We combine high-redshift Type Ia supernovae from the first three years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality ...joint sample of 472 SNe (123 low-z, 93 SDSS, 242 SNLS, and 14 Hubble Space Telescope). SN data alone require cosmic acceleration at >99.999% confidence, including systematic effects. For the dark energy equation of state parameter (assumed constant out to at least z = 1.4) in a flat universe, we find w = --0.91+0.16 --0.20(stat)+0.07 --0.14(sys) from SNe only, consistent with a cosmological constant. Our fits include a correction for the recently discovered relationship between host-galaxy mass and SN absolute brightness. We pay particular attention to systematic uncertainties, characterizing them using a systematic covariance matrix that incorporates the redshift dependence of these effects, as well as the shape-luminosity and color-luminosity relationships. Unlike previous work, we include the effects of systematic terms on the empirical light-curve models. The total systematic uncertainty is dominated by calibration terms. We describe how the systematic uncertainties can be reduced with soon to be available improved nearby and intermediate-redshift samples, particularly those calibrated onto USNO/SDSS-like systems.
The ATP synthases are multiprotein complexes found in the energy-transducing membranes of bacteria, chloroplasts and mitochondria. They employ a transmembrane protonmotive force, Δp, as a source of ...energy to drive a mechanical rotary mechanism that leads to the chemical synthesis of ATP from ADP and Pi. Their overall architecture, organization and mechanistic principles are mostly well established, but other features are less well understood. For example, ATP synthases from bacteria, mitochondria and chloroplasts differ in the mechanisms of regulation of their activity, and the molecular bases of these different mechanisms and their physiological roles are only just beginning to emerge. Another crucial feature lacking a molecular description is how rotation driven by Δp is generated, and how rotation transmits energy into the catalytic sites of the enzyme to produce the stepping action during rotation. One surprising and incompletely explained deduction based on the symmetries of c-rings in the rotor of the enzyme is that the amount of energy required by the ATP synthase to make an ATP molecule does not have a universal value. ATP synthases from multicellular organisms require the least energy, whereas the energy required to make an ATP molecule in unicellular organisms and chloroplasts is higher, and a range of values has been calculated. Finally, evidence is growing for other roles of ATP synthases in the inner membranes of mitochondria. Here the enzymes form supermolecular complexes, possibly with specific lipids, and these complexes probably contribute to, or even determine, the formation of the cristae.
Circadian rhythms refer to biologic processes that oscillate with a period of ∼24 hr. These rhythms are sustained by a molecular clock and provide a temporal matrix that ensures the coordination of ...homeostatic processes with the periodicity of environmental challenges. We demonstrate the circadian molecular clock controls the expression and function of Toll-like receptor 9 (TLR9). In a vaccination model using TLR9 ligand as adjuvant, mice immunized at the time of enhanced TLR9 responsiveness presented weeks later with an improved adaptive immune response. In a TLR9-dependent mouse model of sepsis, we found that disease severity was dependent on the timing of sepsis induction, coinciding with the daily changes in TLR9 expression and function. These findings unveil a direct molecular link between the circadian and innate immune systems with important implications for immunoprophylaxis and immunotherapy.
► The circadian molecular clock modulates Tlr9 expression and function ► There are in vivo daily variations in the responsiveness to CpG ODNs (TLR9 ligand) ► The time of day determines disease severity in a TLR9-dependent sepsis model ► Timing of immunization determines TLR9 ligand-adjuvanted vaccine responsiveness
The structure of the dimeric ATP synthase from bovine mitochondria determined in three rotational states by electron cryo-microscopy provides evidence that the proton uptake from the mitochondrial ...matrix via the proton inlet half channel proceeds via a Grotthus mechanism, and a similar mechanism may operate in the exit half channel. The structure has given information about the architecture and mechanical constitution and properties of the peripheral stalk, part of the membrane extrinsic region of the stator, and how the action of the peripheral stalk damps the side-to-side rocking motions that occur in the enzyme complex during the catalytic cycle. It also describes wedge structures in the membrane domains of each monomer, where the skeleton of each wedge is provided by three α-helices in the membrane domains of the b-subunit to which the supernumerary subunits e, f, and g and the membrane domain of subunit A6L are bound. Protein voids in the wedge are filled by three specifically bound cardiolipin molecules and two other phospholipids. The external surfaces of the wedges link the monomeric complexes together into the dimeric structures and provide a pivot to allow the monomer–monomer interfaces to change during catalysis and to accommodate other changes not related directly to catalysis in the monomer–monomer interface that occur in mitochondrial cristae. The structure of the bovine dimer also demonstrates that the structures of dimeric ATP synthases in a tetrameric porcine enzyme have been seriously misinterpreted in the membrane domains.
La sequía es un fenómeno que genera grandes pérdidas económicas para la sociedad y se están observando más frecuentemente debido al cambio climático. En Centroamérica este fenómeno se relaciona con ...la distribución anómala de la precipitación (P) en un período corto, dentro de la estación lluviosa. Específicamente, en El Salvador, el fenómeno denominado “canícula”, está asociado a una disminución importante de la P cuya duración es de pocos días, por lo que es difícil de monitorearlo sólo con la P, como se hace actualmente. En el presente se han desarrollado muchos indicadores para caracterizar las sequías; en particular, se destacan la precipitación estandarizada y los índices de condición propuestos por Kogan (1995), que admiten diversas fuentes de información. En este trabajo se aplicaron cinco indicadores de déficit hídrico - la P estandarizada, la evapotranspiración (ET), el índice de condición de la humedad del suelo (HSCI), el índice de condición de la vegetación (VCI) y estrés hídrico (EH) - para evaluar las sequías en El Salvador. Para ello se utilizó información satelital, bases de datos climáticas y la interface de programación disponible en la plataforma Google Earth Engine. Se analizó el comportamiento de los indicadores en el periodo 2015-2019 y en particular, el año extremadamente seco 2015, para determinar la capacidad de monitoreo de los indicadores utilizados. Los resultados obtenidos sugieren que el conjunto de índices propuesto permite monitorear la sequía, identificando el inicio, el impacto y la extensión territorial en El Salvador.
Pigs have substantial potential as biomedical models for studying human developmental processes, congenital diseases, and pathogen response mechanisms in addition to utility as xenotransplant organ ...donors and tools for vaccine and drug design. The similarity of pigs to humans in anatomical size and structure, physiology, immunology, and genome enhances their potential as models for humans. Hence, it is imperative that research is relevant and reproducible in animal models that more closely resemble humans, such as the pig. This review summarizes the current status of pigs as an investigative model for humans and highlights their future applications.
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► We propose a method for decisionmaking under uncertain change: Dynamic Adaptive Policy Pathways. ► The DAPP approach stimulates planners to include adaptation over time in their ...plans. ► Adaptation pathways provide insights into options, lock-in possibilities, and path dependencies. ► Triggers are used to indicate when a new action should come into force. ► Contingency actions are used to stay on track of a preferred pathway.
A new paradigm for planning under conditions of deep uncertainty has emerged in the literature. According to this paradigm, a planner should create a strategic vision of the future, commit to short-term actions, and establish a framework to guide future actions. A plan that embodies these ideas allows for its dynamic adaptation over time to meet changing circumstances. We propose a method for decisionmaking under uncertain global and regional changes called ‘Dynamic Adaptive Policy Pathways’. We base our approach on two complementary approaches for designing adaptive plans: ‘Adaptive Policymaking’ and ‘Adaptation Pathways’. Adaptive Policymaking is a theoretical approach describing a planning process with different types of actions (e.g. ‘mitigating actions’ and ‘hedging actions’) and signposts to monitor to see if adaptation is needed. In contrast, Adaptation Pathways provides an analytical approach for exploring and sequencing a set of possible actions based on alternative external developments over time. We illustrate the Dynamic Adaptive Policy Pathways approach by producing an adaptive plan for long-term water management of the Rhine Delta in the Netherlands that takes into account the deep uncertainties about the future arising from social, political, technological, economic, and climate changes. The results suggest that it is worthwhile to further test and use the approach.
Measuring quality of recovery-15 after day case surgery Chazapis, M.; Walker, E.M.K.; Rooms, M.A. ...
British journal of anaesthesia : BJA,
February 2016, 20160201, 2016-Feb, 2016-02-00, Letnik:
116, Številka:
2
Journal Article
Recenzirano
Odprti dostop
‘Quality of recovery’ scores are patient-reported outcome measures evaluating recovery after surgery and anaesthesia. However, they are not widely used in the clinical or research setting. The ...Quality of Recovery-15 (QoR-15) is a recently developed, psychometrically tested and validated questionnaire.
We conducted a prospective study of all adult patients undergoing orthopaedic day case surgery over a period of six months (June 2013–November 2013). Patients completed the QoR-15 score preoperatively, and then were asked to repeat the score by telephone at 24 h, 48 h and seven days after surgery.
633 patients from a possible 714 (89%) completed the preoperative questionnaire and data from 437 patients who completed scores at all four time points were analysed. Most patients returned to their preoperative score by 48 h, and had exceeded it by seven days. Construct validity was supported by a negative correlation with duration of surgery and total inpatient opioid use. There was also excellent internal consistency (Cronbach’s alpha 0.80–0.83).
The QoR-15 is a clinically acceptable and feasible patient-centred outcome measure after day case surgery. The score demonstrated good validity, reliability and responsiveness. However, measurement of the QoR-15 score on the day of surgery may not provide a true baseline value. We suggest one follow-up call at 48 h would enable an adequate patient-centred assessment of postoperative recovery after day case orthopaedic surgery.
Mutations in Parkin or PINK1 are the most common cause of recessive familial parkinsonism. Recent studies suggest that PINK1 and Parkin form a mitochondria quality control pathway that identifies ...dysfunctional mitochondria, isolates them from the mitochondrial network, and promotes their degradation by autophagy. In this pathway the mitochondrial kinase PINK1 senses mitochondrial fidelity and recruits Parkin selectively to mitochondria that lose membrane potential. Parkin, an E3 ligase, subsequently ubiquitinates outer mitochondrial membrane proteins, notably the mitofusins and Miro, and induces autophagic elimination of the impaired organelles. Here we review the recent rapid progress in understanding the molecular mechanisms of PINK1- and Parkin-mediated mitophagy and the identification of Parkin substrates suggesting how mitochondrial fission and trafficking are involved. We also discuss how defects in mitophagy may be linked to Parkinson's disease.
The artificial glow of the night sky is a form of light pollution; its global change over time is not well known. Developments in lighting technology complicate any measurement because of changes in ...lighting practice and emission spectra. We investigated the change in global sky brightness from 2011 to 2022 using 51,351 citizen scientist observations of naked-eye stellar visibility. The number of visible stars decreased by an amount that can be explained by an increase in sky brightness of 7 to 10% per year in the human visible band. This increase is faster than emissions changes indicated by satellite observations. We ascribe this difference to spectral changes in light emission and to the average angle of light emissions.
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