Abstract: Efforts to use RNA-cleaving DIMA enzymes (DNAzymes) as gene silencing agents in therapeutic applications have stalled due to their low efficacy in clinical trials. Here the present invention reports a xeno-nucleic acid (XNA) modified version of the classic DNAzyme 10-23 that achieves multiple turnover activity under cellular conditions and resists nuclease digestion. The new reagent overcomes the problem of product inhibition limiting previous 10-23 designs using molecular chemotypes with DNA. FANA, and TNA backbone architectures that balance the effects of enhanced biological stability with RNA hybridization and divalent metal ion coordination. In cultured mammalian cells. X 10-23 facilitates persistent gene silencing by efficiently degrading exogenous and endogenous mRNA transcripts. Together, these results demonstrate that new molecular chemotypes can improve the activity and stability of DNAzymes, and may provide a new route for nucleic acid enzymes to reach the clinic.

Abstract: The current disclosure provides for the simultaneous isolation and selection of antigen-specific T cells by providing engineered proteins, cell lines, and viruses that have a peptide-major histocompatibility complex (pMHC) on the surface of the virus that facilitates transduction of the T cell that, through the T cell receptor (TCR), specifically binds to the peptide in the pMHC complex. Accordingly, aspects of the disclosure relate to proteins, cells, and viral particles that can achieve these methods.

Abstract: An apparatus including a source of electromagnetic radiation comprising one or more first frequencies; a source of an input signal comprising an alternating (AC) electric field comprising one or more second frequencies; a control circuit synchronizing application of the electromagnetic radiation and the AC electric field applied to a sample, so that an output signal comprising a modulation of the AC electric field is outputted from the sample in response to (1) the one or more second frequencies tuned to drive hopping of ions between ion sites in the sample, and the one or more first frequencies tuned to drive excitations in the sample that interact with the ions. The apparatus further includes a detection system measuring and/or detecting a change in the output signal in response to the electromagnetic radiation; and a computer determining at least one of a conductivity or impedance of the sample from the output signal and as a function of the first frequencies and the second frequencies.

Abstract: HH culture media and methods are provided to allow for recovery from injury or stress associated with cell isolation procedures and freeze/thaw cycle(s) by the use of a DMSO-supplemented medium, i.e., Phase 1 (recovery-phase). Moreover, HH culture media and methods are provided to allow for support of hepatic functionality of cultured HH at a comparable level to that of the human liver by the use of a DMSO, DMSO2, or TMSO-supplemented medium, i.e., Phase 2 (maintenance-application phase). These HH are suitable for the in vitro study of liver biology, diseases drug metabolism and pharmacokinetics. Furthermore, the culture supernatant of HH during Phase 2, namely, conditioned culture medium of human hepatocytes (CMHH), is provided, which facilitates iHeps maturation and supports the cell fate maintenance of hepatocytes. Methods of preparing CMHH are also provided, including culturing humanized liver chimeric animal derived-human hepatocytes and/or primary human hepatocytes in a medium to be collected.

Abstract: The present disclosure provides a method of using mocetinostat in combination with vinorelbine to treating a patient with rhabdomyosarcoma (RMS). The patient can be a child, an adolescent, or an adult having a locally advanced RMS, an unresectable RMS, a metastatic RMS, or a recurrent RMS.

Abstract: Retinal optical coherence tomography (OCT) with intraretinal layer segmentation is increasingly used not only in ophthalmology but also for neurological diseases such as multiple sclerosis (MS). Signal quality influences segmentation results, and high-quality OCT images are needed for accurate segmentation and quantification of subtle intraretinal layer changes. Among others, OCT image quality depends on the ability to focus, patient compliance and operator skills. Current criteria, for OCT quality define acceptable image quality, but depend on manual rating by experienced graders and are time consuming and subjective. In this paper, we propose and validate a standardized, grader-independent, real-time feedback system for automatic quality assessment of retinal OCT images. We defined image quality criteria for scan centering, signal quality and image completeness based on published quality criteria and typical artifacts identified by experienced graders when inspecting OCT images.

Abstract: The present disclosure provides the ability of low-cutting gRNAs to circumvent the maternal effect by delaying their action in time. Low-cutting gRNAs lead to a compounding dynamic drive efficiency, which results in drive efficiencies comparable to that of high-cutting gRNAs. Additionally, a gene drive system with a low-cutting gRNA outperforms a more efficient gRNA in laboratory caged populations.

Abstract: Provided herein are methods and compositions for modifying the genome of human T cells.

Abstract: A high gravimetric and volumetric power density heat exchanger is provided for high-temperature and high-pressure applications with counter-flowing hot and cold agents that enter via respective inlet headers, transit parallel and adjacent flow passages, and exit via respective outlet headers. One or more headers for conveying one of the substances may be situated within the flow of the other substance. Structures within the flow passages promote the transfer of heat while limiting pressure drop on one or both sides. The structures may include microscale pins, an array of pins (with specified aspect ratios and spacing), a lattice of interconnected pins, parallel ridges, and/or other features. Through an additive manufacturing process, the headers are monolithically integrated into the heat exchanger instead of being separately constructed and attached.

Abstract: The present disclosure provides methods for generating insect strains that can be used for genetic suppression or modification of insect populations. The method of the present disclosure covers both gene drive (GD) approaches and genetic sterile insect technique (gSIT, aka pgSIT), and uses an RNA-guided nuclease, such as Cpf1 (aka Cas12a), which has a temperature-dependent activity and turns genetic approaches for insect control to temperature-controllable systems.

Abstract: A method assessing tissue morphology using machine learning includes a step of training a machine learnable device to predict the status of a diagnostic feature in stained tissue samples. The machine learnable device is trained with a characterized set of digital images of stained tissue samples. Each digital image of the characterized set has a known status for the diagnostic feature and an extracted feature map provides values for a extracted feature over an associated 2-dimensional grid of spatial locations. A step of inputting the set of extracted feature maps is inputted into the machine learnable device to form associations therein between the set of extracted feature maps to and the known status for the diagnostic feature to form a trained machine learnable device. The status for the diagnostic feature of a stained tissue sample of unknown status for the diagnostic feature is predicted from the trained machine learnable device.

Abstract: Use of GABA-receptor agonists, either alone or with one or more positive PAMs, anti-inflammatory compounds, and/or antiviral treatments, e.g., one that limits viral replication or impacts other viral functions, to ameliorate, treat, and/or prevent illness arising from infections, including bacterial, fungal, and/or viral infections, in patients, including to: ameliorate infection-related medical conditions; ameliorate and/or prevent coronavirus-related medical conditions; inhibit viral replication; inhibit corona virus replication; ameliorate and/or treat coronavirus-induced medical conditions; ameliorate and/or prevent respiratory virus-related medical conditions; and ameliorate and/or modulate dysregulated immune responses.

Abstract: The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular in the treatment of diseases or disorders associated to increased relative to physiological or desired RhoJ/Cdc42 levels of expression or function.

Abstract: An interconnected corrugated carbon-based network comprising a plurality of expanded and interconnected carbon layers is disclosed. In one embodiment, each of the expanded and interconnected carbon layers is made up of at least one corrugated carbon sheet that is one atom thick. In another embodiment, each of the expanded and interconnected carbon layers is made up of a plurality of corrugated carbon sheets that are each one atom thick. The interconnected corrugated carbon-based network is characterized by a high surface area with highly tunable electrical conductivity and electrochemical properties.

Abstract: Provided by the inventive concept are methods for fabricating semiconductor devices, such as methods of atomic layer deposition (ALD). Aspects of the inventive concept include methods for depositing and forming Ru metal layers having low resistivity, forming Ru metal layers without the need for a post-deposition annealing step, forming Ru metal layers selectively on portions of a substrate without the need for passivation, and providing Ru metal layers for use in back end of the line (BEOL) applications in semiconductor devices that do not require a liner/barrier layer.

Abstract: The disclosed embodiments provide various compensated charge pumps (CPs) which have a current mismatch compensation circuitry and various CP output-current-mismatch compensation structures based on using a dummy charge pump (CPdum) and feedback loops. In some embodiments, the CPdum is identically biased as the CP to be compensated. CPdum is configured to sense the output voltage and use the feedback loops to generate compensation currents for the CP. The compensation currents simultaneously compensate CP and CPdum. Moreover, CPdum is loaded with high impedance so that the compensation current makes sure CPdum doesn't have current mismatch. Because CP and CPdum have identical biasings and are compensated in the same manner with the same amount of current, CP output current mismatch is hence effectively eliminated.

Abstract: Systems and methods for transmitting data using various Modulation on Zeros schemes are described. In many embodiments, a communication system is utilized that includes a transmitter having a modulator that modulates a plurality of information bits to encode the bits in the zeros of the z-transform of a discrete-time baseband signal. In addition, the communication system includes a receiver having a decoder configured to decode a plurality of bits of information from the samples of a received signal by: determining a plurality of zeros of a z-transform of a received discrete-time baseband signal based upon samples from a received continuous-time signal, identifying zeros that encode the plurality of information bits, and outputting a plurality of decoded information bits based upon the identified zeros.

Abstract: A system and method for joint dynamic interest request forwarding and dynamic cache placement and eviction and provided within the context of the Named Data Networking (NDN) architecture. The system and method employ a virtual control plane that operates on the user demand rate for data objects in the network, and an actual plane that handles Interest Packets and Data Packets. Distributed algorithms within the virtual plane achieve network load balancing through dynamic forwarding and caching, thereby maximizing the user demand rate that the NDN network can satisfy. A method of congestion control is also provided to achieve optimal network fairness using the VIP framework.

Abstract: Disclosed herein include methods and compositions for incorporating an effector gene into the genome of a cell. The method can comprise introducing into a cell a donor nucleic acid comprising a recognition site, a splice acceptor site, a self-cleaving peptide sequence, an effector gene, and an optional transcript stabilization element. The donor nucleic acid can be incorporated into the intron of a target gene differentially expressed in a unique cell type and/or in a cell during a unique cell state via non-homologous end joining (NHEJ)-dependent DNA repair. There are also provided, in some embodiments, methods and compositions for treating a disease or disorder in a subject.