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Biosynthetic Production Of L-4-Chlorokynurenine

The non‐proteinogenic amino acid l‐4‐chlorokynurenine (l‐4‐Cl‐Kyn) is a next‐generation, fast‐acting oral prodrug for the treatment of major depressive disorder. Additional studies report that this drug candidate is effective in animal models for the treatment of neuropathic pain, epilepsy, and Huntington's disease.  After active transport across the blood–brain barrier, it is enzymatically converted into the active agent 7‐chlorokynurenic acid, which is a highly selective competitive antagonist of the N‐methyl‐d‐aspartic acid (NMDA) receptor.   Suicide is 2-7x higher in Veterans than non-veterans, and may be related to brain kynurenine pathway (KP) dysregulation and NMDA receptor (NMDAR) hyperactivation.  L-4-Chlorokynurenine (L-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder (Double-Blind, Placebo-Controlled, Phase 2 Trial to Test Efficacy and Safety of AV-101 (L-4-chlorokynurenine) as Adjunct to Current Antidepressant Therapy in Patients With Major Depressive Disorder (the ELEVATE Study)).

Microfluidic Dispenser for Automated, High-Precision, Liquids Handling

Researchers at the University of California, Davis have developed a robotic dispensing interface that uses a microfluidic-embedded container cap – often referred to as a microfluidic Cap-to-Dispense or μCD - to seamlessly integrate robotic operations into precision liquids handling.

Wearable Voltammetric Monitoring of Electroactive Drugs

UCLA researchers in the Department of Electrical and Computer Engineering have developed a voltammetric wearable device capable of monitoring electroactive drug circulation and abundance in biofluids. This non-invasive monitoring system can be used for electroactive drug therapy management, drug compliance/abuse monitoring, drug-drug interaction studies, and personalized dosing.

A novel method for increasing MHC presentation of oncogene derived neoantigens

The invention describes a platform technology that increases MHC presentation of oncogene derived peptide neoantigens that do not normally occur in the cell. The platform has already been used to identify a method of increasing KRAS G12 D/V derived peptide presentation on MHC- I.

Preserving Protein Function Via Statistically Random Heteropolymers

Protein-based materials have the potential to change the current paradigm of materials science. However, it still remains a challenge to preserve protein hierarchical structure and function while making them readily processable. Protein structure is inherently fluid, and it is this property that contributes to their fragility outside of their native environment. Through the use of rationally designed statistically random heteropolymers, it is possible to stabilize proteins at each hierarchical level and process them in organic solvents, a common need for materials fabrication. The chemical and architectural complexities of statistically random heteropolymers provide a modular platform for tunable protein-polymer-solvent interactions. This provides opportunities not offered by small molecule surfactants or amphiphilic block copolymers. Through evaluation of horseradish peroxidase and green fluorescent protein structure, we show that statistically random heteropolymers can stabilize enzymes. Allowing for activity retention when stored in organic solvent, over 80% activity was observed after 24 hours. Furthermore, horseradish peroxidase and chymotrypsin proteins, when encapsulated in statistically random heteropolymers, are still accessible to their substrates while remaining inaccessible to the denaturing organic solvent. Statistically random heteropolymers have potential in creating stimuli-reponsive materials and nanoreactors composed of proteins and synthetic materials.

Method of Reducing Placebo/Nocebo Effects Associated with the Tapering of Medication and Storing Drug Tablet Fragments

UCLA researchers in the Department of Medicine have developed drug tapering schedule software to reduce factors that may impede patients’ discontinuation of a drug.

New Mosquitocidal Protein

Prof. Sarjeet Gill and  his colleagues at UCR have identified a potent mosquitocidal protein, PMP1, that is active against Anopheles and Aedes mosquitos. This protein was identified from a bacterial strain that has high mosquitocidal activity specifically against Anopholes. PMP1 bears 30 percent chemical similarity to botulinum or tetanus however it has no affect on humans, vertebrates or fish. Fig. 1 shows the toxicity of PMP1 and inactive PMP1 E209Q mutant to mosquito larvae by injection in a dose–mortality plot.    Fig. 2 shows the percentage of adult mosquitoes and Drosophila flies (percent) stopped flying after 24 hours of injection with PMP1.    

Use of VMAT2 Inhibitors as a Therapy for Stuttering

Dr. Gerald Maguire and his colleagues from the University of California, Riverside have developed a stuttering therapy that uses vesicular monoamine transporter 2 (VMAT2) inhibitors. The safety of VMAT2 inhibitors have been established given that small molecule VMAT2 inhibitors are approved for the treatment of hyperkinetic movement disorders. Treatment of stuttering provides relief from symptoms like facial tics, lip tremors, excessive blinking, facial tension, and frustration when attempting to communicate. This therapy holds promise for improving on the current treatments for both children and adults. Fig 1 shows the mechanism of action of VMAT2 inhibitors where in  a) VMAT2 sequesters dopamine in presynaptic vesicles and then b) VMAT2 inhibitors block vesicular storage of dopamine. Stuttering may be caused by high dopamine levels and VMAT2 inhibitors would decrease dopamine levels to treat stuttering.  

Triazolo/Phenylpyrimidine Compounds as Novel Candidate Treatments for Schistosomiasis

Schistosomiasis is a disease caused by infection with parasitic flatworms called schistosomes. The three major medically important species are Schistosoma mansoni (causing intestinal schistosomiasis in Africa and South America), S. japonicum (intestinal schistosomiasis in East Asia), and S. haematobium (causing genitourinary schistosomiasis in Africa and the Middle East). Signs and symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine.  The treatment of schistosomiasis serves three purposes: reversing acute or early chronic disease, preventing complications associated with chronic infection, and preventing neuroschistosomiasis. The goal of treatment is to remove the worms that produce the eggs which, in turn, are responsible for disease morbidity and mortality. There is no effective vaccine against schistosomiasis.

A Wearable Platform for In-Situ Analysis of Hormones

UCLA researchers in the Department of Electrical and Computer Engineering have developed a highly sensitive, wearable hormone monitoring platform.

Blocking Synaptogenesis For Chronic Pain Management

Gabapentin is used for treatment of seizures and hypersensitivity to pain. Researchers at UCI have employed low-dosage gabapentin immediately after injury to block the development of chronic pain.

Development of a Method to Treat Alzheimer’s Disease by Protection of Synapses

NMDA receptors (NMDARs) are principal regulators of synaptic signaling in the brain. Modulation of NMDARs’ function and trafficking is important for the regulation of synaptic transmission and several forms of synaptic plasticity. Postsynaptic density protein 95 (PSD-95) acts as a scaffolding protein and stabilizes the surface and synaptic expression of NMDARs. NMDA receptors (NMDARs) are ionotropic glutamate receptors that are expressed throughout the nervous system and play crucial roles in neuronal development, synaptic plasticity, learning and memory. PSD-95 (Post Synaptic Density protein) or SAP90, a membrane-associated guanylate kinase (MAGUK), is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. It is almost exclusively located in the post synaptic density of neurons and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels. Postsynaptic loss does not precede obvious Aβ (beta-amyloid or amyloid beta) and Tau deposition, but instead appears to occur as Aβ and Tau pathologies advance. This indicates that PSD-95 is an excellent intrinsic biomarker for post synaptic mechanisms and its expression is reduced in brain tissue from patients with Alzheimer’s Disease (AD) as well as in mouse models of AD.

Healthcare Hand Hygiene Medical Training Software

UCI researchers have developed a curriculum for training and evaluation of customers performing Healthcare Hand Hygiene.

Advanced Airway Management: Intubation medical Training Software

UCI researchers have developed a curriculum for training and evaluation of customers performing Advanced Airway Mangement: Intubation.

Clinical Prognostication Test In Uveal Melanoma

Uveal melanoma commonly known as ocular or choroidal melanoma, is a rare cancer of the eye. It is an intraocular malignancy that arises from melanocytes of the choroid, ciliary body, and iris of the eye. Ocular melanoma is diagnosed in approximately 2,000-2,500 adults annually in the United States. In both the U.S. and Europe, this equates to about 5 - 7.5 cases per million people per year and, for people over 50 years old, the incidence rate increases to around 21 per million per year. While the primary tumor is highly treatable, about half of the patients will develop metastasis —typically to the liver. Metastatic disease is universally fatal. While traditional staging methods such as tumor size and location, still play a role in assessing metastatic risk, they are rarely used to individualize patient management plans. Newer methods include chromosomal gene expression analysis, yet these methods have their technical limitations. Clearly, what is needed is a better, cheaper and reproducible prognostic test.

Variable Friction Shoe

The Variable Friction Shoe, which ameliorates the effects of drop foot.

Very-Small-Nuclear Circulating Tumor Cell (vsnCTC) as a Diagnostic Biomarker of Visceral Metastasis in Advanced Prostate Cancer

UCLA researchers in the Department of Molecular and Medical Pharmacology have identified a novel biomarker that can be used to diagnose prostate cancer patients for the presence of visceral metastasis with 54% sensitivity and 100% specificity.

Device and Method for Microscale Chemical Reactions

UCLA researchers in the Departments of Bioengineering and Molecular and Medical Pharmacology have developed a passive microfluidic reactor chip with a simplified design that is less costly than existing microfluidic chips.

A Built-In Mechanism Of Gas Maintenance In Microfeatures On A Submerged Surface

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a novel superhydrophobic surface for drag reduction and anti-biofouling applications.

Thermodynamic Integration Simulation Method for Filling Molecular Enclosures Using Spliced Soft-Core Interaction Potential

Researchers have developed a simulation method to determine the properties of molecular enclosures based on slow growth thermodynamic integration (SGTI).

Combination Therapy as Enhanced Antidote to Poisoning

Certain pesticides can be harmful, and there is a need for effective antidotes that can reverse accidental over-exposure by farm workers. UC San Diego researchers have recently developed a therapeutic modality that is a combination of compositions that may be effective as an antidote.

Continuously Variable Inverse Harmonic Drive

A transmission that uses a variable sized drum, a rotating tensioner arm, and a dry adhesive band to create a compact, continuously-variable transmission that behaves like an inside-out harmonic drive.

Novel Clotrimazole Analogs As Blockers Of Intermediate Conductance Kca Channels

Researchers at the University of California, Davis, have developed a method for preparing therapeutically effective amounts of triarylmethane compounds for immunosuppressive treatment of autoimmune disorders, graft rejection, and graft or host disease.

Self-Locking Optoelectronic Tweezer And Its Fabrication

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a novel self-locking optoelectronic tweezer (SLOT) for single cell manipulation in conductive buffer over large areas.

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