365 research outputs found

    Comparison theorems for Gromov–Witten invariants of smooth pairs and of degenerations

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    We consider four approaches to relative Gromov-Witten theory and Gromov-Witten theory of degenerations: Jun Li's original approach, Bumsig Kim's logarithmic expansions, Abramovich-Fantechi's orbifold expansions, and a logarithmic theory without expansions due to Gross-Siebert and Abramovich-Chen. We exhibit morphisms relating these moduli spaces and prove that their virtual fundamental classes are compatible by pushforward through these morphisms. This implies that the Gromov-Witten invariants associated to all four of these theories are identical.Comment: 42 pages. Some minor changes. To appear in Annales de l'Institut Fourie

    Exebacase for Staphylococcus aureus bloodstream infection and endocarditis

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    BACKGROUND: Novel therapeutic approaches are critically needed for Staphylococcus aureus bloodstream infections (BSI), particularly for methicillin-resistant S. aureus (MRSA). Exebacase, a first-in-class antistaphylococcal lysin, is a direct lytic agent that is rapidly bacteriolytic, eradicates biofilms, and synergizes with antibiotics. METHODS: In this superiority-design study, we randomly assigned 121 patients with S. aureus BSI/endocarditis to receive a single dose of exebacase or placebo. All patients received standard-of-care antibiotics. The primary efficacy endpoint was clinical outcome (responder rate) at Day 14. RESULTS: Clinical responder rates at Day 14 were 70.4% and 60.0% in the exebacase + antibiotics and antibiotics alone groups, respectively (difference=10.4, 90% CI [-6.3, 27.2], p-value=0.31), and were 42.8 percentage points higher in the pre-specified exploratory MRSA subgroup (74.1% vs. 31.3%, difference=42.8, 90% CI [14.3, 71.4], ad hoc p value=0.01). Rates of adverse events (AEs) were similar in both groups. No AEs of hypersensitivity to exebacase were reported. Thirty-day all-cause mortality rates were 9.7% and 12.8% in the exebacase + antibiotics and antibiotics alone groups, respectively, with a notable difference in MRSA (3.7% vs. 25.0%, difference= -21.3, 90% CI [-45.1, 2.5], ad hoc p-value=0.06). Among MRSA patients in the United States, median length-of-stay was 4-days shorter and 30-day hospital readmission rates were 48 percentage points lower in the exebacase-treated group compared with antibiotics alone. CONCLUSIONS: This study establishes proof-of-concept for exebacase and direct lytic agents as potential therapeutics and supports conduct of a confirmatory study focused on exebacase to treat MRSA BSI

    Thermoelectric properties of lead chalcogenide core-shell nanostructures

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    We present the full thermoelectric characterization of nanostructured bulk PbTe and PbTe-PbSe samples fabricated from colloidal core-shell nanoparticles followed by spark plasma sintering. An unusually large thermopower is found in both materials, and the possibility of energy filtering as opposed to grain boundary scattering as an explanation is discussed. A decreased Debye temperature and an increased molar specific heat are in accordance with recent predictions for nanostructured materials. On the basis of these results we propose suitable core-shell material combinations for future thermoelectric materials of large electric conductivities in combination with an increased thermopower by energy filtering.Comment: 12 pages, 8 figure

    The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

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    Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology
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