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Software Defined Pulse Processing (SDPP) for Radiation Detection

Radiation detectors are typically instrumented with low noise preamplifiers that generate voltage pulses in response to energy deposits from particles (x-rays, gamma-rays, neutrons, protons, muons, etc.). This preamplifier signal must be further processed in order to improve the signal to noise ratio, and then subsequently estimate various properties of the pulse such as the pulse amplitude, timing, and shape. Historically, this “pulse processing” was carried out with complex, purpose-built analog electronics. With the advent of digital computing and fast analog to digital converters, this type of processing can be carried out in the digital domain.There are a number of commercial products that perform “hardware” digital pulse processing. The common element among these offerings is that the pulse processing algorithms are implemented in hardware (typically an FPGA or high performance DSP chip). However this hardware approach is expensive, and it's hard to tailor for a specific detector and application.To address these issues, researchers at UC Berkeley developed a solution that performs the pulse processing in software on a general purpose computer, using digital signal processing techniques. The only required hardware is a general purpose, high speed analog to digital converter that's capable of streaming the digitized detector preamplifier signal into computer memory without gaps. The Berkeley approach is agnostic to the hardware, and is implemented in such a way as to accommodate various hardware front-ends. For example, a Berkeley implementation uses the PicoScope 3000 and 5000 series USB3 oscilloscopes as the hardware front-end. That setup has been used to process the signal from a number of semiconductor and scintillator detectors, with results that are comparable to analog and hardware digital pulse processors.In comparison to current hardware solutions, this new software solution is much less expensive, and much more easily configurable. More specifically, the properties of the digital pulse shaping filter, trigger criteria, methods for estimating the pulse parameters, and formatting/filtering of the output data can be adjusted and tuned by writing simple C/C++ code.

Anti-Acinetobacter Baumannii Polyclonal Antibody (AB-pAb)

The inventors have constructed a polyclonal antibody (pAb) for the specific detection of the multi-drug resistant (MDR) bacterial pathogen, Acinetobacter baumannii (A. baumannii), producing the antibody entitled, 'AB-pAb'. The AB-pAb was raised against a recombinant (His-tagged) 22 kDa outer membrane protein (OMP22), an antigenic protein which is conserved across the species. The gene encoding OMP22 was amplified from the clinical A. baumannii isolate, AR_0056, which belongs to the international clonal lineage II, a lineage associated with outbreaks worldwide. The AB-pAb is capable of recognizing purified, denatured, OMP22 by Western blot, in addition to the native protein in whole cells of A. baumannii in vitro. The pAb was optimized for diagnostic use by, firstly, removing antibodies within the heterogeneous pAb pool which were cross-reactive to other, clinically-relevant Gram-negative bacteria (GNB). This eliminates the issue of cross-reactivity often associated with polyclonal antibodies, which can limit their use as diagnostic tools. Moreover, testing was performed under conditions which mimic those of the blood and urine, further enhancing the novel AB-pAb's ability to recognize target bacteria in patient samples. When tested against a panel of clinical isolates by indirect-ELISA, for the recognition of A. baumannii from other clinically relevant GNB, the optimized AB-pAb had a sensitivity of 85.5% (95 % confidence interval: 76.11% to 92.3%) and a specificity of 99.5% (95 % confidence interval: 99.53% to 99.99%) at a cutoff, signal-to-noise ratio (SNR) of 0.1275. To our knowledge, no commercial anti-A. baumannii pAbs are currently available which target OMP22, specifically optimized for diagnostic purposes.

Chimeric Cas9 Variants With Novel Engineered Enzymatic Activities

In this invention, the HNH domain of a Cas9 is replaced by a domain that could have diverse enzymatic activities. This invention enables engineering of Cas9 chimeras that possess novel, conformation-sensitive enzymatic activity to perform specific genome editing in vitro, in vivo, and ex vivo.Prior to this invention, all of the strategies to engineer Cas9 fusion proteins and provide Cas9 with non-natural enzymatic activity for genome manipulations were engineered by fusing specific domains to the N- or C-terminus of Cas9 via long and flexible linkers, or through domain insertion approach. The disadvantages of these synthetic Cas9 chimeras are that the attached domain is on the long flexible linker, and it is very dynamic. Thus, these fusions have a broad activity window and they are large, which makes it difficult to deliver them to the cells. 

Composition and Methods of a Nuclease Chain Reaction for Nucleic Acid Detection

This invention leverages the nuclease activity of CRISPR proteins for the direct, sensitive detection of specific nucleic acid sequences. This all-in-one detection modality includes an internal Nuclease Chain Reaction (NCR), which possesses an amplifying, feed-forward loop to generate an exponential signal upon detection of a target nucleic acid.Cas13 or Cas12 enzymes can be programmed with a guide RNA that recognizes a desired target sequence, activating a non-specific RNase or DNase activity. This can be used to release a detectable label. On its own, this approach is inherently limited in sensitivity and current methods require an amplification of genetic material before CRISPR-base detection. 

Cycloadditions In Biological Systems Promoted By Strained Pi-bonds

The present invention provides modified cycloalkyne compounds; and method of use of such compounds in modifying biomolecules. The present invention features a cycloaddition reaction that can be carried out under physiological conditions. In general, the invention involves reacting a modified cycloalkyne with an azide moiety on a target biomolecule, generating a covalently modified biomolecule. The selectivity of the reaction and its compatibility with aqueous environments provide for its application in vivo (e.g., on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).

Cellular Potassium Imaging Using A Ratiometric Fluorescent Sensor

The inventors developed a ratiometric fluorescent small molecule probe for potassium ion detection composed of a duo-fluorophore system (KR-1). UV-vis detector and fluorometer measurement support ratiometric response of the probe towards potassium ion concentration. The probe was further applied to cellular potassium level detection using confocal microscope imaging technique. KR-1 enables simple determination of potassium levels in various cancer or non-cancer cell lines.

Expressing Multiple Genes From A Single Transcript In Algae And Plants

Green algae have been promoted as vehicles for the production of biofuels, pharmaceuticals, food additives, vaccines, and for toxic substance remediation, and many plants are the focus of efforts to produce drought tolerant, pest resistant, or more nutritious crops. Many of these engineering efforts rely on expression of multiple transgenes (e.g. in a multistep metabolic pathway to avoid accumulation of a toxic intermediate). It can also be useful to produce two or more proteins in a particular stoichiometry, as in a heterodimer that requires equimolar production of two polypeptides. Whether the goal is to express one transgene, or several, most efforts to transform plants and algae require cotransformation of the gene of interest with a selectable marker, such as a gene that confers resistance to a drug or herbicide, or complements an auxotrophy. Unfortunately, commonly used methods for co-transformation of algae and other plants are very inefficient. UC Berkeley investigators have developed a method for polycistronic gene expression,  and show how to achieve this using the organism's own sequences, without recourse to viral elements or other foreign elements, which is important for any technology where bioproducts are generated, since these may be used on humans (cosmetics) or in humans (food additives), especially crop technology.

System For Determining Trademark Similarity

Many areas of intellectual property law involve subjective judgments regarding confusion or similarity. For example, in trademark or trade dress lawsuits a key factor considered by the court is the degree of visual similarity between the trademark or product designs under consideration. Such similarity judgments are nontrivial, and may be complicated by cognitive factors such as categorization, memory, and reasoning that vary substantially across individuals. Currently, three forms of evidence are widely accepted: visual comparison by litigants, expert witness testimonies, and consumer surveys. All three rely on subjective reports of human responders, whether litigants, expert witnesses, or consumer panels. Consequently, all three forms of evidence potentially share the criticism that they are subject to overt (e.g. conflict of interest) or covert (e.g. inaccuracy of self-report) biases.To address this situation, researchers at UC Berkeley developed a technology that directly measures the mental state of consumers when they attend to visual images of consumer products, without the need for self-report measures such as questionnaires or interviews. In so doing, this approach reduces the potential for biased reporting.