Short time evolved wave functions for solving quantum many-body problems

The exact ground state of a strongly interacting quantum many-body system can be obtained by evolving a trial state with finite overlap with the ground state to infinite imaginary time. In this work, we use a newly discovered fourth order positive factorization scheme which requires knowing both the potential and its gradients. We show that the resultaing fourth order wave function alone, without further iterations, gives an excellent description of strongly interacting quantum systems such as liquid 4He, comparable to the best variational results in the literature.Comment: 5 pages, 3 figures, 1 tabl

Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid

Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective dynamic model of the nanoparticle protein corona in a body fluid, namely human plasma. The model predicts the time evolution and equilibrium composition of the corona based on affinities, stoichiometries and rate constants. An application to the interaction of human serum albumin, high density lipoprotein (HDL) and fibrinogen with 70 nm N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles is presented, including novel experimental data for HDL. Conclusions: The simple model presented here can easily be modified to mimic the interaction of the nanoparticle protein corona with a novel biological fluid or compartment once new data will be available, thus opening novel applications in nanotoxicity and nanomedicine

Projecting coral responses to intensifying marine heatwaves under ocean acidification

Over this century, coral reefs will run the gauntlet of climate change, as marine heatwaves (MHWs) become more intense and frequent, and ocean acidification (OA) progresses. However, we still lack a quantitative assessment of how, and to what degree, OA will moderate the responses of corals to MHWs as they intensify throughout this century. Here, we first projected future MHW intensities for tropical regions under three future greenhouse gas emissions scenario (representative concentration pathways, RCP2.6, RCP4.5 and RCP8.5) for the near-term (2021-2040), mid-century (2041-2060) and late-century (2081-2100). We then combined these MHW intensity projections with a global data set of 1,788 experiments to assess coral attribute performance and survival under the three emissions scenarios for the near-term, mid-century and late-century in the presence and absence of OA. Although warming and OA had predominately additive impacts on the coral responses, the contribution of OA in affecting most coral attributes was minor relative to the dominant role of intensifying MHWs. However, the addition of OA led to greater decreases in photosynthesis and survival under intermediate and unrestricted emissions scenario for the mid- and late-century than if intensifying MHWs were considered as the only driver. These results show that role of OA in modulating coral responses to intensifying MHWs depended on the focal coral attribute and extremity of the scenario examined. Specifically, intensifying MHWs and OA will cause increasing instances of coral bleaching and substantial declines in coral productivity, calcification and survival within the next two decades under the low and intermediate emissions scenario. These projections suggest that corals must rapidly adapt or acclimatize to projected ocean conditions to persist, which is far more likely under a low emissions scenario and with increasing efforts to manage reefs to enhance resilience

Factors Limiting the Range Extension of Corals into High-Latitude Reef Regions

Reef-building corals show a marked decrease in total species richness from the tropics to high latitude regions. Several hypotheses have been proposed to account for this pattern in the context of abiotic and biotic factors, including temperature thresholds, light limitation, aragonite saturation, nutrient or sediment loads, larval dispersal constraints, competition with macro-algae or other invertebrates, and availability of suitable settlement cues or micro-algal symbionts. Surprisingly, there is a paucity of data supporting several of these hypotheses. Given the immense pressures faced by corals in the Anthropocene, it is critical to understand the factors limiting their distribution in order to predict potential range expansions and the role that high latitude reefs can play as refuges from climate change. This review examines these factors and outlines critical research areas to address knowledge gaps in our understanding of light/temperature interactions, coral-Symbiodiniaceae associations, settlement cues, and competition in high latitude reefs.</jats:p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. KCa3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective KCa3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion. Following 7 days of culture with TGFβ1, 41 IPF- and fibrosis-associated genes were significantly upregulated. Immunohistochemical staining demonstrated increased expression of ECM proteins and fibroblast-specific protein after TGFβ1-stimulation. Collagen secretion was significantly increased following TGFβ1-stimulation. These pro-fibrotic responses were attenuated by senicapoc, but not by dexamethasone. This 7 day ex vivo model of human lung fibrogenesis recapitulates pro-fibrotic events evident in IPF and is sensitive to KCa3.1 channel inhibition. By maintaining the complex cell-cell and cell-matrix interactions of human tissue, and removing cross-species heterogeneity, this model may better predict drug efficacy in clinical trials and accelerate drug development in IPF. KCa3.1 channels are a promising target for the treatment of IPF.This work was supported by The Dunhill Medical Trust, project grant R270/1112, the MRC, project grant MR/K018213/1, and The British Lung Foundation, grant PPRG15-8. The work was also supported in part by the National Institute for Health Research Leicester Respiratory Biomedical Research Unit

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN