Abstract: The present disclosure relates to compositions, methods, and kits for increasing the viability of bacteria that have been subjected to freeze-drying/lyophilization. In particular, the disclosure relates to compositions and methods for increasing the viability of living medicines (e.g.

Abstract: Disclosed herein are shelf-stable compositions based on synthetic gene networks and/or cell-free systems that are lyophilized on a solid support. The compositions can be easily transported and stored for a period of time, and activation can be done by simply adding water. Methods of use are also disclosed herein, including, but are not limited to, sensing and a variety of logic functions. The invention permits straightforward, sterile and abiotic distribution of synthetic biology-based technology to clinical settings, food processing and industry, the military and consumer products.

Abstract: The invention provides novel and versatile classes of riboregulators, including inter alia activating and repressing riboregulators, switches, and trigger and sink RNA, and methods of their use for detecting RNAs in a sample such as a well and in modulating protein synthesis and expression.

Abstract: A method and wearable system and for enhancing human balance and gait and preventing foot injury through neurological stimulation of the foot and the ankle. Subthreshold stimulation for neurosensory enhancement is provided via electrodes or vibrational actuators, or combination thereof, disposed in or on a wearable a platform, such as an insole, sock shoe, removable shoe insert, or applied without the support of a platform, to the skin surface of an individual. Suprathreshold stimulation for therapeutic purposes, such as improving blood flow, is also provided by the vibrational actuators. The actuators and electrodes are driven by bias signals generated by a bias signal generator that is coupled to a controller. The signal generator under the control of the controller is adapted to generate a non-deterministic random signal, a repetitive pattern or series of patterns.

Abstract: Disclosed herein are a high-throughput continuous culture system and novel methodologies for the experimental evolution of natural and synthetic microbes using the continuous culture system. The microbial culture is exposed to a stress ramp function which is overlaid on top of a culture fitness function. The amount of stress applied to the culture is increased in response to increased fitness of the microbial culture.

Abstract: Described herein are compositions and methods for in vitro detection of nucleic acids. Nucleic acid sensors are activated for cell-free expression of an encoded reporter protein based on the presence of a target nucleic acid. The system is designed to function in low-cost cell extract without the need for instrumentation or stringent temperature control. These features are advantageous for point-of-use molecular diagnostics applications in consumer health, pet/animal health, food safety, and other areas where cost and portability are key factors.

Abstract: Provided herein are pharmaceutical compositions and kits useful for sensitizing a microorganism or a population of microorganisms to a quinolone antibiotic. In a particular aspect, a carbon source and an electron acceptor can sensitize an antibiotic persistent microorganism to treatment with a fluoroquinolone antibiotic. Methods for sensitizing a microorganism to a quinolone antibiotic, reducing the density-dependent persistence (DDP) of an antibiotic resistant microorganism, and reducing the number of persistent cells in a population are also provided. Theses compositions and methods are useful in treating infections resulting from high-density bacterial cultures, such as pneumonia, genitourinary infections, biofilms, prosthetic graft infections, sepsis, and endovascular infections.

Abstract: The present disclosure is related to an engineered nucleic acid encoding a post-poly A signal RNA 3? to a terminator for expression of protein, and/or non-coding RNA. Also provided herein are methods for reducing epigenetic silencing, genetic modification, transcriptional regulation of the engineered nucleic acid described herein.

Abstract: Disclosed herein are hydrogels comprising a polynucleotide-based structural component. Methods of altering a property of a hydrogel based on user-defined nucleic acid input sequences are also disclosed. In addition, various applications are described that utilize these hydrogels and methods.

Abstract: Disclosed herein are a high-throughput continuous culture system and novel methodologies for the experimental evolution of natural and synthetic microbes using the continuous culture system. The microbial culture is exposed to a stress ramp function which is overlaid on top of a culture fitness function. The amount of stress applied to the culture is increased in response to increased fitness of the microbial culture.

Abstract: The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enzymes or fragments thereof for targeting a broad spectrum of bacterial hosts, and for the long-term suppression of bacterial phage resistance for reducing bacterial infections. In some embodiments, bacteriophages express antimicrobial peptides or antimicrobial polypeptides (e.g. phage lytic enzymes) which are secreted from the host bacteria, or alternatively released upon lysis of the bacterial host cell. Aspects of the present invention also relate to the use of the engineered bacteriophages for the reduction of bacterial infections, both in a subject or for bioremediation purposes, in clinical settings and wound healing.

Abstract: Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and high, localized concentrations of one or more PMF stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known. These approaches and therapeutic methods are also useful with non-metabolic chemicals that induce proton-motive force in bacteria.

Abstract: A wearable system is directed to neurological stimulation of a human foot, and includes a controller with at least one bias signal generator for outputting a driving signal. The system further includes a power source that provides electrical energy to the controller, including providing electrical energy to the bias signal generator. The system also includes a platform in the form of an insole insert of a shoe, the insole insert having a plurality of actuators positioned in a medial arch region of the foot. The plurality of actuators stimulate the medial arch region in response to receiving the driving signal from the controller. The stimulation of the plurality of actuators provides a subthreshold bias signal to target cells with a subthreshold bias signal magnitude that is below a threshold where the target cells are activated by a stimulus. The plurality of actuators is surrounded with a vibration dissipating material.

Abstract: Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.

Abstract: Methods for detecting the presence of a pathogen infection are described. In particular, this document provides a method of detecting target nucleic acids, such as pathogen-specific RNA, in a biological sample obtained from a subject, where the method comprises using one or more toehold switch sensors and an isothermal amplification step to detect the target nucleic acid. Methods specific for detecting and identify the presence of a virus such as Zika virus are also provided.

Abstract: Embodiments disclosed herein provide artificial expression systems comprising multivalent transcription factor complexes for cooperative transcription factor assembly and modulating gene expression. More specifically, engineered synthetic transcription factors are recruited and structurally organized on synthetic gene circuits using molecular clamps, where the strength of intra-complex interactions can be modulated for fine tuning of gene expression as desired.

Abstract: Provided herein are pharmaceutical compositions and kits useful for sensitizing a microorganism or a population of microorganisms to a quinolone antibiotic. In a particular aspect, a carbon source and an electron acceptor can sensitize an antibiotic persistent microorganism to treatment with a fluoroquinolone antibiotic. Methods for sensitizing a microorganism to a quinolone antibiotic, reducing the density-dependent persistence (DDP) of an antibiotic resistant microorganism, and reducing the number of persistent cells in a population are also provided. Theses compositions and methods are useful in treating infections resulting from high-density bacterial cultures, such as pneumonia, genitourinary infections, biofilms, prosthetic graft infections, sepsis, and endovascular infections.

Abstract: Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and high, localized concentrations of one or more PMF stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known. These approaches and therapeutic methods are also useful with non-metabolic chemicals that induce proton-motive force in bacteria.

Abstract: The present invention provides nucleic acid molecules, DNA constructs, plasmids, and methods for post-transcriptional regulation of gene expression using RNA molecules to both repress and activate translation of an open reading frame. Repression of gene expression is achieved through the presence of a regulatory nucleic acid element (the cis-repressive RNA or crRNA) within the 5? untranslated region (5? UTR) of an mRNA molecule. The nucleic acid element forms a hairpin (stem/loop) structure through complementary base pairing. The hairpin blocks access to the mRNA transcript by the ribosome, thereby preventing translation. In particular, in embodiments of the invention designed to operate in prokaryotic cells, the stem of the hairpin secondary structure sequesters the ribosome binding site (RBS). In embodiments of the invention designed to operate in eukaryotic cells, the stem of the hairpin is positioned upstream of the start codon, anywhere within the 5? UTR of an mRNA.

Abstract: Provided herein are systems, methods and compositions for rendering cells or the expression of an effector protein sensitive to a predetermined condition. In one aspect, cells can be rendered dependent upon the presence of an environmental agent, e.g., an exogenous agent, without which the cell will default to expression of a death protein and be killed. In another aspect, cells can be rendered sensitive to the presence of a set of predetermined conditions such that cells will only grow when two or more necessary exogenous agents are supplied, and without either of which, the cells are killed. In this aspect, hybrid transcription factors provide a vast array of possible predetermined conditions.