40results about How to "Tight regulation" patented technology

The present invention provides delivery vectors for transferring a nucleic acid sequence to a cell in vitro, ex vivo or in vivo. The delivery vector comprises a segment encoding a secretory signal peptide. In embodiments of the invention, the delivery vector is an adeno-associated virus (AAV) vector. In other embodiments, the secretory signal peptide is a fibronectin secretory signal peptide (including variations and modifications, thereof). The delivery vectors of the invention may further comprise a heterologous nucleic acid sequence encoding a polypeptide of interest for transfer to a target cell, where the polypeptide of interest is operably associated with the secretory signal. Also disclosed are methods of transferring a nucleic acid of interest to a cell using the delivery vectors of the invention.

A step-down switching voltage regulator includes M high-side switches connected between an input voltage and a node; N synchronous rectifiers connected between the node Vx and a ground voltage and an inductor connected between an input voltage and a node Vx and an inductor connected between the node Vx and an output node. An interface circuit decodes a control signal to identify: 1) a subset (m) of the high-side switches, 2) a subset (n) of the synchronous rectifiers. A control circuit drives the high-side switches and synchronous rectifiers in a repeating sequence that includes an inductor charging phase where the high-side switches in the subset m are activated to connect the node Vx to the input voltage; and an inductor discharging phase where the synchronous rectifiers in the subset n are activated to connect the node Vx to the ground voltage.

Described herein are carbamate compounds. Such compounds are capable of modulating the activity of a checkpoint kinase, and described herein are methods for utilizing such modulation to treat cell proliferative disorders. Also described are pharmaceutical compositions containing such compounds. Also described are the therapeutic or prophylactic use of such compounds and compositions, and methods of treating cancer as well as other diseases associated with unwanted cellular proliferation, by administering effective amounts of such compounds in combination with anti-neoplastic agents.

A step-up switching voltage regulator includes an inductor connected between an input voltage and a node Vx, M low-side switches connected between the node Vx and a ground voltage and N synchronous rectifiers connected between the node Vx and an output node. An interface circuit that decodes a control signal to identify: 1) a subset (m) of the low-side switches, 2) a subset (n) of the synchronous rectifiers, and 3) a reference voltage V_ref. A control circuit drives the synchronous rectifiers and low-side switches in a repeating sequence that includes an inductor charging phase where the low-side switches in the subset m are activated to connect the node Vx to the ground voltage; and an inductor discharging phase where the synchronous rectifiers in the subset n are activated to connect the node Vx to the output node.

A circuit and method of providing three dc voltage buses and transforming power between a low voltage dc converter and a high voltage dc converter, by coupling a primary dc power circuit and a secondary dc power circuit through an isolation transformer; providing the gating signals to power semiconductor switches in the primary and secondary circuits to control power flow between the primary and secondary circuits and by controlling a phase shift between the primary voltage and the secondary voltage. The primary dc power circuit and the secondary dc power circuit each further comprising at least two tank capacitances arranged in series as a tank leg, at least two resonant switching devices arranged in series with each other and arranged in parallel with the tank leg, and at least one voltage source arranged in parallel with the tank leg and the resonant switching devices, said resonant switching devices including power semiconductor switches that are operated by gating signals. Additional embodiments having a center-tapped battery on the low voltage side and a plurality of modules on both the low voltage side and the high voltage side are also disclosed for the purpose of reducing ripple current and for reducing the size of the components.

The present invention relates to a protein binding to GARP in the presence of TGF-β and uses thereof.

Described herein are aminopyrazole compounds of formula I:

wherein R¹, R², L and Ar are as defined in the specification. Such compounds are capable of modulating the activity of a checkpoint kinase and methods for utilizing such modulation to treat cell proliferative disorders. Also described are pharmaceutical compositions containing such compounds. Also described are the therapeutic or prophylactic use of such compounds and compositions, and methods of treating cancer as well as other diseases associated with unwanted cellular proliferation, by administering effective amounts of such compounds in combination with anti-neoplastic agents.

The present invention is directed to the production and in vitro assembly of recombinant viral capsid proteins into virus like particles. In particular, the present invention provides rapid, scalable, and cost efficient methods for the production of multivalent virus like particles utilizing separate populations of capsid fusion peptides containing differing antigenic peptide inserts that are combined in vitro to produce homogenous populations of multivalent virus like particles. The virus like particles produced according to the present invention can be utilized to induce an immunological response in human or animal.

In a high power system, plural batteries provide back-up power when primary power is unavailable. Each battery has an associated discharge controller which is controlled by a local bus control amplifier which regulates the power bus voltage set-point lower than the main bus voltage set-point. A single main bus control amplifier tightly regulates the power bus to a main bus voltage set-point and controls charging and discharging of all batteries to prevent charging of one battery at the expense (discharge) of another battery. There is one master battery discharge controller, with the remaining controllers being slave units. A local bus voltage set-point of each slave unit varies under the control of a slave unit current sharing amplifier which compares its own discharge current to the average discharge current, and an error signal modifies the reference voltage in the local bus control amplifier to allow equal discharge current from all batteries.

The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

Expression vectors are disclosed that are comprised of (a) one or more silencer elements and conditionally inducible elements to form silencer-inducible regions and (b) promoters in operative linkage upstream of at least one expressed region. The expression vector thereby regulates expression of at least one downstream region by conditional silencing in which an expressed DNA region of a gene is transcribed to produce RNA transcripts, which may or may not be translated to produce polypeptides. Genetically engineered mammalian cells and non-human mammals can be made using such expression vectors through transfection and transgenesis techniques. Moreover, processes of making and using the aforementioned products are disclosed (e.g., the expression vector may be used diagnostically, therapeutically, or prophylactically).

The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

A self-regulating gene expression construct comprises a single promoter in operative association with a repressor sequence (e.g., bacterial repressor lacI or gaiR), operator sequence(s) responsive to the expressed repressor protein, and a transgene. A dual-regulating construct comprises a single promoter controlling expression of a bacterial repressor sequence and a transgene, and which, in the presence of a first inducer molecule, transcribes the transgene and repressor; and a ribozyme in association with an aptamer sequence, the aptamer sequence capable of interacting with a second inducer molecule to terminate mRNA degradation by the ribozyme. Also provided are recombinant vectors or viruses containing the self-regulating or dual self-regulating constructs and cells containing the vectors. Such compositions are useful in methods of treating a diseases using gene therapy.