40 research outputs found

    Towards a large-scale quantum simulator on diamond surface at room temperature

    Full text link
    Strongly-correlated quantum many-body systems exhibits a variety of exotic phases with long-range quantum correlations, such as spin liquids and supersolids. Despite the rapid increase in computational power of modern computers, the numerical simulation of these complex systems becomes intractable even for a few dozens of particles. Feynman's idea of quantum simulators offers an innovative way to bypass this computational barrier. However, the proposed realizations of such devices either require very low temperatures (ultracold gases in optical lattices, trapped ions, superconducting devices) and considerable technological effort, or are extremely hard to scale in practice (NMR, linear optics). In this work, we propose a new architecture for a scalable quantum simulator that can operate at room temperature. It consists of strongly-interacting nuclear spins attached to the diamond surface by its direct chemical treatment, or by means of a functionalized graphene sheet. The initialization, control and read-out of this quantum simulator can be accomplished with nitrogen-vacancy centers implanted in diamond. The system can be engineered to simulate a wide variety of interesting strongly-correlated models with long-range dipole-dipole interactions. Due to the superior coherence time of nuclear spins and nitrogen-vacancy centers in diamond, our proposal offers new opportunities towards large-scale quantum simulation at room temperatures

    Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

    Get PDF
    A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies

    Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

    Get PDF
    BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

    Pan-cancer analysis of whole genomes

    Get PDF
    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    Harmful Elements in Estuarine and Coastal Systems

    Get PDF
    Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities

    Effect of decompressive laparotomy on organ function in patients with abdominal compartment syndrome: a systematic review and meta-analysis

    Get PDF
    Abstract Background Decompressive laparotomy has been advised as potential treatment for abdominal compartment syndrome (ACS) when medical management fails; yet, the effect on parameters of organ function differs markedly in the published literature. In this study, we sought to investigate the effect of decompressive laparotomy on intra-abdominal pressure and organ function in critically ill adult and pediatric patients with ACS, specifically focusing on hemodynamic, respiratory, and kidney function and outcome. Methods A systematic review and meta-analysis of the literature was performed. Articles reporting data on intra-abdominal pressure (IAP), hemodynamic (mean arterial pressures [MAP], central venous pressure [CVP], cardiac index [CI], heart rate [HR], systemic vascular resistance index [SVRI] and/or pulmonary capillary wedge pressure [PCWP]), respiratory (positive end-expiratory pressure [PEEP], peak inspiratory pressure [PIP] and/or ratio of partial pressure arterial oxygen and fraction of inspired oxygen [P/F ratio]), and/or urinary output (UO) following decompressive laparotomy were analyzed. Results A total of 15 articles were included; 3 included children only (aged 18 years or younger). Of the 286 patients who were included, 49.7% had primary ACS. The baseline mean IAP in adults decreased with an average of 18.2 ± 6.5 mmHg following decompression, from 31.7 ± 6.4 mmHg to 13.5 ± 3.0 mmHg. There was a decrease in HR (12.2 ± 9.5 beats/min; p = 0.04), CVP (4.6 ± 2.3 mmHg; p = 0.022), PCWP (5.8 ± 2.3 mmHg; p = 0.029), and PIP (10.1 ± 3.9 cmH2O; p < 0.001) and a mean increase in P/F ratio (70.4 ± 49.4; p < 0.001) and UO (95.3 ± 105.3 ml/h; p < 0.001). In children, there was a significant increase in MAP (20.0 ± 2.3 mmHg; p = 0.006), P/F ratio (238.2; p < 0.001), and UO (2.88 ± 0.64 ml/kg/h; p < 0.001) and a decrease in CVP (7 mmHg; p = 0.016) and PIP (9.9 cmH2O; p = 0.002). The overall mortality rate was 49.7% in adults and 60.8% in children following decompressive laparotomy. Conclusions Decompressive laparotomy resulted in a significantly lower IAP and had beneficial effects on hemodynamic, respiratory, and renal parameters. Mortality after decompressive laparotomy remains high in both adults and children
    corecore