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3D spheroids have emerged as powerful drug discovery tools given their high-throughput screening (HTS) compatibility. The present invention presents a method for generating functional neural spheroids with differentiated human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain.

This technology includes Cyclopentane-modified Peptide Nucleic Acids (cp-PNAs) which can be combined with (forced-intercalation) FIT-PNAs to create highly sensitive probes that detect the presence of complementary RNA sequences. We have studied the beneficial effects of incorporating cyclopentane groups into the backbone of PNAs, which leads to proper preorganization of the PNA backbone into the conformations needed to bind complementary RNA sequences. The cp-PNAs typically have improved thermodynamic stability for binding to complementary nucleic acids compared to unmodified PNAs.

This technology includes a sensitive and specific method to rapidly detect antibodies in biofluids. This assay has been used for the detection of antibodies in blood, urine, and saliva. Until now, no one has used LIPS to detect clinically relevant antibodies to SARS-CoV-2 Nucleocapsid (N) or Spike (S) in saliva. Briefly, LIPS employs recombinantly synthesized target proteins or peptides (e.g., S and N proteins) tagged with light-emitting proteins as targets to be captured by host produced immunoglobulins. These immunoglobulins can be captured by protein A/G beads and immobilized.

This technology includes an alternative synthetic biotin-streptavidin replacement system for use in the development of clinical diagnostics. Peptide nucleic acids (PNA) when functionalized onto the surface of microspheres are capable of targeting short RNA targets from solutions. However, when the target nucleic acid becomes longer and complicated in structure, the PNA no longer efficiently binds due to steric hindrance from the microspheres and/or slow hybridization kinetics of larger nucleic acid targets.

This technology includes compounds that are selective agonists of the A3 receptor for the treatment of various disorders such as cancer and autoinflammatory diseases. Structurally, these compounds extend the class of (N)-methanocarba derivatives that are selective agonists of the A3 receptor.

This technology includes a new class of oligomeric molecules called thyclotides for diagnostic and therapeutic development. Thyclotides is described where chiral tetrahydrofuran (THF) diamine units are linked together with alternating glycines, and nucleobases are attached to this backbone as sidechains. The thyclotide sequence consists of a series of nucleobases similar to that of a nucleic acid sequence. Thyclotides are easily synthesized and purified with excellent solubility in water. Thyclotide sequences bind to complementary DNA and RNA sequences with very strong affinity.

This technology includes novel hyperactive Hermes Transposase mutants and their encoding genes. These transposases are easily purified in large quantity after expression in bacteria. The modified Hermes Transposases are soluble and stable and exist as smaller active complexes compared to the native enzyme. The consensus target DNA recognition sequence is the same as the native enzyme and shows minimal insertional sequence bias.

This technology includes a model for providing a patient-specific diagnosis of disease using clinical data. Specifically, the present invention relates to a fully unsupervised, machine-learned, cross-validated, and dynamic Bayesian Belief Network model that utilizes clinical parameters for determining a patient-specific probability of transplant glomerulopathy. Kidney failure is a growing problem worldwide, in part related to the increase incidence of diabetes and hypertension. Renal replacement therapy includes dialysis or renal transplantation.

This technology includes a system for automatic artifact-free measurement and visualization of tissue strain by MRI at native resolution. The investigation of regional soft tissue mechanical strain can serve as a unique indicator for different related disorders. For example, measurement of myocardial tissue during contraction can help calculate, track, and assess cardiac stress. Currently, methods such as tagging MRI (tMRI) are used for imaging soft tissue deformation. Despite being well validated, methods such as tMRI suffer from low spatial and temporal resolution.

Local inflammation processes are crucially important in the host defense against pathogens and for successful immunization because proinflammatory cytokines are necessary for initiation and propagation of an immune response. However, normal inflammatory responses are eventually terminated by physiological termination mechanisms, thereby limiting the strength and duration of immune responses, especially to weak antigens. The inventors have shown that adenosine A2a and A3a receptors play a critical role in down-regulation of inflammation in vivo.