94 research outputs found

    Evolutionary fates within a microbial population highlight an essential role for protein folding during natural selection

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    Physicochemical properties of molecules can be linked directly to evolutionary fates of a population in a quantitative and predictive manner.Reversible- and irreversible-folding pathways must be accounted for to accurately determine in vitro kinetic parameters (KM and kcat) at temperatures or conditions in which a significant fraction of free enzyme is unfolded.In vivo population dynamics can be reproduced using in vitro physicochemical measurements within a model that imposes an activity threshold above which there is no added fitness benefit

    Teleportation Systems Toward a Quantum Internet

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    Quantum teleportation is essential for many quantum information technologies, including long-distance quantum networks. Using fiber-coupled devices, including state-of-the-art low-noise superconducting nanowire single-photon detectors and off-the-shelf optics, we achieve conditional quantum teleportation of time-bin qubits at the telecommunication wavelength of 1536.5 nm. We measure teleportation fidelities of ≥90% that are consistent with an analytical model of our system, which includes realistic imperfections. To demonstrate the compatibility of our setup with deployed quantum networks, we teleport qubits over 22 km of single-mode fiber while transmitting qubits over an additional 22 km of fiber. Our systems, which are compatible with emerging solid-state quantum devices, provide a realistic foundation for a high-fidelity quantum Internet with practical devices

    Teleportation Systems Toward a Quantum Internet

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    Quantum teleportation is essential for many quantum information technologies, including long-distance quantum networks. Using fiber-coupled devices, including state-of-the-art low-noise superconducting nanowire single-photon detectors and off-the-shelf optics, we achieve conditional quantum teleportation of time-bin qubits at the telecommunication wavelength of 1536.5 nm. We measure teleportation fidelities of ≥90% that are consistent with an analytical model of our system, which includes realistic imperfections. To demonstrate the compatibility of our setup with deployed quantum networks, we teleport qubits over 22 km of single-mode fiber while transmitting qubits over an additional 22 km of fiber. Our systems, which are compatible with emerging solid-state quantum devices, provide a realistic foundation for a high-fidelity quantum Internet with practical devices

    The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

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    Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

    Picosecond Synchronization of Photon Pairs through a Fiber Link between Fermilab and Argonne National Laboratories

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    We demonstrate a three-node quantum network for C-band photon pairs using 2 pairs of 59 km of deployed fiber between Fermi and Argonne National Laboratories. The C-band pairs are directed to nodes using a standard telecommunication switch and synchronized to picosecond-scale timing resolution using a coexisting O- or L-band optical clock distribution system. We measure a reduction of coincidence-to-accidental ratio (CAR) of the C-band pairs from 51 ±\pm 2 to 5.3 ±\pm 0.4 due to Raman scattering of the O-band clock pulses. Despite this reduction, the CAR is nevertheless suitable for quantum networks

    Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

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    Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

    Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

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    Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo–derived senescence signature (SenSig) using a foreign body response–driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type–specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34–CSF1R–TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.</p

    Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

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    Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo–derived senescence signature (SenSig) using a foreign body response–driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type–specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34–CSF1R–TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.</p

    Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

    Get PDF
    Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo–derived senescence signature (SenSig) using a foreign body response–driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type–specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34–CSF1R–TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.</p

    A dense mini-Neptune orbiting the bright young star HD 18599

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    © 2022 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stac2845Very little is known about the young planet population because the detection of small planets orbiting young stars is obscured by the effects of stellar activity and fast rotation which mask planets within radial velocity and transit data sets. The few planets that have been discovered in young clusters generally orbit stars too faint for any detailed follow-up analysis. Here we present the characterization of a new mini-Neptune planet orbiting the bright (V=9) and nearby K2 dwarf star, HD 18599. The planet candidate was originally detected in TESS light curves from Sectors 2, 3, 29, and 30, with an orbital period of 4.138~days. We then used HARPS and FEROS radial velocities, to find the companion mass to be 25.5±\pm4.6~M_\oplus. When we combine this with the measured radius from TESS, of 2.70±\pm0.05~R_\oplus, we find a high planetary density of 7.1±\pm1.4~g cm3^{-3}. The planet exists on the edge of the Neptune Desert and is the first young planet (300 Myr) of its type to inhabit this region. Structure models argue for a bulk composition to consist of 23% H2_2O and 77% Rock and Iron. Future follow-up with large ground- and space-based telescopes can enable us to begin to understand in detail the characteristics of young Neptunes in the galaxy.Peer reviewe
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