摘要:
The clustered regularly interspaced short palindromic repeat (CRISPR) gene editing technique, based on the non-homologous end-joining (NHEJ) repair pathway, can efficiently generate gene knockouts of variably sizes. More precise genome editing, either the insertion or deletion of a desired fragment, can be done by combining the homology-directed-repair (HDR) pathway with CRISPR cleavage. HDR-mediated gene knock-in experiments are inefficient, with no reports of successful gene knock-in with DNA fragments larger than 4 kb. Targeted insertion of large DNA fragments (7.4 and 5.8 kb) into the genomes of mouse embryonic stem cells and zygotes, respectively, using the CRISPR/HDR technique without NHEJ inhibitors was performed and indicate that CRISPR/HDR without NHEJ inhibitors can result in highly efficient gene knock-in, equivalent to CRISPR/HDR with NHEJ inhibitors. Although NHEJ is the dominant repair pathway associated with CRISPR-mediated double-strand breaks (DSBs), and biallelic gene knock-ins are common, NHEJ and biallelic gene knock-ins were not detected.
摘要:
Anti-cytokine therapy has revolutionized immunological disease treatment, but is not always effective and subject to treatment resistance as the cytokine cascade is highly redundant and multiple cytokines are involved in inflammation. Targeting a critical common regulator of inflammatory effectors is desirable. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) is a master regulator of multiple genes important for inflammation. Subcellular localization shows that LRBA translocated to the nucleus upon LPS stimulation and colocalized with multiple proteins associated with the endosome membrane system, indicating a critical role in membrane/vesicle trafficking essential for deposition, secretion and signal transduction of immune effectors. Deregulation, deficiency, down-regulation and overexpression of LRBA causes defective trafficking and signaling of immune effector molecules, resulting in immunodeficiency and autoimmunity diseases associated with a broader spectrum of severe symptoms when compared to other CVID genes. Modulating LRBA through antibodies, dominant negative mutants, or small interference RNA can be used to treat inflammatory diseases.
摘要:
A system that incorporates teachings of the present disclosure may include, for example, a coordinator device having a memory, and a controller. The memory can have computer instructions, which when executed by the controller, causes the controller to facilitate establishing a first virtual personal area network with a first sensor by executing computer instructions associated with a first application profile, and facilitate establishing a second virtual personal area network with a second sensor by executing computer instructions associated a second application profile. The first application profile can be defined by a first protocol specification, while the second application profile can be defined by a second protocol specification. The first protocol specification can also be operationally distinct from the second protocol specification. Other embodiments are disclosed.
摘要:
Providing object information on the Internet includes configuring a plurality of front-end categories for a plurality of network objects and a plurality of screening conditions for screening the plurality of network objects, where each of the plurality of screening conditions uniquely corresponding to a respective one of the plurality of the front-end categories. Providing object information further includes receiving object information pertaining to a network object, the object information including a screening condition for the network object; storing the object information in a back-end category, determining a front-end category to which the network object belongs, according to the screening condition and storing correlation information of the object and the front-end category, wherein the back-end category is separate from and different than the front-end category.
摘要:
A system that incorporates teachings of the present disclosure may include, for example, obtaining regression coefficients that quantify a relationship between premises feedback and first network and premises performance indicators, obtaining second network performance indicators for the network elements, obtaining second premises performance indicators for the customer premises equipment, and predicting customer complaints by applying the obtained regression coefficients to at least the second network performance indicators and the second premises performance indicators. Other embodiments are disclosed.
摘要:
A method for use in electronic design software efficiently and optimally produces minimized or reduced register flip flop area or number of registers/flip flops in a VLSI circuit design without changing circuit timing or functionality. The method dynamically generates constraints; maintains the generated constraints as a regular tree; and incrementally relocates registers/flip flops and/or the number of registers/flip flops in the circuit design.
摘要:
A method and apparatus for classifying packets, e.g., at wire speed are disclosed. The method receives a packet and processes the packet through a hardware-based packet classifier having at least one evolving rule. The method then processes the packet through a software-based packet classifier if the hardware-based packet classifier is unable to classify the packet. In one embodiment, the at least one evolving rule is continuously modified in accordance with learned traffic characteristics of the received packets.
摘要:
The present invention provides materials and methods for detecting, quantifying, and/or profiling microRNAs. Advantageously, the present invention is sensitive, specific, convenient, and cost-effective. In one embodiment, the present invention provides a universal primer for reverse transcription of miRNAs, a universal reverse primer for PCR amplification reaction, and a universal probe. In another embodiment, the present invention provides assays that allow the detection and/or quantification of a plurality of target miRNAs using a single reverse transcription reaction and a single qPCR reaction.
摘要:
A method includes receiving network distance information, receiving a request from a client for an identity of a peer providing content, and identifying a first peer and a second peer providing the content. The network distance information includes a compilation of network distance information provided by a plurality of service providers. The method further includes determining that a network distance between the first peer and the client is less than a network distance between the second peer and the client based on the network distance information, and providing the identity of the first peer to the client.