tagging is used with additional gradient pulses applied across the tagging plane to encode the data with information about the location of the feeding arteries. In most implementations, prior information on the locations of feeding arteries in the tagging plane has been used to optimize the encoding process. However, in some cases, the relevant supplying arteries are not known ahead of time, as there may be variant or collateral circulation. In addition, the resonance offset in the tagging plane is known to affect the tagging efficiency. (more...)

Molecular imaging of cancer has the potential to facilitate early detection and to provide a more detailed assessment of disease and tumor margin.  Molecular imaging probes have been heralded by the FDA Critical Path Initiative as tools to increase the speed and cost-effectiveness of clinical trials for cancer therapies.  However, imaging probes currently in use in the clinic are limited by a lack of specificity and/or sensitivity or are limited to a small subset of cancers.  Therefore, new molecular imaging probes with more broad applications to cancer are needed. (more...)

The invention provides methods and devices in which microscopic particles or cells within a fluid flowing in microfluidic channels are selectively manipulated, normally by being pushed with optical pressure forces at branching junctions in the channels so as to enter into selected downstream branches, thereby realizing particle switching and sorting. Transport of the particles thus transpires by microfluidics while manipulation in the manner of optical tweezers arises either from pushing due to optical scattering force, or from pulling due to an attractive optical gradient force. Whether pushed or pulled, the particles within the flowing fluid may be optically sensed, and highly-parallel, low-cost, cell- and particle-analysis devices thus may be efficiently realized, including as integrated on bio-chips. (more...)

There are more than 23 million patients with type-2 diabetes in the U.S. and ~18 million of those might have as much as 50% higher risk than a non-diabetic to develop Alzheimer's disease (AD).  The increased AD risk factor is also true for the ~51 million patients in the U.S. who are obese at midlife.  No new drugs to battle AD have been approved by the U.S. FDA since 2003 and the few medications currently available only address cognitive loss symptoms, with some patients having no relief of symptoms at all.  It is also believed that none of the medications currently available can either delay or modify disease progression.  UC Davis researchers believe that a major problem in understanding the AD pathology and in improving the treatment is the lack of early biomarkers to signal potential risk and provide insight into disease progression.  Finding efficient biomarkers can improve diagnosis and help target drugs to the right pathological processes at the right time.  (more...)

The ability to capture and study circulating tumor cells is an emerging field with implications for early detection, diagnosis, determining prognosis, and monitoring of cancer, as well as for understanding the fundamental biology of metastasis. Current techniques of identifying and isolating such cells usually involve flowing cells in a chip across an antibody coated surface. However, these devices usually require complex geometries to ensure effective contact of the target cells with the functionalized surfaces. Such a problem can be avoided by using micro/nanoscale motors that can be programmed to scower an entire static sample as many times as needed. Further, the movement of the nano/microscale motor increases the solution convection thereby improving the diffusion of the target antigen, making for a quicker and more favorable recognition reaction. This also helps eliminate non-specific binding of the antigen while on its way to a clean environment for post-capture analysis. (more...)

Metastasis is a leading cause of death in cancer patients.  In this process, cells shed by a primary tumor, known as circulating tumor cells, enter the circulatory and lymph systems and spread to different organs where they can initiate the growth of new tumors.  An accurate quantification of these cells would provide invaluable information regarding the staging and prognosis of a patient's cancer, as well as helping to determine the most appropriate treatment options.  However, such cells are extremely rare and very diffcult to detect using current techniques, hampering the potential of this approach.  Furthermore, current techniques can suffer from either high false positive or false negatie rates, depending on the assay used. (more...)

Lymphatic dysfunction has been found in many disorders from transplant rejection to cancer metastasis, but there is little effective treatment for lymphatic diseases. The cornea is an ideal site for lymphatic research due to its accessible location, transparent nature, and lymphatic-free but –inducible features. Because there are no pre-existing vessels to consider at this site, it is exceptionally straightforward and accurate to evaluate new lymphatic events in the cornea. Since lymphatic vessels are not easily visible, previous studies using the cornea have relied on traditional immunohistochemistry assays with dead tissues. Currently, there is no means of direct and harmless visualization of lymphatic vessels within live cornea.   Investigators at University of California at Berkeley have addressed this challenge by developing the first live imaging of corneal lymphatic vessels. Lymphatic specific dye is injected into the subconjunctival space to visualize lymphatic vessels at various stages in the cornea under a fluorescence stereo-, confocal, or two-photon microscope. Lymphatic vessels can be labeled in different colors to produce two-, three-, and four-dimensional images or live videos at a molecular level. The investigators have demonstrated a proof of principle in live mouse cornea. The technique allows time course tracking of dynamic lymphatic processes within the same tissue or subject over a short or long period of time. Live imaging of corneal lymphatic vessels allows visualization of lymphatic vessels in their natural morphology, state, and interactions with the local environment. Live imaging of corneal lymphatic vessels is readily applicable to patient examination as the lymphatic dye of dextran is bio-degradable and harmless to human health. (more...)

Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large (0.500-kilobase) CNVs at several loci. However, these CNVs collectively account for a small fraction (2 to 4 percent) of cases, and the relevant genes and neurobiological mechanisms are not well understood. A majority of the rare CNVs that have been implicated in schizophrenia involve large (500 kb) genomic regions where local segmental duplication architecture promotes frequent and nearly identical rearrangements by non-allelic homologous recombination (NAHR). Because of the high structural mutation rates at these loci, the strong phenotypic effects of the causal variants, and the excellent power of most array platforms to detect such large CNVs, these genomic hotspots were the first to be detected in studies of CNVs in schizophrenia.Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are two closely related peptides that bind two homologous G protein-coupled receptors, VIP/PACAP receptor 1 (VPAC1R) and VIP/PACAP receptor II (VPAC2R). Vasointestinal Peptide Receptor 2 (VIPR2) encodes the vasoactive intestinal peptide (VIP) receptor VPAC2, a G protein-coupled receptor that is expressed in a variety of tissues including, brain, suprachiasmatic nucleus, hippocampus, amygdala, and hypothalamus. VIPR2 is known to play a role in the cardiovascular and gastrointestinal system and it is this application that has driven early efforts to develop selective agonists and antagonists of VPAC2R. Peptide derivatives and small molecules have been identified that are selective VPAC2 agonists or antagonists. (more...)

Infertility affects about 10% of couples in the United States, and the cause of infertility in up to 30% of affected couples remains unexplained. In Vitro Fertilization (IVF) is the most commonly used Assisted Reproductive Technique to address the issue of infertility in couples; however, the low IVF success rates (30-40% for women aged 34 and younger, with decreased success rates for older women) reveals a need for methods to accurately predict IVF success. Current methods for predicting IVF success use pre-implantation genetic diagnosis or morphological assessment of oocytes. However, pre-implantation genetic diagnosis requires embryo biopsy and does not improve live-birth success rate. In addition, morphological assessment is subjective and unquantitative, and often fails to predict IVF success. Therefore, the development of new methods to predict oocyte competence that are non-invasive, quantitative, and accurate would represent a great advance in the field. (more...)

Researchers at the University of California, Irvine have developed a novel, label-free imaging and evalution method that enables users to track cell metabolism in vivo.The technique is a novel phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM), a multi-photon microscopy technique that excites cells and then detects their fluorescence activity over time. In this approach, the data from these images is transformed mathematically into a phasor representation. The subsequent analysis identifies, locates, and calculates the concentration of important metabolic cell components, such as: collagen, FAD, free and bound NADH, retinol, and retinoic acid.Overall, this novel method provides a straightforward and quantitative interpretation of the physiological processes occurring in tissues. It enables users to visualize cellular metabolism and retinoid gradients, distinguish between the unique metabolic states of cells, and map their level of differentiation. (more...)

Hepatic fibroblasts are activated in response to chronic liver injury and are the source of the fibrous scar in liver fibrosis. Liver fibrosis is known to be reversible. It is thought that reversal of fibrosis is accompanied by senescence and/or apoptosis of the myofibroblasts, which are responsible for the fibrosis. However, it was unknown if myofibroblasts can escape cell death and revert to an inactive phenotype during regression of fibrosis. (more...)

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Researchers at the University of California, Irvine have developed methods to enable greater multiplexing abilities for digital polymerase chain reaction (PCR) so that up to 100 genetic targets may be analyzed. In the past multiplexing of digital PCR samples has been limited to only one probe per color. However multiple probes may be labeled by using combinatorial encoding of color, exploiting reaction rates of PCR cycles and modulating the intensity of Taqman and/or intercalating dyes therefore allowing a greater number of probes to be labeled. (more...)

There are approximately 20-40 million people in the United States with sleep apnea. Obstructive sleep apnea has been recognized as a very common disorder and an important cause of morbidity and mortality. Obstructive sleep apnea is characterized by repetitive interruptions of breathing during sleep due to the collapse of the upper airway. Sleep apnea can lead to severe health complications including hypertension, heart failure, memory impairment, motor vehicle and work accidents, decreased work productivity, and increased risk of death. The development of a novel, simple, rapid, minimally invasive method for the diagnosis and optimization of treatment of patients with obstructive sleep apnea would be a tremendous advance for these millions of patients. Optical coherence tomography (OCT) is an imaging modality that can perform cross section views of tissue. OCT is analogous to ultrasound except that imaging is performed with light instead of acoustic waves. OCT is non invasive and non ionizing allowing study over lengthy periods during both sleep and wakefulness. Conventional OCT which is based on time domain technique has very limited imaging speed which precludes its use in real-time, dynamic monitoring and large volume detection. Researchers at the University of California have developed a technique including the step of combining a narrow line-width sweptsource based Fourier domain OCT (FDOCT) system with an endoscopic probe to enable an ideal upper airway imaging technology which is low-cost, compact, noninvasive, non-ionizing, dynamic (to visualize apneic events), suitable for supine position study, and capable of high resolution three dimensional images. This technology provides a mechanism for dynamic evaluation of obstructive sleep apnea. (more...)

Researchers at the University of California, Irvine have developed a novel method for capturing cellular resolution images of biological tissue at depths of up to several millimeters. Conventional fluorescence detection methods utilize microscope objectives for emission light collection, a less effective approach that is only capable of imaging up to one millimeter deep.To improve upon this standard, the UC researchers minimized light losses by optimizing the system’s excitation and detection optics. (more...)

High sensitivity sensors for specific antigens in solution are in high demand for medical diagnostics and biological assays all over the world. For widespread applicability, these sensors must be low-cost, require minimal need for additional instrumentation, minimize handling of instable proteins such as enzymes, and yet still produce a strong signal in response to a single antigen. To meet all of these requirements, one potential method would be to generate an optical signal or change due to the presence of a particular analyte. However, in order to still have highly sensitive sensors that require minute amounts of antigen, a platform capable of generating amplified responses upon molecular binding must be developed.In order for protein diagnostics to have worldwide utility, especially in regions of the world with limited equipment and cold storage facilities, methods must be established to rapidly screen for the presence of particular analytes without requiring thermally unstable enzymes or specialized detection apparati, such as microscopes or spectrophotometers. Furthermore, it would be much more efficient and highly advantageous to amplify the signal directly from the sensing agent without extensive synthesis or engineering of new materials. A platform providing optical signal changes as well as the identity of the antigens within a complex mixture would be highly advantageous for protein diagnostics. (more...)

This invention is a portable alveolar oxygen and carbon dioxide meter that shows the concentration or partial pressures of oxygen and/or carbon dioxide in the alveolar gas in the depths of the lung. It is the first portable oxygen meter and would compete only with pulse oximeters. However, pulse oximeters measure the oxygen saturation of the hemoglobin in the blood and this type of measurement does not give an accurate estimate of the alveolar oxygen content of the lung. Alveolar content is important information, useful in assessing the efficiency of respiration, especially the level of ventilation. (more...)

With lung cancer, early detection is critical and would significantly reduce mortality from this disease. According to the National Cancer Institute, the 5-year relative survival rate for patients with localized lung tumors is 53%. This survival rate decreases significantly however, once the cancer has advanced to the regional lymph nodes, or if the cancer has fully metastasized. Consequently, early screening and detection methods have played a large role in improving survival for patients with breast, colon, and cervical cancers. There are currently no known methods to screen for lung cancer. Recently the National Cancer Institute released early results from the National Lung Screening Trial which showed that screening with low-dose helical Computed Tomography (CT) resulted in a 20% reduction in mortality from lung cancer in smokers screened with this modality. This method however was associated with a false positive rate of 25%, leading clinicians to perform additional diagnostic procedures on a large cohort of patients who have benign diagnoses. These work-ups often occur in the setting of other co-morbidities thus heightening potential complications. Clearly, there is a pressing need to develop safer, more effective non-invasive techniques to reliably screen for early stage tumors in the lung. (more...)

To introduce temporal control in genetic experiments targeting the endothelium, we established a mouse line expressing tamoxifen-inducible Cre-recombinase (Cre-ERT2) under the regulation of the vascular endothelial cadherin promoter (VECad). Specificity and efficiency of Cre activity was documented by crossing VECad-Cre-ERT2 with the ROSA26R reporter mouse, in which a floxed-stop cassette has been placed upstream of the -galactosidase gene. We found that tamoxifen specifically induced widespread recombination in the endothelium of embryonic, neonatal, and adult tissues. Recombination was also documented in tumor-associated vascular beds and in postnatal angiogenesis assays. Furthermore, injection of tamoxifen in adult animals resulted in negligible excision (lower than 0.4%) in the hematopoietic lineage. The VECad-Cre-ERT2 mouse is likely to be a valuable tool to study the function of genes involved in vascular development, homeostasis, and in complex processes involving neoangiogenesis, such as tumor growth. (more...)

Researchers at the University of California, Irvine have developed a novel method to continuously pattern nanofibers on 2D and 3D substrates. A unique polymer ink formulation provides the right balance of viscosity and elasticity necessary to enable controlled, seamless near-field electrospinning of nanofibers at very low voltages. (more...)

Researchers at the University of California, Irvine have developed a novel centrifugal-based colorimetric lateral flow assay system for detection of analytes of interest. The system consists of a low-cost and disposable plastic CD disk incorporated with a lateral flow assay that enables complex sample preparation, precise volume definition, automation, and reproducibility.The conjugation of the microfluidic CD with lateral flow membrane allows for multiplexing and semi-quantitative rapid analysis of samples of interest. (more...)

The conventional approach to small molecule screening involves the use of liquid handling robotics in multi-well format. Typically, the cells are cultured in multi-well plates (e.g., 96, 384, or 1536 wells) and small molecules are added into each well. The unit culture area in each well for each compound in a 1536 well-plate is about 2 mm2. A costly liquid-handling robot is required for large-scale screening, and each test requires 10-100nl of 1mM compound for a 1526 well assay. There is a need to develop a procedure that requires fewer cells, fewer small molecules, and less expensive instruments. (more...)

Magnetoencephalography (MEG) is a functional imaging modality that directly detects neuronal activity with a millisecond temporal resolution. UC San Diego researchers previously developed a multi-core beamformer (MCBF, see SD2010-340) approach that reconstructs common-mode source time-courses and their correlations networks from noisy MEG data, without requiring both a priori information and expensive and impractical computation. However, the performance of MCBF degrades at low correlations and cannot reconstruct individual source time-courses.A detailed description for the related technology SD2010-340 can be found at http://invent.ucsd.edu/technology/cases/2010/SD2010-340.shtml. (more...)

In patients with stenosed heart valves, hemodynamic performance of the heart valve is routinely assessed to determine risk stratification and timing of intervention. Hemodynamic performance is also used to evaluate the success of a valve transplant and monitor the performance of the valve over time. Current measures of hemodynamic performance include measures of transvalvular pressure gradient, effective orifice area, and blood flow velocity.  These common criteria only allow assessment of forward flow and do not take into account paravalvular leak and paravalvular regurgitation (backward flow). Leak and regurgitation are commonly seen in stenosed valves, deformed prostheses, and particularly in transcatheter valves. Assessment of valvular hemodynamics during both forward and backward flow would improve risk stratification of patients and timing of interventions.      Valve hemodynamics during both forward and backward flow can be assessed by measuring energy loss. Until now, routine clinical application of energy loss measurement has been hindered by its invasive nature and a lack of simple tools to obtain the data. Energy loss measurement currently requires catheterization and placement of pressure transducers inside the artery on opposite sides of the valve in question.  A non-invasive and simple way to measure energy loss would provide clinicians with a tool to improve assessment of hemodynamics and improve patient care.      (more...)

Reduction in scan time for MRI translates to savings in machine usage and to patient’s comfort by shortening the time to stay motionless. (more...)

Currently, methods for detecting early myocardial dysfunction include the use of cardiac derived biomarkers (b-type natriuretic peptide, pre-pro-B type natriuretic, and cardiac troponins I and T) and systemically derived markers (C-reactive protein). These rely on the release of proteins into the bloodstream after irreversible cardiac muscle death and an inflammatory response. Although myocardial biopsies may offer unique insights on cardiac disease and failure in select patients, these require complicated invasive procedures that prove to be high risk to the patient/individual. Also, non-invasive imaging modalities are playing an important emerging role in early detection of physical changes to the heart (velocity and displacement as well as strain and strain rate for deformation of muscle) and molecular imaging events in the heart (labeling of metabolites, angiogenic regulators, neuroreceptors, and remodeling factors). However, these molecular events are based on inactive byproducts, which are released to the bloodstream, found in the heart as a result of cardiac muscle death, inflammation, and/or late-onset diseases processes, and are not necessarily specific to cardiac muscle cells. Better diagnostic biomarkers are needed. (more...)

Existing magnetic resonance imaging (MRI) methods are built around the 40-year old concept that MRI data should be the Fourier transform of the desired image. Compressed sensing (CS) technology for reconstructing images and other data from incomplete data has the potential to reduce MR data acquisition time. The ideal raw data for CS reconstruction is randomly sampled data rather than the Fourier sampled data used by the current technologies. (more...)

Researchers at the University of California, Irvine have developed a new controllable method to fabricate functionalized carbon nanowires that can then be covalently bound to antibodies, proteins, mRNA, DNA or other reagents. These antibodies and reagents may then bind with analytes of interest in solution causing a measurable change in the electrical current. Additionally, interdigitated electrode arrays may also be fabricated by using nanowires made from this method. (more...)

Researchers at the University of California, Irvine have developed a microfluidic device that has a combination of side wall and planar electrodes designed to generate magnetohydrodynamics (MHD) and dielectrophoresis (DEP) forces on cells in solution. The MHD and DEP forces can separate a heterogeneous population of cells based on their different dielectric properties and sizes. (more...)

Researchers at the University of California, Irvine (UCI) have developed a limited field of view (LFOV) single photon emission coherence tomography (SPECT) reconstruction technique that can be implemented on a multi-modality MRI/SPECT system. This technique may be used to obtain simultaneous MRI and SPECT images on a shorter time scale with improved resolution and at a lower cost when compared to other image reconstruction techniques. (more...)

UCSF researchers have identified a set of biomarkers that can be used to diagnose sarcoidosis in whole blood samples. Currently, there are no routinely used non-invasive tests for diagnosing sarcoidosis, therefore these biomarkers are promising for the development of rapid and standardized diagnostic tests that can be widely implemented in the clinics. (more...)

Researchers at the University of California, Irvine have developed a simple method for the rapid self-assembly of predictable high density droplet-reactor arrays for high throughput microfluidic applications in biology and chemistry. By controlling the ratio of the chamber height to droplet diameter, the resulting self-assembled 3D colloidal, lattice droplet pattern formations can be selectively tuned for optimal real-time and/or long-term 2D visualization and image capture of reactions occuring in the droplet micro-reactors. (more...)

Researchers at UCSF and Stanford have developed an improved method for hyperpolarized magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) that increases the observation window while minimally disturbing substrates, allowing for optimal imaging of both substrates and metabolic products. This method can also be tailored to control the parameters required for optimal imaging of individual compounds (more...)

Several study have suggested that fat composition and site of deposition can indicate the risk of many disorders, including cancer, type 2 diabetes, heart disease, and liver disease (NASH). In addition, regional differences in fat composition throughout the body suggest a depot-specific impact of stored fatty acids on adipocyte function and metabolism. Current diagnostic tools include MR spectroscopy, which has high spectral resolution but poor spatial resolution, and MRI IDEAL (iterative decomposition of water and fat with echo asymmetry and least squares estimation) gradient echo imaging, which can measure the amount but not the type of fat. (more...)

Heart failure is a leading cause of mortality in the U.S. and Europe and can present acutely as myocarditis or chronically as dilated cardiomyopathy. Although up to 30% of patients with acute onset of non-ischemic cardiomyopathy or dilated cardiomyopathy show evidence of enteroviral infection, diagnosis remains extremely difficult as enteroviral infections of the heart can only be confirmed by biopsying cardiac tissue. As viral myocarditis is generally in the differential diagnosis for patients that present with heart failure of unknown cause, there is a clear, unmet need for a non-invasive assay to better diagnose and treat this disease. (more...)

Researchers at the University of California, Irvine have developed a Laplace pressure trap that can fuse droplets from different inlets and fuse droplets generated at different frequencies. The device traps and fuses droplets passively by balancing the driving hydrostatic pressure with increasing Laplace pressure imposed by the device’s design geometry. Above are video frames showing the Laplace pressure trap and of a single droplet fusion event at the Laplace trap. Frame A - Reference droplet can be seen waiting for its fusion partner. Excess partner droplets can be seen exiting towards the outlet. Frames B and C show the reference droplet and its fusion partner fuse and move toward the outlet. Frame D shows the next reference droplet approaching the trap. (more...)

Researchers at the University of California have developed a method to extract and identify biomarkers from nail clippings. (more...)

UC San Diego researchers have developed novel non-peptoid transport molecules that, when coupled to a "cargo" such as an antibiotic or a fluorophore, facilitate the crossing of the cargo across cell membranes into the cytoplasm. A key feature of these transport molecules is their unique three-dimensional structure, which is non-linear and contains peripheral guanidine moieties. Through specific linkers designed by UC San Diego scientists, it is possible to attach a variety of cargo molecules to the transporters via a cleavable covalent bond. Unlike peptide-based molecular transporters, these molecules are non-toxic, non-antigenic, resistant to degradation, and highly efficient in crossing cell membranes, with or without the cargo. They are also easy and inexpensive to synthesize, and can be uniquely adapted to specific types of cargo. (more...)

Researchers at the University of California, Irvine have developed a laser imaging system that accurately assesses the pulp vitality of a tooth. This system can assess and image the pulp vitality without pain to the patient and the method used by the system is non-invasive. (more...)

A novel system and methods that provides efficient display and screening of peptide libraries at the cell surface, and enables rapid and quantitative characterization of the candidate peptides. (more...)

A novel method for measuring the precise visual distortion experienced by an individual MD patient. This measurement is the stepping stone for the development of updateable visual aids. (more...)

Researchers at the University of California, Irvine have developed a rotating gantry system that can be inserted and integrated into any magnetic resonance imaging (MRI) system to acquire images with a second modality (i.e. SPECT, PET, optical tomography, etc). (more...)

A microfluidic device that measures mitochondrial membrane potential that may be used as a clinical diagnostic or a research tool. (more...)

Researchers at the University of California, Irvine have developed a centrifugal microfluidic device with removable modular components. The use of these modular components gives the user flexibility to assemble his or her own fluidic system with standard modules that are connected with unique fluidic connectors. (more...)

Nanoparticles capable of reversible changes in morphology in response to specific stimuli are expected to have broad utility in designing targeted drug-delivery, detection strategies, self-healing materials, and templates for hierarchical directed assembly. While there are several elegant examples of stimuli-responsive soft nanoparticles, programmable materials with the requisite shape-change properties remain elusive. (more...)

During their lifetime, some form of cancer affects more than 40 percent of the U.S. population. It is known that the catch-all term “cancer” includes a variety of diseases with varying etiology and prognoses. It is also known that the progression to metastasis radically changes treatment options. Despite the trend toward better understanding of the nuances of various types of cancer, the critical aspect of effective therapy remains early detection. An early indicator of cancer would allow physicians to proactively test and choose appropriate treatments, before disease progression has ruled out the most effective, early options. (more...)

Each of the traditional diagnostic tools currently used for assessing atherosclerosis have their limitations. The "gold standard" cardiac angiography is an invasive method with risks associated with the catheterization procedure and there is no reliable non-invasive method to identify and quantify the severity of atherosclerotic plaque. The main obstacle to the development of a non-invasive technique is the lack of specific agents that recognize atherosclerotic plaque and the means for differentiating the atherosclerotic lesion from normal tissue. This is largely due to the high background signal that interferes with the immunological and radiological approaches being explored. (more...)

Two UC researchers have discovered a class of new analytes and new methods for using them, both are directed to in vitro diagnostic assays for diseases of abnormal protein glycosylation. This invention provides a technological base for a new line of diagnostic products to address this emerging area—the diagnosis and treatment of glycosylation abnormalities leading to peri- and post-natal disease, the widespread nature of which has recently become recognized. (more...)

BACKGROUND:   Pancreatic cancer strikes more than 42,000 Americans per year and claims over 35,000 lives annually. It is the fourth leading cause of cancer mortality in the United States. Early pancreatic cancer is frequently asymptomatic, thus resulting in malignant metastasizing tumors and poor prognosis by the time it is first detected. Unfortunately to date, there is no method for early detection of pancreatic cancer.   One of the hallmarks of early stage tumor growth is the continuous formation of new blood vessels by angiogenesis. It is thought that av-integrins and their arginine-glycine-aspartate (RGD) binding peptide facilitate neovasculature growth, and thus are promising targets for early tumor detection.   TECHNOLOGY:    Scientists at UCSF have developed a novel imaging tool that takes advantage of a new tumor homing peptide (termed iRGD) and can be used with existing imaging modalities for early tumor detection. These multivalent iRGD-biopolymers bind to integrin-expressing tumor cells, and subsequently are internalized into tumor cells and tissues. Our investigators have observed iRGD-biopolymers selectively binding to pancreatic ductual carcinoma cells in an ex vivo animal model for pancreatic cancer. Furthermore, in live animal studies using optical and PET imaging technologies, iRGD-biopolymers specifically incorporated into tumor sites.  (more...)

More than 60,000 people in the United States are diagnosed with lymphoma each year and the prognosis for those affected is usually poor. In many cases, patients may respond initially to first-line treatments (e.g. chemotherapy, radiotherapy), but subsequently suffer a relapse. In other cases, a patient may fail to respond to any treatment (refractory cancer). For patients diagnosed with relapsing cancers or patients resistance to conventional treatment, there are no optimal or preferred treatment options, resulting in a poor prognosis. Additional treatment options are needed for this group of lymphoma patients. (more...)

Amyloids are insoluble fibrous protein aggregates that accumulate in various organs throughout the human body. It has been clinically proven that abnormal accumulation of beta-amyloids in the brain is associated with various neurodegenerative diseases, including Alzheimer disease. Diagnostic biomarkers currently in clinical development are limited to small radio-labeled molecules for detection of amyloidosis through PET or SPECT imaging modes. There remains a pressing need for the design and development of new imaging agents for conclusive early diagnosis of Alzheimer’s disease, ideally through widely accessible detection platforms. (more...)

Researchers at the University of California, Irvine have developed a self-venting centrifugal microfluidic CD platform that mechanically lyses and homogenizes biological samples; after this sample processing, the purified NAs are then extracted on the same system and then run on a microarray that is also on the platform. (more...)

Surface-enhanced Raman spectroscopy (SERS) is an analytical chemistry technique for rapid and accurate detection of chemicals and bioagents by scattering laser light from a sample. The Raman signals are enhanced tremendously when samples are deposited onto specially prepared metal surfaces (substrates), which create localized amplification of the laser’s electromagnetic field. The result is an enhancement of the intensity of the spectral peaks by several orders of magnitude, bringing the level of detection down to a single molecule. A good nanostructure substrate is the key to SERS applications. Silver has optimal properties for Raman scattering, but is chemically unstable, requiring complex and expensive equipment for substrate fabrication. Current SERS substrates typically cost over $100 and are not reusable. For a wide range of commercial SERS applications, better methods are needed to make nanosubstrates that are inexpensive, stable, and easy to make. Scientists as UC Berkeley developed an easy and cost-effective way of producing substrates suitable for enhancement of Raman, fluorescent, or luminescent signals. The method allows for producing bulk amounts of silver dendrites in powder form that can be used as is, attached to adhesive substrate, or compressed into a tablet. The final cost of each substrate can be substantially less than $1 because of the simplicity of the process and the low cost of the materials and reagents used. (more...)

Determining oxygen levels in tumors is critical for advancing cancer diagnosis and therapy. A detailed knowledge of real-time changes in oxygen gradients within a tumor can assist in the profiling of tumor growth and improve the effectiveness of current treatment strategies, which function optimally at different oxygen concentrations. Small molecule luminescence has been suggested as a low cost, non-invasive alternative to traditional methods for sensing oxygen levels that are invasive, expensive, and/or lack sufficient spatio-temporal resolution to monitor real-time changes. In addition to sensing oxygen in tumors, luminescent small molecules, such as porphyrins, have been used for photodynamic therapy (PDT) to treat certain cancers by sensitizing oxygen for the production of cytotoxic reactive oxygen species (ROS). However, the utility of porphyrins has been hampered by low biocompatibility, lack of targetable delivery, and limited photophysical properties. The current invention describes a method for incorporating emissive porphyrins into proteins that offers a novel platform to enhance both oxygen sensing capabilities and targeted delivery to tumors. The bioluminescent proteins described not only have promising photophysical properties for biological use, but also are readily modifiable, biocompatible, and biostable. (more...)

Enzyme-based logic gates and their networks are recent developments in the field of biochemical information processing or biocomputing. Chemical logic gates mimic Boolean logic operations and are composed of chemical systems where the input and output signals are represented by concentrations of reactants and products, respectively. In particular, enzyme-based logic gates perform enzyme-biocatalyzed reactions resembling properties of Boolean logic systems. (more...)

The present invention relates to a system and method to provide item-level monitoring of environmental quantities including, but not limited to, temperature, humidity, air gas components, radiation. (more...)

Nanotechnology applied to medicine provides new approaches for the diagnosis and treatment of diseases. Ultrasensitive imaging for early detection of cancers and efficient delivery of therapeutics to malignant tumors are two primary goals in cancer bionanotechnology. However, developing nontoxic, functional nanoparticles that can successfully home to tumors presents some significant challenges. An emerging theme in nanoparticle research is to control biological behavior and/or electromagnetic properties by controlling shape. (more...)

The invention provides a method to identify women subjects with symptoms of menopausal transition who will benefit from hormone replacement therapy. (more...)

Target definition is a critical step in treatment planning for radiotherapy. The success of the treatment hinges on the accuracy of the delineation of the target and organs at risk. One of the major difficulties with accurate target definition is that the target motion (for example, patient respiration) may cause significant motion artifacts in conventional free-breathing computed tomography (CT) scans. (more...)

Heart disease remains by far the major cause of morbidity and mortality in the US and other Western countries. Effective treatments for coronary artery disease (CAD) include statins and blood pressure medications. However, therapies involving different treatment strategies are needed to enhance clinical outcomes for heart disease patients. Researchers at UCLA have identified a 5-Lipoxygenase (5LO) as a possible target for pharmaceutical intervention in CAD. The gene may further be used as a genetic diagnosis of individuals with predispositions to CAD. (more...)

Various diseases of iron metabolism are caused by abnormal hepcidin production, either too much or too little. In the case of anemia of inflammation, the production of hepcidin is stimulated by various cytokines including IL-6. Increased hepcidin levels cause the loss of ferroportin from the surfaces of macrophages engaged in the recycling of iron from senescent red cells. As a result, iron is trapped in macrophages and blood iron concentration decreases, restricting the flow of iron to the bone marrow, and thus slowing the production of hemoglobin and consequently decreasing the production of erythrocytes. In another iron metabolism disease, juvenile hemochromatosis (JH), the decreased expression of hepcidin, is the result of the mutations in the HJV gene. The decreased expression of hepcidin results in severe iron overload. (more...)

Conventional chemotherapy, currently used in the treatment of cancer is not capable of differentiating between cancer cells and any other cell types with elevated metabolism. Therefore, normal tissue toxicity is the limiting factor of non-specific chemotherapeutics. To avoid destruction of normal cells, targeted cancer therapeutics are delivered specifically at the tumor site, where they exert their cytotoxic effect. Targeting is achieved via recognition of a specific tumor antigen that is abundantly expressed by the tumor cells and either completely absent or present in miniscule amounts in normal tissues. Successful targeting of a tumor antigen is a function of both specificity and affinity; however the serum pharmacokinetics (PK) of the agent defines its bioavailability and ability to achieve maximum anti-tumor effect. Furthermore, PK is crucial in molecular imaging applications, where the tumor targeting molecule may be a carrier of a positron or gamma emitting radionuclide (PET, SPECT), or a paramagnetic agent (MRI). The PK profile of the carrier molecule controls how early suitable contrast is achieved, in order to differentiate the disease from the general background. It is important to note that the optimal PK for therapy is not suitable for imaging and vice versa. Therefore, it is absolutely advantageous to be able to control the PK of targeted anti-tumor drugs and diagnostics for achieving maximum tumor killing and acquiring unambiguous images, respectively. (more...)

The number of people with diabetes continues to increase in the United States. The medical complications associated with diabetes are very serious. Diabetes is the leading cause of blindness, kidney failure, and limb amputation, and a major contributor to cardiovascular disease mortality. Current tests for diabetes include the Fasting Plasma Glucose (FPG) test and Oral Glucose Tolerance Test (OGTT). These tests are time consuming, invasive, require overnight fasting and long seating time, and are not practical for routine screening. In addition, these tests do not provide reliable pre-diabetic screening. Furthermore, although insulin and other drugs exist, many patients suffer adverse effects or become resistant to these drugs over time. Therefore, there is a need for an efficient test that can predict risk for diabetes and to diagnose the disease. Novel methods for the prevention and treatment of type 2 diabetes would also be beneficial. (more...)

The vast majority of Type 1 diabetes (T1D) patients have sera which contain auto-antibodies and T cells reactive to glutamic acid decarboxylase (GAD) and/or peptide fragments of GAD. The present UCLA invention involves the cloning and production of GAD polypeptides for use in detection of autoantibodies and T cells reactive to GAD in biological samples. This method, therefore, may be developed into antibody and T cell-based diagnostic kits for identifying individuals at risk of developing T1D and to distinguish late onset T1D patients from Type II diabetes patients. Furthermore, the invention may also be used for purposes of screening drugs, such as those that alter GAD function, and for generation of polyclonal and monoclonal antibodies which, in turn, can be used diagnostically to detect GAD. Please see http://techtransfer.universityofcalifornia.edu/NCD/20095.html  for diagnostic and therapeutic strategies for IDDM based on TH1 and TH2 responses. (more...)

The invention is the discovery of several new forms of secreted IgE. These forms have potential applications in the diagnosis of immediate hypersensitivity-allergic disease. Previously thought to include only one or two forms, UCLA researchers have now determined that circulating IgE is expressed in four different forms. These four specific forms, which primarily differ at their C-terminal ends, are believed to have differential specificities and binding affinities for the cells that cause allergic reactions (mast cells/basophils). Currently, serum tests of allergic antibodies (IgE) measure either total IgE protein or IgE vs. specific allergens, essentially measuring this family of proteins as a single type. By establishing a set of solid phase IgE immunoassays for these different forms of IgE, it should be possible to establish far more accurate diagnostic tests for human IgE-mediated hypersensitivity disorders related to specific allergens such as ragweed, dust mite, etc. (more...)

Increasing concerns about biological hazards of minute quantities of lead have recently resulted in downward revision of national toxicity standards from the previous 40 micrograms lead/deciliter of blood to 20g lead/dl, creating a need for sensitive biomarkers of very low body burdens. Currently available tests are subject to numerous limitations such as unreliability and lack of sensitivity for values below 10-20g/dl. This limitation is significant because blood lead concentrations in this region have recently been shown to induce irreversible neuropsychologic damage in children. Another limitation of currently available tests is that blood lead concentrations generally reflect recent acute exposure rather than total body burden. Furthermore, traditional tests for lead overburden, such as blood lead, free erythrocyte protoporphyrin, and -amino levulinic acid synthetase, have no internal controls to adjust for patient variables such as anemia, exposure to other substances, age, gender, ethnicity or sex, any of which might skew test results. (more...)

Head and neck squamous cell carcinomas (HNSCCs) are a heterogeneous group of tumors that make up the 6th most common malignancy in humans. Despite improvements in treatments over the last decade, the prognosis for patients with HNSCC has more or less been unchanged. This is because patients continue to die from metastatic disease at regional and distant sites. Currently, the detection of nodal metastasis and extracapsular spread (ECS) is based on routine histopathological evaluation of the lymph nodes in the neck. Histopathological evaluation involves surgical neck dissection procedures that seriously impact patients quality of life. Also, the detection methods are not accurate. In 10-20% of individuals who have been clinically diagnosed with metastasis-positive lymph nodes (N+ individuals) and have undergone surgical procedures, find that they are metastasis-free (N0 status). Clinical diagnosis of N0 individuals is even less accurate. One-third of clinically diagnosed N0 individuals have metastasis-positive lymph nodes in the neck. Due to the lack of accuracy in clinical diagnosis, there is a need for molecular biomarkers to be available and included in clinical work-up strategies for patients. (more...)

Currently real time PCR is dependent on the detection of amplified DNA using optical device, which is expensive and limits the portability. As the demand for rapid, point-of-care diagnostics continues to rise, there is a need to find attractive solutions. Electrochemical biosensors have become a potential solution due to the minimal instrumentation that is needed and its scalability. However, the challenge arises with the integration of electrochemical biosensors into microscale devices. Currently, microscale devices, such as chip-based PCR, enable the user to use small quantities of reagents to detect biological samples. Even so, sequence-specific detection of PCR products is not integrated and does not detect PCR products in real-time. Therefore, there is a need for a microscale PCR device integrated with the real-time monitoring of electrochemical biosensors. (more...)

Detection of serum-derived antibodies against microbial antigens is routinely used for the diagnosis and prognosis of some infectious diseases. In the past 10 years, strong evidence has emerged to support the theory that the human immune system also mounts spontaneous humoral responses against autologous tumor-associated antigens (TAA). Up to now, there are at least 1800 TAA identified based on recognition by antibodies present in patients sera. These TAA include targets from many cancer types, such as melanoma, renal cancer, Hodgkins disease, esophageal cancer, lung cancer, colon cancer, gastric cancer, breast cancer, prostate cancer and so on.The discovery of these TAA awakens the old hope of finding serological markers for cancer detection, diagnosis and prognosis. However, the development of a sensitive, cost effective and comprehensive cancer diagnostic based on serological profiles to TAA has been limited by practical problems. For example, most of the antigens react with few - or no -- allogeneic sera. This indicates that an effective diagnostic for a given cancer must test for the presence of antibodies to a large number of TAA associated with that cancer. Such a test would require the recombinant production and purification of multiple TAA proteins, which is expensive and difficult to achieve. Multiplying these problems by each cancer for which a screen is desired makes developing a comprehensive test unfeasible.What is needed is a platform solution that enables the sensitive detection of serum antibodies to multiple TAA for multiple cancers. (more...)

With the rapid advances of modern pharmacology, effective drugs have been discovered for many diseases; however, most of those drugs have undesirable side effects due to their inability to distinguish between diseased and healthy cells. For instance, chemotherapy that is commonly used for treatment of cancer does not only target the cancer cells, but also damages healthy cells. (more...)

Ataxia-telangiestasia (A-T) is a rare genetic disease that presents in early childhood and progresses to various neurodegenerative disorders. The clinical symptomatology of A-T is primarily characterized by a degenerative state of the brain known as cerebellar ataxia and the subsequent formation of spider-like veins in the corners of the eye referred to telangiectases. Further manifestations of the disease often result in immunodeficiency, increased susceptibility to malignancies and hypersensitivity to radiation. As the phenotypes of the A-T gene are well defined, the disease is often diagnosed from the characteristic symptoms. However, this process is not completely accurate nor does it provide insight into the etiology of the disease. Moreover, early detection is also limited as parents of A-T afflicted individuals are asymptomatic for the gene is inherited in an autosommal recessive manner.The identification of the A-T gene and the isolation of a mutated A-T gene (ATM) in recent years have made genetic screening possible. (more...)

Lung cancer causes more deaths than the next three most common cancers (colon, breast, and prostate) combined, accounting for more than 174,000 new cancer diagnoses and greater than 160,000 deaths each year. In lung cancer management, surgical resection is generally beneficial only for early-stage disease, and even if diagnosed when the tumor is still localized in the lung, about 50% of the cases will succumb to relapse and subsequent death. Therefore, it is critical to understand details of the biologic features of lung tumor cell proliferation and to develop targeted therapies aimed at specific proteins involved in these biologic behaviors. As well known, smoking is the most important cause of lung cancers accounting for 90% for the men and 70% of the cases in women. Life-time smokers have 20 to 30 fold higher risk of developing lung cancer compared to life-time non-smokers. However, only 11% of heavy smokers ultimately develop lung cancer, suggesting implication of genetic factors predisposing to lung cancer risk. Identification of the genes that undergo frequent somatic mutation in the lung, the so-called lung cancer genes, should facilitate the development of effective treatment as well as better detection and prevention strategies. (more...)

Over the past decade, the field of microfluidics has begun to show great promise for research assays and diagnostics as well as for clinical applications. The field has evolved from devices comprised of simple microfluidic channels into complex devices that can mix fluids, pump liquids, perform digital logic, etc. Flow cytometry provides the field with a technology base from which both microfluidic and photonic components can be developed and integrated into a useful device. (more...)

Quantification of pulmonary blood flow (PBF) is essential for the assessment of efficient gas exchange. The ability to quantitatively evaluate changes in regional PBF (rPBF) can enhance our understanding of the relationship between lung structure and function in both health and disease. Aerial spin labeling (ASL) is a powerful MRI technique for noninvasive perfusion imaging of organs. It uses arterial blood water as the endogenous contrast agent without the exposure of ionizing radiation, the limitation of spatial or temporal resolution, or the need for an exogenous contrast agent, making possible for this non-invasive procedure to be widely available at relatively low cost. Pulsed ASL techniques have been validated for cerebral blood flow; however, because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain. (more...)

UC San Diego researchers have developed an extensive platform of technologies based on porous silicon and/or polymeric nano-particles (“smart dust”). This platform encompasses multiple uses of nano-scale particles of porous silicon photonic crystals and takes advantage of the optical properties and other physical characteristics of this material. (more...)

Carcinoma of cervix is the major malignancy of women. For cervical cancer diagnostics, there are about 55-million Pap smear tests performed every year in the United States. Pap smear screening for cervical cancer can result in 20% to 40% of false-negative results that lead to sometimes painful biopsies and put women at risk for pregnancy complications such as preterm labor and low-birth weight infants. Therefore there is a great need for a more accurate test of developmental stages of cervical cancers. (more...)

This technology includes systems and methods that provide a comprehensive high-throughput approach toward the sequential identification, prioritization, verification, and validation of etiologic factors in neuropsychiatric disorders, some of which can also be utilized as biomarkers for these illnesses. The systems and methods determine patterns of gene expression in various tissues from various samples under various experimental and non-experimental conditions, and use the differences and similarities between the gene expression profiles observed under these conditions to delineate distinct gene expression profiles of risk and treatment of neuropsychiatric disorders. Specifically, this technology provides a method to detect brain disease, including neuropsychiatric disorders, cancer, stroke, or any disease affecting the brain, by using a novel combination of biostatistical analysis and genetic profiles to match the gene transcripts in peripheral blood. (more...)

Researchers in the School of Engineering at The University of California, San Diego, have invented a novel laser trapping technique for manipulating, analyzing and parallel sorting of self-propelled cells (sperm, algae, bacteria) based on mobility and biotropism. A unique optical design is used to create a tunable 3-D annular trap (tens to hundreds of microns in diameter) with high-power efficiency and constant numerical aperture. The laser trap only provides optical confinement in the radial direction.  The design is different than the single spot laser trap which focuses hundreds of milli-watts to immobilize a single sperm; the annular trap can be used to investigate and sort tens to hundreds of sperm in parallel, and distributes only tens of milli-watts on a sperm to allow study of sperm dynamics.  A functioning optical apparatus has been assembled and has yielded preliminary experimental data. (more...)

MR perfusion imaging based on arterial spin labeling (ASL) uses arterial blood water as the endogenous contrast agent, making possible for this non-invasive procedure to be widely available at relatively low cost. To date, most perfusion studies carried out by MRI have obtained perfusion maps that include contributions from all the arteries feeding the brain. In perfusion territory imaging, blood in individual or groups of feeding arteries are tagged separately and the images acquired map the vascular distribution of those feeding arteries. A researcher at UC San Diego has developed a non-invasive mapping approach of perfusion territories using MRI. It allows one to place a person in an MRI scanner, without the use of any exogenous agents, and map the tissue regions that are supplied with blood from different feeding arteries in a time-efficient manner practical for clinical applications. Compared to the pulsed methods developed for this use by others, the UC San Diego’s pseudo-continuous tagging approach is superior in four ways: • Higher SNR • Better vessel selectivity • Flexibility in tagging geometry • Potential for separation of vascular territories above the Circle of Willis in the brain The relative tagging efficiency for each vessel is measured directly from the ASL data and is used in the decoding process to improve the separation of vascular territories. High SNR maps of left carotid, right carotid, and basilar territories are generated in six minutes of scan time. Software has been developed on a GE MRI scanner and can be adapted to other MRI scanners. (more...)

UCSD inventors have come up with an approach to patient selection and assessment of response to therapy that is very different from traditional pharmacogenomic approaches. This novel approach allows doctors to make various health prognosis tailored to individuals. It can also be used to estimate the life span, predisposition to diseases, and reaction to various chemotherapies in a variety of patient groupings. This invention would allow a company to profitably leverage the large sets of genome data soon to be available. (more...)

One of the most widely used techniques for functional brain imaging is magnetoencephalography (MEG), which works by measuring the magnetic fields generated by the electrical activity in the brain. It can measure the brain’s neuronal activity with millisecond temporal resolution. Because the brain’s magnetic field is considerably smaller than the magnetic noise within an urban environment, extremely sensitive measurement devices have been developed to measure MEG. In order to reduce the ambiguity that inevitably results from measuring such a signal weaker than the white noise of an urban environment, additional specific assumptions must be made about the nature of the neuronal sources (termed “source models”). Several problems are often associated with these source models, ranging from the lack of ability to produce high quality images to unrealistic assumptions. Minimum L1-norm solution source models, which provide high spatial resolution images, have been used by many investigators to analyze MEG responses. However, conventional minimum L1-norm approaches suffer from instability in spatial construction, and poor smoothness of the reconstructed temporal courses. One often sees activity “jumping” from one grid point to the neighboring grid points and the temporal-course of one specific grid point can show substantial “spiky-looking” discontinuities. (more...)

Brain development and aging, as well as neurological and psychiatric disorders are often associated with structural changes in the brain. Alzheimer’s Disease (AD) is one such neurological disorder, which afflicts up to 5.2 million people in the U.S. alone. Unfortunately, the diagnosis of AD relies on such limited tools as behavior monitoring and performance on standard neuropsychological tests. If therapy is to be maximally effective, AD needs to be correctly diagnosed as early as possible. (more...)

Researchers at UC San Diego 's BioEngineering Department have recently developed a novel new dielectrophoretic (DEP) system for cell separation that will possess great advantages over state-of-the-art systems. Existing DEP technologies rely upon the difference in crossover AC frequencies between various cell populations to separate them into distinct groups. The technique becomes less effective as the cell types become more similar and the surrounding fluid becomes more complex (higher ionic strength), as in whole blood. This problem is overcome by the present invention, which will allow cell separation to be carried out under high ionic strength conditions.  (more...)

Researchers at the University of California, Irvine have developed an improved method utilizing microfluidic systems for the controlled generation of dual-layer microbubble lipospheres that may be used for drug delivery. (more...)

Cardiac arrhythmia is the leading cause of death in adults. Arrhythmic sites and triggers of arrhythmia can be precisely mapped by programmed electrical stimulation and intracardiac recordings. Arrhythmias occur preferentially in areas derived from developing cardiac conduction system (CCS) (which consists of the sinoatrial node, atrioventricular node, and His-Purkinje fibers). Abnormalities in CCS development have been postulated to predispose individuals to arrhythmias and sudden death. Therefore, an understanding of genes and signaling pathways underlying CCS development is of critical importance to gain molecular insights into human cardiac arrhythmogenesis and to develop effective interventive and regenerative therapies. Cellular automaticity and excitability in the CSS result from activities of a diversity of ion channels. The pacemaker current is encoded by a family of Hyperpolarization-activated, Cyclic Nucleotide gated (HCN) channels and plays a key role in the generation and autonomic regulation of sinus rhythm and rate. Four mammalian HCN isoforms (HCN1–4) have been identified, of which HCN4 is most abundantly expressed in the sinoatrial node. (more...)

BACKGROUND:  Patients with certain types of tumors, in particular brain tumors, will frequently rely on radiologic imaging, such as magnetic resonance imaging (MRI), for diagnosis and treatment monitoring. Unfortunately, MRI and similar modalities are often subject to interpretation and can be highly subjective in nature, making it difficult to differentiate between actual tumor recurrence and treatment effect. Subsequent or alternate methodology involving biopsy or other surgical procedures, can be highly invasive, dangerous, and lead to an extensive recovery time in patients undergoing such procedures. A less invasive method to reliably identify tumor recurrence would be valuable to clinicians and their patients during evaluations following treatment and/or surgical resection of a tumor.   TECHNOLOGY:   UCSF inventors have discovered a novel cancer biomarker that is expressed on the surfaces of myeloid cells, so that tumors can be evaluated for recurrence by screening small amounts of peripheral blood in patients. So far, these findings have been done in glioblastoma and prostate cancer patients, but further studies are underway for other types of solid tumors. (more...)

Colon cancer is the second leading cause of cancer deaths in the US and is the third most common cancer worldwide.  The National Cancer Institute estimates 147,500 new cases and over 57,000 deaths in the United States in 2003, with a greater incidence in men than women. UCSD investigators have shown that decreased expression of 2 anti-apoptotic proteins in colon epithelial cells can inhibit colon cancer progression.  Raising the expression of these 2 anti-apoptotic proteins in colon epithelial cells contributes to colon cancer development or progression.  These 2 proteins work through the cyclooxygenase (COX)-2 pathway.  COX-2 is overexpressed in colorectal cancers and its inhibition has a cancer-protective effect. (more...)

UC San Diego researchers have developed a new nanotechnology platform called "smart dust" with state-of-the art applications in almost every field of use, ranging from biological sensing and screening to communications technology. The invention utilizes micron-sized particles of silicon that have been etched and then chemically modified in such a way that each individual particle has its own addressable identity. This feature allows one to use thousands of particles together, each with its own tag, for high-sensitivity chemical or biological sensing, diagnostics, and low- and high-throughput screening of biomolecular compounds. The method does not require the use of fluorescent tags, but could be used in conjunction with them. (more...)

Today there are a variety of treatment options for cancer, but many are non-specific, which results in normal cells being destroyed along with the malignant ones. Anemia, fatigue, immunodeficiency, and vomiting are just a few side effects of chemotherapy. Current monoclonal antibody lymphoma treatments most B cells in the patient, thus crippling the immune system. Rare infections and skin cancers can result. Moreover, a specific marker for Chronic Lymphocytic Leukemia (CLL) does not exist on the market today. Patients "wait and see" if the symptoms progress in the early stages of the disease before a diagnosis is made. Instead of being treated immediately, the disease could lurk for years. Detection of residual disease after therapy is problematic as well. (more...)

Therapeutic options for patients with chronic lymphocytic leukemia (CLL) are limited, and in most cases ineffective, or with a limited period of effectiveness. Relapse of the disease often occurs and patients acquire resistance, not only to the drug used, but to other drugs as well. Moreover, a specific marker for CLL does not exist on the market today. Patients ‘wait and see’ if the symptoms progress in the early stages of the disease before a diagnosis is made. Instead of being treated immediately, the disease could lurk for years. (more...)

Protein tyrosine phosphatases (PTPs) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. PTPs have a seminal role in human health and disease. A subset of PTP is known to dephosphorylate a unique group of signaling molecules collectively termed phosphoinositides (PI). Phosphoinositides regulate metabolism and growth by altering the activity of a variety of cellular enzymes, thus playing a critical role in achieving proper cellular responses to outside stress. PTP localized to the mitochondrion (PTPMT1) is a member of this PTP superfamily. While mitochondria are responsible for the production of over 90 percent of the cell’s energy, they are also the site of more specialized mitochondrial functions in various tissues, such as orchestrating the coupling of glucose metabolism to insulin secretion in pancreatic Beta cells. Disruption of these and other mitochondrial functions is known to result in more than forty diseases, including diabetes. Despite the level of effort given to mitochondrial function during the past fifty years, researchers have a limited understanding of the role of phosphorylation within this organelle. (more...)

The prevalence of unipolar depression (major depression) in the U.S. is 5 to 10 percent, with women having approximately a two-fold greater risk than men. In contrast, the prevalence of bipolar disorder (manic-depressive illness) is approximately 1 percent, is less variable, and affects men and women equally. There is a strong familial association for unipolar, as well as bipolar disorder. Bipolar disorder is characterized by cycling mood shifts of mania and depression, and the depressive episodes of bipolar patients are virtually indistinguishable from those of patients with major depression. Thus, misdiagnosis of bipolar disorder is common and as many as 40 percent of bipolar patients are initially misdiagnosed. It is also not uncommon for clinicians to misclassify bipolar patients as depressed or schizophrenic on the basis of their mental status. This may lead to serious problems, particularly in the administration of medications that may critically worsen the patient’s physical and mental status. (more...)

UCSD researchers have developed an invention useful for: augmenting immunity (both cellular and antibodies) against cancer and infectious diseasesExpanding immune cells (B cells, dendritic cells, macrophages and T cells) in vitro for reinfusion of them or their productsImmunological testing of immune function. In one embodiment, the invention is a soluble recombinant fusion protein containing multiple CD40 ligands ("CD40L"). This protein affects macrophages and B cells in the same manner as membrane CD40L. The same technology can be applied to produce other members of the TNF family, such as TNF-alpha, FasL, TRAIL, RANKL, 4-1BBL, and others. (more...)

Chronic lymphocytic leukemia (CLL) is a disease that leads to the fatal accumulation of B cells. It is the most common adult leukemia. The cause of CLL is unknown and there are no animal models of this disease. There are two forms of CLL, indolent and aggressive. Patients with aggressive CLL should immediately undergo chemotherapy but patients with the indolent form should not be treated. Currently there are no biomarkers that enable the facile distinction of the two forms of CLL and, consequently, patients do not always receive the appropriate treatment. (more...)

An ultrathin silicon nitride membrane has been fabricated and tested to be useable in temperatures in excess of 1000 °C with mass flux rates several orders of magnitude greater than existing technlogies. Pore shape and size are also tunable. (more...)

The present invention is related generally to a method for screening subjects to determine those subjects more likely to develop diabetes by quantization of insulin producing cells. The present invention is also related to the diagnosis of diabetes to monitor disease progression or treatment efficacy of candidate drugs. (more...)

Current nanoparticle-based approaches for treating disease include constructs composed of polymer, silica, gold nanoparticles, liposomes, or carbon nanotubes, to name a few. These structures are typically coated with a variety of functionalizing entities such as polyethylene glycol (to increase biocompatibility) and may be conjugated to various targeting peptides, antibodies, small molecules, or some form of therapeutic. A major disadvantage of these approaches is the need to develop complex conjugation chemistries for targeting specificity, biocompatibility, and drug incorporation by nanoparticles. Another limitation of this approach is the frequent requirement of additional clinical testing of the new nanoparticle coatings and entities. DNA itself provides a simpler nanoparticle approach. One of the most thoroughly characterized molecules with regard to physical structure, chemistry, and modification, DNA may be employed as a scaffold for the integration of varying entities due to its well defined ability to base-pair hybridize. Also, DNA particles may be easily loaded with DNA-binding chemotherapy agents. (more...)

Detection and quantification at the level of single molecules is the ultimate goal of analytical assays. This sensitive, platform technology could transform diverse fields, from environmental monitoring and medical diagnostics to the fundamental studies of chemical and biochemical processes. The early potential of synthetic, ion channel-forming peptides was has not been realized; one factor of many has been the inability to translate the technology to low cost, large scale production of stable and portable devices. The absence of generalized modalities for sensing a broad range of analytes left few incentives to clear the hurdles. (more...)

Multifunctional nanoparticles have the potential to deliver both therapeutics and diagnostics to tissues simultaneously using a single nanodevice. To date, several types of hybrid nanosystems have been developed and used in vitro for magnetic cell separation and targeting. However, the in vivo utility of these nanocomposites may be limited due to poor stability or short systemic circulation times. Furthermore, existing technologies do not adequately allow for co-delivery of a therapeutic and an agent enabling advanced diagnostic imaging. (more...)

UCSF scientists have identified novel compounds to treat glaucoma. Specifically, topical or intraocular application of synthetic thyroid hormones increases aqueous outflow. Scientists have uncovered the direct biochemical mechanism by which synthetic thyroid hormones may reduce IOP. Based upon this knowledge, they have developed methods to screen for novel therapeutic drugs that target this pathway and lower IOP in glaucoma patients. (more...)

UCSF investigators have demonstrated that breast cancer cells express a specific protein epitope that has not previously been recognized in cancer cells, and expression of this epitope correlates with the breast tumor subtypes. The protein epitope could be used as a biomarker for screening metastatic-prone cancer, and modulation of the epitope may block the cancer metastasis. The investigators analyzed approximately 50 breast cancer cell lines derived from primary breast tumors obtained from women of various ethnicity and age groups. The genetic expression patterns of these cells lines have been extensively analyzed and shown to mirror those of primary breast tumors and clustered into luminal- and basal-like subtypes similar to primary tumors. (more...)

UCSF researchers have identified novel biomarkers of CMV replication that permit early detection of virus transmission before the onset of symptomatic disease. Quantification of these biomarkers is a more sensitive and reliable method than detection of viral DNA and therefore could result in novel tests for diagnosis of congenital infection in early gestation. Additionally, these biomarkers could be used to measure efficacy of treatment in pregnancies at high risk for congenital CMV disease and to serve as endpoints for successful antiviral therapy. (more...)

Magnetic resonance angiography and arterial spin label perfusion techniques are currently used for imaging the vasculature and hemodynamic state of the brain. These techniques have important applications in the detection and treatment of various diseases such as stroke, tumors, vascular malformations, Alzheimers, and epilepsy. However, current techniques require background suppression methods to increase the contrast-to-noise ratio during imaging. This involves the subtraction of label and control images to remove background noise. As a result, image time is increased, leading to a greater chance of movement from the patient, thus further degrading the images.An imaging sequence developed by a UCSF investigator provides a new spin-lock method of background suppression for time-of-flight imaging. While previous methods have used the spin-lock technique to store angiographic signal, this novel method uses spin-lock to eliminate static tissue signal. Additionally, the use of this method could be extrapolated to other organ systems, such as the heart. (more...)

Membrane type serine protease 1 (MT-SP1), or matriptase, is a serine protease that is over-expressed on the surface of epithelial cells involved in a variety of cancers, including breast, colon and prostate. UCSF inventors have developed a novel antibody inhibitor of MT-SP1 (A11) which gains potency and specificity through interactions with the protease surface loops and binds in the active site in a catalytically non-competent manner.  The A11 antibody has applications as a therapeutic, diagnostic, and research tool. (more...)

BACKGROUND: Vaccine targets for prostate cancer have generally been identified either by tissue specific expression in prostate cancer or by assessing immune responses in cancer patients. However, UCSF investigators have taken a novel approach to identify the targets of an immune response in patients who are either responding or not responding to an immune-based treatment (anti-CTLA4 antibody) in a clinical trial at UCSF. CTLA4 blockade with antibody treatment can augment endogenous anti-tumor immunity in animal models and is being developed as an immunotherapy for cancer patients. Defining the antigen-specific responses induced by this treatment can lead to immunological identification of therapeutic targets that may be relevant in prostate cancer patients. These studies provide a unique opportunity to determine the antigen-specific responses that are relevant for immune-mediated clinical responses in prostate cancer, can provide opportunities to predict which patients may respond to therapy, and can provide novel approaches to prostate cancer treatment and vaccination. DESCRIPTION: UCSF investigators found that immune-mediated clinical responses to CTLA4 blockade is seen in the absence of a specific vaccination, suggesting that endogenous antigen-specific immune responses can be potentiated through this treatment. By focusing on immune responses unique to those patients that responded to immunotherapy, the UCSF investigators were able to identify candidate antigens that correlated with clinical outcome in prostate cancer patients. In addition, a patient’s immune response to the prostate cancer-associated antigens can be used as a diagnostic assay to determine the likelihood that an individual having prostate cancer will exhibit a clinically beneficial response to an immunomodulatory treatment. Furthermore, targeting these antigens with antibodies and/or vaccination may lead to novel therapies for prostate cancer. One antigen in particular has shown promise because it is expressed at a higher intensity in prostate cancer patients and in prostate cancer cell lines compared to other previously described antigens. Kaplan-Meier survival curves for tumor challenge were plotted for C57BL/6 and FVB mice (5 control and 5 test mice per mouse model) that were immunized with a mouse homolog of the particular antigen. The mice were challenged with Tramp cells or Myc-Cap prostate cancer cells respectively. Immunization with the novel antigen induced anti-tumor responses in both models of prostate cancer. (more...)

The success of gene therapy methods such as small fragment homologous recombination and cDNA-based gene therapies is often difficult to quantify. These methods often lack an endogenous selection mechanism that can be used to differentiate and quantify targeted cells. Therefore, it is difficult to monitor and map the success of gene therapy in patients. UCSF investigators have developed methods and compounds enabling the measurement of expression of mutated and non-mutated alleles in the tissue or cells of a human subject. The method, an in situ RT-PCR assay, can be used for diagnosis of allelic variation and the monitoring of gene therapy for a variety of gene-based diseases, especially cystic fibrosis. (more...)

BACKGROUND: In recent years, there has been a dramatic increase in the incidence of diabetes worldwide. According to the International Diabetes Foundation, about 246 million people worldwide have diabetes and this number is expected to increase to 380 million by 2025. Type 2 diabetes accounts for about 90% of all cases. The current gold standard for diagnosing diabetes is a test for elevated blood sugar level following an overnight fast. Another test frequently used is the oral glucose tolerance test. However, these tests based on blood glucose can overlook approximately 25% of people who will develop type 2 diabetes, yet have normal blood glucose levels several years before diagnosis. Just in the US alone, 57 million people have pre-diabetes with blood glucose levels that are higher than normal but not high enough to be classified as diabetes. Recent research has shown that some long-term damage to the body, especially the heart and circulatory system, may already be occurring during pre-diabetes. Therefore, there is a need for assays to detect risk for type 2 diabetes a) prior to the onset of pre-diabetes as well as b) in individuals who have normal blood glucose levels. DESCRIPTION: Researchers at UCSF in collaboration with researchers at the University of Catanzaro have discovered mutations in a nuclear regulatory gene that are predictive of type 2 diabetes. The gene encodes a transcription factor necessary for cells to make insulin receptor, and low levels of insulin receptor lead to insulin resistance and type 2 diabetes. Researchers sequenced genomic samples from 3000 type 2 diabetes patients and 2000 sex and age matched non-diabetic controls. These mutations were observed in 10% of type 2 diabetes patients, while mutations were observed in less than half a percent of control patients. Since these mutations were 20-fold lower in controls, a robust diagnostic with high positive predictive value can be developed. Such a gene-based approach to assessing susceptibility to type 2 diabetes provides a more definitive diagnosis than todays diagnostics, allowing physicians to change patient care. Furthermore, genetic tests are accurate as early as infancy, when diet and exercise habits are being formed. (more...)

BACKGROUND: Breast cancer is one of the most commonly diagnosed cancers among women in the US. There are 2.4 million women living with breast cancer in the US and upwards of ~180,000 new cases each year. Breast cancer tumors are currently evaluated on the basis of several histopathological features including tumor size, grade, and lymph node status, all of which contribute to assessing the overall stage of cancer development. In addition, hormone receptor (ER, PR) and HER2 expression in tumors, together with the histopathological features, are used to classify the progression of the disease (e.g. tendency to stay localized or metastasize) and thus currently provide the rational basis for aggressiveness of treatment. Despite these common biomarker analyses and the information they provide regarding molecular features and stage of breast tumors, they still do not enable accurate predictions as to which early stage breast cancers will progress or recur if removed surgically; thus, many women with breast cancer end up being over-treated or under-treated for the disease. For example, some women receive chemotherapy or anti-hormone therapy, which both can reduce the risk of metastasis by one third but also can have dangerous side-effects. Moreover, 70-80% of patients receiving these treatments could have survived without them, as those patients presumably have a less aggressive form of breast cancer. In addition, 40% of women diagnosed with breast cancer die from the disease regardless of the treatment regimen, and there are no reliable biomarkers to predict the fate of this subset of breast cancers as of yet. Thus, the current cellular, molecular, and histopathological classifications of breast cancer have limited prognostic ability. There is a need for a more accurate means of predicting the progression of breast cancer in a wider range of cases in order to improve the selection of patients for adjuvant treatments such as systemic chemotherapy. DESCRIPTION: University College Dublin and UCSF investigators have discovered that the immune environment around tumor cells can influence the outcomes of cancer patients. Specifically, they have found that the relative expression of three leukocyte proteins can predict the clinical outcome of breast cancer patients. This “immune signature” has been validated by evaluating the progression-free survival of two independent cohorts of invasive breast cancer patients that had 5 year follow-up data available, now totaling about 1000 samples. Based on relative protein expression as a measure of leukocyte infiltration, assessed in a multivariate manner, the investigators found that the biomarkers could be used to predict clinical outcomes, such as recurrence or metastatic progression, of early stage breast cancer. Importantly, these predictions can be made independently of tumor grade, stage, lymph node status, and ER, PR and HER2 gene expression, indicating that the immune signature is applicable to a wide range of breast cancer types. The investigators have also provided compelling evidence from 5000 samples that two of the markers could be assayed at the RNA level to predict outcomes (see Denardo et al 2011). While most other breast cancer tests currently available focus on genes expressed within the cancer cells themselves, this signature focuses on the immune environment and its influence on the cancer cells. Therefore, the signature has the potential to stratify and classify different groups of patients than current tests on the market. Specifically, the investigators believe that the main utility of the immune signature biomarkers will be to identify patients with tumors designated as "high-risk" under current classifications, but whose immune environment may nonetheless suppress aggressive growth and distant metastases. These patients would normally be prescribed adjuvant therapy, but may do well even in the absence of toxic adjuvant therapy. Conversely, patients with tumors designated as "low-risk" by current classifications may possess an immune environment that is permissive or promotes progression of the tumor. These patients normally would not be prescribed adjuvant therapy due to their "low-risk" status, however, their immune signature suggests that over the long-term, they could benefit from adjuvant therapy.  The investigators have also evaluated the utility of the signature in ovarian cancer and pancreatic ductal adenocarcinoma (PDAC) cohorts. (more...)

Scientists at the University of California, Irvine, have isolated a candidate gene that may be responsible for increasing the risk of schizophrenia and bipolar disorder. This elusive gene encodes for a potassium ion channel that acts like an "off switch" by dampening electrical activity in neurons. It has been known that street drugs such as PCP create schizophrenia-like symptoms by blocking NMDA receptors in neurons. Over-activity of this potassium ion channel blocks the same NMDA receptors, which psychiatrists believe may cause schizophrenia.The gene sequence contains the trinucleotide CAG repeats thought to cause neurodegenerative diseases such as Huntington's Disease and ataxias. Although specific proteins are still unknown, scientists have implicated the CAG repeats in mental illnesses.While the gene itself may not predict a person's chances of developing schizophrenia or bipolar disorder, its presence combined with other genetic risk factors and environmental stresses may increase susceptibility to the diseases. UCI researchers and their collaborators found that in schizophrenia patients, there was a significant excess of genes containing the CAG repeat sequences, a possible contributing factor to the molecular origins of the illness. Similar results were found in studies involving bipolar disorder. (more...)

Recently, activation of the P2Y12 G-protein coupled receptor (GPCRs) has been shown to be central to platelet aggregation. Drugs preventing platelet aggregation are being tested, but one that would be specific to the P2Y12 receptor would capture a large market share. Developing drugs for the P1Y12 receptor is difficult, because it is a receptor that is naturally activated by ADP. Since practically every cell expresses ADP-activatable receptors, developing a drug screening program directed specifically at the P2Y12 receptor has not been possible. (more...)

Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction. Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T lymphocytes (CTL) biased immune responses and are generally observed for proteins expressed in the intracellular compartment, and less prominently with extracellular or secreted proteins. Rapid degradation of a protein containing polyepitopes can contribute to establishing a bias in the immune response, facilitate antigen presentation and, perhaps assist in establishing specificity of the immune response. This type of immunological response should result in immunological cellular destruction. (more...)

University of California, Irvine researchers have developed a novel transgenic mouse model that contains the three major genes that contribute to the hallmark pathological features of Alzheimer's disease. These mice are exceedingly valuable for therapeutic investigations and for basic research aimed at understanding the behavioral, physiological, molecular/cell biological, and pharmacological processes leading to dementia in an animal model. Even though these mice contain three transgenes, the mice essentially breed as readily as a "single" transgenic line, greatly facilitating the establishment and maintenance of an animal colony. (more...)

In many disciplines, quantitative measurements of color are required to evaluate nondestructively the state of an object (e.g., quality of produce). This characterization is typically performed using contact point measurement devices. A limitation of these devices is that multiple measurements are required to characterize an entire object; if multiple objects must be characterized, then this process may be time consuming. Furthermore, these devices interrogate both superficial and deeper structures in the object, and do not possess the ability to discriminate between these structures. (more...)