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The first eigenvalue of the Laplacian on a surface can be viewed as a functional on the space of Riemannian metrics of a given area. Critical points of this functional are called extremal metrics. The only known extremal metrics are a round sphere, a standard projective plane, a Clifford torus and an equilateral torus. We construct an extremal metric on a Klein bottle. It is a metric of revolution, admitting a minimal isometric embedding into a 4-sphere by the first eigenfunctions. Also, this Klein bottle is a bipolar surface for the Lawson's {3,1}-torus. We conjecture that an extremal metric for the first eigenvalue on a Klein bottle is unique, and hence it provides a sharp upper bound for the first eigenvalue on a Klein bottle of a given area. We present numerical evidence and prove the first results towards this conjecture. 20 pages; minor corrections

Communities are social entities whose actors share common needs, interests, or practices: they constitute the basic units of social experience. With regard to communities, social capital captures the structural, relational and cognitive aspects of the relationships among their members. Social capital is defined as a set of properties of a social entity (e.g. norms, level of trust, and intensive social networking) which enables joint activities and cooperation for mutual benefit. It can be understood as the glue which holds communities together. On this panel we will discuss whether and how information technology can strengthen communities by fostering social capital.

An X-ray flaring source was found near the galaxy NGC 4697. Two flares were seen, separated by four years. The flux increased by a factor of 90 on a timescale of about one minute. Both flares were very brief. There is no optical counterpart at the position of the flares, but if the source was at the distance of NGC 4697, the luminosities were 10^39 erg/s. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar such flares. We found two flaring sources in globular clusters or ultra-compact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 x 10^40 erg/s, while the other flared five times to 10^40 erg/s. All of the flare rise times were <1 minute, and they then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron star or black hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft gamma repeaters that have repetitive flares of similar luminosities. Published in the Oct 20 2016 issue of Nature

We consider some of the earlier work and some recent results on diet and cancer (since the 2007 WCRF/AICR report on Diet and Cancer), discuss challenges facing nutritional cancer epidemiology, and consider the field from the perspective of the need to apply what we know in cancer control. We highlight 2 current difficulties; first, we are uncertain on the stage of carcinogenesis on which many nutritional factors act, second, we often do not know what dose of a nutritional factor is needed to achieve its expected protective effect in humans. Part of the difficulty is the measurement error associated with food frequency questionnaires. Calibration studies (as in the European Prospective Investigation on diet and Cancer) have helped to reduce this, and pooled studies have helped to clarify associations. However, there is too little work on new biomarkers of nutrition; with the new techniques available (especially proteomics, and metabolomics) it should be possible to identify more and better biomarkers that could be used in repeated blood or urine samples and give very good information on diet. In cancer control we need to determine how to reduce the prevalence of obesity and increase physical activity in populations, not whether they are causal factors. This could be achieved by community-based interventions linked to some of the new cohort studies being initiated. We conclude we have reached the stage in nutritional cancer epidemiology where we need to concentrate more on applying the lessons we have learnt, than in seeking new aetiological associations.

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P&gt; 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS: The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES: Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02010073.

This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A. P. Sloan Foundation; the Bundesministerium für Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, United Kingdom; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; the Australian Research Council (ARC); and the EU community Marie Curie Fellowship Contract No. 302103. This work was also supported by the Shrum Foundation, the Weizman Institute of Science and the Israel Science Foundation. Results of a study of the substructure of the highest transverse momentum (pT) jets observed by the CDF Collaboration are presented. Events containing at least one jet with pT>400 GeV/c in a sample corresponding to an integrated luminosity of 5.95 fb−1, collected in 1.96 TeV proton-antiproton collisions at the Fermilab Tevatron collider, are selected. A study of the jet mass, angularity, and planar-flow distributions is presented, and the measurements are compared with predictions of perturbative quantum chromodynamics. A search for boosted top-quark production is also described, leading to a 95% confidence level upper limit of 38 fb on the production cross section of top quarks with pT>400 GeV/c. Peer Reviewed et al.

ABSTRACTHuman cytomegalovirus (HCMV) infection causes severe illness in newborns and immunocompromised patients. Since treatment options are limited there is an unmet need for new therapeutic approaches. Defensins are cationic peptides, produced by various human tissues, which serve as antimicrobial effectors of the immune system. Furthermore, some defensins are proteolytically cleaved, resulting in the generation of smaller fragments with increased activity. Together, this led us to hypothesize that defensin-derived peptides are natural human inhibitors of virus infection with low toxicity. We screened several human defensin HNP4- and HD5-derived peptides and found HD5(1-9) to be antiviral without toxicity at high concentrations. HD5(1-9) inhibited HCMV cellular attachment and thereby entry and was active against primary as well as a multiresistant HCMV isolate. Moreover, cysteine and arginine residues were identified to mediate the antiviral activity of HD5(1-9). Altogether, defensin-derived peptides, in particular HD5(1-9), qualify as promising candidates for further development as a novel class of HCMV entry inhibitors.AUTHOR SUMMARYDefensins are peptides produced by various human organs which take part in the natural defense against pathogens. Recently, it has been shown that defensins are further cleaved to smaller peptides that have high intrinsic anti-microbial activity. We here challenged the hypothesis that these peptides might have antiviral activity, and due to their presumably natural occurrence, low toxicity. Indeed, we found one peptide fragment that turned out to block the attachment of the human cytomegalovirus (HCMV) to cells. Furthermore, this peptide did not show toxicity in various cellular assays or impede the embryonic development of zebrafish at the concentrations used to block HCMV. This is important, since HCMV is one of the most important viral congenital infections. Altogether, our results hold promise for the development of a new class of antivirals against HCMV.