We present the first results of ionospheric conductivities at Titan based on measurements during 17 Titan flybys from the Cassini spacecraft. We identify an ionospheric region ranging from
1450
±
95
...km
(approximately the location of the exobase) to approximately 1000
km where electrical currents perpendicular to the magnetic field may become important. In this region the ionosphere is highly conductive with peak Pedersen conductivities of 0.002–0.05
S/m and peak Hall conductivities of 0.01–0.3
S/m depending on Solar illumination and magnetospheric conditions. Ionospheric conductivities are found to be typically higher on the sunlit side of Titan. However, Hall and Pedersen conductivities depend strongly on the magnetic field magnitude which is highly variable, both in altitude and with respect to the draping configuration of Saturn's magnetic field around Titan. Furthermore, a consistent double peak nature is found in the altitude profile of the Pedersen conductivity. A high altitude peak is found to be located between 1300 and 1400
km. A second and typically more conductive region is observed below 1000
km, where the magnetic field strength drops sharply while the electron density still remains high. This nature of the Pedersen conductivity profile may give rise to complicated ionospheric–atmospheric dynamics and may be expected also at other unmagnetized objects with a substantial atmosphere, such as e.g. Mars and Venus. Estimates of the total Pedersen conductance are found to range between 1300 and 22,000
S. The Pedersen conductance is always higher than the local Alfvén conductance but the difference varies by two orders of magnitude (from a factor 4 to 100). Thus, the conditions for reflection or absorption of Alfvén waves in Titans ionosphere are highly variable and depends strongly on the magnetic field strength.
Understanding how demographic processes influence mating systems is important to decode ecological influences on sexual selection in nature. We manipulated sex ratio and density in experimental ...populations of the sex-role reversed pipefish Syngnathus typhle. We quantified sexual selection using the Bateman gradient (β′ ss ), the opportunity for selection (l), and sexual selection (l s ), and the maximum standardized sexual selection differential (s′ max ). We also measured selection on body length using standardized selection differentials (s′) and mating differentials (m′), and tested whether the observed l and l s differ from values obtained by simulating random mating. We found that l, l s , and s′ max , but not β′ ss , were higher for females under female than male bias and the opposite for males, but density did not affect these measures. However, higher density decreased sexual selection (m′ but not s′) on female length, but selection on body length was not affected by sex ratio. Finally, l s but not l was higher than expected from random mating, and only for females under female bias. This study demonstrates that both sex ratio and density affect sexual selection and that disentangling interrelated demographic processes is essential to a more complete understanding of mating behavior and the evolution of mating systems.
Patients with atrial fibrillation (AF) are at an increased risk of ischaemic stroke. The efficacy of stroke prevention with vitamin K antagonists in these patients has been well established. However, ...associated bleeding risks may offset the therapeutic benefits in patients with risk factors for bleeding. Despite improvements achieved by novel oral anticoagulants, bleeding remains a clinically relevant problem, especially gastrointestinal bleeding. Percutaneous occlusion of the left atrial appendage (LAA) may be considered as an alternative stroke prevention therapy in AF patients with a high bleeding risk. This paper explores patient groups in whom oral anticoagulation may be challenging and percutaneous LAA occlusion (LAAO) has a potentially better risk–benefit balance. The current status of LAAO and future directions are reviewed, and particular challenges for LAA occlusion requiring further clinical data are discussed. This article is a summary of the Third Global Summit on LAA occlusion, 15 March 2013, Barcelona, Spain.
Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell ...infection. The signaling mechanisms underlying parasite development remain largely elusive even though Leishmania mitogen-activated protein kinases (MAPKs) have been linked previously to environmentally induced differentiation and virulence. Here, we unravel highly unusual regulatory mechanisms for Leishmania MAP kinase 10 (MPK10). Using a transgenic approach, we demonstrate that MPK10 is stage-specifically regulated, as its kinase activity increases during the promastigote to amastigote conversion. However, unlike canonical MAPKs that are activated by dual phosphorylation of the regulatory TxY motif in the activation loop, MPK10 activation is independent from the phosphorylation of the tyrosine residue, which is largely constitutive. Removal of the last 46 amino acids resulted in significantly enhanced MPK10 activity both for the recombinant and transgenic protein, revealing that MPK10 is regulated by an auto-inhibitory mechanism. Over-expression of this hyperactive mutant in transgenic parasites led to a dominant negative effect causing massive cell death during amastigote differentiation, demonstrating the essential nature of MPK10 auto-inhibition for parasite viability. Moreover, phosphoproteomics analyses identified a novel regulatory phospho-serine residue in the C-terminal auto-inhibitory domain at position 395 that could be implicated in kinase regulation. Finally, we uncovered a feedback loop that limits MPK10 activity through dephosphorylation of the tyrosine residue of the TxY motif. Together our data reveal novel aspects of protein kinase regulation in Leishmania, and propose MPK10 as a potential signal sensor of the mammalian host environment, whose intrinsic pre-activated conformation is regulated by auto-inhibition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims Out-of-hospital cardiac arrest is fatal without treatment, and time to defibrillation is an extremely important factor in relation to survival. We performed a cost-benefit analysis of dual ...dispatch defibrillation by ambulance and fire services in the County of Stockholm, Sweden. Methods and results A cost-benefit analysis was performed to evaluate the effects of dual dispatch defibrillation. The increased survival rates were estimated from a real-world implemented intervention, and the monetary value of a life (€ 2.2 million) was applied to this benefit by using results from a recent stated-preference study. The estimated costs include defibrillators (including expendables/maintenance), training, hospitalisation/health care, fire service call-outs, overhead resources and the dispatch centre. The estimated number of additional saved lives was 16 per year, yielding a benefit-cost ratio of 36. The cost per quality-adjusted life years (QALY) was estimated to be € 13,000, and the cost per saved life was € 60,000. Conclusions The intervention of dual dispatch defibrillation by ambulance and fire services in the County of Stockholm had positive economic effects. For the cost-benefit analysis, the return on investment was high and the cost-effectiveness showed levels below the threshold value for economic efficiency used in Sweden. The cost-utility analysis categorises the cost per QALY as medium.
Broad‐nosed pipefish Syngnathus typhle were used to investigate whether males used scent in their search for mates. When the males in an experiment had access to olfactory cues only, they did not ...locate females better than they located males. Thus, S. typhle, was less successful in mate search when visual cues were absent.
Summary
During its life cycle, the protozoan pathogen Leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra‐ ...and intracellular survival. Combining null mutant analysis with phosphorylation site‐specific mutagenesis and functional complementation we genetically tested the requirement of the L. donovani chaperone cyclophilin 40 (LdCyP40) for infection. Targeted replacement of LdCyP40 had no effect on parasite viability, axenic amastigote differentiation, and resistance to various forms of environmental stress in culture, suggesting important functional redundancy to other parasite chaperones. However, ultrastructural analyses and video microscopy of cyp40−/− promastigotes uncovered important defects in cell shape, organization of the subpellicular tubulin network and motility at stationary growth phase. More importantly, cyp40−/− parasites were unable to establish intracellular infection in murine macrophages and were eliminated during the first 24 h post infection. Surprisingly, cyp40−/− infectivity was restored in complemented parasites expressing a CyP40 mutant of the unique S274 phosphorylation site. Together our data reveal non‐redundant CyP40 functions in parasite cytoskeletal remodelling relevant for the development of infectious parasites in vitro independent of its phosphorylation status, and provide a framework for the genetic analysis of Leishmania‐specific phosphorylation sites and their role in regulating parasite protein function.
Abstract
Monochloramine is used to regulate microbial regrowth in drinking water distribution systems (DWDS) but produces carcinogenic disinfection byproducts and constitutes a source of energy for ...nitrifying bacteria. This study followed biofilm-dispersed microbial communities of a full-scale DWDS distributing ultrafiltered water over three years, before and after removal of monochloramine. Communities were described using flow cytometry and amplicon sequencing, including full-length 16S rRNA gene sequencing. Removal of monochloramine increased total cell counts by up to 440%. Increased abundance of heterotrophic bacteria was followed by emergence of the predatory bacteria
Bdellovibrio
, and a community potentially metabolizing small organic compounds replaced the nitrifying core community. No increased abundance of
Mycobacterium
or
Legionella
was observed. Co-occurrence analysis identified a network of
Nitrosomonas
,
Nitrospira
,
Sphingomonas
and
Hyphomicrobium
, suggesting that monochloramine supported this biofilm community. While some species expanded into the changed niche, no immediate biological risk to consumers was indicated within the DWDS.
Objective: To study if a modified triage system at an Emergency Department (ED) combined with educational efforts resulted in reduced time to antibiotics and decreased length of hospital stay (LOS) ...for patients with severe infection.
Methods: A retrospective, observational study comparing patients before and after the start of a new triage model at the ED of a University Hospital. After the implementation of the model, patients with fever and abnormal vital signs were triaged into a designated sepsis line (Sepsis Alert) for rapid evaluation by the attending physician supported by a infectious diseases (IDs) specialist. Also, all ED staff participated in a designated sepsis education before Sepsis Alert was introduced. Medical records were evaluated for patients during a 3-month period after the triage system was started in 2012, and also during the corresponding months in 2010 and 2014.
Results: A total of 1837 patients presented with abnormal vital signs. Of these, 221 patients presented with fever and thus at risk of having severe sepsis. Among patients triaged according to the new model, median time to antibiotics was 58.5 at startup and 24.5 minutes at follow-up two years later. This was significantly less than for patients treated before the new model, 190 minutes. Also, median LOS was significantly decreased after introduction of the new triage model, from nine to seven days.
Conclusions: A triage model at the ED with special attention to severe sepsis patients, led to sustained improvements of time to antibiotic treatment and LOS.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•A dynamic greenhouse climate regime is energy efficient.•Incidence of extreme microclimate conditions and plant stress can occur in greenhouse.•A new approach of leaf temperature prediction and ...monitoring is proposed.•Model based plant stress monitoring and decision-making is put forward.•A multi-model approach with self-selective sub-models is suggested.
While dynamic greenhouse climatic regimes are often applied to achieve energy efficiency, dynamic mechanistic models can assist in climate control decisions, and to elucidate plant stress under extreme microclimatic conditions. The present study developed a couple model with three integrated sub-models to predict net leaf photosynthesis (Pnl), stomatal conductance (gs), and leaf temperature under different microclimatic conditions: (1) a C3 photosynthesis biochemical model; (2) a stomatal conductance model; and (3) a leaf energy balance model. Leaf photochemical efficiency and maximum gross photosynthesis using a negative exponential light response curve were modelled with different leaf temperatures, light levels, and CO2 concentrations. The stomatal conductance and leaf energy balance models were calibrated independently. Pnl, gs, and leaf temperature model predictions were validated with independent measurements and climate input data. Model performance was evaluated by a linear regression of predicted values relative to observed values. The coupled model estimated Pnl with a 2–12% mean difference between the observed and the model, and a 1.82°C maximum leaf temperature difference between the observed and the model. An additional stomatal model was implemented for comparison, and tested against the model system. Our model showed a better fit to Pnl, leaf temperature, and stomatal conductance validation data. The coupled model was therefore a good predictor for crop growth and microclimate. We suggest a multi-model approach with self-selective sub-models to assist in decisions optimising light, temperature, and CO2 for maximum photosynthetic rates for climatic conditions applied in the model (i.e. high light, temperature, and CO2 concentration). Furthermore, the model leaf temperature prediction could be used for leaf temperature monitoring under unfavorable microclimatic conditions.