Peroxisomes are degraded by various autophagic mechanisms, some specifically requiring peroxisomal membrane-associated acyl-CoA binding protein. UCSD researchers have demonstrated that inhibiting the binding activity of this protein will specifically prevent autophagic degradation of peroxisomes (specifically pexophagy but not autophagy in general), resulting in an increase of cellular peroxisomal mass.Increased peroxisome mass is known to have therapeutic effects in various neurologic diseases, including X-linked adrenoleukodystrophy, infantile Refsum’s disease and Alzheimer ’s disease.HDAC inhibitors or certain organic acids are often used to induse peroxisome proliferation, but both these approaches have clinical limitations. Small organic acids like 4-PBA (4-phenylbutyrate) have a short half life and over time the level of effectiveness has been observed to decrease in certain conditions. HDAC inhibitors have non-specific effects on gene expression, such as upregulation of related genes in the same pathway.There is therefore, an unmet need for a more specific approach to peroxisome proliferation.The investigators have identified a new selectivity factor for pexophagy, whose inhibition may provide a new approach to specifically increasing peroxisome number.  (more...)

Laparoscopic surgery is a minimally invasive surgical procedure, in which operations are performed via multiple small incisions. These have gained popularity over conventional open procedures since the smaller incisions result in reduced hemorrhaging, minimal scaring, reduced pain, shorter recovery times and reduced infection and contamination risks. However, laparoscopic surgeries face mid-surgery visibility loss due to fogging, bleeding or tissue smearing, and as such laparoscopic instruments must be removed and cleaned several times over the course of a procedure. To address these challenges, investigators at UC Berkeley have developed a self-cleaning laparoscope, which will circumvent to need to remove the instrument from the patient mid-surgery. In vivo cleaning will not only reduce surgery times but also reduce risk of complications and interruptions from removing and reinserting the instrument. In addition, visibility will remain high throughout the procedure. By encasing the imaging lens in a rotating sphere, no waste is introduced to the patient’s body and the optical pathway will remain clear. The self-cleaning laparoscope has a simple mode of operation, where it is controlled by an external switch on the handle area, and has the potential to eventually replace conventional laparoscopes. (more...)

Available for licensing are patent rights in a method of marking products and goods with unique identifiers, using safe and consumable polymers. The system of marking can be applied as a coating or intrinsic to single or multiple ingredients that become a final product, allowing for authentication of a good, inventory control, and as a means to combat counterfeit goods. (more...)

Currently, TB treatment requires a course of antibiotics taken for 6 months or longer. Since it is required that the patient adhere to the schedule of treatment, or else resistance will develop, practitioners must monitor the patient taking the drugs daily. This is labor intensive and burdensome to patients. Utilizing the Video Directly Observed Therapy (VDOT) system, the patient records his dose taken via phone-based video and this is transmitted to a server where it is stored for viewing by the provider. In the event a patient misses a dose (or is late) the patient receives a text message as a reminder. (more...)

University researchers have developed a new method and associated agents to reduce and remove fatty tissue. The method enables tunable melting of fat (lipolysis) and the tightening of skin only in surgeon-defined regions with fine spatial and temporal control. The technique has been demonstrated in vitro and animal trials are underway. (more...)

Certain diseases of metabolism may be the result of a decrease or blockage of one more autophagic pathways (pexophagy, mitophagy, or ribophagy). An example, such as SSADH (succinate semialdehyde dehydrogenase deficiency) which causes developmental delay, hypotonia and mental retardation. Patients exhibit increased levels of GABA and GABA metabolites, and UCSD researchers have found that this is indicative of blockages in autophagy-related pathways, which may account for the symptoms of the disease(s). Autophagy inducing drugs, such as rapamycin, may affect a decrease in the associated symptoms.Histone deacetylase inhibitors (HDACs), such as valproic acid, long used for epilepsy, seizures and mood disorders are now under investigation and development as anti-cancer drugs. They also block autophagy related pathways which may be the cause of severe side effects. It is possible that rapamycin, or related drugs or analogs, may provide a new approach to reducing the side effects of this class of therapeutic.   (more...)

Heparin and Low Molecular Weight Heparin (LMWH) are widely used anticoagulants, drugs which prevent blood clotting. However, they have the risk of potentially serious bleeding side effects. Protamine is currently the only approved drug used to reverse the action of heparin, and there is no approved reversing agent for LMWH. However, there are serious potential side effects associated with protamine. UCR researchers have demonstrated significant binding affinity in two synthetic peptide analogues of the HIP heparin-binding domain. Both peptide analogues have been found to be equally effective in neutralizing heparin activity using the Coatest heparin in vitro assay. Fig. Ball and stick model of s9-mer docked to heparin, shown in molecular surface format. For heparin, the sulfur atoms are shown in yellow, the oxygens are shown in red and the carbons are shown in white.   (more...)

Available for licensing are patent rights in a method of fabricating long, narrow ceramic ridges with sharp edges for the purpose of shaving, or other hair and tissue cutting purposes. The method can optimize the shaving capability of the blades by allowing for arbitrary variation in angle, size and position of the blades. (more...)

Infertility affects approximately 10% of human males, yet there are surprisingly few markers that aid in diagnosing this condition. A physical exam and semen analysis, which includes measuring sperm count, motility, and morphology, are the first steps in identifying the etiology of male infertility. However, the large natural variation in these parameters renders them poor indicators for fertility. The semen analysis looks for defects in sperm motility and morphology as well as a critical concentration of sperm. This method is not only a poor indicator of fertility, but a large number of men do not even have detectable defects by these analyses. There is currently no diagnostic tool for men who fall into this latter category. The X-linked reproductive homeobox (RHOX) gene cluster is a candidate to have roles in male infertility for several reasons. Reproductive Homeobox genes (Rhox) genes are a cluster of x-linked genes that are preferentially expressed in reproductive tissues in mice and in the testis in particular. The founding member of the gene family, Rhox5, is the only known direct target of androgen receptor and it is responsible for directing at least part of the androgen response in the testis. Knockout of Rhox5 leads to increased sperm apoptosis and subfertility, while knockout of another member, Rhox3, leads to a dramatic reduction in sperm number and testis size resulting in infertility. There is extensive evidence to support an inverse relationship between DNA methylation and the expression of several Rhox genes in mice. This is particularly significant for X-linked genes involved in spermatogenesis since changes at either the genetic or epigenetic level have direct penetrance for male infertility. (more...)

Exposure to organophosphates (OP) can lead to inhibition of acetylcholinesterase (AChE), a build-up of acetylcholine in the body, and potentially death. Every year, there are over two million suicidal cases and over one million accidental cases of OP poisoning from insecticides worldwide. Furthermore, terrorist attacks in the past have involved the use of different nerve agents to induce organophosphate poisoning. Current antidotes can reactivate OP-inhibited AChE in the blood and peripheral tissue, but are often incapable of crossing the blood-brain barrier to reactivate inhibited AChE in the brain. Thus, there is a strong need for an antidote capable of efficient reactivation and blood brain barrier penetration. (more...)

Conventional intermittent hemodialysis delivery (IHD) systems were designed for adult human hemodialysis, yet are routinely used for dialysis delivery to infants and small animal patients. However, these conventional systems are not sufficiently flexible to permit the slow rates of dialysis delivery that are necessary for patients that are severely uremic or small patients (less than 15 kg) including infants and companion pets. Researchers at the University of California, Davis, have invented an economical add-on system which slows the rate of dialysis delivery while preserving all the functionality of the conventional IHD delivery system. The system allows for a single IHD platform (machine) to provide both conventional IHD for typical applications and prolonged slow hemodialysis, for small or severely uremic patients, without requiring modification to the standard IHD delivery system. The requisite slow blood flow rate required for slow dialysis delivery to small or severely uremic patients (1 to 10 ml/minute) is typically below the approved operational design of conventional IHD delivery systems. Even if such slow blood flow rates are obtainable on conventional systems, they predispose the patients to clotting in the extracorporeal circuit during extended dialysis sessions.   Also, the rapid solute shifts caused by conventional IHD procedures potentially precipitate the dialysis disequilibrium syndrome (DDS) in those patients with a very high blood urea nitrogen concentration and in children and animal patients, who, according to studies, may be at an increased risk for DDS.  In addition, for patients with low blood volume or hemodynamic instability, extended dialysis sessions permit the removal of a large volume of fluid with less risk or likelihood of hypotension. This invention allows for the necessary slow rate of solute clearance that is required for slow dialysis delivery to small or highly uremic patients on a conventional platform independent from the deliverable or desired extracorporeal blood flow rate while maintaining controlled ultrafiltration. (more...)

A computer-aided fluid delivery device that administers metered volumes of medication intravenously from pre-filled cartridges. This device can be operated by health providers with ease by their pressing clearly marked electronic buttons and other options on a touchpad. (more...)

Researchers at University of California, Davis, have developed a novel method for increasing the rate of muscle growth after exercise by inhibiting known proteins. (more...)

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

Most of the contact lenses on the market today are made of rigid gas permeable plastics (RGP), hydrogels, or composite silicone-hydrogel materials. An essential property of all contact lenses is sufficient access of the non-vascularized cornea to atmospheric oxygen, a requirement for the health of eyes while wearing contact lens. Contact lenses are normally worn either on the eye cornea (more common, small corneal lenses) or sclera (less common, large size scleral lenses). Scleral contact lenses are more expensive, but have several advantages and are exclusively prescribed to people with certain eye disorders. Scleral lenses are normally machined from rigid gas permeable plastics, whose oxygen permeability practically limits lens thickness to ~0.5 mm. Nevertheless, there are some applications, for which it may be desirable to have scleral lenses of substantially greater thickness, and no rigid optical-grade materials with sufficient oxygen permeability is available for this task at present. (more...)

Otitis media is one of the most common diseases of childhood, resulting in more physician visits and surgeries than any other pediatric disorder. Persistent or recurrent otitis media can damage the middle or inner ear and cause permanent hearing loss. There exists a need to identify targets for potential new therapies in this disease. (more...)

Researchers at the University of California, Irvine have developed a practical cutting device for obtaining uniformly thick cartilage slices from the costal (rib) cartilage.The cartilage slices are used for surgical reconstruction procedures.The importance of this device is that it yields highly uniform slices from the central core of a rib cartilage specimen.These slices are used as grafts in facial reconstructive procedures such as rhinoplasty and otoplasty. (more...)

Researchers at the University of California, Davis, have developed a novel and high throughput production process of making nano/submicro-sized fibers.  By extruding in-situ micro or submicrofibrillar blend of cellulose acetate butyrate (CAB) and  polymers (polyolefin, polyesters, and proteins) into regular size fibers, CAB serves as a sacrificial matrix and other polymers as micro/nano-fibrills in the matrix in coarse fiber form. After removal of CAB with acetone extraction, micro, as well as, submicro fibers can be produced. (more...)

In synthetic organic chemistry aryl boronic acids and esters are of extreme importance due to their ability to form C-C bonds through metal catalyzed cross-coupling reactions. The cross-coupling reaction of both alkyl and aryl boronic acids with aryl halides or aryl triflates has become one of the most widely applied methods for constructing unsymmetrical biaryl systems. Unsymmetrical biaryls are widely utilized in pharmaceuticals, agrochemical industries, and are present in bioactive natural products. The most popular method for synthesizing unsymmetrical biaryls is the Suzuki-Miyaura coupling reaction. Due to the general applicability and efficiency of this reaction it has been widely used for carrying out cross coupling reactions involving boronic acids and esters.   The popularity of these coupling reactions has prompted researchers to explore efficient methods for the synthesis of boronic acids. The traditional method for producing arylboronic acids is the transmetallation of Grignard reagents or organolithium reagents with trialkylborates, followed by acid hydrolysis.   The selectivity of these reactions is often poor giving a mixture of mono- and dialkylated products, even with excess trialkylborate and at low temperatures. However, moderate to good yields of the alkylboronic acid can be isolated from these reactions.   Several alternative methods for synthesizing boronic acids have been reported requiring transition metals and various exotic ligands. These procedures involve the cross-coupling of expensive boron sources, such as tetra(alkoxo)diboron derivatives or dialkoxyborane derivatives, with aryl halides, and aryl triflates. In addition, these methods invariably require an excess of the boron reagent and low reaction temperatures. Boronic ester syntheses by these methods also suffer from the use of expensive and toxic catalysts including iridium, rhodium, and palladium. (more...)

The purpose of this device is to create a void in bone (e.g. the vertebral body) coaxially through an introducer needle, so that bone cement can be injected to fill the void, for the purpose of bone strengthening andlor stabilization. (more...)

Heart disease is the No.1 killer of Americans today, responsible for 1 of every 5 deaths in 2004. There were 1,200,000 new and recurrent cases of myocardial infarction (or heart attack) per year. More importantly, about 38% of people who experience a heart attack will die from it. The options of post-infarction treatments are very limited. The extreme shortage of healthy heart donors and common immunological complications after heart transplantation make heart transplantation unfeasible. Autologous cell transplantation is a promising alternative approach, however, the success of this treatment hinges on the search for ideal sources of donor cells. Currently, two types of cells, pluripotential stem cells and skeletal myoblasts, have been considered. Skeletal myoblasts have several advantages over pluripotential stem cells, such as the ease to obtain them, resistance to the ischemic conditions and no possible tumorigenicity. Nevertheless, a major drawback of using skeletal myoblasts is that these cells are inefficient in engaging in the mechanical performance of the surrounding heart tissue, leading to arrhythmias (or abnormal heart rhythms). (more...)

The recent identification of rare cell populations within tissues that are associated with specific biological behaviors, for example, progenitor cells, has illuminated a limitation of current technologies to study such adherent cells directly from primary tissues. The micropallet array is a recently developed technology designed to address this limitation by virtue of its capacity to isolate and recover single adherent cells on individual micropallets. The capacity to apply this technology to primary tissues and cells with restricted growth characteristics, particularly adhesion requirements, is critically dependent on the capacity to generate functional extracellular matrix (ECM) coatings. The discontinuous nature of the micropallet array surface provides specific constraints on the processes for generating the desired ECM coatings that are necessary to achieve the full functional capacity of the micropallet array. We have developed strategies, reported herein, to generate functional coatings with various ECM protein components: fibronectin, EHS tumor basement membrane extract, collagen, and laminin-5; confirmed by evaluation for rapid cellular adherence of four dissimilar cell types: fibroblast, breast epithelial, pancreatic epithelial, and myeloma. These findings are important for the dissemination and expanded use of micropallet arrays and similar microtechnologies requiring the integrated use of ECM protein coatings to promote cellular adherence. (GunnN.M., MS; Bachman M., Li G.P., Nelson E.L.Fabrication and biological evaluation of uniform extracellular matrix coatings on discontinuous photolithography generated micropallet arrays. J Biomed Mater Res A. 2010 Nov;95(2):401-12.) (more...)

The field of the invention generally relates to methods of constructing high surface area structures using photoresist patterning in combination with electrochemical polymer deposition.The methods described herein can be used to create structures for a wide variety of applications including, but not limited to, micro-reactors, electrodes, and sensors (e.g., biosensors). (more...)

As pharmaceutical companies become increasingly interested in drugs to treat neurodegenerative diseases (Alzheimer’s/Parkinson’s), ocular diseases (macular degeneration, glaucoma) or psychological diseases (schizophrenia, manic-depression), an automated animal-testing system would provide a clear advantage in making go/no-go decisions as well as for obtaining regulatory approvals. (more...)

Researchers at the University of California, Irvine have developed methods to attenuate inflammation and decrease tissue damage for patients undergoing laparoscopic prostatectomy through the use of cold irrigation to deliver preemptive local hypothermia; thus resulting in improved early post-operative urinary continence. Successful implementation has lead to the development of additional novel methods and devices that could improve upon current intraoperative and post-operative bladder cooling techniques as well as minimize collateral tissue damage in various surgical settings. (more...)

A physician at the University of California, Irvine (UCI) has developed a novel marking system to mark anatomical landmarks on patients. This novel marking system allows the physician to maintain the anatomical landmarks on patients sterile during and after the use of this marking system. (more...)

A physician at the University of California, Irvine has developed a personal chemical protective suit that may be used by emergency department personnel or in other conditions where a chemical protective suit is required. This suit may be used when treating patients contaminated by industrial chemicals or nerve agents like sarin. Or, the suit may be used in situations when an individual may potentially be exposed to hazardous chemicals. (more...)

A new platform to mimic the in-vivo formation of angiogenesis. (more...)

Obesity is a major health problem and is associated with metabolic consequences such as diabetes, cardiovascular disease, stroke, osteoarthritis, and cancer. Two types of fat exist, white (WAT) and brown adipose tissue (BAT). WAT stores energy in the form of triacylglycerol (TAG) to hydrolyze and release fatty acids into the circulation during times of energy shortage. BAT, on the other hand, hydrolyzes TAG to use fatty acids to activate the enzyme, uncoupling protein 1 (UCP-1), and generate heat (thermogenesis). Therefore, strategies aimed at converting WAT to BAT could be an ideal for treating and preventing obesity and related diseases. We have recently identified a major adipocyte-lipase, desnutrin, which is involved in the regulation of lipolysis (fat breakdown). Furthermore, we have shown that as a major regulator of adipocyte lipolysis, densutrin is critical in the conversion of WAT to BAT. We found that mice overexpressing desnutrin are resistant to obesity and have WAT that resembles BAT. We also found that mice lacking desnutrin in adipose tissue are obese and exhibit a conversion of BAT to WAT. Desnutrin appears to promotes FA oxidation in adipose tissue and thereby reduces obesity. The modulation of adipocyte lipolysis via pharmacological activation of desnutrin may be a useful therapeutic target for treating obesity. (more...)

To occlude blood flow mechanical clamps are usually employed which tends to induce mechanical stress. This may cause potential future complications including blood clot formation and physical damage to the vessel. Researchers at UCI’s Beckman Laser Institute have developed a novel method to control blood flow without exposing the vessels to stress or damage. (more...)

Researchers at the University of California, Irvine have developed FLAG tagged wild-type and mutant FGFR3 expression plasmids. (more...)

High molecular weight biomolecules, such as certain proteins and nucleic acids, display therapeutic potential. However, their limited cellular uptake hampers utilization and has prompted the development of delivery technologies. Lysosomal storage disorders are the best studied examples of genetic diseases caused by missing intracellular enzymes. The most direct remedy involves the injection of recombinant enzymes, which are targeted to lysosomes by cell surface mannose-6-phosphate receptors. While this approach restores enzyme activity in many tissues, it is compromised by (i) inefficient delivery to diverse cell types, (ii) delivery only to the lysosomal compartment of cells, and (iii) the inability to cross the blood-brain-barrier to reach neural tissues. (more...)

In the eyeglass industry there is a conflict between a customers desire for personalized design and the mass production employed by the industry. On one hand, it is believed that eyeglasses greatly influence the looks and perceived character of a customer. This influence drives a desire to obtain a personalized design that fits a variety of criteria. On the other hand, the manufacturing industry operates on a large scale production in which eyeglasses are distributed to consumers via retailers. This causes the need for standardized design of eyeglasses. It appears that the industry has addressed this conflict by producing a large variety of shapes and styles that customers review in a lengthy and often complex selection process. In addition, retailers stock a large inventory of eyeglass frames, which changes often, and hire a relatively large number of experienced employees to guide customers in their selection process.In todays optical stores, it is typically the responsibility of the retailer to translate a customers personality, style, and social preferences into shapes and styles of eyeglass frames, leading to a lengthy and frustrating process for the customer. The process becomes even more lengthy and frustrating for the customer when the retailer is not experienced or esthetically sensitive, does not properly communicate with the customer, or is just trying to serve more than one customer at a time. (more...)

UCSF cardiologists have developed a novel topical anesthetic composition that facilitates radial artery cannulation. This composition can be delivered either as a topical cream or through a transdermal patch and can be co-marketed with radial catheterization sheaths and cannulaes to increase product appeal to clinical users. In clinical trials, this novel composition causes local increase of the arterial diamter (by 25% or more for at least 30 minutes) and provides local anesthesia in the patient, without inducing undesirable systemic effects, thus enabling clinicians to insert radial arterial catheters with greater ease, reduce the risk of spasm, and reduce pain experienced by patients undergoing this procedure.  (more...)

Compounds for inhibiting viral entry into cells offer a promising component of microbiocidal creams or gels for prevention of HIV infections. The basis for such HIV entry inhibition is to block one or more of the interactions between HIV envelope glycoproteins (the gp120 cap and gp41 stem proteins) and surface proteins on the target immune system cells (the CD4 co-receptor and a chemokine receptor, usually CCR5 or CXCR4) that are necessary for HIV's attachment and fusion to the target cell. The protein Griffithsin and its derivatives are known to be a potent anti-HIV agents that function in this manner, binding to the sugar groups on the surface of gp120 and gp41. Griffithsin can also be cheaply produced in large quantities, and is therefore a strong candidate for use in microbiocidal formulations. Notwithstanding Griffithsin's advantages, it still suffers from some problems that also plague other potential HIV entry inhibitors, namely the greatly elevated concentrations required for efficacy in vivo and the potential for HIV mutations to create resistance to Griffithsin-based prophylactic compounds. (more...)

UC San Diego inventors have identified and cloned a nitric oxide (NO) synthase gene from plants, AtNOS1, which has been shown to play a role in plant growth, stomatal movement, hormonal signaling and fertility. The protein was expressed in bacteria as a fusion protein with glutathione-S-transferase (GST-AtNOS1), purified and assayed. The inventors were able to show that extracts from bacteria expressing the fusion protein had higher levels of NOS activity. It is particularly interesting that this gene in plants has been known, but never isolated. (more...)

Human blood is in short supply. Blood saving techniques and artificial blood are the two principal approaches to remedy shortfalls in the blood supply. Clinicians facing significant blood loss in patients with significant trauma or surgical intervention choose plasma expanders. In emergencies, the first priority is to re-establish a patient’s blood volume, which may be accomplished with a transfusion of plasma expanders. Once the blood volume is addressed, the next priority is to restore the oxygen carrying capacity of the blood, which requires a transfusion of blood. There are more than 200 million transfusions of plasma expanders in the U.S. annually and a novel plasma expander would be a valuable addition to the clinician's toolbox. (more...)

Although algorithms and chemistries for developing new therapeutic entities are constantly evolving, none can replicate the path and novelty of natural selection over eons of time. Inventors at the Scripps Institution of Oceanography have engaged their fleet of research ships to cull the oceans for marine organisms from which new compositions are isolated.  Using a variety of culture systems, selective fractionation and bioassays, two, distinct classes of compounds, isolated from actinomycetes, have demonstrated potent anti-tumor activity and considerable selectivity toward some cancers. One class of compounds, the ammosamides, are unique molecules that target a previously untargeted intracellular pathway. It is anticipated that proprietary methods and naturally evolved compositions may yield therapeutics that are significantly differentiated from those developed by limited iteration of pre-defined platforms. (more...)

Most optical transducers for label-free biosensing involve measurement of a change in the refractive index of a material induced upon analyte binding. While surface plasmon resonance (SPR) films, resonant and nonresonant diffraction gratings, reflectometric interference (RIFS) layers and Fabry-Perot interferometers show very sensitive responses to small changes in refractive index, these methods are all limited by zero-point-drift arising from changes in temperature, matrix composition, or nonspecific binding to the analytical surface. A double-beam (Michelson-type) interferometer, in which one optical path acts as a reference channel, provides an excellent means of compensating for such effects. Various implementations of double-beam correction have been employed in micro-scale biosensor systems, generally involving two spatially distinct regions of a chip. However, because the sample and reference channels are separated in the X-Y plane, such designs pose significant alignment and manufacturability challenges, especially upon incorporation into high-throughput arrays. (more...)

The development of therapies for central nervous system (CNS) disorders is hampered by the lack of human cells and drug development is often based on results derived from cloned proteins, channels and receptors and/or from immortalized rodent cells. In the former case, one must make the extraordinary leap from isolated components to the complexity of an intact cell. In the latter case, one cannot completely differentiate cells and one must make the unrealistic assumption that non-human cells predict human cell physiology. Differentiable, human CNS lines expressing functional receptors would clearly be preferable. Thus far, however, it has not been possible to generate such cell lines, and the techniques for generating the rat progenitor cell lines have been largely unsuccessful when applied to human cells. The present invention bridges this gap and moves the technology forward to the stage of treating patients. (more...)

Septic shock occurs from an overwhelming bacterial infection and is characterized by severe hypotension with low blood flow. It is the 13th leading cause of death in the United States with a mortality rate of 30%-50% due to the lack of effective treatments. In addition to the devastating effects of this syndrome on individuals, it incurs billions of dollars annually in healthcare costs. (more...)

UCSD researchers have developed a gene therapy for preventing the blindness and correcting the deafness associated with Usher 1B Syndrome, an inherited recessive loss-of-function disorder caused by mutations in the myosin VIIa gene. These patients are born deaf, and later develop retinal degeneration (retinitis pigmentosa) in their teens. The method utilizes state-of-the-art recombinant lentiviral technology and incorporates full-length human Myosin VIIa cDNA, as well as promoters to direct the expression of the gene. (more...)

Bacterial sepsis remains a major challenge for modern medicine. Septic shock is the most severe form of sepsis, in which perfusion of the liver, kidney, and other vital organs are compromised. This syndrome, which can be caused by both gram-negative and gram-positive bacteria, has a mortality rate of 30-60 percent. Systemic infection is a complication of many types of medical therapy, such as surgery, immuno-suppression for transplant, or cancer chemotherapy. There are currently no effective treatments for sepsis and the number of patients in the U.S. and Europe is large and will likely increase as intensive medical therapy becomes more widespread.A key component of the mammalian innate immune system that acts as a first line of defense against pathogens is a family of toll like receptors (TLRs). Lipopolysaccharide (LPS), a major component of gram-negative bacteria, activates a variety of cells to produce inflammatory cytokines leading to septic shock in humans. MD2 is a pattern recognition receptor that binds LPS with a high affinity and without the need for LPS binding protein to catalyze the reaction. It is an extracellular protein that is co-expressed with TLR4, and necessary for TLR4 LPS receptor function. Truncation of MD2 leads to LPS non-responsiveness, and a monoclonal antibody that recognizes the MD2/TLR4 complex, blocks LPS activation of cells. (more...)

Studies have shown that a compound under investigation causes inhibition of blood clotting in mice. The compound, when administered by intravenous tail injection, destroys circulating coagulation factors and therefore acts as a potent anti-coagulant. The in vivo experiments, in combination with in vitro tests on isolated blood clotting factors, support the theory that the compound causes its effects by proteolysis. (more...)

The compound prosaposin and its methods of use, already tested successfully in Phase I clinical trials, is available for licensing. Prosaposin is the precursor of the saposins and has both neurotrophic and myelinotrophic activity in vitro and in vivo. It is an injury-repair protein that acts on both neurons and glia.Prosaposin also has myotrophic properties and can attenuate loss of muscle mass after nerve injury. Prosaposin and peptide derivatives of it will promote neurite outgrowth in vitro. A peptide consensus sequence was determined by comparing the active neurite outgrowth-inducing saposin C peptide sequence with that of various hematopoietic and neuropoietic cytokines. These cytokine-derived peptides will promote the same processes as their corresponding cytokines. In addition, prosaposin and saposin C promote increased nerve cell myelination ex vivo. Demyelination is a defect common to a number of central nervous system disorders, the most common being multiple sclerosis. (more...)

Salinosporamide A (Sal A) is a potent proteasome inhibitor produced by the marine bacterium Salinispora tropica. This natural product is biosynthesized from three metabolic building blocks, namely acetate, a chlorinated tetrose from S-adenosylmethionine, and the non-proteinogenic amino acid cyclohexenylalanine. Sal A exhibits potent cancer cell cytotoxicity apparently through inhibition of the 20S proteasome, a multisubunit protease responsible for proteolysis of proteins targeted for degradation in the cell. Tumor cells may be more sensitive to proteasome inhibitors than normal cells and proteasome inhibition increases the sensitivity of cancer cells to anticancer agents. (more...)

Comparative genomics has, historically been limited to the study of changes that occurred over millions of years. Evolution, however, is a dynamic and recurring reality, which can be responsible for such vexing realities as the emergence of new pathogens and the acquisition of drug-resistance. From a more proactive stance, the ability to design, manipulate and evaluate the consequences of specific stressors could dramatically improve the ability to design beneficial mutations for industrial processes that use bacteria for anything from food and chemical production to the clean-up of oil spills. (more...)

High-level over-expression of commercially important proteins in B. subtilis has been difficult to achieve. While there are several different types of B. subtilis plasmids that have been used, such as pUB110, pE194, pMTLBS72, or pSM.beta.1, these plasmids are unstable and don’t segregate well during cell growth, making them relatively difficult to use for gene expression. During large scale fermentation without antibiotic selection, a significant number of cells (50-99.9 percent) lose their plasmids.  Even under antibiotic selection, the bacteria may lose their plasmids unless they have this stable segregation system. (more...)

The present invention relates to a hearing device and, more particularly, to a device that can mechanically drive the ossicular chain while being located  in the ear canal. (more...)

Surgical procedures often involve working close to vital nerve tissue and careful dissection is needed in order to preserve as much function as possible. Although some nerves are easily visualized, there are many types of procedures, such as the excision of tumors, the presence of inflammation or infection at the surgical site, scar tissue resulting from previous procedures or nerves encased in bone, where the precise location is not easily determined. Currently nerves are typically visualized one at a time using fluorescent dyes that label nerves in either an antero- or retro-grade manner. These techniques have several drawbacks including excessively long labeling times to accumulate the imaging agent and limited accumulation of the agent along the axonal tract. (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...)

Current state of the art in the field of organ transplantation employs various immunosuppressive agents to prevent post-surgical allograft rejection by the host. However, these pharmacological agents often result in many adverse side effects due to the quantities of medication that are required following transplantation. Cyclosporins, tacrilomus, mycophenclate mofetil and rapamycin are among the drugs commonly used today.The efficacy of these drugs can be attributed to their ability to act as immunosuppressive agents, whereby inhibiting the lymphocyte activation pathway. In turn, the transplanted tissue is not subject to the deleterious effects of the host immune response.Cytotoxic agents may also be utilized in immunosuppression. Upon antigenic activation, lymphocytes rapidly proliferate as part of the immune response. Cytotoxic agents kill rapidly dividing cells, such as lymphocytes and therefore inhibit activation. (more...)

compounds synthesized as described in US patent 6,166,299. Amino acids have been derivatized for use in peptide synthesis by conversion to N-carboxyanhydrides that are N-protected by either a trityl or a phenylfluorenyl group. N-trityl-N-carboxyanhydrides (TNCAs)and N-phenylfluorenyl-NCAs (PFNCAs) have been synthesized to increase stability and to inhibit epimerization of N-carboxyanhydrides for peptide synthesis. See US patent 6,166,229 and PCT publication WO (more...)

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A method for detecting cyclization of acyclic compounds is disclosed. In particular, the invention relates to a method of screening for macrocyclic peptidase inhibitors, and is useful for screening a combinatorial library of compounds. (more...)

The purine ring system is a key structural element of the substrates and ligands of many biosynthetic, regulatory, and signal transduction proteins including cellular kinases, G proteins, and polymerases. Consequently, combinatorial libraries based on this scaffold should facilitate the search for inhibitors of many biomedically significant processes. Here, UC Berkeley scientists have developed libraries around the purine scaffold in connection with our efforts to generate selective inhibitors of the cell cycle kinases. (more...)

The biomedical industry seeks to replace stainless steel hypodermic injection needles with needles that have smaller diameters and sharper tips, to minimize pain and tissue damage. Also desirable in an improved needle is added functionality, such as the capability of providing integrated electronics for chemical concentration monitoring, cell stimulation, and the control of fluid flow such as through an integrated pump or valve. Researchers at the University of California, Berkeley have developed an improved process for fabrication of a microneedle with the features and advantages described above. A microneedle fabricated by the process developed at Berkeley has a body less than 700 microns wide and less than 200 microns thick. Isotropic etching of the microneedle tip yields sharper instruments than prior art processes. In addition, processing does not require boron doping of silicon to define the body of the microneedle, and the etching step may be carried out at relatively low temperatures (below 1100 C) without using the carcinogen ethylenediamin pyrocatechol. Integrated circuitry or micromachined devices such as micropumps may be formed on the instruments during the fabrication process. Microlancets and blades as well as microneedles may be formed. (more...)

See also: Rine, J. et. al., "Modulation of Ras and a-Factor Functio by Caroxyl-Terminal Proteolysis," Science, Vol. 275, March 21, 1997, pp. 1796 - 1800. Two genes which encode polypeptides that mediate post-prenylation processing steps in CAAX polypeptides such as Ras are provided. The two genes (AFC1 and RCE1) encode polypeptides that mediate the removal of the AAX tripeptide from the CAAX polypeptide following prenylation. The genes and encoded polypeptides provide assays for testing compounds for an effect on post-prenylation processing steps. A heat shock assay for assessing Ras activity is also provided. (more...)

Specific BRCA1 mutations, PCR primers and hybridization probes are used in nucleic acid-based methods for diagnosis of inheritable breast cancer susceptibility. Additionally, binding agents, such as antibodies, specific for peptides encoded by the subject BRCA1 mutants are used to identify expression products of diagnostic mutations/rare alleles in patient derived fluid or tissue samples. Compositions with high binding affinity for transcription or translation products of the disclosed BRCA1 mutations and alleles are of potential use in therapeutic intervention. Such products include anti-sense nucleic acids, peptides encoded by the subject nucleic acids, and binding agents such as antibodies, specific for such peptides. (more...)

UC Case Nos.: B92-094 & B99-097 1-HYDROXY 2(1H)-PYRIDONATES (HOPOs) FOR USE AS MRI CONTRAST AGENTS The GdIII complexes based on a hexadentate, hetero-tripodalhydroxypyridonate (HOPO) ligand are promising candidates for second-generation MRI contrast agents as they allow for high stability and fast water exchange, which allows for low toxicity, image enhanced MRI contrast agents. The primary clinical contrast agents are nine-coordinate gadolinium (GdIII) complexes, based on poly- (amino carboxylate) ligands, and function by enhancing the relaxation rate of water protons. The image enhancement capability (proton relaxivity) of current clinical contrast agents is only a few percent of that theoretically possible due to the presence of only one inner sphere water molecule, it?s slow exchange rate, and a short rotational correlation time. When the rotational correlation time is optimized, the slow water exchange rate becomes the limiting factor in attaining higher relaxivities and ultimately image enhancement. Therefore, any rational design of a high-relaxivity contrast agent requires a fast water exchange complex that retains a high degree of stability. In these complexes (HOPOs), the metal ion is eight coordinate and possesses two inner sphere water molecules. This design allows for generally high stability and fast water exchange which makes them highly desirable as candidates for MRI use. B92-094-2 (U.S. patent no.: 5,624,901); B92-094-3 (U.S. patent no.: 5,892,029); B92-094 (PCT international patent application, Serial No. PCT/US95/07766); B92-094 (EPO patent application 95923971.6); B99-097-2 (U.S. patent applicaton no.: 10/194,502, U.S. 6,846,915); B99-097 (PCT international patent application Serial No.:PCT/02/26026); B99-097-3 (U.S. Patent Application 10/902,772); (more...)

To date, syringe pump feedback control has required a pressure sensor or a flow sensor located close to the syringe in the system. In many applications, this is not possible or is inhibited by cost. Typical syringe pumps range in price from $2500-$4000, and those in the $500 range suffer from extremely poor performance where the fluidic time constant is large. To address these problems, Researchers at UC Berkeley have developed a novel feedback controlled syringe pump with no wetted feedback components. Their design enables the measurement of flow as well as pressure and includes hardware and software components. (more...)

Magnetic Particle Imaging (MPI) is new imaging modality that relies on different physical principles from X-ray, magnetic resonance, ultrasound, and nuclear methods. This novel, ultra-sensitive and affordable 3D scanner images the distribution of a magnetic contrast agents in vivo. MPI directly detects a nanoparticle?s electronic magnetism which is 1 million times more intense than the nuclear paramagnetism detected in MRI, A mouse MPI scanner suitable for cell tracking in vivo has been developed and demonstrated. The first applications provide improved stem cell tracking, angiography, and inflammation imaging. The MPI method has promise for 200-fold greater sensitivity than MRI for each of these applications. The system has been proven out in mice, with current research to extend MPI to rabbits and rats. Initial research was reported after filing of a patent application. Advantages: A key advantages of MPI is an improvement of 200X over currently available methods of sensitivity and contrast to noise (CNR). Other advantages are substantial improvements in image resolution, an eight week in vivo observation window, virtually unlimited penetration, few artifact problems, and ease of use. Many limitations of currently available systems can be overcome using MPI. By example, X-ray techniques do not provide adequate contrast sensitivity for cardiovascular stem cell tracking in the clinical setting. Bioluminescence is limited to small animal studies and NIR fluorescence to near-surface and histological applications. Ultrasound/echocardiography has the potential for single cell detection but has limited anatomic accessibility, resolution, and quantification. High-energy photon imaging (SPECT or PET) has high sensitivity, but for long-term tracking it requires genetic manipulation of the stem cell, stable expression of a transgene, and multiple exposures to ionizing radiation. MRI provides 3-dimensional anatomy but some contrast techniques have low sensitivity. Publication Link: Narrowband Magnetic Particle Imaging (more...)

Many research inroads have been made into understanding data from human brain activity. New brain assessment devices beond classing EEG data, such as MRIs and PET scans, have increased this available data stream. However, the information is often only inferentially related to specific brain activity. There is an important need for individuals with limited physical capacity to control devices and communicate with others. Work towards this end has been persued in BMI research. There is the potential in brain activity sensing devices to provide these capacities by other means as well. Researchers at the University of California, Berkeley have made important strides in accomplishing these goals with software which can identify natural images from human brain activity. This provides an opterunity for a visual BMI. An encoding model is constructed that describes how visual stimuli are represented in the pattern of activity across visual cortex. The activity that the image produces in visual cortex has proven out to be systematically related to the particular visual stimulus that is being viewed at any point in time. Currently, the system identifies the image from a large, known set of potential images. The UCB model is a variant of those that have been developed by the sensory neuroscience community over the last 50 years. The current research suggests that fMRI-based measurements of brain activity contain much more information about underlying neural processes than might have been expected. In fact so much information is available in these signals that one day it may even be possible to reconstruct the visual contents of dreams or visual imagery. To identify which of the images elicited the measured activity the decoder scans through all possible images, and for each image it predicts what pattern of brain activity should have been elicited if that image had actually been seen. Then the decoder simply chooses the image whose predicted brain activity is most similar to the measured brain activity. The current research is described in Nature Letters, Vol. 452, March 2008. Decoding visual content is conceptually related to the neural-motor prosthesis BMI work build a decoder that can be used to drive a prosthetic arm or other device from brain activity. While the current research is focused on visual perception, other sensory systems, such as touch, taste, hearing, etc, are also amenable to analysis using the innovative software. The potential use of this technology in the legal system brings with it most of the problems that are already known regarding eyewitness testimony. UCB investigators for this innovation are: Jack Gallant, Thomas Naselaris, Kendrick Kay, and Ryan Prenger. (more...)

UC Berkeley researchers have previously presented a unique label-free method to detect biomolecular binding based on impedance changes using microparticles or nanoparticles in microfluidic channels. This method requires no florescent labeling of analyte and allows a simple readout at a given frequency. This demonstrated microfluidic integration of the nanocavity system is also advantageous, allowing easy introduction of analyte solution and measurement buffer. Because the detection technique is essentially label-free and just depends on the specific binding of anibody-antigen, DNA-DNA, DNA-RNA, DNA-protein, antibody-small molecule, or antibody-cell, this invention could be used to diagnose virtually any disease. Researchers at UC Berkeley have expanded upon this innovation to demonstrate the ability to sequentially load different sized and different types of beads into a microfluidic channel. This has numerous applications, including the ability to successively capture smaller and smaller beads that otherwise would be impossible to capture. In addition, the cells can be mechanically lysed. (more...)

Scientific progress is often associated with the invention of a new experimental apparatus. New tools can increase the ease and efficiency of routine experiments as well as provide the means to make new discoveries by making possible novel experiments. The development of Lab on Chip (LOC) devices is playing an important role in the progression of many different areas of research ranging from point of care diagnostics to the search for life on Mars. LOC devices hold promise to replace existing techniques with processes that are not only more automated and consistent but also require less time and valuable reagents. Researchers at the University of California have developed an integrated LOC for cell-based studies/analysis/research. The device has integrated biological fluidic circuits with the capability of culturing cells inside of a microfluidic ?chip?, the ability to lyse the cells on demand, and the ability to perform on chip analysis of the lysate, which contains both genetic and proteinaceous material. The device is essentially a completely integrated cell-based platform capable of performing practically all of the common cell-based studies currently employed in laboratories across the world. (more...)

Current diagnosis of many neurological diseases are made by highly trained and experienced clinicians observing the gait of patents. This process is not only limited by the availability of these specialized clinicians, it also requires gait monitoring systems that are bulky, expensive and correspondingly limited to the clinician's office. To address those limitations, researchers at UC Berkeley have developed new measuring and analytical tools that enable various gait and movement disorders to be quantitatively characterized in physiological terms to facilitate diagnosis, classification and prognostication of a number of neurological diseases. This innovative measuring system gives clinicians a new tool by which to objectify and quantify the diagnosis process. In comparison to current approaches, this new system is less expensive, easier to use, and mobile -- all of which more readily enable the system to collect data outside of the clinician's office (i.e. in a patient's home or remote location) thereby improving access to the technology and quality of the data (as patients can behave unnaturally in a clinician's office). (more...)

This invention embodies a platform technology consisting of novel approaches for functionalizing a polymer matrix to enhance its ability to control cell behavior. In order to replace or repair damaged tissues in the human body the field of regenerative medicine requires a reliable, specific source of cells from which to implant or engineer into tissue equivalents. Cell behavior can be difficult to control outside of the body, and stem cells in particular can be difficult to culture. it would be highly advantageous to develop systems to precisely control the behavior of such cells. In particular, stem cells are capable of extended self-renewal ( proliferation in an immature state while maintaining the potential to differentiate) or differentiation into one or more mature cell types. It would be highly desirable to control these behaviors in order to achieve reliable sources of cells for tissue repair. This invention describes a novel approach to create synthetic micro-environments for a cell to provide signals to expand the immature stem cells (i.e. promote self-renewal) as well as to control and/or support the differentiation of the stem cells into mature cells. (more...)

The study of the human neuron network and other complex biological systems requires the ability to stimulate and record the response of many individual cells. Large metal electrodes and invasive patch clamps, routinely used to administer stimuli to cells, become impossibly cumbersome and inaccurate when applied to systems involving more than just a few cells, making these conventional tools ill suited for the study of complex biological systems. Researchers at the University of California have addressed this problem by inventing a new way of administering stimuli to many cells that is both scalable and non-invasive. Using an optical platform, scientists have been able to stimulate, inhibit, guide, manipulate, and record the behavior many cells simultaneously. This technology may have further applications in computer science and bio-engineering -potentially contributing to artificial neural network theory and new findings in plasticity and integration at the neural network level. (more...)

A variety of nanostructures have been developed for use in biomolecular detection. The nanosphere is the most widely used structure because of unique, highly desirable properties that make it a superior detection platform for life science research, in vitro diagnostic testing, and in vivo imaging. Other structures such as nanotips, nanorings, and nanocups have also been demonstrated for use in high resolution SERS spectroscopy and imaging. These structures provide significant field enhancement in experiments and in simulations but they have proved to be difficult to fabricate consistently. Researchers at the University of California, Berkeley have developed a new nanostructure that is biocompatible and incorporates the advantages of nanotips, nanospheres, and nanorings. Unlike present nanosphere-based SERS spectroscopy and imaging, which uses a wavelength of 500-600 nm, the new structure can be excited at near the infrared range. Excitation at longer wavelengths provides deeper penetration into tissue with minimal photothermal damage, and excitation of the nanostructure does not cause fluorescence of other biomolecules. The structure developed at Berkeley has a much stronger field emitting or "antenna" effect than previously seen even from nanotips and nanorings. The excited "hotspot" of the structure has been demonstrated to have an enhancement factor larger than 10^10. Batch fabrication is straightforward and does not require e-beam lithography. These characteristics make the improved nanostructure ideal for application in molecular medicine and in ultrasensitive Raman, biomolecular, and cellular imaging. http://biopoems.berkeley.edu (more...)

Research at the University of California, Berkeley has resulted in the formulation of a new medium for the preservation of cellular tissues. The new tissue preservation medium is based on fundamental physiological principles and on research findings from UC Berkeley regarding maintenance of cell membrane integrity. The understanding of the mechanism of cell membranes showed that repair normally requires an active process. This led to the invention of a medium that facilitates repair of membrane breaks under conditions where normal metabolism is shut down, such as the storage of donated tissues for transplantation. Using this technology, investigators at UCB have developed a corneal preservation medium. Testing the new media against the current American standard, Optisol, demonstrated that corneas stored in the new media retained an acceptable percent of viable endothelial cells up to three times longer than those stored in Optisol. (more...)

Diabetes is a huge healthcare problem, and in particular the inability of diabetics to continuously monitor their glucose levels causes some of the most severe complications for this condition due to undetected hypoglycemic or hyperglycemic events. The traditional fingerstick test is an invasive, painful and inconvenient method of measuring glucose levels, and it often fails to detect rapidly fluctuating glucose levels. This manual method is also is not conducive to identifying hypoglycemia or hyperglycemia during sleep. Recently, devices that automatically and continuously monitor glucose levels have been introduced. However, these products either (a) don't provide accurate everyday glucose level control, (b) still require fingerstick test for calibration, and/or (c) require trained personnel to insert a sensor under the skin. To address this tragic situation, researchers at the University of California, Berkeley have developed a MEMS-based continuous glucose monitor. This miniature monitor uses an array of hollow, out-of-plane microneedles to reach the interstitial fluid in the epidermal skin layer. The device samples glucose by diffusion, and therefore interstitial fluid does not need to be sampled. The glucose of the interstitial fluid permeates an integrated dialysis membrane and then is channeled to an electrochemical glucose sensor. The integrated system is fabricated using well-established MEMS processes and a novel in-device enzyme immobilization technique. In comparison to currently available continuous glucose monitoring systems, this low-cost batch fabricated device is painless, easy to use, suitable for everyday operation, and doesn't require fingerstick calibration. (more...)

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus infecting more than 75% of the U.S population. It is a leading cause of birth defects in newborns, a major cause of morbidity and mortality in immunocompromised individuals, such as transplant recipients and patients with AIDS, and even in healthy adults, this virus causes a life-long subclinical infection that may be associated with the development of atherosclerosis. Study of murine cytomegalovirus (MCMV) serves as a model for understanding of HCMV- associated diseases. The reagents covered in this invention include (1) MCMV mutant (RvM78) that contained a mutation at viral open reading frame M78, (2) an expression plasmid construct (pM78-FLAG) that contains M78 coding sequence driven by an eukaryotic expression cassette, and (3) a mouse 3T3 cell line that contains pM78-Flag and expresses M78 protein. References: Zhan et al. 2000 Virology 266:264-74. Zhan et al. 2000 J. Virology 74:7411-21 (more...)

This invention embodies a platform technology consisting of a polymer matrix that aids in cell transplantation for either tissue formation ex vivo or tissue regeneration in vivo, drug or chemotherapy agent delivery, and gene therapy. Ideally, these matrices can deliver mammalian cells, and/or therapeutic agents into the body and act as three-dimensional templates to support and promote tissue growth. These polymer networks are tunable in terms of their delivery, drug dosing, and mechanical and biochemical properties. The polymer networks are injectable through minimally invasive methods, and do not exhibit macroscopic fracture following injection. (more...)

Synopsis: This invention consists of an artificial promoter system that can be fused upstream of any desired gene, enabling reversible and light-switchable induction or repression of gene expression in any suitable host cell. New data to be filed in a provisional patent application demonstrates optimized expression conditions and a "switching off" mechanism in addition to the "switching on" mechanism. (more...)

Telomerase is a ribonucleoprotein (RNP) DNA polymerase that extends the ends of chromosomes in most eukaryotes. DNA synthesis by telomerase can compensate for the incomplete replication of linear chromosome ends by DNA-dependent DNA polymerases and can be required for indefinite cellular proliferation. The telomerase RNP contains a catalytically essential RNA subunit. UC Berkeley researchers have discovered functionally significant elements of the human telomerase RNA. They have demonstrated that functionally significant RNA elements can be required either for RNA stability (in vivo) or for catalytic activity (in vivo and in vitro), and discovered RNA structural requirements and RNA-protein interactions of the functionally significant RNA elements. This technology can be applied to develop screens for molecules that (a) interact with, disrupt, enhance or otherwise affect any of the functionally significant RNA elements; (b) recognize, disrupt, enhance, or otherwise affect any of the functionally significant RNA protein interactions; and (c) disrupt, enhance, or otherwise affect the catalytic activity of telomerase reconstituted with functionally significant RNA elements, including the use of differentially reconstituted telomerases as tests of specificity. In addition, this technology can be applied to (d) affect telomerase activity in vivo or in vitro; and (e) further characterize the functionally significant elements of human telomerase. (more...)

Two-component systems (sensor kinase-response regulator pairs) dominate bacterial signal transduction. Regulation is exerted by phosphorylation of an aspartate residue in receiver domains of response regulators. Lability of the acyl phosphate linkage has limited the structural characterization of active, phosphorylated forms of receiver domains. This invention features methods and compositions for production of persistent acyl phosphate analogues (e.g., aspartyl phosphate analogues) using beryllofluoride (BeF.sub.x), as well as polypeptides with an acyl phosphate analogue and antibodies that specifically bind to these polypeptides. The BeFx analogues can be used in screening assays to identify compounds that modulate activity of polypeptides that normally exhibit activity due to the presence of an acyl phosphate linkage (e.g., a phosphorylated aspartate residue as in, e.g., polypeptides involved in signal transduction, polypeptides involved in ion transport across biological membranes, phosphotransferases, etc.). The BeFx polypeptide analogues can also be used to facilitate determination of the structure of the corresponding phosphorylated polypeptide and in rationale drug design. (more...)

Novel Device for Treatment of Swallowing Disorders (more...)

Composite nanostructures fabricated in the form of micro or nanopillar arrays with re-usable substrate for solar cells, tactile sensing and other applications. (more...)