Abstract: The invention provides a series of conformationally stable and selective, irreversible kinase inhibitors, and methods of using the kinase inhibitors. The effect of atropisomerism on kinase selectivity was assessed, finding improved selectivity compared to rapidly interconverting parent compounds. The compounds herein are atropisomers having increased kinase selectivity and are for use in treating conditions that benefit from selective BTK kinase inhibition.

Abstract: This patent document discloses techniques, systems, and devices for detecting a target substance using optical nonlinear wave mixing for enhanced detection sensitivity and accuracy. In one aspect, a method for measuring ?-synuclein in a body fluid of a patient with high detection sensitivity and accuracy and providing early stage Parkinson's disease detection is provided. The method may comprise: supplying to a capillary analyte cell a fluidic sample that includes a body fluid of a patient containing ?-synuclein, wherein the capillary analyte cell is located in a nonlinear optical four-wave mixing device; directing laser light from the nonlinear optical four-wave mixing device into the capillary analyte cell to cause nonlinear optical four-wave mixing in the fluidic sample to generate a four-wave mixing signal that contains information on the ?-synuclein in the fluidic sample; and processing the four-wave mixing signal to extract information on the ?-synuclein in the fluidic sample.

Abstract: Fluorescent nucleobase surrogates capable of Watson-Crick hydrogen bonding are essential probes of nucleic acid structure and dynamics. Their limited brightness and short absorption and emission wavelengths have rendered them unsuitable for single-molecule detection. Herein, we synthesized a new tricyclic pyrimidine nucleoside analogue with a push-pull conjugated system. The resulting C-linked 8-(diethylamino)benzo[b][1,8] naphthyridin-2(1H)-one nucleoside (ABN), exhibits ?442=20,000 M?1 cm?1 and ?em,540=0.39 in water, increasing to ?em=0.50-0.53 when base paired with adenine in duplex DNA oligonucleotides. Single-molecule fluorescence measurements of ABN using both one-photon and two-photon excitation demonstrate its excellent photostability and indicate that the nucleoside is present to >95% in a bright state with count rates of at least 15 kHz per molecule.

Abstract: Nature is capable of storing solar energy in chemical bonds via photosynthesis through a series of C—C, C—O and C—N bond-forming reactions starting from CO2 and light. Direct capture of solar energy for organic synthesis is a promising approach. Lead (Pb)-halide perovskite solar cells reach 24.2% power conversion efficiency, rendering perovskite a unique type material for solar energy capture. We show that photophysical properties of perovskites is useful in photoredox organic synthesis. Because the key aspects of these two applications are both relying on charge separation and transfer. Here we demonstrated that perovskites nanocrystals are exceptional candidates as photocatalysts for fundamental organic reactions, i.e. C—C, C—N and C—O bond-formations. Stability of CsPbBr3 in organic solvents and ease-of-tuning their bandedges garner perovskite a wider scope of organic substrate activations.

Abstract: The invention provides a series of conformationally stable kinase inhibitors, and methods of using the kinase inhibitors. The effect of atropisomerism on kinase selectivity was assessed, finding improved selectivity compared to rapidly interconverting parent compounds.

Abstract: Devices and techniques for using four wave mixing in optical sensing of various materials, including isotopes, chemical and biological substances.

Abstract: The present invention relates generally to methods and compositions for expression of polypeptides or delivery of interfering RNAs in various cell types.

Abstract: Techniques and systems for using nonlinear four wave mixing to optically measure microarrays with sample cells of biological or chemical materials. Examples of suitable microarrays include but are not limited to DNA microchips and capillary electrophoresis microarrays.

Abstract: Devices and techniques for using four wave mixing in optical sensing of various materials, including isotopes, chemical and biological substances.

Abstract: The present invention relates generally to methods and compositions for expression of polypeptides or delivery of interfering RNA's in various cell types.

Abstract: The invention provides compositions (e.g., pharmaceutical compositions) comprising nucleic acids encoding the serine/threonine kinase PIM-1, and methods for making and using them; including methods for inducing cellular proliferation, and protecting cardiac cells from hypoxia and cellular apoptosis. The invention provides compositions (e.g., pharmaceutical compositions) comprising nucleic acids encoding PIM-1, and methods for enhancing the regenerative potential of stem cells in the heart.

Abstract: The invention provides methods and compositions for the treatment of asthma and bronchial inflammation, e.g., as induced by an allergen or toxin. In one aspect, the invention provides inhibitors of “Inducible T Cell Kinase” (ITK) polypeptides and methods of making and using them, e.g., as agents and pharmaceutical compositions to treat asthma. In one aspect, the invention is directed to ITK protein expression and/or activity inhibitors. In one aspect, these ITK protein expression and/or activity inhibitors are used with targeting agents. In one aspect, the ITK protein inhibitors of the invention are used to treat asthma. In one aspect, the invention is directed to ITK protein inhibitors as chimeric proteins comprising fragments or altered or truncated forms of ITK protein, or equivalent. In other aspects ITK protein is joined or fused to another moiety (e.g., a targeting domain) or to an antibiotic.

Abstract: Compositions and methods useful in facilitating or conducting a reaction at effective conditions, such as room temperature (e.g. about 70 degrees F.), utilize a compound including at least two different heteroatoms, and optionally a heterocycle, and a transition metal. The compound is effective in facilitating a variety of reactions including hydrolysis reactions, alcoholysis reactions, aminolysis reactions, carbon dioxide conversion reactions, hydroamination reactions, hydration reactions, and the like.

Abstract: The invention provides a method of nonenzymatic ligation of a nucleic acid. The method consists of contacting a polynucleotide-3? phosphorothiolate with an acceptor polynucleotide under conditions that allow formation of a phosphodiester bond between the polynucleotide-3? phosphorothiolate and the acceptor polynucleotide. The invention also provides methods of molecular cloning. In one embodiment, the method consists of contacting an insert comprising a polynucleotide-3? phosphorothiolate with an acceptor vector under conditions that allow formation of a phosphodiester bond between the insert and the acceptor vector to generate a vector comprising an insert polynucleotide. The invention further provides a compound consisting of a polynucleotide-3? phosphorothiolate and a kit containing a polynucleotide-3? phosphorothiolate. Also provided is a method of ligating a nucleic acid using a non-sequence specific topoisomerase.

Abstract: A method for identifying endogenous microbial proliferation genes for growth and viability is disclosed herein. The method involves exogenous nucleic acids that are used to conditionally produce antisense inhibitors of endogenous complementary mRNAs in a microorganism. Antisense fragments that result in lethality when expressed indicate that the endogenous gene is a proliferation gene. The method can also be used with sequences in sense orientation. The strategy can be used to identify new gene targets for novel antibiotics.

Abstract: The present invention relates to reporter gene constructs encoding a cytoplasmic form of chitobiase (N,N?-diacetylchitobiase) and methods of using these reporter gene constructs. The use of a cytoplasmic form of chitobiase as a reporter enzyme is generally applicable to the study of gene expression in organisms which do not contain N-acetyl-?-D-glucosaminidases.

Abstract: The present invention relates to a device and method for measuring force, primarily due to fatigue. In one embodiment, a finger fatigue measuring system is provided which measures the force output from fingers while the fingers are repetitively generating forces as they strike a keyboard. Force profiles of the fingers are generated from the measurements and evaluated for fatigue. The system can be used clinically to evaluate patients, to ascertain the effectiveness of clinical intervention, pre-employment screening, to assist in minimizing the incidence of repetitive stress injuries at the keyboard, mouse, joystick, and to monitor effectiveness of various finger strengthening systems. The system can also be used in a variety of different applications adapted for measuring forces produced during performance of repetitive motions.

Abstract: Compositions and methods are described for hydrating terminal alkynes catalytically in anti-Markovnikov fashion. The compositions comprise a transition metal complex including at least one organic ligand having at least two heteroatoms, wherein the heteroatoms are directly bonded or located one atom away. Preferably, at least one of the heteroatoms is nitrogen, which is typically provided as part of a heterocyclic ring. Other preferred heteroatoms include S, P, N, As or Se. A particularly preferred catalyst employs a P-linked imidazole ligand bound to Ru. Such complexes have a controlled adaptable proton transfer ability and/or a hydrogen bonding ability making them particularly useful as chemical reaction facilitators.

Abstract: The method and system of the present invention is designed to minimize exergy consumption consistent with a given level of product purity. For example, in a distillation system, the design employs a plurality of thermostatted trays which are maintained at a sequence of temperatures specified by finding the optimal control for an irreversible thermodynamic process. The specified temperatures at each tray are achieved with the help of a tandem heat pump which works over the range of required temperatures and which delivers the specified heat demands.

Abstract: Disclosed herein are chemical methods for reducing concentrations of perchlorate ion in sources of water to be used for potable purposes. The disclosed methods include contacting water containing perchlorate ion with iron metal to chemically reduce the perchlorate ion to a more innocuous ion species. The metal can then be removed. The instant methods also relate to contacting perchlorate contaminated water with iron metal or a metal oxide in the presence of phosphoric acid to form a complex with perchlorate ion and adsorb the complex onto the iron, which is then removed from the water. These methods provide an environmentally safe and economically efficient means to effectively remove perchlorate ion from potable water sources, resulting in water that is safe for human use and consumption.