Abstract: The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.

Abstract: Methods, systems and devices that allow independently applied pressures to a BGE reservoir and a sample reservoir for pressure-driven injection that can inject a discrete sample plug into a separation channel that does not require voltage applied to the sample reservoir and can allow for in-channel focusing methods to be used. The methods, systems and devices are particularly suitable for use with a mass spectrometer.

Abstract: Chondroitin sulfate compounds comprising chondroitin sulfate backbone 19 mer, CS-A 19 mer, CS-C 19 mer, CS-E 19 mer, C8 backbone 13 mer, C8-A 13 mer, CS-C 13 mer, CS-E 13 mer and/or combinations thereof are provided. Methods of treating histone toxicity in a subject are provided, the methods including administering to a subject a chondroitin sulfate compound to treat the histone toxicity in the subject. Pharmaceutical compositions for use in treating histone toxicity and/or sepsis are provided. Methods of treating sepsis in a subject are provided, the methods including administering to a subject a chondroitin sulfate compound to treat the sepsis in the subject.

Abstract: Viral promoters and compositions and methods of use thereof are provided. Compositions include viruses with impaired ability to reactivate from latency, and pharmaceutical compositions and method of use thereof. The genome of the viruses include one or more mutations that reduce expression from one or more promoters that regulate expression of viral genes during reactivation from latency. The mutation(s) are typically in a region of the viral genome that includes (i) promoter elements of the iP1 promoter of human cytomegalovirus, or the sequence of another virus corresponding thereto (e.g., an iP1 promoter homolog); (ii) promoter elements of the iP2 promoter of human cytomegalovirus, or sequence of another virus corresponding thereto (e.g., an iP2 promoter homolog); or (iii) a combination thereof. In some embodiments the virus encodes one or more heterologous antigens. The viruses can be used as vaccines to induce prophylactic and therapeutic immune responses in subjects in need thereof.

Abstract: In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, these compounds may be used to reduce the pain of a patient. These compounds may be used in pain relief and show an improved pharmaceutical profile relative to other commonly used opiates and opioid derivatives.

Abstract: Systems and methods for measuring micro-architectural properties of vascular networks are described herein. An example method can include injecting an ultrasound contrast agent into a medium, and transmitting a plurality of acoustic pulses into the medium using a ultrasound transducer array. Each respective acoustic pulse can be transmitted from one or more elements of the ultrasound transducer array. The method can also include receiving a plurality of backscattered signals with the ultrasound transducer array in response to each respective acoustic pulse, and obtaining a response matrix including the backscattered signals. The method can further include extracting a coherent or incoherent contribution to the backscattered signals from the response matrix, and quantifying a property of a vascular network based on the coherent or incoherent contribution to the backscattered signals.

Abstract: Phase-incrementing MRSI (pi-MRSI) method has resolved overlapping biomarker images in the presence of a read-gradient. On a Bruker 9.4T MRI spectrometer, the pi-SEE-HSelMQC sequence was implemented. The choline-selective and lactate CH-selective RF pulses were phase incremented by 10° in opposite signs, synchronized with the phase-encoding steps. The lactate and choline images from a yogurt phantom displayed opposite image offsets without image overlapping. In vivo one-dimensional pi-SEE-HSelMQC CSI images of lactate and choline, acquired from the MDA-MB-231 human breast cancer xenograft in a nude mouse, as well as two-dimensional pi-SEE-HSelMQC imaging of lactate and choline acquired from the PC3 human prostate cancer xenograft in a nude mouse, also had opposite image offsets, shifted away from the spurious residual water signals in the image center. The pi-SEE-HSelMQC method completely suppresses lipid and water with potential clinical applications in disease diagnosis and therapeutic interventions.

Abstract: A system for estimating maximum heart rate and maximal oxygen uptake from submaximal exercise intensities can include an exercise intensity monitor, a cardiopulmonary monitor, and one or more computers. The computers can be configured, by virtue of appropriate programming, to receive submaximal exercise intensity data from the exercise intensity monitor and submaximal cardiopulmonary data from the cardiopulmonary monitor while a user, who coupled to the exercise intensity monitor and the cardiopulmonary monitor, is performing an exercise at a submaximal exercise intensity. The one or more computers then determine a heuristic estimate of a maximal cardiopulmonary state of the user based on the submaximal exercise intensity data and the submaximal cardiopulmonary data.

Abstract: The invention generally relates to methods of making substituted arenes via direct C—H amination. More specifically, methods of making para- and ortho-substituted arenes via direct C—H amination are disclosed. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: A system, mixing-enhanced microfluidic container, and methods for small volume sample collection and/or analysis is disclosed. Namely, the invention is directed to a small volume sample collection system that includes a mixing-enhanced microfluidic container and a durable reusable actuation chuck. The mixing-enhanced microfluidic container is used to collect small volumes of sample fluid and includes a means for mixing the sample fluid with reagents disposed within the microfluidic container. The mixing means utilize an array of surface-attached structures (e.g., a micropost array). The application of an “actuation force,” such as a magnetic or electric field, actuates the surface-attached structures into movement, wherein the actuation chuck in close proximity to the mixing-enhanced microfluidic container provides the “actuation force.

Abstract: A microfabricated device having at least one gas-entrapping feature formed therein in a configuration that entraps air bubbles upon wetting the feature with a solvent or solution is described. The device includes a sacrificial residue in contact with the gas-entrapping feature, the dissolution of which guides the wetting of the gas-entrapping feature.

Abstract: The present invention is directed to methods and compositions for norovirus therapeutics, such as vaccines, and diagnostics.

Abstract: The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

Abstract: This invention relates to polynucleotides encoding mini-dystrophin proteins, viral vectors comprising the same, and methods of using the same for delivery of mini-dystrophin to a cell or a subject.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: The invention relates to synthetic liver-specific promoters and expression constructs for producing polypeptides and functional nucleic acids in the liver of a subject. The invention further relates to optimized polynucleotide sequences encoding Factor IX proteins, vector comprising the same, and methods of using these compositions to treat a bleeding disorder.

Abstract: Described herein are methods for improving or maintaining the barrier integrity of gingival tissue comprising administering an oral care composition comprising a curcurninoid, to the oral cavity of a subject in need thereof.

Abstract: Active surface devices for and methods of providing dried reagents in microfluidic applications is disclosed. In one example, the active surface devices include one or more dried reagent spots in relation to an active surface in the reaction (or assay) chamber thereof. In another example, the active surface devices include a dried reagent coating on the surfaces of the reaction (or assay) chamber including the active surface. In one example, the presently disclosed active surface devices are micropost-based active surface devices for providing active mixing therein. Further, a method of forming a dried reagent spot in the active surface devices is provided. Further, a method of forming a dried reagent coating in the active surface devices is provided. Further, a method of using the active surface devices for providing dried reagents in microfluidic applications is provided.

Abstract: This invention relates to polynucleotides comprising a nucleotide sequence encoding a PPT1 polypeptide or a fragment thereof, vectors (viral or non-viral vectors) comprising the same, and methods of using the same for delivery of the open reading frame to a cell or a subject and to treat infantile neuronal lipofuscinosis (infantile Batten disease). The polynucleotides comprise an optimized CLN1 open reading frame.

Abstract: This invention relates to SARS-CoV-2 viruses adapted with nanoluciferase reporter molecules and mouse-adapted SARS-CoV-2 viruses, compositions including the same and methods of use thereof.