Harvard University

Methods of volumetric imaging of a three-dimensional matrix of nucleic acids within a cell is provided. An automated apparatus for sequencing and volumetric imaging of a three-dimensional matrix of nucleic acids is provided.

Systems, devices, and techniques for performing wavelength division multiplexing or demultiplexing using one or more metamaterials in an optical communications systems are described. An optical device may be configured to shift one or more phase profiles of an optical signal using one or more stages of metamaterials to multiplex or demultiplex wavelengths of optical signals. The optical device may be an example of a stacked design with two or more stages of metamaterials stacked on top of one another. The optical device may be an example of a folded design that reflects optical signals between different stages of metamaterials.

Forced expression of a handful of transcription factors (TFs) can induce conversions between cell identities; however, the extent to which TFs can alter cell identity has not been systematically assessed. Here, we assembled a human TFome, a comprehensive expression library of 1,578 human TF clones with full coverage of the major TF families. By systematically screening the human TFome, we identified 77 individual TFs that induce loss of human-induced-pluripotent- stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression profiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.

The invention concerns a method for identifying cognate pairs of a ligand species and a receptor species, comprising co-compartmentalising ligand species and receptor species to form a set of microreactors, each microreactor comprising at least one ligand species and preferably at least one receptor species; assaying the recognition between ligands and receptors in each microreactor and based on this assay, classifying each microreactor as positive when at least one ligand species and at least one receptor species in the microreactor recognize one with the other or negative when no ligand species and no receptor species recognize in the microreactor; identifying ligand species and receptor species contained in each positive microreactor; establishing a subset of positive microreactors containing the same receptor species; determining the probability that in a given subset of positive microreactors containing the same receptor species, the ligand species recognizing the receptor species corresponds to the most frequent co-compartmentalized ligand species; and if the determined probability is greater than a predetermined threshold, identifying as a cognate pair the receptor species and the most frequent co-compartmentalized ligand species.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

Provided are lincosamide compounds for the treatment of infectious diseases. The lincosamides described herein are modified at the amino acid (southern) region. The lincosamides may have further modification at the C-1 and C-7 positions of the aminooctose (northern) region, thus distinguishing them from lincomycin and clindamycin. Also provided are methods for preparing the lincosamide compounds, pharmaceutical compositions comprising the lincosamide compounds, and methods of treating infectious diseases using the disclosed lincosamide compounds.

Methods, apparatus, systems, and methods are described that relate to microneedle-assisted aptamer-based electrochemical sensing for label-free, continuous real-time monitoring of biomarkers in a biofluid. One example device for electrochemical monitoring of one or more analytes in a biofluid includes a substrate and at least two microneedles coupled to the substrate. Each microneedle in the at least two microneedles includes a protruded needle structure and an electrode probe structure. The electrode probe structure of a first microneedle in the at least two microneedles includes an aptamer sequence which is specific for a first analyte and the electrode probe structure of the first microneedle is operable as a working electrode for detection of the first analyte using a first electrochemical detection technique.

The present disclosure provides an optical component, which may be a metasurface grating, including (a) a substrate; and (b) an array of subwavelength-spaced phase-shifting elements, which are tessellated on the substrate to produce, when illuminated with a polarized incident light, a diffracted light beam with a distinct polarization state for each of a finite number of diffraction orders, wherein the finite number is 2 or more.

A device includes a grouping of N qubits, where N is equal to two or more, and a coherent light source configured to, given selected values for a set of parameters of at least a first and a second laser pulse, the parameters selected from a relative phase shift, a laser frequency, a laser intensity, and a pulse duration: apply at least the first and second laser pulses to all qubits within the grouping of N qubits, thereby coupling a non-interacting quantum state |1〉 to an interacting excited state |r〉, such that each qubit that begins in quantum state |1〉 returns to the state |1〉 upon completion of the at least first and second laser pulses, and such that qubits in the grouping are mutually blockaded.

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