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IgEvolution: A Novel Tool for Clonal Analysis of Antibody Repertoires

Constructing antibody repertoires is an important error-correcting step in analyzing immunosequencing datasets that is important for reconstructing evolutionary (clonal) development of antibodies. However, the state-of-the-art repertoire construction tools typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction. Thus, although repertoire construction is a prerequisite for follow up clonal tree reconstruction, the existing repertoire reconstruction algorithms are not well suited for this task because they typically miss low-abundance antibodies that often represent internal nodes in clonal trees and are crucially important for clonal tree reconstruction.

Bioactive Plastics With Programmable Degradation And Microplastic Elimination

Although the plastic waste crisis has reached a breaking point, current recycling approaches are unable to remediate microplastic pollution. Biodegradable and renewable plastics have shown promise but impact neither microplastic elimination nor complete plastic recycling due to diffusion-limited enzymatic surface erosion and random chain scission. Here it is shown that nanoscopic dispersion of trace enzyme (e.g. lipase) in plastics (e.g. polycaprolactone [PCL]) leads to fully functional plastics with eco-friendly microplastic elimination and programmable degradation. Nanoscopic enzyme encapsulation leads to:continuous degradation to achieve 95% microplastic eliminationa single chain-based degradation mechanism with repolymerizable small molecule by-products via selective chain end scission rather than random chain scissionspatially- and temporally-programmable degradation of melt-processed host matrix due to the dependence of single chain degradation on local lamellae thickness regardless of bulk percent crystallinity formulation of conductive ink for 3-D printing with full recovery of the precious metal filler With recent developments in synthetic biology and genome information, nanoscopically embedding catalytically active enzymes in plastics may lead to an immediate, environmentally friendly and technologically viable solution toward microplastic elimination and material recycling.

High External-Efficiency Nanofocusing for Lens-Free Near-Field Optical Microscopy

Profs. Ruoxue Yan, Ming Liu, and their colleagues from the University of California, Riverside have developed a two-step sequential broadband nanofocusing technique with an external nanofocusing efficiency of ~50% over nearly all the visible range on a fibre-coupled nanowire scanning probe. By integrating this with a basic portable scanning tunneling microscope, the technology captured images with spatial resolution as low as one nanometer at high resolution. The high performance and vast versatility offered by this fibre-based nanofocusing technique allows for the easy incorporation of nano-optical microscopy into various existing measurement platforms.  Fig. 1: High-resolution NSOM mapping. a, scanning tunnelling microscope topographic image of single wall carbon nanotubes on a gold film. Top inset: cross-sectional profile along the dashed line. Bottom inset: the possible configurations of the bundle.  

Method For Production Of Fatty Acids In Blue-Green Algae

Currently, renewable fatty acids are obtained solely from plant oils. Medium chain fatty acids (C8-C14) are typically sourced from coconut and palm oil, whereas longer chain saturated and unsaturated fatty acids are typically sourced from tallow, soy, corn or sunflower oil. Fatty acids are widely used for food, personal care products, industrial applications (e.g., lubricants, adhesives, detergents and plastics), as well as increasingly as biofuels. The demand for renewable fatty acids is rising and expanding. Given the current understanding of biological pathways it becomes possible to utilize other organisms, especially microorganisms, for the production of renewable chemicals such as fatty acids.

A Microplatform For Performing High Throughput, Multiplexed Assays On Adherent Cells

Systems and methods are providing for performing high-throughput, programmable, multiplexed assays of biological, chemical or biochemical systems. Preferably, a micro-pallet includes a small flat surface designed for single adherent cells to plate, a cell plating region designed to protect the cells, and shaping designed to enable or improve flow-through operation. The micro-pallet is preferably patterned in a readily identifiable manner and sized to accommodate a single cell to which it is comparable in size. Each cell thus has its own mobile surface. The cell can be transported from place to place and be directed into a system similar to a flow cytometer. Since, since the surface itself may be tagged (e.g., a bar code), multiple cells of different origin and history may be placed into the same experiment allowing multiplexed experiments to be performed.

Software for Automated Microfluidic Chip Design

Professor Brisk’s research group at the University of California, Riverside, has developed software to design and analyze an entire microfluidic chip. This is done using Microfluidic Design Automation (MDA) software to synthesize and physically lay out the devices.This software uses Microfluidic  Design  Automation (MDA) to  physically  render chips.  This  approach  is  similar  to  Electronic  Design Automation (EDA) in the semiconductor industry. The  software  automatically creates a chip architecture that is converted to MHDL, a  human-readable microfluidic hardware design language, enabling manual refinement. When  the  chip  designer  is  satisfied  with  the  architecture,  the software  physically  lays  out  the  different  layers  of  the  chip. The  output  is  an  AutoCAD  DXF  (or  other  vector  graphics) file that can be transferred to a foundry for fabrication. Fig. 1 shows a microfluidic device layout designed and laid-out by the UCR software.  

Effective Repetitive Transcranial Magnetic Stimulation (rTMS) Taking in Account Real-Time Frequency and Phase Of Intrinsic Brain Activity

Current research and practice in the field of therapeutic rTMS is not taking into account 1) inter-individual variability 2) variability between brain areas 3) variability or differences between oscillations in distinct and overlapping frequency bands, 4) existence of high- and low-excitability phase periods in each oscillatory cycle. Clinical treatments with rTMS and experimental research findings show mixed effects, with rTMS protocols inducing variable degrees of brain plasticity over subjects and sessions.

Stamping-based Method for Microwell Production and Cell Aggregate Formation

Researchers at the University of California, Davis have developed a 3-D printed stamping system (the “Aggrestamp”) with the capability for in-situ production of microwells that facilitate cell aggregate formation.

Automated Drosophila Maintenance System

Drosophila spp., also known as fruit flies, are widely used in genetic research. Drosophila lines (e.g. flies with a particular mutation) can only be stored as live animals – they cannot be frozen and remain viable. So to maintain the stocks, the live flies are manually transferred from an old vial to a new vial on a regular basis (every 1-2 weeks). Some Drosophila labs maintain hundreds or even thousands of individual lines and so maintenance of these lines can be very time consuming. A UC Santa Cruz Drosophila researcher has developed a simpler and more efficient method of transferring the flies that requires significantly less hands-on work.

Crosslinkable Polymer Coating Prevents Bacterial Infection on Implant Surface

UCLA researchers in the Department of Orthopedic Surgery have developed a polymer implant coating that mitigates bacterial infections on the implant surface.

Reactive Oxygen Species (ROS) Resistant Platform Strains for Bioproduction

The survival of bacteria is associated with the ability to respond to changing environmental conditions. For example, during situations of environmental pressure (e.g. UV, heat, or drug exposure) ROS levels can increase, leading to damage of DNA, lipids and an initiation of signaling events that can lead to cell death. Fortunately, bacterial possess enzymes such as superoxide dismutase (SOD) and catalase enzymes, as well as other antioxidant agents that can reduce ROS. However, when the balance between the production and elimination of ROS is upset, it can have unwanted effects. Thus, the ability of bacteria to increase their tolerance to ROS would be beneficial to the cell’s survival.

Low-Intrusion Plasma Probe

UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed an inexpensive and easily implemented plasma diagnostic tool, the Low-Intrusion Probe.

Identification of a New Molecular Target and Methods for Treating Pancreatic Cancer

Pancreatic cancer is an aggressive disease with limited treatment options and a high mortality rate. Pancreatic cancer is the 3rd leading cause of cancer death in the United States; despite some recent advances in systemic therapy, survival remains dismal in large part due to its profound drug resistance and its propensity for early metastasis. Typically, diagnosis of pancreatic cancer occurs only with advanced stages of the disease since there are currently no early markers for detection. Individuals with pancreatic cancer have a poor prognosis due to the late diagnosis, the extent of metastasis, and ineffective treatments. Survival rates are dismal, with a one-year survival rate of 25% and a 5-year survival rate of 6%. Currently, approximately 20% of pancreatic cancer patients are able to undergo the Whipple procedure; this surgical procedure involves removal of the affected portion of the pancreas, leading to an increased survival rate. However, the remaining 80% of pancreatic cancer patients cannot undergo this treatment because their tumors or the extent of metastasis are too severe. In addition, pancreatic cancer is not typically responsive to radiation and chemotherapy. An alternative approach for the treatment of pancreatic cancer is a complete pancreatectomy followed by continual supplementation with digestive enzymes and insulin. Thus, more effective drugs are needed to increase the survival rate of pancreatic cancer patients. Targeting RORγ may lead to the design of a new class of therapeutics that can be used to treat this devastating disease.

The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination

UCLA researchers in the Department of Chemistry and Biochemistry have developed a novel use of the cryogenic electron microscopy (CryoEM) method electron micro-diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules.

Head-Mounted Display EEG Device

Diagnosis and detection of progression of neurological disorders remain challenging tasks. For example, a validated portable objective method for assessment of degenerative diseases would have numerous advantages compared to currently existing methods to assess functional loss in the disease. An objective EEG-based test would remove the subjectivity and decision-making involved when performing perimetry, potentially improving reliability of the test. A portable and objective test could be done quickly at home under unconstrained situations, decreasing the required number of office visits and the economic burden of the disease. In addition, a much larger number of tests could be obtained over time. This would greatly enhance the ability of separating true deterioration from measurement variability, potentially allowing more accurate and earlier detection of progression. In addition, more precise estimates of rates of progression could be obtained.

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.

Device and Method for Accurate Sample Injection in Analytical Chemistry

Researchers in the UCLA Departments of Bioengineering and Medical and Molecular Pharmacology and the UCSF Department of Bioengineering and Therapeutic Sciences have developed a novel microvalve injector for capillary electrophoresis (CE) that improves injection repeatability and consistency.

System For Fast Multi-Photon Imaging Using Spectrally Diffracted Excitation

UCLA researchers in the Department of Electrical Engineering have developed a new system for fast multi-photon imaging using spectrally diffracted excitation.

Array Atomic Force Microscopy Enabling Simultaneous Multi-point and Multi-modal Nanoscale Analyses

Nanoscale multipoint structure-function analysis is essential for deciphering the complexity of multiscale physical and biological systems. Atomic force microscopy (AFM) allows nanoscale structure-function imaging in various operating environments and can be integrated seamlessly with disparate probe-based sensing and manipulation technologies. However, conventional AFMs only permit sequential single-point analysis. Widespread adoption of array AFMs for simultaneous multi-point study is still challenging due to the intrinsic limitations of existing technological approaches.

Vascularized Tissue Engineering

Tissue engineering and/or regenerative medicine are fields of life science employing both engineering and biological principles to create new tissues and organs and to promote the regeneration of damaged or diseased tissues and organs. Major advances and innovations are being made in the fields of tissue engineering and regenerative medicine and have a huge impact on three-dimensional bioprinting (3D bioprinting) of tissues and organs. 3D bioprinting holds great promise for artificial tissue and organ bioprinting, thereby revolutionizing the field of regenerative medicine. One of the main roadblocks of 3D bioprinting tissues is the lack of efficient techniques to generated vascularized structures. This is critical for grafting applications as limited supply of nutrients and oxygen resulting in premature death of cells.

Carborane-Based Histone Deacetylase (HDAC) Inhibitors

UCLA researchers from the Department of Chemistry & Biochemistry have developed a new class of Histone Deacetylase (HDAC) inhibitors that can be tuned for isoform specificity and other properties.

Multiplex Charge Detection Mass Spectrometry

Native mass spectrometry (MS), in which electrospray ionization (ESI) is used to transfer large macromolecules and macromolecular complexes directly from solution into the gas phase, is a powerful tool in structural biology.  However, charge-state distributions of individual components in mixtures of macromolecular complexes or synthetic polymers are often unresolved making it impossible to obtain mass information directly from an ESI mass spectrum. Other conventional methods can provide accurate masses of individual ions, but often at the expense of analysis time.     Weighing ions individually with charge detection mass spectrometry (CDMS) has the advantage that fast measurements are possible depending on the accuracy and sensitivity required. However, a limitation of trapping CDMS technology is the need to weigh single ions individually in order to eliminate potential interferences between the signals of multiple ions or ion-ion interactions that can potentially interfere with these measurements. UC researchers have created multiplex charge detection mass spectroscopy, particularly for high throughput single ion analysis of large molecules and measuring the masses of large molecules, macromolecular complexes and synthetic polymers that are too large or heterogeneous for conventional mass spectrometry measurements.  The new multiplexing method makes it possible to measure the masses of many ions simultaneously.  

Source Tracking Though Spectral Matching To Mass Spec Databases

Modern metabolomics, proteomics and natural product datasets have now reached into the millions of tandem mass (MS/MS) spectra. The rapidly growing size of these datasets precludes laborious manual data interpretation of all of the data. While MS/MS spectral library search approaches match spectra in an automated fashion, the limited size of available spectral libraries limits identification rates of datasets to single digit percentages. In addition, the sharing of experimental MS/MS data between researchers is not that common. What is needed is a way to organize both identified and unidentified spectra into structurally related molecular families that is searchable.

Discovery Of A Novel Protease With High Specificity Toward Serine Side Chains

Pyrroloquinoline quinone (PQQ), a prominent redox cofactor in a variety of prokaryotes, is produced from a ribosomally synthesized and post-translationally modified peptide PqqA via a pathway comprised of four conserved proteins PqqB-PqqE. These four proteins are now fairly well characterized and span Radical SAM activity (PqqE), aided by a peptide chaperone (PqqD), a dual hydroxylase (PqqB), and an eight electron, eight proton oxidase (PqqC). A full description of this pathway has been hampered by a lack of information regarding a protease/peptidase required for the excision of an early, cross-linked di-amino acid precursor to PQQ.    UC Berkeley researchers have isolated and characterized a two component, heterodimer protein that is able to rapidly catalyze cleavage of PqqA into smaller peptides.  The UC researchers have developed: novel proteases that can cut peptide bonds both N- and C- terminal to the amino acid serine; compositions comprising such proteases; and methods of use, including to assay the extent, position, and time course of protein phosphorylation at serine side chains. 

Methods To Biosynthesize Kainic Acid And Analogues Thereof

Kainic acid is a chemical first derived from seaweed. Neuroscientists routinely use Kainic acid to simulate brain degeneration in lab experiments. Certain inotropic receptors in the brain--known as kainate receptors--are selectively activated only by kainic acid. Research into kainate receptors helps researchers to understand Alzheimer's disease, epilepsy, and other brain disorders. Some scientists use kainic acid to find answers to more fundamental questions such as the function of glutamate receptors. Currently, there are two procedures for generating kainic acid commercially. The first involves the farming and collection of kainic acid-containing seaweed and that method is impacted by seasonal fluctuations of seaweed growth and kainic acid production. The second involves synthetic processes, but the current procedures generally require at least 6 synthetic steps with yields less than 40% and generate environmentally toxic byproducts including heavy metals, cyanides, or halogenated organics.

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