Abstract: Genetically modified non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.
Type:
Grant
Filed:
April 16, 2018
Date of Patent:
February 18, 2020
Assignees:
Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
Inventors:
Dietmar Herndler-Brandstetter, Richard A. Flavell, Davor Frleta, Cagan Gurer, Markus Gabriel Manz, Andrew J. Murphy, Noah W. Palm, Liang Shan, Sean Stevens, Till Strowig, George D. Yancopoulos, Marcel de Zoete
Abstract: Brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery (CED) have been developed. In the preferred embodiment, these are loaded with FDA-approved compounds, identified through library screening to target brain cancer stem cells (BSCSs). The particles are formed by emulsifying a polymer-drug solution, then removing solvent and centrifuging at a first force to remove the larger particles, then collecting the smaller particles using a second higher force to sediment the smaller particles having a diameter of less than 100 nm, more preferably less than 90 nanometers average diameter, able to penetrate brain interstitial spaces.
Type:
Grant
Filed:
May 6, 2013
Date of Patent:
February 11, 2020
Assignee:
Yale University
Inventors:
Jiangbing Zhou, Toral R. Patel, Joseph M. Piepmeier, William Mark Saltzman
Abstract: An isolated transport peptide, which crosses the cell membrane of a cell and/or binds to a target cell is described. The transport peptide can be incorporated into a transport construct in which the transport peptide is linked to a cargo moiety to be delivered into a cell. Also described herein is a method of delivering a transport construct into and/or to a cell.
Abstract: The present invention provides novel methods of accurately and efficiently reconstructing parameter maps in MRI data. In certain embodiments, the methods have reduced data acquisition time or improved spatial resolution when compared to methods standard in the art. In other embodiments, the methods have reduced acquisition and reconstruction time when compared to other acceleration methods in the art in parametric mapping. In other embodiments, the methods are less susceptible to influence of eddy currents when compared to other acceleration methods in the art in parametric mapping.
Abstract: Edge-emitting laser diodes having high confinement factors and lattice-matched, porous cladding layers are described. The laser diodes may be formed from layers of III-nitride material. A cladding layer may be electrochemically etched to form a porous cladding layer having a high refractive index contrast with an active junction of the device. A transparent conductive oxide layer may be deposited to form a top-side cladding layer with high refractive index contrast and low resistivity.
Abstract: Techniques are provided to optomechanically couple light to a crystal structure, thereby producing stable, coherent bulk acoustic modes within the structure. In some embodiments, a resonator may comprise a plano-convex crystal structure to which pump light may be applied. The pump light may transfer energy to acoustic phonon modes of the crystal structure so as to create acoustic phonon modes with a coherence length greater than a length of the crystal structure. High frequency and high quality factor resonators may thereby be produced and operated.
Type:
Application
Filed:
February 28, 2018
Publication date:
January 30, 2020
Applicant:
Yale University
Inventors:
Peter Rakich, Prashanta Kharel, William Renninger, Ryan Orson Behunin
Abstract: The present invention relates to uniform nanostructure biosensors and methods of calibrating the response of nanostructure biosensors. The invention overcomes device to device variability that has made quantitative detection difficult. The described biosensors have uniform characteristics that allow for more reliable comparison across devices. The methods of the invention comprise normalizing the initial current rate, as measured by the nanostructure biosensor following the addition of an analyte, to device characteristics of the biosensor. The device characteristics of the biosensor which can be used to normalize the response include baseline current and transconductance, Calibration of responses allows for the generation of calibration curves for use in all devices to quantitatively detect an analyte, without the need for individual device calibration.
Type:
Grant
Filed:
March 10, 2017
Date of Patent:
January 28, 2020
Assignee:
Yale University
Inventors:
Tarek M. Fahmy, Aleksandar Vacic, Mark A. Reed
Abstract: A low-noise directional amplifier includes a first port, a second port, a first coupler and a second coupler. The first port is coupled to a first coupler. The low-noise directional amplifier also includes at least two phase preserving amplifiers, a first phase preserving amplifier connected to the first coupler and a second coupler, and the second phase preserving amplifier connected to the first coupler and the second coupler.
Type:
Grant
Filed:
October 15, 2014
Date of Patent:
January 21, 2020
Assignee:
Yale University
Inventors:
Baleegh Abdo, Katrina Sliwa, Luigi Frunzio, Robert J. Schoelkopf, III, Michel Devoret
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. 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: According to some aspects, a method is provided 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 electromagnetic pulse to the physical qubit based on a number state of the quantum mechanical oscillator, wherein the first electromagnetic pulse causes a change in state of the quantum mechanical oscillator, and applying, subsequent to application of the first electromagnetic pulse, a second electromagnetic pulse to the quantum mechanical oscillator that coherently adds or removes energy from the quantum mechanical oscillator.
Type:
Grant
Filed:
February 26, 2016
Date of Patent:
January 21, 2020
Assignee:
Yale University
Inventors:
Reinier Heeres, Brian Vlastakis, Victor V. Albert, Stefan Krastanov, Liang Jiang, Robert J. Schoelkopf, III
Abstract: The present invention includes compositions and methods for identifying cancer driver mutations through use of an AAV-CRISPR library and molecular inversion sequencing probes (MIPs).
Abstract: A medical device for retrieving an inferior vena cava filter from an inferior vena cava having a handle having a distal end, wherein a longitudinal axis is defined thereby; a grasping assembly coupled to the handle, wherein the grasping assembly comprises a grasper for grasping the inferior vena cava filter positioned within the inferior vena cava, and an articulation assembly coupled to the grasping assembly for causing the grasping assembly to move laterally with respect to the longitudinal axis of the handle. Methods of retrieving an inferior vena cava filter from an inferior vena cava are also disclosed.
Type:
Grant
Filed:
September 3, 2015
Date of Patent:
January 7, 2020
Assignee:
Yale University
Inventors:
Cassius Iyad ochoa Chaar, Daniel Rodion Rathbone, Joseph Zinter
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: A method of differentiating benign melanocytic nevi from malignant melanomas is disclosed. The method generally includes treating and subjecting a skin lesion sample from a patient to mass spectrometry to obtain a mass spectrometry proteomic profile. This profile is compared to mass spectrometry proteomic profiles of reference samples, which include benign melanocytic nevi and/or malignant melanomas. Classification of the skin lesion sample as a benign melanocytic nevus or a malignant melanoma is based on similarities and/or difference between the mass spectrometry proteomic profiles.
Type:
Application
Filed:
July 10, 2019
Publication date:
December 26, 2019
Applicants:
New River Labs, LLC, Yale University
Inventors:
Rossitza Zinovieva Lazova, Erin Heather Seeley, Katy Ryan Smoot
Abstract: The invention relates to methods of evaluating the quality of a batch of an herbal composition, the method comprising subjecting a test batch of the herbal composition to one or more biological analysis methods and comparing the results derived from the test batch to the results of a known batch of herbal composition which has a known in vivo effect.
Abstract: Compositions, systems, and methods for preparation of polypeptides having multiple iterations of non-standard amino acids are provided. The compositions and method can be used to produce recombinant proteins at a greater yield than the same or similar polypeptides made using conventional compositions, systems, and methods. Accordingly, in some embodiments, the polypeptides are ones that could not be made using conventional methods and reagents, or could not be made a sufficient yield or purity to serve a practical purpose using conventional methods and reagents. Polypeptides made using the disclosed compositions, systems, and methods are also provided.
Type:
Grant
Filed:
February 6, 2015
Date of Patent:
December 10, 2019
Assignee:
Yale University
Inventors:
Farren J. Isaacs, Miriam Amiram, Adrian Haimovich, Dieter Söll
Abstract: Compositions for delivery of growth factors needed for stable Tregs and methods of use thereof are provided. In preferred embodiments, the compositions can induce, increase, or enhance a functionally robust induced CD4 Treg population (e.g., Foxp3+ Treg) in vivo or ex vivo. The compositions generally include delivery vehicles including TGF-? and IL-2. Delivery vehicles include, for example, polymeric particles, silica particles, liposomes, or multilamellar vesicles. The TGF-? and IL-2 are typically co-loaded into, attached to the surface of, and/or enclosed within the delivery vehicle into the same particle for simultaneous co-delivery to cells such as T cells. Preferably the delivery vehicles are targeted to CD4. The compositions and cells treated therewith can be used in various methods of treating, for example, inflammation, inflammatory and autoimmune diseases and disorders, and inducing or maintaining tolerance including graft and transplant tolerance.
Abstract: Provided herein, in some embodiments, are devices, systems and methods for high-throughput single-cell polyomics (e.g., genomic, epigenomic, proteomic and/or phenotypic profile) analyses.
Abstract: Carbon nanotube (CNT)-based compositions for activating cellular immune responses are provided. The CNTs function as high surface area scaffolds for the attachment of T cell ligands and/or antigens. The CNT compositions function as artificial antigen-presenting cells (aAPCs) or as modular vaccines. The disclosed CNT aAPCs are efficient at activating T cells and may be used to activate T cells ex vivo or in vivo for adoptive or active immunotherapy.
Type:
Grant
Filed:
March 17, 2017
Date of Patent:
November 26, 2019
Assignee:
Yale University
Inventors:
Tarek M. Fahmy, Lisa D. Pfefferle, Gary L. Haller, Tarek R. Fadel
Abstract: Various aspects and embodiments of the present disclosure are directed to methods and compositions (e.g., kits) for the identification of subjects with misfolded proteins in their urine. For example, methods and compositions for determining that a urine sample from a pregnant woman contains or does not contain misfolded are provided. In some embodiments, the presence of misfolded proteins in a urine sample from a pregnant woman is an indication of preeclampsia.
Type:
Application
Filed:
May 8, 2019
Publication date:
November 21, 2019
Applicant:
Yale University
Inventors:
Irina Buhimschi, Catalin S. Buhimschi, Michael Choma, Hemant Tagare, Stephan Michael Jonas