Abstract: The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids as well as new methods for fluorescent in situ sequencing (FISSEQ) in a new process referred to herein as “expansion sequencing” (ExSEQ).

Abstract: The present invention relates to a method for amplifying at least one target RNA in a fixed and, optionally, expanded biological sample. In an embodiment of the invention, the method comprises incubating the fixed biological sample with a pair of polynucleotides complementary to non-overlapping and proximal sequences of a target RNA, wherein the polynucleotide pair hybridizes to the target RNA; ligating the polynucleotide pair using a ligase; and amplifying the ligation product. The invention further provides methods for detecting and optionally quantifying and/or sequencing the amplification product. As the method comprises hybridizing polynucleotide pairs to a target RNA in a fixed biological sample, the target RNA can be hybridized in situ.

Abstract: The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids in a process referred to herein as “expansion sequencing” (ExSEQ).

Abstract: Provided is a novel method of isolating and producing human antibodies with desired specificity from human B cells. In particular, a method of isolating human antibodies from memory B cells obtained from patients which suffer from a disease which is caused by or involves activation of the immune system, for example autoimmune and inflammatory disorders is described.

Abstract: A navigational user interface element includes a navigational bar displaying thereon labels associated with a plurality of sections, and a highlight indicating a section of a page that a user is currently viewing. The navigational user interface element is configured to allow a user to click on the highlight and drag it to effect navigation to a section associated with a displayed label. The navigational user interface element is configured to, when the highlight is clicked and dragged and then released, snap the highlight to the section label the highlight is closest to when the highlight is released, and display that same section. The navigational user interface element is configured to, when a label is clicked, effect navigation to the section corresponding to that label.

Abstract: In an automated methodology for carrying out in vivo cell patch clamping, a cell patch clamping device is automatically moved into position and targeted to a neuron. Neuron contact is determined by analyzing the temporal series of measured resistance levels at the cell patch clamping device as it is moved. The difference between successive resistance levels is computed and compared to a threshold, which must be exceeded for a minimum number of computations before neuron contact is assumed. Pneumatic control methods are used to achieve gigaseal formation and cell break-in, leading to whole-cell patch clamp formation. An automated robotic system capable of performing this methodology automatically performs patch clamping in vivo, automatically detecting cells by analyzing the temporal sequence of electrode impedance changes.

Abstract: The invention provides a method termed protein retention ExM (proExM), in which proteins, rather than labels, are anchored to the swellable gel, using a cross-linking molecule. This proExM strategy can be used to perform nanoscale imaging of immunostained cells and tissues as well as samples expressing various FPs as fluorescent signals from genetically encoded fluorescent proteins and/or conventional fluorescently labeled secondary antibodies and streptavidin that are directly anchored to the gel are preserved even when subjected to the nonspecific proteolytic digestion.

Abstract: A method for facilitating editing of a toggle item includes displaying an interface comprising one or more toggle items, each toggle item being configured to be toggled on and off when clicked on; receiving input corresponding to movement of a pointer to be disposed over a first toggle item of the one or more toggle items; determining that a predetermined amount of time has passed with the pointer being disposed over the first toggle item; displaying a cursor in the first toggle item at the location of the pointer; receiving input corresponding to a click while the cursor is displayed in the first toggle item; receiving input corresponding to editing of the first toggle item; and updating, based on the input corresponding to editing of the toggle item, the text of the toggle item.

Abstract: The invention enables in situ genomic and transcriptomic assessment of nucleic acids to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ genomic and transcriptomic assessment of nucleic in a new process referred to herein as “expansion fluorescent in situ hybridization” (ExFISH).

Abstract: Provided are novel binding molecules of human origin, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize antigens such as native endogenous proteins associated with, e.g., immune response, autoimmune disorders, inflammatory diseases, metabolic disorders, vascular function, neurodegenerative diseases or tumors. More particularly, a human Auto-Immunosome and corresponding monoclonal antibody reservoir are provided. In addition, pharmaceutical compositions, kits and methods for use in diagnosis and therapy of are described.

Abstract: The invention relates to methods for preventing stress-associated disorders. These disorders may be treated with a serotonin 2c receptor (5-HT2CR) antagonist prior to, during, or following a stress-related event. Stress-associated disorders include, for instance, post-traumatic stress disorder (PTSD).

Abstract: In an automated method for in vivo multiple cell patch clamping, cell patch clamping devices are automatically moved into position and targeted to multiple corresponding cells. Cell contact is determined by analyzing the temporal series of measured resistance levels at the clamping devices as they are moved. The difference between successive resistance levels is computed and compared to a threshold, which must be exceeded for a minimum number of computations before neuron contact is assumed. Pneumatic control methods are used to achieve cell-attached or gigaseal formation and subsequent cell break-in, leading to whole-cell patch clamp formation. An automated robotic system automatically performs patch clamping in vivo, automatically detecting cells according to the methodology by analyzing the temporal sequence of electrode impedance changes.

Abstract: Provided are novel binding molecules of human origin, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize antigens such as native endogenous proteins associated with, e.g., immune response, autoimmune disorders, inflammatory diseases, metabolic disorders, vascular function, neurodegenerative diseases or tumors. More particularly, a human Auto-Immunosome and corresponding monoclonal antibody reservoir are provided. In addition, pharmaceutical compositions, kits and methods for use in diagnosis and therapy of are described.

Abstract: The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids as well as new methods for fluorescent in situ sequencing (FISSEQ) in a new process referred to herein as “expansion sequencing” (ExSEQ).

Abstract: The present invention leverages the techniques for expansion microscopy (ExM) to provide improved high-throughput super-resolution whole-organ imaging methodology to image protein architectures over whole organs with nanoscale resolution by using high-throughput microscopes in combination with samples that have been iteratively expanded more than once, in a method referred to herein as “iterative expansion microscopy” (iExM). In the ExM method, biological samples of interest are permeated with a swellable material that results in the sample becoming embedded in the swellable material, and then the sample can be expanded isotropically in three dimensions The process of iteratively expanding the samples can be applied to samples that have been already expanded using ExM techniques one or more additional times to iteratively expand them such that, for example, a 5-fold expanded specimen can be expanded again 3- to 4-fold, resulting in as much as a 17- to 19-fold or more linear expansion.

Abstract: A navigational user interface element includes a navigational bar displaying thereon labels associated with a plurality of sections, and a highlight indicating a section of a page that a user is currently viewing. The navigational user interface element is configured to allow a user to click on the highlight and drag it to effect navigation to a section associated with a displayed label. The navigational user interface element is configured to, when the highlight is clicked and dragged and then released, snap the highlight to the section label the highlight is closest to when the highlight is released, and display that same section. The navigational user interface element is configured to, when a label is clicked, effect navigation to the section corresponding to that label.

Abstract: The present invention relates to an enlarged sample of interest for microscopy and methods for enlarging a sample of interest and the optical imaging of a sample of interest with resolution better than the classical microscopy diffraction limit, by synthesizing a swellable polymer network within a sample, it can be physically expanded, resulting in physical magnification.

Abstract: An electronic intravascular device is placed in tight contact with vessel walls and is used for electrical stimulation and/or electrical recording of the vessel wall and surrounding target tissue. The electrodes may operate via connectors interfacing them to external hardware or may incorporate electronics to allow wireless power, information transfer, and control. The device includes an internal skeleton, a flexible substrate attached to the exterior of the skeleton, at least one pair of electrodes located on the substrate, and power and control circuitry connected to the electrodes. The power and control circuitry may include connectors for direct powering of the electrodes or circuit elements for wireless powering of the device by RF-based, optical-based, ultrasound-based, piezoelectric, or vibrational energy harvesting methods.

Abstract: A navigational user interface element includes a navigational bar displaying thereon labels associated with a plurality of sections, and a highlight indicating a section of a page that a user is currently viewing. The navigational user interface element is configured to allow a user to click on the highlight and drag it to effect navigation to a section associated with a displayed label. The navigational user interface element is configured to, when the highlight is clicked and dragged and then released, snap the highlight to the section label the highlight is closest to when the highlight is released, and display that same section. The navigational user interface element is configured to, when a label is clicked, effect navigation to the section corresponding to that label.

Abstract: The present invention provides compositions and methods for light-activated cation channel proteins and their uses within cell membranes and subcellular regions. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-activated cation channels to specific cells or defined cell populations. In particular the invention provides millisecond-timescale temporal control of cation channels using moderate light intensities in cells, cell lines, transgenic animals, and humans. The invention provides for optically generating electrical spikes in nerve cells and other excitable cells useful for driving neuronal networks, drug screening, and therapy.