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 mll2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/ll2rg 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: As microbial drug-resistance increases, there is a critical need for new classes of compounds to combat infectious diseases. The Ixodes scapularis tick antifreeze glycoprotein, IAFGP, functions as an anti-infective agent against diverse bacteria including methicillin-resistant Staphylococcus aureus. Recombinant IAFGP and a peptide, P1, described herein and derived from this protein, bind to microbes and alter biofilm formation. Transgenic iafgp-expressing flies and mice challenged with bacteria, as well as wild-type animals administered IAFGP or P1, were resistant to infection, septic shock, or biofilm development on implanted biomaterials. Antifreeze protein controls bacterial infection and present new therapeutic strategies to counter pathogens.

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: Core-shell particles have a hydrophobic core and a shell formed of or containing hyperbranched polyglycerol (HPG). The HPG can be covalently bound to the one or more materials that form the core or coated thereon. The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HPG coated nanoparticles.

Abstract: Systems and methods are provided for estimating power breakdowns for a set of one or more appliances inside a building by exploiting a small number of power meters and data indicative of binary power states of individual appliances of such set. In one aspect, a breakdown estimation problem is solved within a tree configuration, and utilizing a single power meter and data indicative of binary power states of a plurality of appliances. Based at least in part on such solution, an estimation quality metric is derived. In another aspect, such metric can be exploited in a methodology for optimally placing additional power meters to increase the estimation certainty for individual appliances to a desired or intended level. Estimated power breakdown and energy breakdown—individually or collectively referred to as consumption breakdown—rely on measurements and numerical simulations, and can be evaluated in exemplary electrical network utilizing binary sensors.

Abstract: Modular nanoparticle vaccine compositions and methods of making and using the same have been developed. Modular nanoparticle vaccine compositions comprise an antigen encapsulated in a polymeric particle and adaptor elements which modularly couple functional elements to the particle. The modular design of these vaccine compositions, which involves flexible addition and subtraction of antigen, adjuvant, immune potentiators, molecular recognition and transport mediation elements, as well as intracellular uptake mediators, allows for exquisite control over variables that are important in optimizing an effective vaccine delivery system.

Abstract: The present invention provides the eutomeric isomer of the compound of formula (I), or a salt or solvate thereof, which can be used to treat epithelial cancer in a subject. In certain embodiments, the compound of formula (I) can be used in combination with AICAR and/or cisplatin.

Abstract: The invention is based upon the discovery that T regulatory type 1 (Tr1) cells express particular cell surface markers that allow for their selection, enrichment, isolation, purification and administration. The ability to use the particular markers described herein to select, enrich, isolate, purify and administer Tr1 cells allows for improved methods of Tr1 therapies for treating a wide variety of diseases and disorders.

Abstract: The present invention relates to compositions and methods for treating diseases of coagulation using a NPP4 polypeptide.

Abstract: Methods for treating a tumor, such as a benign or malignant tumor, are disclosed herein. The methods include administering a therapeutically effective amount of a small molecule that selectively binds to and stabilizes G-quadruplex DNA in the promoter of the c-MYC gene to the subject. The methods are also of use to decrease the size and/or number of metastases. Compounds for use in the disclosed methods are also provided.

Abstract: Methods for correcting inhomogeneities of magnetic resonance (MR) images and for evaluating the performance of the inhomogeneity correction. The contribution of both transmit field and receiver sensitivity to signal inhomogeneity have been separately considered and quantified. As a result, their negative contributions can be fully corrected. The correction method can greatly enhance the accuracy and precision of MRI techniques and improve the detection sensitivity of pathophysiological changes. The performance of signal inhomogeneity correction methods has been evaluated and confirmed using phantom and in vivo human brain experiments. The present methodologies are readily applicable to correct signal intensity inhomogeneity artifacts produced in different imaging modalities, such as computer tomography, X-ray, ultrasound, and transmission electron microscopy.

Abstract: Non-naturally occurring tRNASec and methods of using them for recombinant expression of proteins engineered to include one or more selenocysteine residues are disclosed. The non-naturally occurring tRNASec can be used for recombinant manufacture of selenocysteine containing polypeptides encoded by mRNA without the requirement of an SECIS element. In some embodiments, selenocysteine containing polypeptides are manufactured by co-expressing a non-naturally occurring tRNASec a recombinant expression system, such as E. coli, with SerRS, EF-Tu, SelA, or PSTK and SepSecS, and an mRNA with at least one codon that recognizes the anticodon of the non-naturally occurring tRNASec.

Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

Abstract: Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A sub-set of autoantibodies having nucleolytic activity are capable of nuclear penetration. These antibodies can be used as therapeutic agents targeted towards DNA repair-deficient malignancies.

Abstract: Some aspects are directed to a method of operating a circuit quantum electrodynamics system that includes a physical qubit dispersively coupled to a quantum mechanical oscillator, the method comprising applying a first drive waveform to the quantum mechanical oscillator, and applying a second drive waveform to the physical qubit concurrent with the application of the first drive waveform, wherein the first and second drive waveforms are configured to produce a state transition of the circuit quantum electrodynamics system from an initial state to a final state.

Abstract: Tubular prostheses are provided for use in airways, upper digestive, and urinary tracts. Each of these uses has its own specific sets of biological specifications, based on what it must contain and exclude and the physical and chemical pressures and stresses to which it is subjected. The prostheses may be made from allogeneic cells. Thus they can be manufactured and stored prior to an individual's personal need arising.

Abstract: The present invention provides compositions and methods for treating pulmonary hypertension. In one aspect, a method is included for increasing myocyte enhancer factor 2 (MEF2) activity in an endothelial cell comprising exposing the cell to a class IIa histone deacetylase inhibitor. In another aspect, a method is included for treating pulmonary hypertension, such as restoring MEF2 activity, in a subject in need thereof comprising administering to the subject a composition comprising a class IIa histone deacetylase inhibitor. Pharmaceutical compositions for treating pulmonary hypertension in a subject in need thereof and a kit for diagnosing, detecting and/or monitoring pulmonary hypertension are also included.

Abstract: The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.

Abstract: According to some aspects, a waveform processor is provided for control of quantum mechanical systems. Some embodiments of the waveform processor may be used to control quantum systems used in quantum computation, such as qubits. According to some embodiments, a waveform processor may include a first sequencer configured to sequentially execute master instructions according to a defined order and output digital values in response to the executed master instructions, and a second sequencer coupled to the first sequencer and configured to generate analog waveforms at least in part by transforming digital waveforms according to digital values received from the first sequencer. The analog waveforms may be applied to a quantum system. In some embodiments, the waveform processor may further include a waveform analyzer configured to integrate analog waveforms received from a quantum system and output results of said integration to the first sequencer.

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.