Convergence of time averages of weak solutions of the three-dimensional Navier-Stokes equations

Using the concept of stationary statistical solution, which generalizes the notion of invariant measure, it is proved that, in a suitable sense, time averages of almost every Leray-Hopf weak solution of the three-dimensional incompressible Navier-Stokes equations converge as the averaging time goes to infinity. This system of equations is not known to be globally well-posed, and the above result answers a long-standing problem, extending to this system a classical result from ergodic theory. It is also showed that, from a measure-theoretic point of view, the stationary statistical solution obtained from a generalized limit of time averages is independent of the choice of the generalized limit. Finally, any Borel subset of the phase space with positive measure with respect to a stationary statistical solution is such that for almost all initial conditions in that Borel set and for at least one Leray-Hopf weak solution starting with that initial condition, the corresponding orbit is recurrent to that Borel subset and its mean sojourn time within that Borel subset is strictly positive.Comment: Version 2: fixed some typos; added some references; and expanded some sentences and some remarks for the sake of clarit

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1

Background Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs. Methods ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis. Results A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA. Conclusions The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing

Cerâmica romana importada na Foz do Douro : uma escavação arqueológica no Castelo de Gaia (V. N. Gaia, Norte de Portugal)

A colina do Castelo de Gaia é um dos locais mais emblemáticos da ocupação humanana foz do rio Douro. Numa das intervenções arqueológicas ali realizadas, em 2008, motivada pelanecessidade de avaliação prévia de um projeto imobiliário, encontraram-se restos de estruturasda época romana e signicativo espólio cerâmico.Observaram-se as cerâmicas de importação procedentes desta intervenção a m de analisar acirculação e consumo de recipientes em diferentes momentos da ocupação romana na região. Nasproduções mais antigas destacam-se formas do séc. I a.C., como ânforas vinárias provenientes dazona campana. Muito signicativas são também as produções tardo-antigas, representadas porânforas orientais, a par de sigillata e cerâmicas comuns.The hill known as Castelo de Gaia is one of the main places of ancient human occupationat Douros river mouth. An archaeological excavation that occurred there in 2008, due toa previous archaeological evaluation of a building project, led to the discovery of Roman ruinsand relevant ceramic nds.is paper focuses the imported wares set, providing data to further analyse on certain vesselscirculation and consumption in dierent moments of Roman presence in the region. Amongstthe most ancient wares there are types of the 1st century BC, like Campanian amphorae used forwine trade. Several Late-Antique productions were also identied, like Oriental amphorae, as wellas LRC ne wares and other imported table ceramic

Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films

The properties of water at the nanoscale are crucial in many areas of biology, but the confinement of water molecules in sub-nanometre channels in biological systems has received relatively little attention. Advances in nanotechnology make it possible to explore the role played by water molecules in living systems, potentially leading to the development of ultrasensitive biosensors. Here we show that the adsorption of water by a self-assembled monolayer of single-stranded DNA on a silicon microcantilever can be detected by measuring how the tension in the monolayer changes as a result of hydration. Our approach relies on the microcantilever bending by an amount that depends on the tension in the monolayer. In particular, we find that the tension changes dramatically when the monolayer interacts with either complementary or single mismatched single-stranded DNA targets. Our results suggest that the tension is mainly governed by hydration forces in the channels between the DNA molecules and could lead to the development of a label-free DNA biosensor that can detect single mutations. The technique provides sensitivity in the femtomolar range that is at least two orders of magnitude better than that obtained previously with label-free nanomechanical biosensors and with label-dependent microarrays.D.R. acknowledges the fellowship funded by the Autonomic Community of Madrid (CAM). J.T, M.C, J.M and D.R acknowledge financial support by Spanish Ministry of Science (MEC) under grant No. TEC2006-10316 and CAM under grant No. 200550M056. C.B. acknowledges funding provided by MEC under grant No. BIO2007-67523. Work at Centro de Astrobiología was supported by European Union (EU), Instituto Nacional de Técnica Aeroespacial (INTA), MEC and CAM. All the authors acknowledge A. Cebollada, J.M. García-Martín, J. García, J.L. Costa-Kramer, M. Arroyo-Hernández and J.V. Anguita for their assistance in the gold deposition on the cantilevers.Peer reviewe

Special Issue "On Defining Artificial Intelligence"—Commentaries and Author's Response

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Natural geochemical markers reveal environmental history and population connectivity of common cuttlefish in the Atlantic Ocean and Mediterranean Sea

Natural markers (delta C-13 and delta O-18 stable isotopes) in the cuttlebones of the European common cuttlefish (Sepia officinalis) were determined for individuals collected across a substantial portion of their range in the Northeast Atlantic Ocean (NEAO) and Mediterranean Sea. Cuttlebone delta C-13 and delta O-18 were quantified for core and edge material to characterize geochemical signatures associated with early (juvenile) and recent (sub-adult/adult) life-history periods, respectively. Regional shifts in cuttlebone delta C-13 and delta O-18 values were detected across the 12 sites investigated. Individuals collected from sites in the NEAO displayed more enriched delta C-13 and delta O-18 values relative to sites in the Mediterranean Sea, with the latter also showing salient differences in both markers among western, central and eastern collection areas. Classification success based on cuttlebone delta C-13 and delta O-18 values to four geographical regions (NEAO, western, central and eastern Mediterranean Sea) was relatively high, suggesting that environmental conditions in each region were distinct and produced area-specific geochemical signatures on the cuttlebones ofS. officinalis. A modified delta C-13 and delta O-18 baseline was developed from sites proximal to the Strait of Gibraltar in both the NEAO and Mediterranean Sea to assess potential mixing through this corridor. Nearly, all (95%) of delta C-13 and delta O-18 signatures ofS. officinaliscollected in the area of the NEAO closest to the Strait of Gibraltar (Gulf of Cadiz) matched the signatures of specimens collected in the western Mediterranean, signifying potential movement and mixing of individuals through this passageway. This study extends the current application of these geochemical markers for assessing the natal origin and population connectivity of this species and potentially other taxa that inhabit this geographical area.Portuguese Foundation for Science and Technology: IF/00576/2014info:eu-repo/semantics/publishedVersio

Teprotumumab for Thyroid-Associated Ophthalmopathy

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .)