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Depletion and Replacement of Brain Border Myeloid Cells

A novel method for selectively targeting and modulating brain border-associated myeloid cells for the treatment of neurological disorders.

Neuronal Cell Classification System and Methods

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of brain development, providing an exceptional tool for studying the complexities of biology. Among these, cortical organoids, comprising in part of neurons, have been instrumental in providing early insights into brain formation, function, and pathology. Functional characteristics of cortical organoids, such as cellular morphology and electrophysiology, provide physiological insight into cellular states and are crucial for understanding the roles of cell types within their specific niches. And while progress has been made studying engineered neuronal systems, decoding the functional properties of neuronal networks and their role in producing behaviors depends in part on recognizing neuronal cell types, their general locations within the brain, and how they connect.

Organoid Training System and Methods

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter "organoid") have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Modern methods of interfacing with organoids involve any combination of encoding information, decoding information, or perturbing the underlying dynamics through various timescales of plasticity. Our knowledge of biological learning rules has not yet translated to reliable methods for consistently training neural tissue in goal-directed ways. In vivo training methods commonly exploit principles of reinforcement learning and Hebbian learning to modify biological networks. However, in vitro training has not seen comparable success, and often cannot utilize the underlying, multi-regional circuits enabling dopaminergic learning. Successfully harnessing in vitro learning methods and systems could uniquely reveal fundamental mesoscale processing and learning principles. This may have profound implications, from developing targeted stimulation protocols for therapeutic interventions to creating energy-efficient bio-electronic systems.

Modern Organoid Research Platform System and Methods

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter “organoid”) have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Despite their potential, organoid experiments present several challenges. Organoids require a rigorous, months-long developmental process, demanding substantial resources and meticulous care to yield valuable data on aspects of biology such as neural unit electrophysiology, cytoarchitecture, and transcriptional regulation. Traditionally the data has been difficult to collect on a more frequent and consistent basis, which limits the breadth and depth of modern organoid biology. Generating and measuring organoids depend on media manipulations, imaging, and electrophysiological measurements. Historically these are labor- and skill-intensive processes which can increase risks associated with known human error and contamination.

Improved Processing Method for MRI Contrast Images

A novel method using Diffusion Tensor Imaging (DTI) combined with Statistical Parametric Mapping (SPM) as an effective diagnostic tool for Traumatic Brain Injury.

Electrochemical Point-Of-Care Cerebrospinal Fluid Detection

A revolutionary device for the diagnosis of cerebrospinal fluid (CSF) leaks with rapid, accurate, and low-volume sampling at the point of care.

A System And Method For Telerehabilitation

An innovative system designed to enhance rehabilitation therapy for neurological conditions through comprehensive, computer-based solutions.

Generating Neural Signals From Human Behavior By Neurocognitive Variational Autoencoders

An innovative algorithm linking electroencephalogram (EEG) neural data with cognitive model parameters to predict brain signals from behavioral data.

Newborn Biomarkers of Cumulative Autism Risk Factors

Researchers at the University of California, Davis have identified DNA methylation biomarkers in placenta, as well as maternal and newborn blood, allowing early autism diagnosis and risk assessment.

Genetic Polymorphisms Linked to Age-Related Eye Disorders and Drug Response

Researchers at UC Irvine have identified genetic polymorphisms associated with disease progression and responsiveness to treatment with Tetracosapentaenoic acid (24:5 n-3) for age-related eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. These variations found in the ELOVL2 gene are associated with AMD progression and the varying responses individuals have to AMD treatments, including preventative measures. Additionally, these genetic variations have applications in human identification.

Unsupervised Positron Emission Tomography (PET) Image Denoising using Double Over-Parameterization

Researchers at the University of California, Davis, have developed a novel imaging system that improves the diagnostic accuracy of PET imaging. The system combines machine learning and computed tomography (CT) imaging to reduce noise and enhance resolution. This novel technique can integrate with commercial PET imaging systems, improving diagnostic accuracy and facilitating superior treatment of various diseases.

Systems and Methods of Single-Cell Segmentation and Spatial Multiomics Analyses

Researchers at the University of California, Davis have developed a novel cell segmentation technology for accurate analysis of non-spherical cells and that offers a comprehensive, high-throughput approach for analyzing the transcriptomic and metabolomic data to study complex biological processes at the single-cell level.

Silent Speech Interface Using Manifold Decoding Of Biosignals

Researchers at the University of California, Davis have developed a technology that provides a novel method for decoding biosignals into speech, enhancing communication for individuals with speech impairments.

Stabilized Amyloid Oligomers and Applications for Alzheimer’s Research and Treatment

An innovative approach to advancing Alzheimer's disease research, detection, and treatment through the development of synthetic amyloid peptides and oligomers.

(SD2022-222) Optimized CAG repeat‐targeting CRISPR/cas13d designs

Reseachers from UC San Diego demonstrated a proof of principle for a CAGEX RNA-targeting CRISPR–Cas13d system as a potential allele-sensitive therapeutic approach for HD, a strategy with broad implications for the treatment of other neurodegenerative disorders.

Multilayer Pouch Robot And Manufacturing Method

Inflatable pouches are attractive as actuators and structural links in soft robots due to their low deflated profile and high deformation ratio. Particularly compelling for minimally invasive surgery, deflated robots/actuators may be deployed in small form factors and maneuver delicately in tight spaces once inflated. However, current fabrication methods do not readily scale for production of actuators with less than 1 mm feature sizes; they often require precision handling of separator films; and/or there are limited multilayer integration capabilities. Fully miniaturized, high degree-of-freedom surgical pouch robots and actuators have not yet been realized.To overcome these challenges, UC Berkeley researchers have developed a rapid, monolithic, and scalable manufacturing method for fabricating thin-film-based pneumatic pouch soft robots. Small features (less than 0.3 mm) can be patterned at high speeds and using commercially available manufacturing tools while maintaining film planarity. Resulting robots can have complex, multilayer structures including single- and bi-directional joint actuators, structural links, integrated in-plane air channels, through-holes for interlayer connectivity, and air inlets to a supply manifold—from a single integrated processing step. Researchers have demonstrated a miniature four finger hand which can dexterously manipulate a cube (8 degrees of freedom), as well as an 10 degree-of-freedom planar arm with a gripper which can maneuver around obstacles. Entire pouch robot structures can have un-inflated thickness of less than 300 um and be inherently soft, allowing the robots to be used in tight spaces with fragile tissues for surgical applications.

Use of Ophthalmic Acid for treatment of Parkinson’s disease

Researchers at UC Irvine have identified Opthalmic acid (Ophthalmate, OA) for treatment of Parkinson’s disease (PD), a degenerative neurological disorder that affects 1-2% of people over the age of 60. PD is characterized by progressive motor symptoms such as tremor, rigidity, slowness of movement and difficulty with balance. There is currently no cure for Parkinson’s disease, only treatments to help manage the symptoms. Pharmacological strategies for treating PD depend mainly on replacing lost dopamine due to the degeneration of dopamine neurons in the substantia nigra compacta. Six decades after its initial use, L-3, 4-dihydroxyphenylalalnine (L-DOPA), the dopamine precursor, remains the standard of care for treatment of PD motor symptoms. L-DOPA can readily cross the blood-brain barrier (BBB) and is converted to dopamine by aromatic amino acid decarboxylase (AADC). Initial treatments with L-DOPA can provide great relief from motor symptoms, but over time its therapeutic effects diminish, and dyskinesia (abnormal involuntary movements) can increase in PD patients. Ophthalmic acid acts as a novel neurotransmitter to counteract the motor symptoms in animal models of PD, with a longer duration of action. Ophthalmic acid can be used as a novel drug for treatment of PD and other neurological disorders.

Operant Behavioral Assay

Researchers at the University of California, Davis have developed an operant behavioral assay to study thermosensation, pain, or avoidance and tolerance of an animal to noxious environments.

(SD2022-119) MICROELECTRODE GRID WITH A CIRCULAR FLAP FOR CONTINUOUS INTRAOPERATIVE NEUROMONITORING

Researchers from UC San Diego and Oregon Health Science Univeristy developed a microelectrode grid for continuous interoperative neuromonitoring. The microelectrode grid includes a flexible substrate with low impedance electrochemical interface materials on conducting metal pads. The metal pads are connectable to stimulation/acquisition electronics through metal lead interconnects forming stimulation and recording channels and eventually to bonding pads. A flap within the substrate is movable away from the remainder of the substrate while at least some of the metal pads on the remainder of the substrate can remain in contact with an organ when the flap is moved away from the remainder of the substrate.

Allele Selective Epiediting Of Huntington's Disease Locus

Huntington's disease is an autosomal dominant neurodegenerative disease that has a wide impact on a person's functional abilities and usually results in movement, cognitive, and psychiatric disorders. A treatment for HD that can selectively reduce expression of a mutant copy of the HTT gene (e.g., while having little to no effect on expression of a normal copy of the HTT gene) is highly desirable.UC Berkeley researchers have discovered methods and compositions that take advantage of naturally occurring single nucleotide polymorphisms (SNPs) in the regulatory region of the HTT gene to distinguish between an HTT gene allele containing a pathogenic CAG trinucleotide repeat expansion and an HTT allele that lacks a pathogenic CAG trinucleotide repeat. Potential benefits of using this strategy include 1) lowering both mutant mRNA and mutant protein levels while normal allele remains unaffected, 2) lowering levels of toxic HTTexon11 species and 3) by lowering transcription across the mutant CAG repeats could slow down repeat expansion in mutant allele poten5ally leading to a delay in age of onset. 

Affinity Peptides for Diagnosis and Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 and Zika Virus Infections

Researchers at the University of California, Davis have developed a technology to expedite COVID-19 diagnosis and treatment using viral spike protein (S-protein) targeted peptides Zika virus envelop protein.

Design Of Functional Protein Materials Based on Beta-Rippled Sheet Architectures

The rippled sheet was proposed by Pauling and Corey as a structural class in 1953. Following approximately a half century of only minimal activity in the field, the experimental foundation began to emerge, with some of the key papers published over the course of the last decade. Researchers at UC Santa Cruz have explored the structure of and have discovered ways to form new beta rippled sheets. 

(SD2024-124) Predicting neural activity at depth from surface using multimodal experiments and machine learning models

Researchers from UC San Diego's Neuroelectronic Lab (https://neuroelectronics.ucsd.edu/) demonstrate that they can predict neural activity at deeper layers of the brain by only recording potentials from brain surface. This was achieved by performing multimodal experiments with an ultra-high density transparent graphene electrode technology and developing neural network methods to learn nonlinear dynamic between different modalities. They used cross modality inference to predict the activity at deep layers from surface. Prediction of neural activity at depth have the potential to open up new possibilities for developing minimally invasive neural prosthetics or targeted treatments for various neurological disorders.

(SD2022-177 ) Flexible, insertable and transparent microelectrode array to detect interactions between different brain regions

Researchers from UC San Diego's Neuroelectronics Lab invented an implantable brain electrode technology which allows recording interactions between different cortex regions or interactions of cortex with other subcortical structures. The technology is called Neuro‐FITM. Flexibility and transparency of Neuro‐ FITM allow integration of electrophysiological recordings with any optical imaging (such as high resolution multiphoton imaging) or stimulation technology (such as optogenetics).

(SD2022-066) Simultaneous assessment of afferent and efferent visual pathways using multi‐focal steady‐state visual evoked potenital method to facilitate the diagnosis and prognosis of individuals with neurological diseases.

Researchers from UC San Diego have developed a patent-pending wearable device for concurrently assessing afferent and efferent visual functions. The invention details novel mobile brain-computer interfacing methods and systems for concurrently assessing afferent and efferent visual functions.

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