Global and local controlson continental margin stratigraphy

Integrated Ocean Drilling Program (IODP) Expedition 317 was devoted to understanding the relative importance of global sea level (eustasy) versus local tectonic and sedimentary processes in controlling continental margin sedimentary cycles. The expedition recovered sediments from the Eocene to recent period, with a particular focus on the sequence stratigraphy of the late Miocene to recent, when global sea level change was dominated by glacioeustasy. Drilling in the Canterbury Basin, on the eastern margin of the South Island of New Zealand, takes advantage of high rates of Neogene sediment supply, which preserves a high-frequency (0.1–0.5 m.y.) record of depositional cyclicity. The Canterbury Basin provides an opportunity to study the complex interactions between processes responsible for the preserved stratigraphic record of sequences because of the proximity of an uplifting mountain chain, the Southern Alps, and strong ocean currents. Currents have locally built large, elongate sediment drifts within the prograding Neogene section. Expedition 317 did not drill into one of these elongate drifts, but currents are inferred to have strongly influenced deposition across the basin, including in locations lacking prominent mounded drifts. Upper Miocene to recent sedimentary sequences were cored in a transect of three sites on the continental shelf (landward to basinward, Sites U1353, U1354, and U1351) and one on the continental slope (Site U1352). The transect provides a stratigraphic record of depositional cycles across the shallow-water environment most directly affected by relative sea level change. Lithologic boundaries, provisionally correlative with seismic sequence boundaries, have been identified in cores from each site and provide insights into the origins of seismically resolvable sequences. This record will be used to estimate the timing and amplitude of global sea level change and to document the sedimentary processes that operate during sequence formation. Sites U1353 and U1354 provide significant, double-cored, high-recovery sections through the Holocene and late Quaternary for high-resolution study of recent glacial cycles in a continental shelf setting. Continental slope Site U1352 represents a complete section from modern slope terrigenous sediment to hard Eocene limestone, with all the associated lithologic, biostratigraphic, physical, geochemical, and microbiological transitions. The site also provides a record of ocean circulation and fronts during the last ~35 m.y. The early Oligocene (~30 Ma) Marshall Paraconformity was the deepest drilling target of Expedition 317 and is hypothesized to represent intensified current erosion or nondeposition associated with the initiation of thermohaline circulation following the separation of Australian and Antarctica. Expedition 317 set a number of scientific ocean drilling records: (1) deepest hole drilled in a single expedition and second deepest hole in the history of scientific ocean drilling (Hole U1352C, 1927 m); (2) deepest hole and second deepest hole drilled by the R/V JOIDES Resolution on a continental shelf (Hole U1351B, 1030 m; Hole U1353B, 614 m); (3) shallowest water depth for a site drilled by the JOIDES Resolution for scientific purposes (Site U1353, 84.7 m water depth); and (4) deepest sample taken by scientific ocean drilling for microbiological studies (1925 m, Site U1352). Expedition 317 supplements previous drilling of sedimentary sequences for sequence stratigraphic and sea level objectives, particularly drilling on the New Jersey margin (Ocean Drilling Program [ODP] Legs 150, 150X, 174A, and 174AX and IODP Expedition 313) and in the Bahamas (ODP Leg 166), but includes an expanded Pliocene section. Completion of at least one transect across a geographically and tectonically distinct siliciclastic margin was the necessary next step in deciphering continental margin stratigraphy. Expedition 317 also complements ODP Leg 181, which focused on drift development in more distal parts of the Eastern New Zealand Oceanic Sedimentary System (ENZOSS).Integrated Ocean Drilling Program Management InternationalPublished2.2. Laboratorio di paleomagnetismorestricte

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Understanding social housing tenants' rent payment behaviour: evidence from Great Britain

The Governments of many Western countries have been increasingly concerned with influencing the behaviour of their citizens. One way that they have done this is by giving them new responsibilities. In the UK, an example of this is 'direct payment' which sees social housing tenants in receipt of income-related housing allowance ('Housing Benefit') assuming responsibility for paying their rent. Drawing on a comprehensive data-set generated by the direct payment pilot evaluation, this paper examines tenants' rent payment behaviour. It draws on a conceptual framework from behavioural science - COM-B - which presents behaviour (B) as a result of the interaction between the capabilities (C) of subjects, the opportunity (O) they have to enact behaviours, and their motivation (M). Tenants' behaviour was influenced by all elements of the model, with it being more than just a consequence of opportunity, and their financial circumstances, specifically, although it was the most important one

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Disruption of Rolandic Gamma-Band Functional Connectivity by Seizures is Associated with Motor Impairments in Children with Epilepsy

Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz) is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits

Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis

In Leishmania species, Protein disulfide isomerase (PDI) - a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-γ and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-γ and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient's serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (∼90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-α, IFN-γ and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL)

Muscle-Specific Adaptations, Impaired Oxidative Capacity and Maintenance of Contractile Function Characterize Diet-Induced Obese Mouse Skeletal Muscle

BACKGROUND:The effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology. PRINCIPAL FINDINGS:Compared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8+/-6.6% and 61.8+/-9.1% of control, respectively; p<0.05) with HFD were detected. These reductions were consistent with measures made using intact extensor digitorum longus and soleus muscles. Compared to controls, no difference in succinate dehydrogenase or citrate synthase enzyme activities were observed between groups in any muscle studied, however, short-chain fatty acyl CoA dehydrogenase (SCHAD) activity was elevated in the HFD soleus, but not tibialis anterior muscles. Despite these morphological and metabolic alterations, no significant difference in peak tetanic force or low-frequency fatigue rates were observed between groups. CONCLUSIONS:These findings indicate that HFD induces early adaptive responses that occur in a muscle-specific pattern, but are insufficient to prevent impairments in oxidative metabolism with continued high-fat feeding. Moreover, the morphological and metabolic changes which occur with 8 weeks of HFD do not significantly impact muscle contractile properties

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts