Abstract: Disclosed herein are system, method, and computer program product embodiments for optimizing the determination of a phenotypic impact of a molecular variant identified in molecular tests, samples, or reports of subjects by way of regularly incorporating, updating, monitoring, validating, selecting, and auditing the best-performing evidence models for the interpretation of molecular variants across a plurality of evidence classes.

Abstract: An antiviral agent is provided, having a phosphorodiamidate morpholino oligomer with an antisense sequence to a portion of a genome of a strain of a coronavirus. The coronavirus may be SARS-CoV-2 or another ?CoV. The antiviral agent finds many uses, such as in a pharmaceutical composition, a method of treating coronavirus-mediated disease, a method of preventing coronavirus-mediated disease, a method of reducing or preventing the replication of coronavirus in a host cell, a method of controlling the spread of coronavirus in donated tissue, a treated tissue sample, and in the manufacture of a medicament for the treatment or prevention or coronavirus-mediated disease.

Abstract: The invention relates to a lateral flow assay device for the detection of a target peptide in a liquid sample, comprising: (a) a solid support, (b) a sample pad for initially receiving and optionally pre-treating the sample at a first end of the solid support, (c) an absorbent pad at a second end of the solid support, (d) a conjugate pad comprising in a dry state a mobilizable conjugate of a particle and the target peptide, wherein the target peptide conjugated to said particle is biotinylated and the particle comprises on its surface a biotin-binding protein, (e) a target peptide reaction membrane comprising, (i) a capture region comprising an immobilized first capture reagent against the target peptide, and (ii) optionally a control region comprising an immobilized second capture reagent against particle control conjugate, wherein the sample pad, the conjugate pad, the reaction membrane and the absorbent pad are mounted to the solid support to permit capillary flow from the sample pad to the reaction membra

Abstract: A non-invasive, transcutaneous, real-time viral detection device that is configured for self-administration, e.g., at a user's home. In one embodiment, and after positioning the device relative to the human body part (e.g., the user's finger), light sources in the device are activated (excited), and resulting data captured. In particular, a set of Raman spectra are collected from a configured set of emitters and detectors in the device and delivered to a nearby receiver, preferably wirelessly. The receiver filters and de-convolves the Raman spectra producing a data set representative of the constituent elements in the user's tissue of interest. The data set is applied against a statistical classifier, e.g., a neural network that has been trained to recognize and distinguish the absence or presence of viral components, e.g., C-19, or its associated blood-borne acute phase reactants.

Abstract: Low molecular weight molecules able to penetrate cells and tissues and having high specificity and affinity for the surfaces of proteins. Methods of making same, pharmaceutical compositions comprising same, and methods of treating cancers, infectious diseases, and diseases and disorders associated with aberrant protein expression using same. A method for selecting a therapeutic peptide for binding to an isolated and/or purified protein of interest by screening a phage display library containing phage particles with phage display peptides which have at least one APBA modified cysteine residue. The APBA modified cysteine residues bind to surface lysine residues on the isolated and/or purified protein of interest by dynamic covalent conjugation to form iminoboronates.

Abstract: The invention relates to methods of assessing a patient's risk of developing Progressive multifocal leukoencephalopathy (PML).

Abstract: The quantitation of specific antibodies for at least one redox form of High mobility group box 1 (HMGB1) contained in a biological sample, in particular human serum and/or Cerebrospinal Fluid (CSF) is detailed. An in vitro method for assessing the state of progression of a disease or a disorder in which HMGB1 is involved and an in vitro method for the identification of predisposition, prognostic or diagnostic biomarkers of a disease or a disorder in which HMGB1 is involved are detailed. A kit to quantitate the specific antibodies for at least one redox form of HMGB1, in particular human HMGB1 is detailed.

Abstract: Embodiments of apparatuses, systems, methods for monitoring wound pH are disclosed. In some embodiments, a wound dressing includes one or more optical sensors configured to measure a change in color of a pH-sensitive adhesive that changes color in response to changes in wound exudate pH. In some embodiments, the wound dressing may further comprise hydrophilic channels that direct wound exudate to a pH-sensitive material over the optical sensors. Such dressings may also be used in combination with a negative pressure wound therapy system.

Abstract: Systems, methods, and collection devices are disclosed for rapid, local PCR testing. The PCR testing system may be configured for use with a disposable sample collection device that includes a swab configured for collecting a biological sample from a patient; and a sample container configured to receive the swab and separate a bulk quantity of the biological sample from the swab for containment in a bulk collection chamber, which is located with the sample container, wherein the sample container is configured to meter a selected volume of the biological sample into a PCR sample tube, which contains a lyophilized master mix, releasably attachable to the sample container.

Abstract: Provided herein are compositions, methods, devices, and systems for highly accurate and pure RNA synthesis. Also provided herein are nucleic acid libraries comprising RNAs generated by using devices, compositions and methods disclosed herein.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Abstract: The invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.

Abstract: One example of a flow cell includes a base support and a multi-layer stack positioned over the base support. The multi-layer stack includes a resin layer positioned over the base support; and a hydrophobic layer positioned over the resin layer. A depression is defined in the multi-layer stack through the hydrophobic material and through a portion of the resin.

Abstract: The invention features methods, systems, and cartridges for amplification of target nucleic acids in complex samples, for example, whole blood. The invention also features diagnostic and therapeutic methods based on amplification of target nucleic acids characteristic of pathogens present in complex samples containing cells and/or cell debris, for example, whole blood.

Abstract: This disclosure relates to novel SARS-CoV-2 targeting sequences. Novel SARS-CoV-2 targeting oligonucleotides for the treatment of SARS-CoV-2 infection are also provided.

Abstract: Embodiments described herein may be useful in the detection of analytes. The systems and methods may allow for a relatively simple and rapid way for detecting analytes such as chemical and/or biological analytes and may be useful in numerous applications including sensing, food manufacturing, medical diagnostics, performance materials, dynamic lenses, water monitoring, environmental monitoring, detection of proteins, detection of DNA, among other applications. For example, the systems and methods described herein may be used for determining the presence of a contaminant such as bacteria (e.g., detecting pathogenic bacteria in food and water samples which helps to prevent widespread infection, illness, and even death). Advantageously, the systems and methods described herein may not have the drawbacks in current detection technologies including, for example, relatively high costs, long enrichment steps and analysis times, and/or the need for extensive user training.

Abstract: Described herein are compositions and methods for treating a disease, particularly a cancer, with a Dengue Virus and, optionally, primed dendritic cells recognizing a tumor antigen. Lysis protocols are described where the lysis does not result in complete or less than complete lysis of cells in order to provide cell surface molecules maintained in a cell surface-embedded state. Non-lethal Dengue virus strains are also provided for therapeutic purposes.

Abstract: The present disclosure provides an immunogenic composition comprising: a) i) a hepatitis C virus (HCV) heterodimeric polypeptide that includes HCV E1 and E2 polypeptides; ii) an HCV E1 polypeptide; or iii) an HCV E2 polypeptide; b) a polypeptide (also referred to herein as a “T-cell epitope polypeptide” or an “HCV T-cell epitope polypeptide”) comprising T-cell epitopes (e.g., CD4+ and CD8+ T-cell epitopes that are conserved among some HCV genotypes and that are presented through one or multiple HLA alleles common within the human population) present in an HCV protein other than E1 and E2; and c) a pharmaceutically acceptable excipient. The present disclosure provides a method of inducing an immune response, in an individual, to an HCV polypeptide.

Abstract: Embodiments relate to predicting height information for an object. First distance data is determined at a first time when an object is at a first position that is only partially within the field-of-view. Second distance data is determined at a second, later time when the object is at a second, different position that is only partially within the field-of-view. A distance measurement model that models a physical parameter of the object within the field-of-view is determined for the object based on the first and second distance data. Third distance data indicative of an estimated distance to the object prior to the object being entirely within the field-of-view of the distance sensing device is determined based on the first distance data, the second distance data, and the distance measurement model. Data indicative of a height of the object is determined based on the third distance data.

Abstract: An example method for training a graph convolutional neural network (GCNN) configured for virtual screening of molecules for drug discovery is described herein. The method can include receiving a first data set including a plurality of molecules, and training the GCNN to initialize one or more parameters of the GCNN using the first data set. The method can also include receiving a second data set including a plurality of molecules and respective inhibition rates for a disease, and training the GCNN to refine the one or more parameters of the GCNN using the second data set. The molecules in the first and second data sets can be expressed in a computer-readable format. An example method for virtually screening molecules on Plasmodium falciparum (P. falciparum) is also described herein.

Abstract: A method and system are disclosed for detecting microbial pathogens in a sample suspected of containing the pathogens. The method includes combining loop-mediated isothermal amplification (LAMP) reagents and a polymer gel, such as a hydrogel, together with the sample to form a mixture. The gel polymerizes over a short time to immobilize the viral particles within the mixture. If target DNA/RNA are present in the sample, amplicons are produced. The target microorganisms are detected by visually detecting the presence or absence of the amplicons. The target microorganism concentrations may be determined based on the number of fluorescent amplicon dots after the reaction using a smartphone or a fluorescent microscope. The method may be employed for rapidly and inexpensively quantifying microbial pathogens in environmental water samples with high sensitivity.

Abstract: Certain embodiments may generally relate to various techniques for machine learning. Feed-forward, fully-connected Artificial Neural Networks (ANNs), or the so-called Multi-Layer Perceptrons (MLPs) are well-known universal approximators. However, their learning performance may vary significantly depending on the function or the solution space that they attempt to approximate for learning. This is because they are based on a loose and crude model of the biological neurons promising only a linear transformation followed by a nonlinear activation function. Therefore, while they learn very well those problems with a monotonous, relatively simple and linearly separable solution space, they may entirely fail to do so when the solution space is highly nonlinear and complex. In order to address this drawback and also to accomplish a more generalized model of biological neurons and learning systems, Generalized Operational Perceptrons (GOPs) may be formed and they may encapsulate many linear and nonlinear operators.

Abstract: Provided herein are methods of freezing mammalian cells for storage or improving thaw recovery of cell banks comprising freezing mammalian cells in a freezing medium having a pH of 6.7 to 8.5.

Abstract: The disclosure is directed to kits and methods for amplifying and detecting human papilloma virus (HPV) of genotype 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and/or 68 in a sample, which comprises a variety of combinations of forward oligonucleotide primers, reverse oligonucleotide primers, and oligonucleotide probes.

Abstract: Polypeptides with biophysical properties such as solubility, stability, high expression, monomericity, binding specificity or non-aggregation, including monomeric human heavy and light chain variable domains (VHs and VLs), are identified using a high throughput method for screening polypeptides, comprising the steps of obtaining a phage display library, allowing infection of a bacterial lawn by the library phage, and identifying phage which form larger than average plaques on the bacterial lawn. Sequences of monomeric human VHs and VLs are identified, which may be useful for immunotherapy or as diagnostic agents. Multimer complexes of human VHs and VLs are also identified. The VHs and VLs identified may be used to create further libraries for identifying additional polypeptides. Further, the VHs and VLs may be subjected to DNA shuffling to select for improved biophysical properties.

Abstract: A dust cap assembly including a semi-trailer (2) and a towing vehicle (3). The dust cap assembly is for closing a king pin (21) which has been hollowed out with a borehole (22) for automatic fifth-wheel coupling. A dust cap device (1) is arranged in contact with the underside (20) of the semi-trailer (2) and such that it can rotate about the king pin (21). In order to mount the dust cap device (11) such that it can rotate about the king pin (21), a circular ring-shaped bearing disc (25) having a circular bearing seat (26) is provided, which is secured coaxially to the king pin (21) on the underside (20) of the semi-trailer (2). The circular bearing seat (26) on the circular ring-shaped bearing disc (25) has a first sliding bearing edge (261) on the inner circular opening and a second sliding bearing edge (262) on the outer rim, in which the dust cap device (1) engages. Also, a dust cap device for this assembly.

Abstract: Described herein are compositions for delivering a therapeutic or vaccine. Also described herein are methods for using the compositions described herein for delivering a therapeutic or a vaccine.

Abstract: Methods and systems are provided for point-of-care nucleic acid amplification and detection. One embodiment of the point-of-care molecular diagnostic system includes a cartridge and an instrument. The cartridge can accept a biological sample, such as a urine or blood sample. The cartridge, which can comprise one or more of a loading module, lysis module, purification module and amplification module, is inserted into the instrument which acts upon the cartridge to facilitate various sample processing steps that occur in order to perform a molecular diagnostic test.

Abstract: Disclosed herein are compositions and methods related to mutant viruses, and in particular, mutant influenza viruses. The mutant viruses disclosed herein include a mutant M2 sequence, and are useful in immunogenic compositions, e.g., as vaccines. Also disclosed herein are methods, compositions and cells for propagating the viral mutants, and methods, devices and compositions related to vaccination.

Abstract: A flow test unit (1) with a housing (2) which is sealingly closed to the outside at least when coupled to a sample container. At least one test strip (3) is accommodated in the housing (2), and the housing (2) has at least one admission opening (4). The test strip (3) is arranged inside the housing (2) such that, after a liquid connection (22) to a sample container has been produced, a wetting region (5) can be wetted with liquid (6) entering via the at least one admission opening (4).

Abstract: Fluidic devices and related methods are generally provided. The fluidic devices described herein may be useful, for example, for diagnostic purposes (e.g., detection of the presence of one or more disease causing bacteria in a patient sample). Unlike certain existing fluidic devices for diagnostic purposes, the fluidic devices and methods described herein may be useful for detecting the presence of numerous disease causing bacteria in a patient sample substantially simultaneously (e.g., in parallel). In some embodiments, the fluidic devices and methods described herein provide highly sensitive detection of microbes in relatively large fluidic samples (e.g., between 0.5 mL and about 5 mL), as compared to certain existing fluidic detection (e.g., microfluidic) devices and methods. In an exemplary embodiment, increased detection sensitivity of microbial pathogens present in a patient sample (e.g., blood) is performed by selectively removing human nucleic acid prior to sensitive detection of microbial infection.

Abstract: The invention relates to recombinant measles virus expressing Lassa virus polypeptides, and concerns in particular immunogenic LASV particles expressed by a measles virus and/or virus like particles (VLPs) that contain proteins of a Lassa virus. These particles are recombinant infectious particles able to replicate in a host after an administration. The invention provides means, in particular nucleic acid constructs, vectors, cells and rescue systems to produce these recombinant infectious particles. The invention also relates to the use of these recombinant infectious particles, in particular under the form of a composition, more particularly in a vaccine formulation, for the treatment or prevention of an infection by Lassa virus.

Abstract: The present disclosure is directed to antibodies binding to and neutralizing Japanese Encephalitis virus and methods for use thereof.

Abstract: Disclosed herein are methods and systems for rapid detection of antibiotic resistance of a microorganism in a sample. A modified recombinant phage is also disclosed which comprises an indicator gene in the late gene region. The specificity of infectious agents allows a specific microorganism to be targeted, and an indicator signal may be amplified to optimize assay sensitivity.

Abstract: Described is an aqueous composition comprising: (a) at least one non-ionic cellulose ether, and (b) benzoic acid within the range of from 0.2 wt % to 0.3 wt % based on the total weight of the composition, wherein said composition has a viscosity equal to or above 24 000 cP, an osmolality of from 100 to 400 mOsmol/kg, and a pH of from 3 to 5. The aqueous composition may be used in the treatment and/or prevention of a human fungal infection such as a vaginal fungal infection.

Abstract: Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I): including stereoisomers, salts and tautomers thereof, wherein R1, R2, R3, L1, L2, L3, L4, L5, L6, M1, M2, A, q, w and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

Abstract: Compositions and methods for stimulating toll-like receptor 9 (TLR9) are provided. More particularly, immunostimulatory oligonucleotides, methods of enhancing immunostimulatory properties of oligonucleotides, and methods of eliciting immune responses are disclosed herein.

Abstract: Detector systems are described, based on a primary binding compound and a secondary binding compound used in combination with a support to detect a target in a sample. The detection systems include a liquid medium hosting a first binding compound specific to a target, the first binding compound comprising a label; and a solid medium hosting a second binding compound specific to the target, the second binding compound being different from and non-competitive with respect to the first binding compound.

Abstract: Disclosed is a calibration curve creation method performed by an analyzer, the calibration curve creation method including: preparing a plurality of calibrators at different dilution rates by dispensing a calibrator in a container into one or more different containers; obtaining a plurality of measurement values by measuring each of the prepared plurality of calibrators; creating a calibration curve by use of the plurality of measurement values; selecting a first measurement value to be re-measured, among the plurality of measurement values used for the calibration curve; preparing another calibrator at a dilution rate corresponding to a calibrator from which the selected first measurement value is obtained; obtaining a second measurement value by measuring the prepared another calibrator; and creating a new calibration curve by replacing the first measurement value, among the plurality of measurement values, with the second measurement value.

Abstract: The invention describes a method for determining how to stimulate, monitor and/or inhibit virus production in whole blood culture. The invention relates to a test kit for performing the method and to the use of a suitable blood sampling system. The system can be used to determine how to activate or target latently HIV-infected cells, for clinical management of HIV treatments and for personalized therapeutic strategies.

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having nuclease grafted to one or more capsid proteins. In some aspects, the disclosure relates to isolated AA V capsid proteins having terminally grafted nucleases and isolated nucleic acids encoding the same. Recent approaches to delivering nucleases to cells for gene editing have focused on delivering of expression vectors engineered to express the nucleases in target cells. However, these approaches have proved to be problematic in many instances due to genotoxicity resulting from to prolonged expression of gene editing system in vivo. To prevent such off-target genotoxicity due to prolonged presence of a gene editing system, several studies explored delivery of mRNA or protein instead of delivering the gene coding for the nucleases in cell culture.

Abstract: This disclosure provides, e.g., methods for coupling Formation of Surface Carboxylates on PES an entity to a solid substrate. The method can comprise treating the with Exposure Time substrate with a plasma, e.g., a CO2 plasma, to increase its reactivity. The entity can be, e.g., a biological polymer that binds a microbe. Substrates produced by these methods can be used in a variety of applications, including hemodialysis and diagnostic assays.

Abstract: Methods are provided for a sensitive and specific assay for the determination of viral load and genotyping of RSV in a biological sample. Compositions and kits for use in the methods also are provided, including optimized primers for the amplification of and detection of the RSV open reading frames from subtypes A and B, and probes for distinguishing between the subtypes. Also provided are methods for amplifying and sequencing an open reading from of an RSV F protein, and compositions and kits for use in the methods.

Abstract: A multiplexed lateral flow device includes an impermeable internal reservoir having an opening to receive a sample deposition. A fluid distributor pad is arranged in fluid communication with a lower surface of the internal reservoir. The fluid distributor pad includes a paper based microfluidic element having a pattern of a hydrophobic material to distribute a portion of the sample deposition substantially equally among a plurality of flow paths. Lateral flow assays having a plurality of flow lines are aligned with flow paths of the distributor pad. An impermeable top cover has a first window arranged over the opening of the internal reservoir, and at least a second window arranged over the test results of the lateral flow assays. A housing element houses the reservoir, the distributor pad and lateral flow assays.

Abstract: Disclosed is a method and system for identifying a protein domain based on a protein three-dimensional structure image. According to the present application, the protein domain is identified based on a structure similarity, the identification errors and omissions of the protein domain caused by protein multi-sequence alignment errors when sequence consistency is not high can be effectively solved. According to the present application, the point cloud segmentation model based on the dynamic graph convolutional neural network is constructed, and by integrating global structural features and local structural features, segmentation of the protein domain and acquisition of semantic labels of the protein domain can be completed at the same time.

Abstract: Methods and compositions are provided for improved nucleic acid amplification assays. In some embodiments, the nucleic acid amplification assay is a tagged amplicon primer extension (TAPE) nucleic acid amplification reaction.

Abstract: A method of enhancing a footwear impression formed on a porous surface using a potassium ferrocyanide solution for footwear impression enhancement includes: forming a porous surface sample by leaving footwear impressions into an object having a porous surface; preparing a potassium ferrocyanide solution for footwear impression enhancement; and applying the potassium ferrocyanide solution for footwear impression enhancement to the porous surface sample.

Abstract: Disclosed herein, inter alia, are compositions and methods of use thereof for interrogating a cell.

Abstract: A method and apparatus for monitoring and/or controlling the extent of denaturation and/or bond cleavages of proteins on any surface (e.g., biological tissues, biofilms, etc.). In one embodiment, a low power laser (e.g., a 5 mW, 362 nm diode laser) is directed through a biological sample to a photodetector. The sample is heated by a set of radiant heaters to between about 220° C. and about 250° C. in a time period of between 10 seconds to 60 seconds. The baseline transmissivity of the sample is monitored continuously throughout treatment of the biological sample via continuous monitoring of the signal voltage detected at the photodetector. Upon detection of increase in relative transmissivity in the biological sample, the heating treatment is concluded and the biological sample is removed for in situ protein identification as part of an imaging MALDI-MS measurement.

Abstract: Described herein is a process for protein purification, particularly a process for the purification of a glycoprotein, such as an HIV envelope protein, useful for vaccines or biotherapeutics.