Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Abstract: The invention provides natural IgM antibody inhibitors that may be used to treat various inflammatory diseases or disorders.

Abstract: The present invention relates to methods of making linear nucleic acid probes using rolling circle amplification methods.

Abstract: The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

Abstract: The invention provides methods and compositions, e.g., for tumor imaging and therapy.

Abstract: The present invention relates generally to microfluidic structures, and more specifically, to microfluidic structures and methods including meandering and wide channels. Microfluidic systems can provide an advantageous environment for performing various reactions and analyses due to a reduction in sample and reagent quantities that are required, a reduction in the size of the operating system, and a decrease in reaction time compared to conventional systems. Unfortunately, the small size of microfluidic channels can sometimes result in difficulty in detecting a species without magnifying optics (such as a microscope or a photomultiplier). A series of tightly packed microchannels, i.e., a meandering region, or a wide channel having a dimension on the order of millimeters, can serve as a solution to this problem by creating a wide measurement area.

Abstract: The invention relates to a compound of Formula I:

Abstract: The present invention relates to a method for predicting three-dimensional structure of a protein from its sequence. Three-dimensional structure may be determined by: (a) generating a multiple sequence alignment for a candidate protein having a known sequence; (b) identifying a covariance matrix between all pairs of sequence positions in the multiple sequence alignment; (c) inverting the covariance matrix and identifying predicted evolutionary constraints using a statistical model of the candidate protein; and (d) simulating folding of an extended chain structure of the candidate protein using the predicted constraints.

Abstract: Disclosed are embryonic stem cells and motor neurons derived from mice carrying transgenic alleles of the normal or mutant human SOD1 gene. Also disclosed are in vitro systems employing such SOD1 transgenic motor neurons for the study of neural degenerative disease.

Abstract: The invention provides compounds and methods for modulating the Hedgehog signaling pathway. The compounds modulate the translocation and/or accumulation of smoothened to the primary cilia.

Abstract: An orthodontic maxillary palatal expander device in accord with at least some aspects of the present concepts includes a mid-palatal bar having a first set of connection points configured to permit securement of the mid-palatal bar to the palate and a second set of connection points extending along at least a portion of a length of the mid-palatal bar, the first set of connection points comprising through holes in the mid-palatal bar. A screw assembly includes a left side member, a right side member, at least one arm connector formed in at least one of the left side member or right side member, at least one mid-palatal bar connector configured to releasably connect to the second set of connection points of the mid-palatal bar, and a screw mechanism adapted to, upon activation of the screw mechanism, cause outward lateral movement of the left side member and right side member.

Abstract: Methods, apparatus and systems for collecting thin tissue samples for imaging. Thin tissue sections may be cut from tissue samples using a microtome-quality knife. In one example, tissue samples are mounted to a substrate that is rotated such that thin tissue sections are acquired via lathing. Collection of thin tissue sections may be facilitated by a conveyor belt. Thin tissue sections may be mounted to a thin substrate (e.g., by adhering thin tissue sections to a thin substrate via a roller mechanism) that may be imaged, for example, by an electron beam (e.g., in an electron microscope). Thin tissue sections may be strengthened before cutting via a blockface thinfilm deposition technique and/or a blockface taping technique. An automated reel-to-reel imaging technique may be employed for collected/mounted tissue sections to facilitate random-access imaging of tissue sections and maintaining a comprehensive library including a large volume of samples.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: The present invention comprises compositions, methods, and devices for creating an stimulating an antigen-specific dendritic cell immune response. Devices and methods provide prophylactic and therapeutic immunity to subjects against cancer and infectious agents.

Abstract: The invention involves assays, diagnostics, kits, and assay components for determining levels of K41-glycated CD59 in subjects. Treatments for subjects based upon levels of K41-glycated CD59 also are provided.

Abstract: A microscopy or micro-spectroscopy system is disclosed that includes a first light source, a second light source, a modulator, an optical assembly and a processor. The first light source is for providing a first illumination field at a first optical frequency ?1 and the second light source is for providing a second illumination field at a second optical frequency ?2. The modulator is for modulating a property of the second illumination field at a modulation frequency f of at least 100 kHz to provide a modulated second illumination field. The optical assembly includes focusing optics and an optical detector system. The focusing optics is for directing and focusing the first illumination field and the modulated second illumination field through an objective lens toward the common focal volume along an excitation path.

Abstract: Embodiments of the invention provide lateral flow and flow-through bioassay devices based on patterned porous media, methods of making same, and methods of using same. Under one aspect, an assay device includes a porous, hydrophilic medium; a fluid impervious barrier comprising polymerized photoresist, the barrier substantially permeating the thickness of the porous, hydrophilic medium and defining a boundary of an assay region within the porous, hydrophilic medium; and an assay reagent in the assay region.

Abstract: Synthesis of many proteins is tightly controlled at the level of translation and plays an essential role in fundamental processes such as cell growth and proliferation, signaling, differentiation or death. Methods that allow imaging and identification of nascent proteins allow for dissecting regulation of translation, both spatially and temporally, including in whole organisms. Described herein are robust chemical methods for imaging and affinity-purifying nascent polypeptides in cells and in animals, based on puromycin analogs. Puromycin analogs of the present invention form covalent conjugates with nascent polypeptide chains, which are rapidly turned over by the proteasome and can be visualized and specifically captured by a bioorthogonal reaction (e.g., [3+2]cycloaddition). The methods of the present invention have broad applicability for imaging protein synthesis and for identifying proteins synthesized under various physiological and pathological conditions in vivo.

Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. These compounds are typically attached to the solid support through a covalent interaction. In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.

Abstract: Metal silicates or phosphates are deposited on a heated substrate by the reaction of vapors of alkoxysilanols or alkylphosphates along with reactive metal amides, alkyls or alkoxides. For example, vapors of tris(tert-butoxy)silanol react with vapors of tetrakis(ethylmethylamido)hafnium to deposit hafnium silicate on surfaces heated to 300° C. The product film has a very uniform stoichiometry throughout the reactor. Similarly, vapors of diisopropylphosphate react with vapors of lithium bis(ethyldimethylsilyl)amide to deposit lithium phosphate films on substrates heated to 250° C. Supplying the vapors in alternating pulses produces these same compositions with a very uniform distribution of thickness and excellent step coverage.