Abstract: Provided herein are methods of preparing new 14-membered ketolides via coupling of an eastern and western half moiety, followed by macrocyclization, and optional functionalization. Intermediates in the synthesis of these ketolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using these ketolides are also provided.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5? additions to the guide sequence.

Abstract: A microfluidic device for determining a response of cells comprises a microchannel and a seeding channel. The microchannel is at least partially defined by a porous membrane having cells adhered thereto. The microchannel has a first cross-sectional area. The seeding channel delivers a working fluid to the cells within the microchannel. The seeding channel has a second cross-sectional area that is less than the first cross-sectional area such that a flow of the working fluid produces a substantially higher shear force within the seeding channel to inhibit the attachment of cells within the seeding channel. And when multiple seeding channels are used to deliver fluids to multiple microchannels that define an active cellular layer across the membrane, the seeding channels are spatially offset from each other such that fluid communication between the fluids occurs only at the active region via the membrane, not at the seeding channels.

Abstract: The present invention relates to flow battery systems including a flow battery and an electrolyte rebalancing system. In accordance with certain embodiments, the electrolytes used in the systems of the present invention are aqueous, and in one embodiment, bromine species are used as redox-active species.

Abstract: Methods of making a three-dimensional matrix of nucleic acids within a cell is provided.

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 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 prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. 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 and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: A tape for collecting tissue samples in a manner compatible with imaging in a transmission electron microscopy (TEM) system, includes a tape substrate having two side walls forming a trough. The trough is defined by a bottom surface of the tape substrate and internal surfaces of the side walls, with an open side therebetween. A support film is attached to a top surface of the tape substrate, and a plurality of apertures is spaced at predetermined locations along the length of the tape substrate, each aperture being covered by the support film. The tape includes a stacked configuration in which the tape substrate is wound in layers, the bottom surfaces of the side walls in one layer being in contact with the support film in an immediately adjacent layer. The apertures in the second layer are aligned within the trough of the first layer, between the side walls.

Abstract: Histological images are preprocessed and classified among pathology states using a neural network. In preprocessing, the digital image is electronically partitioned into a grid of identically sized, overlapping subimages, and images are selected for analysis based on a parameter such as density.

Abstract: A soft robot is described, including: a flexible and/or stretchable body; a common fluid pressurization unit; and a plurality of fluid chambers each embedded in the flexible and/or stretchable body and capable of fluidic connection with the common fluid pressurization unit through a pressurizing valve; wherein the pressurizing valve is capable of being activated to allow the pressurized fluid to flow from the common fluid pressurization unit into the fluid chamber to result in actuation. Methods of using the soft robot are also described.

Abstract: In one aspect, a method of cell processing is disclosed, which includes disposing a plurality of cells on a substrate across which a plurality of projections are distributed and an electrically conductive layer at least partially coating said projections, exposing the cells to a cargo to be internalized by the cells, irradiating the substrate surface (and in particular the projections) with continuous wave or pulsed laser radiation. For example, one or more laser pulses having a pulse width in a range of about 1 ns to about 1000 ns can be applied so as to facilitate uptake of the cargo by at least a portion of the cells (e.g., the cells positioned in the vicinity of the projections (e.g., within hundreds of nanometer (such as less than 100 nm) of the projections)). In some embodiments, the laser pulses have a pulse width in a range of about 10 ns to about 500 ns, e.g., in a range of about 5 ns to about 50 ns.

Abstract: The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time-resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.

Abstract: The present invention provides desosamine and mycaminose analogs and nitro sugars and methods for their preparation. The invention also provides methods of cyclizing a compound of Formula (A?) with glyoxal to give a nitro sugar of Formula (B). Methods for the preparation of compound of Formula (D?) are provided comprising cyclization of a nitro alcohol to give a nitro sugar and reduction and alkylation of the nitro sugar to give a desosamine, mycaminose, or an analog thereof.

Abstract: The present invention generally relates to micro- and nanoneedles, e.g., for use in penetrating plant cells, or other cells. In some embodiments, delivery of target biomolecules into cells with protective outer layers (e.g. plant cells or plant pollen), cells in seeds, or cells in tissues may be achieved. These outer layers could be native biological protections (e.g. complex exines for pollens), other types of cells, or general biological materials. In some cases, the needles are attached at an end on a surface. In some cases, pollen or seeds may have substantially thick and tough layers (intine and exine), which may render it more difficult to penetrate such materials, as compared with cell membranes, e.g., in mammalian cells.

Abstract: Void structures, systems and devices with void structures, and methods of fabricating void structures are disclosed. A void structure is disclosed with a repeating elongated-aperture pattern designed to provide negative Poisson's Ratio behavior under macroscopic stress and strain loading. The pattern can include horizontal and vertical elliptically shaped apertures that are arranged on horizontal and vertical lines in a way that the lines are equally spaced in both dimensions. The centers of each aperture is on a crossing point of two of the lines. The vertical and horizontal elliptically shaped apertures alternate on the vertical and horizontal lines such that any vertical aperture is surrounded by horizontal apertures along the lines (and vice versa), and the next vertical apertures are found on both diagonals. The voids can also act as cooling and/or damping holes and, due to their arrangement, also as stress reduction features.

Abstract: The present disclosure provides click-crosslinked hydrogels and methods of use.

Abstract: This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.

Abstract: Provided are lincosamide compounds for the treatment of infectious diseases. The lincosamides described herein are modified at the amino acid (southern) region. The lincosamides may have further modification at the C-1 and C-7 positions of the aminooctose (northern) region, thus distinguishing them from lincomycin and clindamycin. Also provided are methods for preparing the lincosamide compounds, pharmaceutical compositions comprising the lincosamide compounds, and methods of treating infectious diseases using the disclosed lincosamide compounds.

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate STK inhibitors of Formula (III)).

Abstract: The present invention provides vaccine compositions and methods of producing such compositions. Other embodiments of the invention include methods of treating a pathogen infection, methods of vaccinating a subject against a pathogen infection, and methods for treating an antibiotic-resistance bacterial infection in a subject in need thereof. In further embodiments, the invention includes methods of decreasing the level of a pathogen in a subject having a pathogen infection, methods of increasing the surviving rate of a subject having a pathogen infection, methods of reducing the level of pain associated with a pathogen infection, and methods of reducing the level of distress associated with a pathogen infection in a subject in need thereof. Novel scaffold compositions and opsonin-bound or lectin-bound pathogen compositions, and uses thereof, are also provided herein.