Abstract: A CO2 trans-critical freezing system includes: a freezing subsystem, including a first liquid inlet pipe and a first liquid return pipe arranged above the stratum and configured to convey low-temperature liquid CO2 to the stratum for stratum freezing construction; a liquefaction subsystem, configured to compress a volume of normal-temperature gaseous CO2, so that movement of molecules between the gaseous CO2 is limited and reduced, and the gaseous CO2 is converted into the low-temperature liquid CO2; and an inlet and return pipeline subsystem. A CO2 medium used in the system effectively solves problems of flammability, explosion hazard, high risk, difficult disposal, and environmental pollution caused by liquid ammonia and brine used in conventional freezing construction.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof that specifically bind chemokine receptor 4 (CXCR4). These CXCR4 antibodies, or antigen-binding fragments thereof, have a high affinity for CXCR4, function to effectively block SDF-1 binding to CXCR4, thereby inhibiting forskolin stimulated cAMP with low nM IC50, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat CXCR4-associated disorders while avoiding the adverse side effects associated with the current CXCR4 antagonist therapies.

Abstract: This application provides isolated antibodies (Abs), e.g., monoclonal antibodies (mAbs), that bind specifically to C—C Motif Chemokine Receptor 8 (CCR8), and bispecific antibodies targeting CCR8 and CTLA-4, and methods for treating a cancer in a subject comprising administering to the subject an anti-CCR8 Ab as monotherapy or in combination with an anticancer agent such as an immune checkpoint inhibitor.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind endothelin A receptor (ETAR). These ETAR antibodies, or antigen-binding fragments thereof, have a high affinity for ETAR, function to effectively block ET-1 binding to ETAR, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat ETAR-associated disorders. Importantly, compared to small molecule ETAR antagonists, the antibodies of the present invention have advantages of longer serum half-life, higher target specificity, thereby limiting the risk of off-target toxicity and improving therapeutic window.

Abstract: The present invention provides a kit for early screening of hepatocellular carcinoma, comprising a gene marker detection reagent and a protein marker detection reagent. The invention also provides a preparation method and application of the kit. The kit comprising specific gene markers and protein markers of the present invention has been demonstrated to be effective in achieving early screening of HCC in community populations, particularly in prospective studies.

Abstract: The present disclosure relates generally to devices and methods for rapidly and accurately diagnosing single-nucleotide polymorphisms. According to one or more embodiments, a system for identifying a single-nucleotide polymorphism (SNP) includes an oligonucleotide primer with a SNP recognition sequence, a fluorophore conjugated to the oligonucleotide primer at a conjugation site to form a fluorophore-conjugated oligonucleotide primer, a polymerase enzyme to extend the oligonucleotide primer upon binding to an oligonucleotide strand with a complimentary sequence to the oligonucleotide primer, forming a double stranded deoxyribonucleic acid (DNA) amplicon, and wherein the fluorophore-conjugated oligonucleotide primer is a sole primer in the system, such that the fluorophore only emits a fluorescent signal when the fluorophore-conjugated oligonucleotide primer binds to a sequence specifically complementary to the SNP recognition sequence.

Abstract: The present invention relates to bifunctional fusion molecules comprising a mutated polypeptide ligand (e.g., mutated IFN-?) having reduced biological activity attached to a disease tissue targeting biologic or a tumor associated antigen (TAA)-targeting biologic (e.g., anti-PD-L1 antibody), wherein the targeting biologic or TAA-targeting biologic directs the mutated ligands to cells that express on their surfaces the antigens to which said targeting biologic binds, as well as receptors for said ligands. Importantly, because the mutated polypeptide ligands have reduced biological activity, the resultant fusion molecule have reduced off-target activity/toxicity. More importantly, the targeting of the mutated ligand by the targeting biologic restores the activity of the mutated ligand, with the degree of activity restoration apparently correlated with the level of targeting biologic on the cells.

Abstract: A camera may one or more lenses and an image sensor having an array of light-gathering pixels. The pixels may generate image signals based on light passing through the lenses. The camera may include at least one pixel output settling assist circuit. The pixel output settling assist circuit may be electrically coupled to an output signal line of at least one of the pixels. The pixel output settling assist circuit may include a pixel output voltage change detection circuit and a bias current adjustment circuit. During read-out of the image signals of the at least one pixel, the pixel output voltage change detection circuit may detect a change of a voltage at the output of the pixel. The bias current adjustment circuit may generate and adjust a current injected to the output based on the detected change of the voltage at the output.

Abstract: We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in gliblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

Abstract: Disclosed herein are electronic devices and image sensors containing pixel arrays, layouts of electrical signal lines for such pixel arrays, and methods of pixel read out operations, including row read operations, for such pixel arrays. Layouts are disclosed that have reduced sets of shielding or ground lines. In some layouts, shielding ground lines are used only between pairs of adjacent pixel output signal lines (OSLs). Also disclosed is a method of using one OSL within a pair of adjacent pixel OSLs to provide settling assist of the pixel output signal on the other OSL of the adjacent pair of OSLs.

Abstract: A method of ctDNA library construction and sequencing data analysis for simultaneously detecting multiple common mutations in liver cancer. The library construction method and sequencing data analysis process have the following advantages: 1. Simultaneous detection of multiple mutation forms in liver cancer without capturing; 2. Suitable for efficient capture of ultra-small target regions; 3. The library may support 10-20 tests; 4. Ligate the DNA barcode to the starting ctDNA molecule during the library construction process, and cooperate with the biological information analysis process to achieve high specific detection of low-frequency mutations in ctDNA; 5. The library is usable for PCR hot spots detection and sequencing by a capture method at the same time, the added DNA barcode may effectively filter out false positive mutations and achieve high-specificity sequencing based on duplex.

Abstract: Disclosed herein are electronic devices and image sensors containing pixel arrays, layouts of electrical signal lines for such pixel arrays, and methods of pixel read out operations, including row read operations, for such pixel arrays. Layouts are disclosed that have reduced sets of shielding or ground lines. In some layouts, shielding ground lines are used only between pairs of adjacent pixel output signal lines (OSLs). Also disclosed is a method of using one OSL within a pair of adjacent pixel OSLs to provide settling assist of the pixel output signal on the other OSL of the adjacent pair of OSLs.

Abstract: The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, either TERTp mutation leading to telomerase activation or ATRX-mutation leading to an alternative lengthening of telomeres phenotype (ALT). However, about 20% of glioblastomas lack alterations in TERTp and IDH. These tumors, designated TERTpWT-IDHWT glioblastomas, did not have well-established genetic biomarkers or defined mechanisms of telomere maintenance. The genetic landscape of TERTpWT-IDHWT glioblastoma includes tumors that have chromosomal rearrangements upstream of TERT. These rearrangements define a novel molecular subgroup of glioblastoma, that is a telomerase-positive subgroup driven by TERT-structural rearrangements (IDHWT-TERTSV).

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind endothelin A receptor (ETAR). These ETAR antibodies, or antigen-binding fragments thereof, have a high affinity for ETAR, function to effectively block ET-1 binding to ETAR, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat ETAR-associated disorders. Importantly, compared to small molecule ETAR antagonists, the antibodies of the present invention have advantages of longer serum half-life, higher target specificity, thereby limiting the risk of off-target toxicity and improving therapeutic window.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof that specifically bind chemokine receptor 4 (CXCR4). These CXCR4 antibodies, or antigen-binding fragments thereof, have a high affinity for CXCR4, function to effectively block SDF-1 binding to CXCR4, thereby inhibiting forskolin stimulated cAMP with low nM 1050, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat CXCR4-associated disorders while avoiding the adverse side effects associated with the current CXCR4 antagonist therapies.

Abstract: The present disclosure relates to methods for treating type 1 diabetes (T1D) using a glucagon receptor blocking agent. More specifically, the present disclosure relates to methods for treating T1D using substantially lower doses of insulin supplementation, or even in the absence of insulin supplementation, using antigen binding and antagonizing proteins, e.g., fully human antibodies that specifically bind to and antagonize the function of the human glucagon receptor.

Abstract: The present disclosure relates to methods for treating or preventing heart failure using a glucagon receptor blocking agent. In various embodiments, the present disclosure relates to methods for treating or preventing heart failure (e.g., post-myocardial infarction heart failure), diabetic cardiomyopathy heart failure), and lateral ventricular (LV) remodeling, using antigen binding and antagonizing proteins, e.g., fully human antibodies, that specifically bind to and antagonize the function of the human glucagon receptor.

Abstract: A method for preparing an amplicon library for detecting the variation in a region to be tested of a target gene of a sample, including the following steps: 1) designing and synthesizing a forward outer primer F1, a forward inner primer F2, and a reverse primer R according to the target region; 2) carrying out a one-step PCR amplification on the sample to be tested using the forward outer primer F1, the forward inner primer F2, and the reverse inner primer R to obtain an amplified product, i.e., the amplicon library of the target region. This one-step library preparation technology can be applied to all second-generation platforms including IonTorrent, illumina and BGI/MGI platforms. Based on the library preparation method, the present invention has developed detection products for SNP, Ins/Del, CNV and methylation of DNA, as well as detection products for s gene fusion and expression of RNA samples.

Abstract: This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind Programmed Death Ligand-1 (PD-L1). These PD-L1 antibodies, or antigen-binding fragments thereof, have a high affinity for PD-L1, function to inhibit PD-L1, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., a human), are capable of increasing T-cell proliferation and IL-2 secretion in a mixed lymphocyte reaction, and can be used to treat human diseases (e.g., cancer, infectious diseases, autoimmune diseases, asthma, transplant rejection, and inflammatory disorders).

Abstract: The present invention provides a kit for early screening of hepatocellular carcinoma, comprising a gene marker detection reagent and a protein marker detection reagent. The invention also provides a preparation method and application of the kit. The kit comprising specific gene markers and protein markers of the present invention has been demonstrated to be effective in achieving early screening of HCC in community populations, particularly in prospective studies.