Arctic sea-ice decline archived by multicentury annual-resolution record from crustose coralline algal proxy

Northern Hemisphere sea ice has been declining sharply over the past decades and 2012 exhibited the lowest Arctic summer sea-ice cover in historic times. Whereas ongoing changes are closely monitored through satellite observations, we have only limited data of past Arctic sea-ice cover derived from short historical records, indirect terrestrial proxies, and low-resolution marine sediment cores. A multicentury time series from extremely long-lived annual increment-forming crustose coralline algal buildups now provides the first high-resolution in situ marine proxy for sea-ice cover. Growth and Mg/Ca ratios of these Arctic-wide occurring calcified algae are sensitive to changes in both temperature and solar radiation. Growth sharply declines with increasing sea-ice blockage of light from the benthic algal habitat. The 646-y multisite record from the Canadian Arctic indicates that during the Little Ice Age, sea ice was extensive but highly variable on subdecadal time scales and coincided with an expansion of ice-dependent Thule/Labrador Inuit sea mammal hunters in the region. The past 150 y instead have been characterized by sea ice exhibiting multidecadal variability with a long-term decline distinctly steeper than at any time since the 14th century

Saturn 5/Voyager load relief study Final report

Load relief control system to improve launch probability of Saturn 5 booster with Voyager payloa

Saturn 5/Voyager load relief study Data base report

Saturn 5/Voyager load relief control syste

Enigmatic deep-water mounds on the Orphan Knoll, Labrador Sea

Deep-sea mounds can have a variety of origins and may provide hard-substrate features in depths that are normally dominated by mud. Orphan Knoll, a 2 km high bedrock horst off northeast Newfoundland, hosts more than 200 mounds, or mound complexes, of unknown composition, in water depths of 1720–2500 m. Most mounds are 10–600 m high, with average mound height 187 m, and 1–3 km wide. The study objective was to characterize the size, shape, orientation, and composition of the enigmatic Orphan Knoll mounds, in order to determine their age and origin. Archival ship-based side-scan sonar, multibeam sonar, airgun, high-resolution sparker and 3.5 kHz acoustic sub-bottom profiling, and newly acquired ship-based multibeam sonar, video transects by remotely operated vehicle (ROV), rock samples, and near-bottom multibeam sonar data were analyzed. Four mounds were studied during two ROV dives. Archival sidescan sonar data show > 200 mounds. Sparker profiles show that the mound crests are covered by condensed stratified Quaternary sediment and airgun seismic data show faults reaching near the seafloor. New multibeam sonar data show mounds are dominantly conical to elliptical in shape, but without preferred orientation or alignment. Remotely operated vehicle (ROV) transects and near-bottom multibeam showed that three mounds were rounded and symmetrically arranged, while a fourth was more asymmetrical, with steep faces on the southwestern and southeastern flanks, where finely bedded to massive sedimentary bedrock outcropped dipping 15–45°SW. Rock samples from the mounds include Eocene calcareous ooze and mid-Miocene bedded pelagic limestone. Thick ferromanganese crusts were found on many surfaces, obscuring possible outcrops from physical sampling. Polymetallic nodules were found on the slope of one mound. Ice-rafted detritus, including igneous and metamorphic rocks and Paleozoic limestone and dolostone, was common in the sediments immediately surrounding the mounds. Quaternary sub-fossil solitary scleractinian corals accumulated over a span of at least 0.18 Ma at the base of one mound. The presence of uplifted condensed Eocene-Miocene rocks on the mounds and faulting in seismic profiles suggest uplift during reactivation of old rift-related faults during the Neogene, with seabed mass wasting creating residual mounds, which were then draped by Quaternary proglacial muds. Sculpting of hemipelagic Quaternary sediment by bottom currents probably contributed to mound morphology

Liquid-Solid Phase Transition of the System with Two particles in a Rectangular Box

We study the statistical properties of two hard spheres in a two dimensional rectangular box. In this system, the relation like Van der Waals equation loop is obtained between the width of the box and the pressure working on side walls. The auto-correlation function of each particle's position is calculated numerically. By this calculation near the critical width, the time at which the correlation become zero gets longer according to the increase of the height of the box. Moreover, fast and slow relaxation processes like $\alpha$ and $\beta$ relaxations observed in supper cooled liquid are observed when the height of the box is sufficiently large. These relaxation processes are discussed with the probability distribution of relative position of two particles.Comment: 6 figure

Modelling Relevance towards Multiple Inclusion Criteria when Ranking Patients

In the medical domain, information retrieval systems can be used for identifying cohorts (i.e. patients) required for clinical studies. However, a challenge faced by such search systems is to retrieve the cohorts whose medical histories cover the inclusion criteria specified in a query, which are often complex and include multiple medical conditions. For example, a query may aim to find patients with both 'lupus nephritis' and 'thrombotic thrombocytopenic purpura'. In a typical best-match retrieval setting, any patient exhibiting all of the inclusion criteria should naturally be ranked higher than a patient that only exhibits a subset, or none, of the criteria. In this work, we extend the two main existing models for ranking patients to take into account the coverage of the inclusion criteria by adapting techniques from recent research into coverage-based diversification. We propose a novel approach for modelling the coverage of the query inclusion criteria within the records of a particular patient, and thereby rank highly those patients whose medical records are likely to cover all of the specified criteria. In particular, our proposed approach estimates the relevance of a patient, based on the mixture of the probability that the patient is retrieved by a patient ranking model for a given query, and the likelihood that the patient's records cover the query criteria. The latter is measured using the relevance towards each of the criteria stated in the query, represented in the form of sub-queries. We thoroughly evaluate our proposed approach using the test collection provided by the TREC 2011 and 2012 Medical Records track. Our results show significant improvements over existing strong baselines

Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure

The initial step in target cell infection by human, and the closely related simian immunodeficiency viruses (HIV and SIV, respectively) occurs with the binding of trimeric envelope glycoproteins (Env), composed of heterodimers of the viral transmembrane glycoprotein (gp41) and surface glycoprotein (gp120) to target T-cells. Knowledge of the molecular structure of trimeric Env on intact viruses is important both for understanding the molecular mechanisms underlying virus-cell interactions and for the design of effective immunogen-based vaccines to combat HIV/AIDS. Previous analyses of intact HIV-1 BaL virions have already resulted in structures of trimeric Env in unliganded and CD4-liganded states at ∼20 Å resolution. Here, we show that the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are closely comparable to that previously determined for HIV-1 BaL, with the V1 and V2 variable loops located at the apex of the spike, close to the contact zone between virus and cell. The location of the V1/V2 loops in trimeric Env was definitively confirmed by structural analysis of HIV-1 R3A virions engineered to express Env with deletion of these loops. Strikingly, in SIV CP-MAC, a CD4-independent strain, trimeric Env is in a constitutively “open” conformation with gp120 trimers splayed out in a conformation similar to that seen for HIV-1 BaL Env when it is complexed with sCD4 and the CD4i antibody 17b. Our findings suggest a structural explanation for the molecular mechanism of CD4-independent viral entry and further establish that cryo-electron tomography can be used to discover distinct, functionally relevant quaternary structures of Env displayed on intact viruses

Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve – especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4high/CD25high/CD45RAhigh ‘regulatory T cells’ and CD8high/CD62Lhigh/CD45RAneg ‘central memory T cells’, have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomized controlled trials

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition

Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus

The class III phosphoinositide 3-kinase (PI3K) Vps34 (also known as PIK3C3 in mammals) produces phosphatidylinositol 3-phosphate [PI(3)P] on both early and late endosome membranes to control membrane dynamics. We used Vps34-deficient cells to delineate whether Vps34 has additional roles in endocytic trafficking. In Vps34−/− mouse embryonic fibroblasts (MEFs), transferrin recycling and EEA1 membrane localization were unaffected despite elevated Rab5-GTP levels. Strikingly, a large increase in Rab7-GTP levels, an accumulation of enlarged late endosomes, and decreased EGFR degradation were observed in Vps34-deficient cells. The hyperactivation of Rab7 in Vps34-deficient cells stemmed from the failure to recruit the Rab7 GTPase-activating protein (GAP) Armus (also known as TBC1D2), which binds to PI(3)P, to late endosomes. Protein–lipid overlay and liposome-binding assays reveal that the putative pleckstrin homology (PH) domain in Armus can directly bind to PI(3)P. Elevated Rab7-GTP led to the failure of intraluminal vesicle (ILV) formation and lysosomal maturation. Rab7 silencing and Armus overexpression alleviated the vacuolization seen in Vps34-deficient cells. Taken together, these results demonstrate that Vps34 has a previously unknown role in regulating Rab7 activity and late endosomal trafficking