Abstract: A system for monitoring cardiac health of a user including a local sensing subsystem, a contactless interrogation subsystem, and a remote monitoring subsystem. The local sensing subsystem may include a sensor patch configured to attach to the user and include a substrate, a passive radio-frequency identification transponder, and a first antenna. The contactless interrogation subsystem may include an interrogator separated from the sensor patch, which may include a second antenna, a demodulator, and a communications link. The remote monitoring subsystem may include a computing system comprising a processor for executing instructions. The local sensing subsystem may be adapted to perform at least one scan. The contactless interrogation subsystem may be adapted to operate the demodulator to receive a cardiac event and to operate the communications link to transmit the cardiac event. The remote monitoring subsystem may be adapted to execute the instructions to detect an arrhythmia from the cardiac reading.

Abstract: A finger ring health status monitoring device comprising an inner ring member and an outer ring member positioned radially outward from and operably connected to the inner ring member. The inner ring member features a conductor characterized by at least one physiological-type sensor, and an annular bladder that defines an adjustable aperture sized to receive a finger of a patient. Adjustment of the aperture is accomplished by rotating the outer ring member in a first direction about an axis of rotation common to the outer ring member and to the inner ring member, thereby causing the bladder to expand radially inward so as to reduce an inside diameter of the aperture. Rotating the outer ring member in a second direction opposite the first direction causes the bladder to contract, thus increasing the inside diameter of the aperture.

Abstract: A method of monitoring a health status of a patient using a monitoring system comprising a pair of finger ring electrocardiogram (ECG) monitors. Each finger ring monitor comprises an inner ring member and an outer ring member positioned radially outward from and operably connected to the inner ring member. The inner ring member of each monitor features a conductor characterized by at least one physiological-type sensor, and an annular bladder that defines an adjustable aperture sized to receive a left-hand finger of a patient and a right-hand finger of the patient, respectively. Upon triggering by positioning the pair of finger ring ECG monitors substantially together, the conductors of each of the finger ring ECG monitors are configured to receive biopotential signals from skin on the fingers of the patient.

Abstract: A wireless ECG sensor system includes a sensor patch configured to attach to a user. The sensor patch may include a substrate having a positive and a negative electrode, and a passive radio-frequency identification (RFID) transponder carried by the substrate. The RFID may include a first antenna, a non-transitory and non-volatile storage medium in, electrical communication with the first antenna, a load modulation switch in electrical communication with the first antenna, and a microcontroller in electrical communication with the first antenna and in data communication with both the storage medium and the load modulation switch. The system may also include an interrogator device having a second antenna configured to wirelessly transmit electromagnetic radiation having a resonant frequency of the first antenna of the sensor patch, and a demodulator configured to measure a voltage amplitude of the electromagnetic radiation wirelessly transmitted by the second antenna.

Abstract: Disclosed are methods for building a sequence activity model with reference to structural data, which model can be used to guide directed evolution of proteins having beneficial properties. Some embodiments use genetic algorithms and structural data to filter out uninformative data. Some embodiments use a support vector machine to train the sequence activity model. The filtering and training methods can generate a sequence activity model having higher predictive power than conventional modeling methods. Systems and computer program products implementing the methods are also provided.

Abstract: Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.

Abstract: The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-?B in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-?B in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

Abstract: Disclosed herein are a collection of miRNAs and genes whose expression is altered in hypertrophic cardiomyopathy. Accordingly, these miRNAs and genes, singly or in combination, are useful as molecular markers for diagnosis or prognosis of hypertrophic cardiomyopathy. The miRNAs and genes disclosed can also be therapeutic targets for cardiac hypertrophy. For example, agents such as miRNA mimics, miRNA inhibitors or siRNAs for a given miRNA or gene can be used to modulate the level of these molecules thereby inhibiting or preventing hypertrophic cardiomyopathy.

Abstract: The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-?B in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-?B in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

Abstract: The present invention provides compositions and methods for inhibiting gene silencing by the RNAi pathway. The RNAi inhibitors of the invention have a reverse complement (RC) region to the target molecule of interest (e.g., miRNA) in association with at least one flanking region coupled to either at the 3? or 5? end of the RC region. The flanking regions can be single-stranded or can have one or more regions of double stranded nucleic acid with or without a hairpin loop. The RNAi inhibitors described herein can inhibit endogenous targets, including but not limited to microRNAs, or piRNAs, or can be used to inhibit the effects of exogenously introduced molecules, such as synthetic siRNAs, siRNAs expressed from vector constructs (e.g., viral expression systems), or siRNAs generated by enzymatic methods. Inhibition is specific, potent, prolonged, and can be performed on a single target or multiple targets simultaneously.

Abstract: A microarray can be configured for hybridizing with short nucleic acids, such as miRNA or siRNA, contained within a sample. Such a microarray includes a polynucleotide trap coupled to a substrate of a microarray site. The polynucleotide trap includes a probe that selectively hybridizes with short nucleic acid sequences, and a linker that is coupled to the substrate and configured to extend the probe from the substrate. Additionally, the polynucleotide trap can include an enhancer that hybridizes with the linker in order to enhance functionality of the probe. The linker and/or enhancer are configured to inhibit the probe from interacting with the linker or substrate. This can include the linker and/or enhancer being configured to have a minimal secondary structure so as to present the probe region for hybridizing with the target polynucleotide and inhibit the linker region or probe region from interacting with the substrate.

Abstract: The present disclosure provides methods, libraries and computer program products for determining whether a phenotype induced by a candidate siRNA for a target gene in an RNAi experiment is target specific or a false positive. Through the use of a control siRNA that has one or two seed sequences of six or seven bases in combination with a neutral scaffolding sequence, a distinction can be made between false positive and true positive analyses of functionality.

Abstract: The present invention provides methods, libraries and computer program products for selecting siRNA that reduce off-target effects and methods for gene silencing using these siRNAs. By comparing nucleotide sequences at positions 2-7 or 2-8 of the sense and/or antisense regions of candidate siRNAs to the 3? UTR region of mRNAs, one can select siRNAs that have reduced off-target effects.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozymes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozyes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozymes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozymes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.