Abstract: A “nanolipogel” is a delivery vehicle including one or more lipid layer surrounding a hydrogel core, which may include an absorbent such as a cyclodextrin or ion-exchange resin. Nanolipogels can be constructed so as to incorporate a variety of different chemical entities that can subsequently be released in a controlled fashion. These different incorporated chemical entities can differ dramatically with respect to size and composition. Nanolipogels have been constructed to contain co-encapsulated proteins as well as small hydrophobic drugs within the interior of the lipid bilayer. Agents incorporated within nanolipogels can be released into the milieu in a controlled fashion, for example, nanolipogels provide a means of achieving simultaneous sustained release of agents that differ widely in chemical composition and molecular weight. Additionally, nanolipogels can favorably modulate biodistribution.

Abstract: A method of processing BMGs in a non-ideal environment (such as air) to create a uniform and smooth surface is provided. By utilizing the contact-line movement and an engineered flow pattern during TPF the method is able to create complex BMG parts that exhibit uniform smooth appearance or even can be atomically smooth. In addition, to mending surface imperfections, this method also eliminates void formation inside the material, allows for the creation of precise patterns of homogeneous appearance, and forms improved mechanical locks between different materials and a BMG.

Abstract: Compositions and methods for treating or ameliorating the symptoms of inflammatory or autoimmune disease or disorder are described herein. The compositions contain a nanolipogel for sustained delivery of an effective amount of one or more active agents of choice, preferably a drug for treating or ameliorating the symptoms of inflammatory or autoimmune disease or disorder. The nanolipogel includes a lipid bilayer surrounding a hydrogel core, which may optionally include a host molecule, for example, an absorbent such as a cyclodextrin or ion-exchange resin. In preferred embodiments at least one of active agents is an immunosuppressant.

Abstract: Seven protective alleles for IgA nephropathy have been discovered that can be identified by analyzing a DNA sample for seven respective SNPs. A method is provided for identifying and treating subjects at risk of developing IgA neuropathy based on a new seven-SNP genetic risk score. Also provided are screening methods to identify compounds that bind to and reduce the expression or biological activity of a either CFHR1 or CFHR3.

Abstract: Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (>2 years).

Abstract: The present invention relates to a system, device, and method for the high throughput multiplexed detection of a wide number of compounds. The invention comprises of a microwell array coupled to a capture agent array to form a plurality of interfaces between a microwell and a set of immobilized capture agents. The set of capture agents comprises a plurality of distinguishable features, with each feature corresponding to the detection of a particular compound of interest. In certain embodiments, each microwell is configured to contain a single cell. The invention is therefore capable of performing a high throughput analysis of single cell profiles, including profiles of secreted compounds.

Abstract: Described herein are methods of triplex-induced apoptosis, in which multiple triplexes are formed in cells in which gene amplification has occurred (cells comprising/characterized by at least one amplified gene), referred to as target cells, and apoptosis is induced in the target cells.

Abstract: Disclosed are compounds, compositions, and methods relating to fluoride aptamers, fluoride-responsive riboswitches, fluoride-regulated expression constructs, fluoride transporters, nucleic acids encoding fluoride transporters, expression constructs encoding fluoride transporters, and cells containing or including any combination of these.

Abstract: Nucleic acids encoding mutant elongation factor proteins (EF-Sep), phosphoseryl-tRNA synthetase (SepRS), and phosphoseryl-tRNA (tRNASep) and methods of use in site specific incorporation of phosphoserine into a protein or polypeptide are described. Typically, SepRS preferentially aminoacylates tRNASep with O-phosphoserine and the tRNASep recognizes at least one codon such as a stop codon. Due to the negative charge of the phosphoserine, Sept-tRNASep does not bind elongation factor Tu (EF-Tu). However, mutant EF-Sep proteins are disclosed that bind Sep-tRNASep and protect Sep-tRNASep from deacylation. In a preferred embodiment the nucleic acids are on vectors and are expressed in cells such as bacterial cells, archeaebacterial cells, and eukaryotic cells. Proteins or polypeptides containing phosphoserine produced by the methods described herein can be used for a variety of applications such as research, antibody production, protein array manufacture and development of cell-based screens for new drug discovery.

Abstract: Conductivity-selective lateral etching of III-nitride materials is described. Methods and structures for making vertical cavity surface emitting lasers with distributed Bragg reflectors via electrochemical etching are described. Layer-selective, lateral electrochemical etching of multi-layer stacks is employed to form semiconductor/air DBR structures adjacent active multiple quantum well regions of the lasers. The electrochemical etching techniques are suitable for high-volume production of lasers and other III-nitride devices, such as lasers, HEMT transistors, power transistors, MEMs structures, and LEDs.

Abstract: Methods and structures for forming epitaxial layers of semipolar III-nitride materials on patterned sapphire substrates are described. Semi-nitrogen-polar GaN may be grown from inclined c-plane facets of sapphire and coalesced to form a continuous layer of (2021) GaN over the sapphire substrate. Nitridation of the sapphire and a low-temperature GaN buffer layer is used to form semi-nitrogen-polar GaN.

Abstract: Nucleic acids encoding mutant elongation factor proteins (EF-Sep), phosphoseryl-tRNA synthetase (SepRS), and phosphoseryl-tRNA (tRNASep) and methods of use in site specific incorporation of phosphoserine into a protein or polypeptide are described. Typically, SepRS preferentially aminoacylates tRNASep with O-phosphoserine and the tRNASep recognizes at least one codon such as a stop codon. Due to the negative charge of the phosphoserine, Sept-tRNASep does not bind elongation factor Tu (EF-Tu). However, mutant EF-Sep proteins are disclosed that bind Sep-tRNASep and protect Sep-tRNASep from deacylation. In a preferred embodiment the nucleic acids are on vectors and are expressed in cells such as bacterial cells, archeaebacterial cells, and eukaryotic cells. Proteins or polypeptides containing phosphoserine produced by the methods described herein can be used for a variety of applications such as research, antibody production, protein array manufacture and development of cell-based screens for new drug discovery.

Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the nanoparticles are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

Abstract: Methods and structures for forming flat, continuous, planar, epitaxial layers of semipolar III-nitride materials on patterned sapphire substrates are described. Semipolar GaN may be grown from inclined c-plane facets on a patterned sapphire substrate, and coalesced to form a continuous layer of semipolar III-nitride semiconductor over the sapphire substrate. Planarization of the layer is followed by crystal regrowth using a nitrogen carrier gas to produce a flat, microfabrication-grade, process surface of semipolar III-nitride semiconductor across the substrate. Quality multiple quantum wells can be fabricated in the regrown semipolar material.

Abstract: A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Abstract: The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumours expressing HER2, wherein the human solid tumour expressing HER2 is endometrial cancer, in particular uterine serous carcinoma (USC). In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of endometrial cancer, notably USC, with HER2 IHC 2? or 1+ and HER2 FISH negative tumour tissue status.

Abstract: A lymphoma cell line was engineered to express surface IgG1 Fc. These tumor cells were taken up rapidly by DCs, leading to enhanced cross-presentation of tumor-derived antigen to CD8 T cells. IgG1-Fc tumors failed to grow in vivo and prophylactic vaccination in an animal model resulted in rejection of unmanipulated tumor cells. Furthermore, IgG1-Fc tumor cells were able to slow the growth of an unmanipulated primary tumor when used as a therapeutic tumor vaccine. This demonstrates that engagement of Fc receptors by tumors expressing the Fc region of IgG1 can induce efficient and protective anti-tumor CD8+ T cell responses without prior knowledge of tumor-specific antigen.

Abstract: The invention provides novel heterocyclic compounds, pharmaceutical compositions and methods of treatment that modulate levels of MIF expression and treat disorders associated with high or low levels of MIF expression.

Abstract: Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (>2 years).

Abstract: Ferroelectric semiconductor devices are provided by including a ferroelectric layer in the device that is made of a material that is not ferroelectric in bulk. Such layers can be disposed at interfaces to promote ferroelectric switching in a semiconductor device. Switching of conduction in the semiconductor is effected by the polarization of a mechanically bi-stable material. This material is not ferroelectric in bulk but can be considered to be when the thickness is sufficiently reduced down to a few atomic layers. Devices including such ferroelectric layers are suitable for various applications, such as transistors and memory cells (both volatile and non-volatile).