Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: Provided herein are macrolide compounds of Formula (I) and (I-N) for the treatment of infectious diseases and inflammatory conditions. The 14-membered ketolides and 14-, 15-, and 16-membered azaketolides described herein comprise modified sugars which are desosamine or mycaminose analogs. Pharmaceutical compositions and methods of treating infection diseases and inflammatory conditions using the inventive macrolides are also provided. This disclosure additionally provides methods of preparing the macrolides by the coupling of an eastern and western half.

Abstract: The present invention generally relates to microfluidics and, in particular, to systems and methods for determining cells using amplification. In one set of embodiments, cells are encapsulated within droplets and nucleic acids from the cells amplified within the droplets. The droplets may then be pooled together and the amplified nucleic acids can be determined using PCR or other suitable techniques. In some embodiments, techniques such as these can be used to detect relatively rare cells that may be present, e.g., if the droplets are amplified using conditions able to selectively amplify nucleic acids arising from the relatively rare cells.

Abstract: The present invention provides high throughput assays for identifying compounds that modulate a contractile function, as well as devices suitable for these assays.

Abstract: Three-dimensional cellular arrays, methods of making three-dimensional cellular arrays, and methods of identifying agents using the arrays are disclosed.

Abstract: There is provided a nanometric structure that includes a self-supporting nanometric material having a thickness of no more than about 5 nm. A plurality of nanopores is provided in the nanometric material, and the nanopore plurality has a density of at least about 1000 nanopores/cm2. Each nanopore in the plurality of nanopores has a diameter that is no greater than about 10 nm. The plurality of nanopores is monodisperse in diameter with a variation of about ±30%. In a further nanometric structure provided herein there is included a self-supporting nanometric material having a thickness of no more than about 5 nm. A plurality of nanopores in the nanometric material includes at least about 50 nanopores. Each nanopore in the plurality of nanopores has a diameter that is no greater than about 10 nm. The plurality of nanopores is monodisperse in diameter with a variation of about ±30%.

Abstract: Systems and methods for inhibiting an occurrence of an apneic or hypoxic event are disclosed. Physiological data is received from a subject and analyzed to detect an impending apneic event or an impending hypoxic event. A stimulation is applied to the subject to inhibit occurrence of the impending apneic or hypoxic event after an occurrence of a predetermined condition. The physiological data can include respiratory data, cardiological data, or a combination thereof. The analyzing includes use of a point-process model and gross body movement data of the subject. Therapeutic effectiveness of the stimulation is increased by accounting for gross body movements of the patient.

Abstract: A method for determining the translation initiation inhibitory potency of a composition having an unknown level of translation initiation inhibitory activity which comprises contacting an eI-F2?-WT cell with said composition for a time and at a temperature effective to inhibit proliferation of said cell, measuring the level of inhibition of proliferation of said eIF2?-WT cells induced by said sample and comparing the level of inhibition of proliferation induced by said sample with the level of inhibition of proliferation induced by a standard having a known amount of said activity, the amount of said translation initiation inhibitory activity in said sample being proportional to the level of inhibition of proliferation of said eIF2?-WT cell.

Abstract: Methods and apparatus for high-throughput fluorescence detection using integrated microfabricated optical element arrays are described. In one example, the optical element arrays may comprise one or more microfabricated Fresnel zone plates, which may be configured to collect light from samples flowing in microfluidic channels. Multiple samples may be inspected in parallel at significantly high rates (e.g., about 200,000 samples per second or higher). A relay lens combined with high numerical aperture integrated microfabricated optical elements provides significant signal enhancement (e.g., on the order of at least 200 times that of conventional fluorescence detection methods).

Abstract: A method and apparatus for delivering one or more fluids. Fluids may be delivered sequentially from a common vessel to a chemical, biological or biochemical process.

Abstract: Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The power of Nature and the flexibility of organic synthesis are combined in nucleic acid-templated synthesis. The present invention provides a variety of template architectures for performing nucleic acid-templated synthesis, methods for increasing the selectivity of nucleic acid-templated reactions, methods for performing stereoselective nucleic acid-templated reactions, methods of selecting for reaction products resulting from nucleic acid-templated synthesis, and methods of identifying new chemical reactions based on nucleic acid-templated synthesis.

Abstract: Novel methods for making high resolution oligonucleotide paints are provided. Novel, high resolution oligonucleotide paints are also provided.

Abstract: The present invention generally relates to nanoscale wire devices and methods for use in determining analytes suspected to be present in a sample. The invention provides a nanoscale wire that has improved sensitivity, as the carrier concentration in the wire is controlled by an external gate voltage, such that the nanoscale wire has a Debye screening length that is greater than the average cross-sectional dimension of the nanoscale wire when the nanoscale wire is exposed to a solution suspected of containing an analyte. This Debye screening length (lambda) associated with the carrier concentration (p) inside nanoscale wire is adjusted by adjusting the gate voltage applied to an FET structure, such that the carriers in the nanoscale wire are depleted.

Abstract: A network element (10), such as a Packet Data Serving Node, detects (31) a change in operational status of a mobile station during a communication session and, in response to detecting such a change, automatically increases (32) memory capacity as is available to support additional communication sessions while simultaneously persisting at least some session information for potential subsequent use during the communication session. For example, this response can occur upon detecting that a mobile station has changed from an active to a dormant status. Then, upon returning to an active status, the network element can use the persisted information to facilitate rapid reconstruction of infrastructure support for the mobile station's call participation.

Abstract: A network element (10), such as a Packet Data Serving Node, detects (31) a change in operational status of a mobile station during a communication session and, in response to detecting such a change, automatically increases (32) memory capacity as is available to support additional communication sessions while simultaneously persisting at least some session information for potential subsequent use during the communication session. For example, this response can occur upon detecting that a mobile station has changed from an active to a dormant status. Then, upon returning to an active status, the network element can use the persisted information to facilitate rapid reconstruction of infrastructure support for the mobile station's call participation.

Abstract: A microfluidic method and device for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid is provided. The device can be fabricated simply from readily-available, inexpensive material using simple techniques.

Abstract: The present invention relates to identification of a gene that is inactivated in a mucolipidosis condition. In particular, the invention concerns mutations that disrupt a mucolipin, preferably MCOLN1, in mucolipidosis IV. Recombinant nucleic acids encoding mutant forms of MCOLN1, oligonucleotides specific for such mutations, and diagnostic and therapeutic applications related to these discoveries, are also contemplated.

Abstract: Disclosed are novel human and clam ubiquitin carrier polypeptides involved in the ubiquitination of cyclins A and/or B. Also disclosed are inhibitors of such polypeptides, nucleic acids encoding such polypeptides and inhibitors, antibodies specific for such polypeptides, and methods of their use.

Abstract: Methods and a device are provided for adhering cells in a specific and predetermined position. The device comprises a plate defining a surface and a plurality of cytophilic islands that adhere cells which are isolated by cytophobic regions to which cells do not adhere. The cytophobic regions can be wide enough such that less than 10 percent of the cells adhered to the cytophilic islands are allowed to form bridges across the cytophobic regions and contact each other. Further, the islands or the regions or both may be formed of a self-assembled monolayer (SAM). The methods are for forming a patterned surface for a population of cells and for selectively manipulating individual cells formed on the surface of the plate of the device. Furthermore, the device is used in immobilization of cells at a surface and for controlling shape of the cells.

Abstract: The invention relates to mutations in the gene encoding 11-cis retinal dehyrogenase. The mutations in the gene and in the resulting encoded protein are correlated to ocular disorders, such as fundus albipunctatus.