1,770 research outputs found
Real time evolution of Anderson impurity models via tensor network influence functionals
In this work we present and analyze two tensor network-based influence
functional approaches for simulating the real-time dynamics of quantum impurity
models such as the Anderson model. Via comparison with recent numerically exact
simulations, we show that such methods accurately capture the long-time
non-equilibrium quench dynamics. The two parameters that must be controlled in
these tensor network influence functional approaches are a time discretization
(Trotter) error and a bond dimension (tensor network truncation) error. We show
that the actual numerical uncertainties are controlled by an intricate
interplay of these two approximations which we demonstrate in different
regimes. Our work opens the door to using these tensor network influence
functional methods as general impurity solvers
Beta cell death by cell-free DNA and outcome after clinical islet transplantation
Background: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss, and was recently validated in new-onset type 1 diabetes and in islet transplant patients.
Methods: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes.
Results: A distinctive peak of cfDNA was observed 1hr after transplantation in 31/37 (83.8%) of subjects. The presence and magnitude of this signal did not correlate with transplant outcome. The 1hr signal represents dead beta cells carried over into the recipient after islet isolation and culture, combined with acute cell death post infusion. Beta cell cfDNA was also detected 24hrs post-transplant (8/37 subjects, 21.6%). This signal was associated with higher 1-month insulin requirements (p=0.04), lower 1-month stimulated C-peptide levels (p=0.01) and overall worse 3-month engraftment, by insulin independence (ROC:AUC=0.70, p=0.03) and Beta 2 score (ROC:AUC=0.77, p=0.006).
Conclusions: cfDNA-based estimation of beta cell death 24hrs after islet allotransplantation correlates with clinical outcome and could predict early engraftment.B.G.-L. is supported through the Alberta Innovates :Health Solutions (AIHS) Clinician Fellowship and through the CNTRP. A.P. is supported through AIHS Postgraduate Fellowship and CNTRP. A.M.J.S. is supported through AIHS, and holds a Canada Research Chair in Transplantation Surgery and Regenerative Medicine funded through the Government of Canada. A.M.J.S. is also funded by AIHS Collaborative Research and Innovation Opportunity Team Award and the Diabetes Research Institute Foundation of Canada (DRIFCan). Supported by grants from the Juvenile Diabetes Research Foundation (JDRF) (3-SRA-2014-38-Q-R, to Y.D. and A.M.J.S.), National Institute of Health (NIH) (HIRN grant UC4 DK104216, to Y.D.), DON foundation (Stichting Diabetes Onderzoek Nederland) (to Y.D), the European Union (ELASTISLET project, to Y.D.) and the Kahn foundation (to Y.D., R.S., and B.G.). Supported in part by a grant from The United States Agency for International Development (USAID) American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University sequencing core facilit
ORMIR_XCT: A Python package for high resolution peripheral quantitative computed tomography image processing
High resolution peripheral quantitative computed tomography (HR-pQCT) is an
imaging technique capable of imaging trabecular bone in-vivo. HR-pQCT has a
wide range of applications, primarily focused on bone to improve our
understanding of musculoskeletal diseases, assess epidemiological associations,
and evaluate the effects of pharmaceutical interventions. Processing HR-pQCT
images has largely been supported using the scanner manufacturer scripting
language (Image Processing Language, IPL, Scanco Medical). However, by
expanding image processing workflows outside of the scanner manufacturer
software environment, users have the flexibility to apply more advanced
mathematical techniques and leverage modern software packages to improve image
processing. The ORMIR_XCT Python package was developed to reimplement some
existing IPL workflows and provide an open and reproducible package allowing
for the development of advanced HR-pQCT data processing workflows
Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer
PurposeAmplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that BET bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven NSCLC with BET inhibition.Experimental DesignWe performed functional assays to evaluate the effects of JQ1 in genetically defined NSCLC cells lines harboring KRAS and/or LKB1 mutations. Furthermore, we evaluated JQ1 in transgenic mouse lung cancer models expressing mutant kras or concurrent mutant kras and lkb1. Effects of bromodomain inhibition on transcriptional pathways were explored and validated by expression analysis.ResultsWhile JQ1 is broadly active in NSCLC cells, activity of JQ1 in mutant KRAS NSCLC is abrogated by concurrent alteration or genetic knock-down of LKB1. In sensitive NSCLC models, JQ1 treatment results in the coordinate downregulation of the MYC-dependent transcriptional program. We found that JQ1 treatment produces significant tumor regression in mutant kras mice. As predicted, tumors from mutant kras and lkb1 mice did not respond to JQ1.ConclusionBromodomain inhibition comprises a promising therapeutic strategy for KRAS mutant NSCLC with wild-type LKB1, via inhibition of MYC function. Clinical studies of BET bromodomain inhibitors in aggressive NSCLC will be actively pursued
Detection of Interstellar HCNC and an Investigation of Isocyanopolyyne Chemistry under TMC-1 Conditions
We report an astronomical detection of HCNC for the first time in the
interstellar medium with the Green Bank Telescope toward the TMC-1 molecular
cloud with a minimum significance of . The total column density
and excitation temperature of HCNC are determined to be
cm and K,
respectively, using the MCMC analysis. In addition to HCNC, HCCNC is
distinctly detected whereas no clear detection of HCNC is made. We propose
that the dissociative recombination of the protonated cyanopolyyne,
HCNH, and the protonated isocyanopolyyne, HCNCH, are the main
formation mechanisms for HCNC while its destruction is dominated by
reactions with simple ions and atomic carbon. With the proposed chemical
networks, the observed abundances of HCNC and HCCNC are reproduced
satisfactorily.Comment: Accepted in the Astrophysical Journal Letter
Detection of Two Interstellar Polycyclic Aromatic Hydrocarbons via Spectral Matched Filtering
Ubiquitous unidentified infrared emission bands are seen in many astronomical
sources. Although these bands are widely, if not unanimously, attributed to the
collective emission from polycyclic aromatic hydrocarbons, no single species
from this class has been detected in space. We present the discovery of two -CN
functionalized polycyclic aromatic hydrocarbons, 1- and 2-cyanonaphthalene, in
the interstellar medium aided by spectral matched filtering. Using radio
observations with the Green Bank Telescope, we observe both bi-cyclic ring
molecules in the molecular cloud TMC-1. We discuss potential in situ gas-phase
formation pathways from smaller organic precursor molecules
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