The Kuiper Belt and Other Debris Disks

We discuss the current knowledge of the Solar system, focusing on bodies in the outer regions, on the information they provide concerning Solar system formation, and on the possible relationships that may exist between our system and the debris disks of other stars. Beyond the domains of the Terrestrial and giant planets, the comets in the Kuiper belt and the Oort cloud preserve some of our most pristine materials. The Kuiper belt, in particular, is a collisional dust source and a scientific bridge to the dusty "debris disks" observed around many nearby main-sequence stars. Study of the Solar system provides a level of detail that we cannot discern in the distant disks while observations of the disks may help to set the Solar system in proper context.Comment: 50 pages, 25 Figures. To appear in conference proceedings book "Astrophysics in the Next Decade

Protic plastic crystal/PVDF composite membranes for Proton Exchange Membrane Fuel Cells under non-humidified conditions

Composite membranes based on the protic plastic crystal N,N-dimethylethylenediammonium triflate [DMEDAH][TFO] and poly(vinylidene fluoride) (PVDF) nanofibers have been developed for proton exchange membrane fuel cells (PEMFCs) under non-humidified conditions. The effect of addition of 5 mol% triflic acid or 5 mol% of the base N,N-dimethylethylenediamine on the thermal and transport properties of the material is discussed. The acid-doped plastic crystal reports more than double the ionic conductivity of the pure plastic crystal. The effects of doping the plastic crystal and the composites, with acid or base, on the ionic conductivity and fuel cell performance are reported. Composite membranes based on PVDF nanofibers and [DMEDAH][TFO] were tested in a single PEMFC. The results show the potential of these composite membranes to be used as electrolytes in this electrochemical application without external humidification.The authors acknowledge funding from the Australian Research Council (ARC) through its Centre of Excellence program, through the Australian Laureate Fellowship scheme for D.R.M and M.F, and Discovery Project DP140101535. In addition, M.D., A.O. and I.O acknowledge Spanish Ministry of Economy and Competitiveness for the project CTQ2015-66078-R (MINECO/FEDER, UE). M. D. is grateful to the Spanish Ministry of Education, Culture and Sport for the FPU2012-3721

Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Alveolar macrophage apoptosis-associated bacterial killing helps prevent murine pneumonia

RATIONALE: Antimicrobial resistance challenges therapy of pneumonia. Enhancing macrophage microbicidal responses would combat this problem but is limited by our understanding of how alveolar macrophages (AM) kill bacteria. OBJECTIVES: To define the role and mechanism of AM apoptosis-associated bacterial killing in the lung. METHODS: We generated a unique CD68.hMcl-1 transgenic mouse with macrophage-specific over-expression of the human anti-apoptotic Mcl-1 protein, a factor upregulated in AM from patients at increased risk of community-acquired pneumonia, to address the requirement for apoptosis-associated killing. MEASUREMENTS AND MAIN RESULTS: Wild-type and transgenic macrophages demonstrated comparable ingestion and initial phagolysosomal killing of bacteria. Continued ingestion (for > 12 h) overwhelmed initial killing and a second late-phase microbicidal response killed viable bacteria in wild-type macrophages, but this response was blunted in CD68.hMcl-1 transgenic macrophages. The late-phase of bacterial killing required both caspase-induced generation of mitochondrial reactive oxygen species (mROS) and nitric oxide (NO), whose peak generation coincided with the late-phase of killing. The CD68.hMcl-1 transgene prevented mROS but not NO generation. Apoptosis-associated killing enhanced pulmonary clearance of Streptococcus pneumoniae and Haemophilus influenzae in wild-type but not CD68.hMcl-1 transgenic mice. Bacterial clearance was enhanced in vivo in CD68.hMcl-1 transgenic mice by reconstitution of apoptosis with BH3 mimetics or clodronate-encapsulated liposomes. Apoptosis-associated killing was not activated during Staphylococcus aureus lung infection. CONCLUSIONS: Mcl-1 upregulation prevents macrophage apoptosis-associated killing and establishes that apoptosis-associated killing is required to allow AM to clear ingested bacteria. Engagement of macrophage apoptosis should be investigated as a novel host-based antimicrobial strategy

Genomic classification and prognosis in acute myeloid leukemia

BACKGROUND: Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice. METHODS: We enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes. RESULTS: We identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNAsplicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2R172 mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co-occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials. CONCLUSIONS: The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification

In vitro biosynthesis of the human cell surface receptor for transferrin

AbstractThe human cell surface receptor for transferrin is a transmembrane phosphoglycoprotein composed of two disulphide linked and apparently identical subunits of Mr 90 000. Using an affinity purified, polyclonal rabbit antibody, we have studied the in vitro biosynthesis of this receptor. The primary translation product, synthesised in a rabbit reticulocyte lysate programmed with human placental RNA, appears to have the same Mr (78 000) as the unglycosylated molecule immunoprecipitated from tunicamycin-treated cells. In the presence of a dog pancreatic microsomal system the cell free system accurately reproduces the glycosylation and the asymmetric transmembrane integratio

What is really behavioral in behavioral health policy? And does it work?

Across health systems, there is increasing interest in applying behavioral economics insights to health policy challenges. Policy decision makers have recently discussed a range of diverse health policy interventions that are commonly brought together under a behavioral umbrella. These include randomized controlled trials, comparison portals, information labels, financial incentives, sin taxes, and nudges. A taxonomy is proposed to classify such behavioral interventions. In the context of risky health behavior, each cluster of policies is then scrutinized under two respects: (i) What are its genuinely behavioral insights? (ii) What evidence exists on its practical effectiveness? The discussion highlights the main challenges in drawing a clear mapping between how much each policy is behaviorally inspired and its effectiveness