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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.

Covalent Organic Framework With Exceptional Water Sorption Properties

A new covalent organic framework (COF) with defective square lattice topology and exceptional water sorption properties stemming fro its unique framework structure. The COF exhibits a working capacity of 0.23 g(H2O)/g(COF) between 20 and 40% relative humidity without displaying hysteretic behavior. Furthermore, it maintains these promising water sorption properties after several uptake and release cycles. This material could be used as a sorbent for water harvesting or other water sorption related applications.

Improved Cas12a Proteins for Accurate and Efficient Genome Editing

Mutated versions of Cas12a that remove its non-specific ssDNA cleavage activity without affecting site-specific double-stranded DNA cutting activity. These mutant proteins, in which a short amino acid sequence is deleted or changed, provide improved genome editing tools that will avoid potential off-target editing due to random ssDNA nicking.

DEVICES AND METHODS FOR GENERATING OLIGODENDROCYTE PROGENITOR CELLS

The emergence of several cell based therapy candidates in the clinic is an encouraging sign for human diseases/disorders that currently have no effective small molecule or biologic based therapy. Stem cells – including adult and pluripotent subtypes – offer tremendous clinical promise for the treatment of a variety of degenerative diseases, as these cells have the capacity to self-renew indefinitely and to mature into functional cell types and thereby serve as a source of cell replacement therapies (CRTs) and pluripotent stem cells (hPSCs) are of increasing interest for the development of CRTs because of their capacity to differentiate into all cell types in an adult, for which adult tissue-specific stem cells may in some cases not even exist. One potential CRT enabled by hPSCs is oligodendrocyte progenitor cells (OPCs) for the treatment of spinal cord injury (SCI). Such hPSC-OPCs have recently advanced to a Phase II clinical trial and are even being considered for additional diseases in the central nervous system (CNS), such as multiple sclerosis (MS), or injury from radiation.   UC researchers have developed a microscale 3D culture screening and analysis methodology that is relevant to the production of several up and coming cell replacement therapy candidates for which derivation from a precursor cell type requires searching through a large in vitro design space of doses, durations, dynamics, and combinations of signaling cues over several weeks of culture, such as oligodendrocyte progenitor cells (OPCs) and midbrain dopaminergic neurons (mDA neurons) derived from human pluripotent stem cells. 

Catechol Functionalized Elastin-Like Polypeptide Adhesives

Reliably reconnecting severed tissues is a critical part of any invasive medical procedure. Although, sutures and staples are ideal choices due to their effectiveness, adhesives hold great promise as alternatives for bonding tissues. Although many bio-adhesives are commercially available, no product yet combines all desirable properties such as consistent adhesion to wet surfaces, mechanical durability, molecular-level customizability and biocompatibility. UC Berkeley research have developed a recombinant protein-based adhesive by chemically functionalizing elastin-like polypeptides (ELPs).  These ELPs form stable and flexible hydrogels de-swell in aqueous conditions. An additional strength of using recombinant proteins is exhibited by significantly enhancing cell binding to this ELP by a simple modular addition of an engineered protein with ‘RGD’ peptides. 

Simultaneous Detection Of Protein Isoforms And Nucleic Acids From Low Starting Cell Numbers

Embryo-specific nucleic acid modifications, including retrotransposon activity-derived genomic modifications and alternative splicing of mRNA, is crucial for the development of mammalian embryos. However, determining if all genomic modifications and mRNA isoforms translate to protein variations remain intriguing questions due to difficulty in measuring protein isoforms and nucleic acids from small starting cell numbers.    UC Researchers have developed a system for performing dual nucleic acid and protein isoform measurements on low starting cell numbers equivalent to the number of blastomeres composing early embryonic development stages (morula and blastocysts).  The system integrates fractionation polyacrylamide gel electrophoresis (fPAGE) with off-chip analysis of nucleic acids in the nuclei. An additional method can be used to remove nuclei for off-chip analysis. The system can measure expression of protein isoforms from the cytoplasmic fraction of 1-100 cells while achieving analysis of either DNA or mRNA retained in the nuclei. The researchers have demonstrated signal from immunoprobed protein correlates strongly with protein expression prior to lysis in TurboGFP-expressing cells and that mRNA levels correlate with protein abundance in TurboGFP-expressing cells.

Integrated Nanocrescent Optical Antenna System (iNOAS) for Rapid Precision Molecular Diagnostics

UC Researchers have developed a hexagonally packed nanocrescent optical antenna array for real-time ultrafast photonic PCR, which can avoid the problem of quenching fluorescent probes by applying well-matched resonance oscillation of electrons instead of random photothermal heating. Matching the plasmon resonance with NIR diode and the design of integrated nanocrescent optical antenna on chip allows effective plasmonic conversion of the light to heat drastically. It improves not only time consuming thermal cycling step, but also real­time PCR detection due to amplified signals without the excessive heating problem of fluorescent molecules. 

NANOPORE MEMBRANE DEVICE AND METHODS OF USE THEREOF

Several chemical, physical, and biological techniques have been used for delivering macromolecules into living cells. Delivery of biomolecules into living cells is essential for biomedical research and drug development as well as genome editing. However, conventional methods of delivery of biomolecules such as viral vectors, cell penetrating peptides, cationic lipids, positive charged polymers, bulk electroporation, and microinjection pose several challenges. Such challenges include safety concerns, toxicity, damage to the cells, limited loading capacity, low delivery efficiencies, low cell viabilities, low cell throughput, high cellular perturbation, and high costs.  Thus, there is a need for delivery devices and methods that allow for permeabilization of the cell membrane to facilitate delivery of biomolecules into cells.   UC Berkeley researchers have developed a universal delivery electroporation system that makes cell transfection very simple for all of types of cells. The technology can be used to replace conventional cellular delivery methods such as cationic lipid, positive charged polymer and bulk electroporation as well as microinjection.  The system can deliver biomolecules (e.g., DNA, RNA, proteins, nucleic acid-protein complexes (e.g., RNPs)) or other reagents into all cell types, including T-cells, which cannot be efficiently transfected with conventional approaches.  

Bioinspired Hydrogels for the Treatment of Volumetric Muscle Loss Injury

Injuries that involve a degree of muscle tissue loss that exceeds the endogenous regenerative capacity of muscle, resulting in permanent cosmetic and functional deficits of either the injured muscle or the muscle unit, are referred to as volumetric muscle loss (VML) injuries. Current treatment for VML injury involves surgical muscle transfer, although these procedures are often associated with poor engraftment and donor site morbidity.    UC Berkeley and U.Va researchers have developed a new technology for the treatment of VML injuries that overcomes the limitations associated with current treatments for VML injury.  The Matrix Assisted Cell Transplantation (MACT) technology developed by the researchers employs “bioinspired” materials designed to emulate regulatory processes that modulate cell function in the stem/progenitor cell microenvironment.  The technology includes: 1) peptide ligands to imitate the natural extracellular matrix (ECM); 2) proteolytic remodeling via matrix metalloproteinase (MMP) sensitive peptide crosslinks; and, 3) growth factors with engineered density and presentation.    The technology and the materials used have been shown to significantly improve donor survival after transplantation, promote angiogenesis, and encourage donor cell integration with the host tissue.

Cas12-mediated DNA Detection Reporter Molecules

Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein (an effector protein, e.g., a type V Cas effector protein such as Cpf1) bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that continues to revolutionize the field of genome manipulation.    Cas12 is an RNA-guided protein that binds and cuts any matching DNA sequence. Binding of the Cas12-CRISPR RNA (crRNA) complex to a matching single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) molecule activates the protein to non-specifically degrade any ssDNA in trans. Cas12a-dependent target binding can be coupled to a reporter molecule to provide a direct readout for DNA detection within a sample.  UC Berkeley researchers have developed compositions, systems, and kits having labeled single stranded reporter DNA molecules that provide a sensitive readout for detection of a target DNA. 

Tissue Projection Electrophoretic Separation Of Protein

A range of related immunoblotting methods have enabled the identification and semi-quantitative characterization of e.g., DNA (Southern blot), RNA (northern blot), proteins (Western blot), and protein-protein interactions (far-western blot); by coupling biomolecule separations and assays.  However, there are a wide number of alternative splicing events, post-translational modifications, and co-translational modifications (e.g., phosphorylation, glycosylation, and protein cleavage) that give rise to proteoforms and protein complexes with distinct function and subsequent cell behavior that cannot be analyzed with conventional methods such as immunohistochemistry (IHC). Analytical variability (lack of isoform- or complex-specific antibody probes), biological variability (small cell subpopulations diluted in bulk analysis), and lack of multiplexing (measurement of multiple proteins from the same tissues) can all render proteoforms and protein complexes undetectable by current technologies.     UC Berkeley researchers have created electrophoretic separation platform that is capable of measuring proteoforms and protein complexes lacking specific antibodies alongside spatial information, at the cellular level.  This platform maintains the architecture of 2D tissue slices while projecting a protein separation in the 3rd dimension. The platform mitigates artifacts induced by tissue dissociation processes, as the intact tissue is lysed and subject to a protein separation. The platform is also compatible with differential detergent fractionation methods for further separation of proteins (e.g. separation by localization within the cell, by cell type, by protein complex formation, or by cellular vs. matrix proteins), opening the door for a novel, refined classification taxonomy using enhanced biomarker signatures for diagnostics and treatment selection in oncology among a wide range of additional future applications.  

Endoribonucleases For Rna Detection And Analysis

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} Bacteria and archaea possess adaptive immune systems that rely on small RNAs for defense against invasive genetic elements. CRISPR (clustered regularly interspaced short palindromic repeats) genomic loci are transcribed as long precursor RNAs, which must be enzymatically cleaved to generate mature CRISPR-derived RNAs (crRNAs) that serve as guides for foreign nucleic acid targeting and degradation. This processing occurs within the repetitive sequence and is catalyzed by a dedicated CRISPR-associated (Cas) family member in many CRISPR systems.  Endoribonucleases that process CRISPR transcripts are bacterial or archaeal enzymes capable of catalyzing sequence- and structure- specific cleavage of a single- stranded RNA. These enzymes cleave a specific phosphodiester bond within a specific RNA sequence.  UC Berkeley researchers discovered variant Cas endoribonucleases, nucleic acids encoding the variant Cas endoribonucleases, and host cells genetically modified with the nucleic acids that can be used, potentially in conjunction with Cas9, to detect a specific sequence in a target polyribonucleotide and of regulating production of a target RNA in a eukaryotic cell.  For example, it was found that the variant Cas endoribonuclease has an amino acid substitution at a histidine residue such that is is enzymatically inactive in the absence of imidazole and is activatable in the presence of imidazole.  

Printed All-Organic Reflectance Oximeter Array

A flexible reflectance oximeter array (ROA) composed of printed organic light-emitting diodes (OLEDs) and organic photodiodes (OPDs), which senses reflected light from tissue to determine the oxygen saturation. Since reflected light is used as the signal, the sensor array can be used beyond the conventional sensing locations. We implemented the ROA to measure SpO2 on the forehead with 1.1% mean error and to create two-dimensional (2D) oxygenation maps of the adult forearm under pressure cuff-induced ischemia. Due to the mechanical flexibility, 2D oxygenation mapping capability, and the ability to place the sensor in diverse places, the ROA is promising for novel medical sensing applications such as mapping oxygenation in tissues, wounds, or transplanted organs.

Type V CRISPR/CAS Effector Proteins for Cleaving ssDNA and Detecting Target DNA

Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Class 2 CRISPR–Cas systems (e.g., type V CRISPR/Cas systems such as Cas12 family systems) are characterized by effector modules that include a single effector protein. For example, in a type V CRISPR/Cas system, the effector protein - a CRISPR/Cas endonuclease (e.g., a Cas12a protein) - interacts with (binds to) a corresponding guide RNA (e.g., a Cas12a guide RNA) to form a ribonucleoprotein (RNP) complex that is targeted to a particular site in a target nucleic acid via base pairing between the guide RNA and a target sequence within the target nucleic acid molecule.  Thus, like CRISPR-Cas9, Cas12 has been harnessed for genome editing based on its ability to generate targeted, double-stranded DNA (dsDNA) breaks.   UC Berkeley researchers have discovered that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules. The researchers found that target-activated, non-specific ssDNase cleavage is also a property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase activation with isothermal amplification, the researchers were able to achieve attomolar sensitivity for DNA detection.  For example, rapid and specific detection of human papillomavirus in patient samples was achieved using these methods and compositions.   

Class 2 CRISPR/Cas COMPOSITIONS AND METHODS OF USE

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation, so there is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   Researchers have shown that Class 2 CRISPR Cas protein and their variants can be used in a complex for specific binding and cleavage of DNA. The Class 2 CRISPR Cas complex utilizes a novel RNA and a guide RNA to perform double stranded cleavage of DNA and the complex is expected to have a wide variety of applications in genome editing and nucleic acid manipulation. 

A Dual-RNA Guided CasZ Gene Editing Technology

Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation, so there is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   UC Berkeley researchers discovered a new type of Cas protein, CasZ.  (CasZ) is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  The researchers have shown that the CRISPR CasZ protein and its variants can be used in a complex for specific binding and cleavage of DNA. The CRISPR CasZ complex utilizes a novel RNA and a guide RNA to perform double stranded cleavage of DNA and the complex is expected to have a wide variety of applications in genome editing and nucleic acid manipulation. 

CRISPR CASY COMPOSITIONS AND METHODS OF USE

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation, so there is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   Previously UC Berkeley researchers discovered a new type of Cas protein, CasY (also referred to as Cas 12d protein).  CasY is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  CasY utilizes a guide RNA to perform double stranded cleavage of DNA. The researchers introduced CRISPR-CasY into E. coli, finding that they could block genetic material introduced into the cell.  Further research results indicated that CRISPR-CasY operates in a manner analogous to CRISPR-Cas9, but utilizing an entirely distinct protein architecture containing different catalytic domains.   CasY is also expected to function under different conditions (e.g., temperature) given the environment of the organisms that CasY was expressed in.  Similar to CRISPR Cas9, CasY enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation. Recent studies have shown that the CasY complex utilizes a novel RNA, in addition to the guide RNA, to perform double stranded cleavage of DNA. Similar to CRISPR Cas9, CasY enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.   

THERMOSTABLE RNA-GUIDED ENDONUCLEASES AND METHODS OF USE THEREOF (GeoCas9)

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets. The programmable nature of these systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation. There is a need in the art for additional CRISPR-Cas systems with improved cleavage and manipulation under a variety of conditions and ones that are particularly thermostable under those conditions.     UC researchers discovered a new type of RNA-guided endonuclease (GeoCas9) and variants of GeoCas9.  GeoCas9 was found to be stable and enzymatically active in a temperature range of from 15°C to 75°C and has extended lifetime in human plasma.  With evidence that GeoCas9 maintains cleavage activity at mesophilic temperatures, the ability of GeoCas9 to edit mammalian genomes was then assessed.  The researchers found that when comparing the editing efficiency for both GeoCas9 and SpyCas9, similar editing efficiencies by both proteins were observed, demonstrating that GeoCas9 is an effective alternative to SpyCas9 for genome editing in mammalian cells.  Similar to CRISPR-Cas9, GeoCas9 enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.   

Au(III) Complexes For [18F] Trifluoromethylation

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The biological properties of trifluoromethyl compounds (e.g, CF3) have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions.  For example, strong, non-interacting C-F bonds lend metabolic stability while simultaneously limiting the ability of chemical transformations to forge the relevant linkages and install the CF3 unit.  When these same synthetic considerations are extended toward the synthesis of trifluoromethylated positron emission tomography (PET) tracers, the situation becomes more complex.   UC Berkeley researchers discovered an unusual alternative mechanism, in which borane abstracts fluoride from the CF3 group in a gold complex. The activated CF2 fragment can then bond to a wide variety of other carbon substituents added to the same gold center. Return of the fluoride liberates a trifluoromethylated compound from the metal. This mechanism would be useful for the introduction of radioactive fluoride substituents for potential tracers to be used for positron emission tomography applications.

Monolithically Integrated Implantable Flexible Antenna for Electrocorticography and Related Biotelemetry Devices

A sub-skin-depth (nanoscale metallization) thin film antenna is shown that is monolithically integrated with an array of neural recording electrodes on a flexible polymer substrate. The structure is intended for long-term biometric data and power transfer such as electrocorticographic neural recording in a wireless brain-machine interface system. The system includes a microfabricated thin-film electrode array and a loop antenna patterned in the same microfabrication process, on the same or on separate conductor layers designed to be bonded to an ultra-low power ASIC.

Configurations for Integrated MRI-linear Accelerators

Researchers at Stanford and University of California, Berkeley, have developed an integrated MRI-Linac hybrid system that can increase the efficacy of image-guided radiotherapy (IGRT). This system allows more aggressive treatment strategies that employ dose escalation, tighter geometric margins and sharper dose gradients which can improve clinical outcomes. This radiotherapy treatment apparatus includes a treatment beam (charged by Linac, particle, proton, or electron beam), a magnetic field disposed parallel collinear to the treatment beam, and a target that is disposed along the treatment beam. MRI is ideal for IGRT, however, there is magnetic field and RF interference between the linear accelerator and MRI scanner. The configurations of this system overcome this issue.

Small Molecule Assisted Cell Penetrating Cas9 RNP Delivery

Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Clustered regularly interspaced short palindromic repeats (CRISPR) Cas systems provide a means for modifying genomic information and have the potential to revolutionize the treatment of genetic diseases. Although RNA-programmed Cas9 has proven to be a versatile tool for genome engineering in multiple cell types and organisms, it has been challenging to develop the therapeutics because they require the simultaneous in vivo delivery of the Cas9 protein, guide RNA and donor DNA. Compositions that can increase the efficiency of such delivery, particular in eukaryotic cells, are greatly needed.   UC Researchers have discovered that the inclusion of an agent that decreases the acidity of an endosome inside eukaryotic cells, in a genome editing composition, increased the efficiency of genome editing.  The agent was included in a composition having an RNA-guided endonuclease and an RNA-guided endonuclease and was used for gene editing.

Simultaneous Doctor Blading Of Different Colored Organic Light Emitting Diodes

Methods for the simultaneous printing via doctor blading of at least two different colored emissive layers for organic light emitting diodes (OLEDs) on a single substrate.

Sensitive Detection Of Chemical Species Using A Bacterial Display Sandwich Assay

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} Endocrine disrupting compounds are found in increasing amounts in our environment, originating from pesticides, plasticizers, and pharmaceuticals, among other sources. These compounds have been implicated in diseases such as obesity, diabetes, and cancer. The list of chemicals that disrupt normal hormone function is growing at an alarming rate, making it crucially important to find sources of contamination and identify new compounds that display this ability. However, there is currently no broad-spectrum, rapid test for these compounds, as they are difficult to monitor because of their high potency and chemical dissimilarity.   To address this, UC Berkeley researchers have developed a new detection system and method for the sensitive detection of trace compounds using electrochemical methods.  This platform is both fast and portable, and it requires no specialized skills to perform. This system enables both the detection of many detrimental compounds and signal amplification from impedance measurements due to the binding of bacteria to a modified electrode. The researchers were able to test the system finding sub-ppb levels of estradiol and ppm levels of bisphenol A in complex solutions. This approach should be broadly applicable to the detection of chemically diverse classes of compounds that bind to a single receptor.  

Heterochronic Blood Exchange As A Modality To Influence Myogenesis, Neurogenesis, And Liver Regeneration

One reason for waning capabilities with advancing age is a progressive decline in organ function. Heterochronic parabiosis rejuvenates the performance of old tissues' stem cells at some expense to the young, but whether this is through shared circulatory factors or shared organ systems is unclear; and parabiosis is not a clinically adaptable approach. The old heterochronic partners have access to young organs, environmental enrichment and youthful hormones/pheromones, while the young parabiont maintains an additional aged body with deteriorating organs. In contrast to the permanent anastomosis of parabiosis, UC Berkeley researchers have used a small animal blood exchange where animals are connected and disconnected at will, removing the influence of shared organs, adaptation to being joined, etc. The effects of heterochronic blood exchange were examined with respect to all three germ layer derivatives: injured-regenerating muscle, ongoing liver cell proliferation and brain - hippocampal neurogenesis, and in the presence and absence of muscle injury.  The influence of heterochronic blood exchange on myogenesis, neurogenesis and hepatogenesis was fast, within a few days.  These findngs suggest a rapid translation of blood apheresis (FDA approved for other diseases, but not for the degenerative pathologies) for therapy to attenuate and reverse liver fibrosis and adiposity, muscle wasting and neuro-degeneration.  

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