Polyphosphate is an inorganic polymer that can potentiate several interactions in the blood coagulation system. Blood platelets contain polyphosphate, and the secretion of platelet-derived ...polyphosphate has been associated with increased thrombus formation and activation of coagulation factor XII. However, the small polymer size of secreted platelet polyphosphate limits its capacity to activate factor XII in vitro. Thus, the mechanism by which platelet polyphosphate contributes to thrombus formation remains unclear. Using live-cell imaging, confocal and electron microscopy, we show that activated platelets retain polyphosphate on their cell surface. The apparent polymer size of membrane-associated polyphosphate largely exceeds that of secreted polyphosphate. Ultracentrifugation fractionation experiments revealed that membrane-associated platelet polyphosphate is condensed into insoluble spherical nanoparticles with divalent metal ions. In contrast to soluble polyphosphate, membrane-associated polyphosphate nanoparticles potently activate factor XII. Our findings identify membrane-associated polyphosphate in a nanoparticle state on the surface of activated platelets. We propose that these polyphosphate nanoparticles mechanistically link the procoagulant activity of platelets with the activation of coagulation factor XII.
•Activated platelets expose insoluble membrane-associated polyphosphate nanoparticles that are complexed with divalent metal ions.•Platelet polyphosphate nanoparticles, but not soluble polyphosphate polymers, activate the contact system.
The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de ...novo serine synthesis, many others rely on exogenous serine for optimal growth. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation). The increased survival following dietary restriction of serine and glycine in these models was further improved by antagonizing the anti-oxidant response. Disruption of mitochondrial oxidative phosphorylation (using biguanides) led to a complex response that could improve or impede the anti-tumour effect of serine and glycine starvation. Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less responsive to depletion of serine and glycine, reflecting an ability of activated Kras to increase the expression of enzymes that are part of the serine synthesis pathway and thus promote de novo serine synthesis.
We report a precision measurement of the parity-violating asymmetry APV in the elastic scattering of longitudinally polarized electrons from 208Pb. We measure APV= 550 ± 16 (stat) ±8 (syst) parts per ...billion, leading to an extraction of the neutral weak form factor FW(Q2= 0.00616 GeV2) = 0.368 ± 0.013. Combined with our previous measurement, the extracted neutron skin thickness is Rn-Rp= 0.283 ± 0.071 fm. The result also yields the first significant direct measurement of the interior weak density of 208Pb: ρ$^0_W$ = -0.0796 ± 0.0036(exp) ± 0.0013(theo) fm-3 leading to the interior baryon density ρ$^0_b$ = 0.1480 ± 0.0036(exp) ± 0.0013(theo) fm-3. Finally, the measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
Drained peatlands are significant hotspots of carbon dioxide (CO2) emissions and may also be more vulnerable to fire with its associated gaseous emissions. Under the United Nations Framework ...Convention on Climate Change (UNFCCC) and the Kyoto Protocol, greenhouse gas (GHG) emissions from peatlands managed for extraction are reported on an annual basis. However, the Tier 1 (default) emission factors (EFs) provided in the IPCC 2013 Wetlands Supplement for this land use category may not be representative in all cases and countries are encouraged to move to higher-tier reporting levels with reduced uncertainty levels based on country- or regional-specific data. In this study, we quantified (1) CO2-C emissions from nine peat extraction sites in the Republic of Ireland and the United Kingdom, which were initially disaggregated by land use type (industrial versus domestic peat extraction), and (2) a range of GHGs that are released to the atmosphere with the burning of peat. Drainage-related methane (CH4) and nitrous oxide (N2O) emissions as well as CO2-C emissions associated with the off-site decomposition of horticultural peat were not included here. Our results show that net CO2-C emissions were strongly controlled by soil temperature at the industrial sites (bare peat) and by soil temperature and leaf area index at the vegetated domestic sites. Our derived EFs of 1.70 (±0.47) and 1.64 (±0.44) t CO2-C ha-1 yr-1 for the industrial and domestic sites respectively are considerably lower than the Tier 1 EF (2.8 ± 1.7 t CO2-C ha-1 yr-1) provided in the Wetlands Supplement. We propose that the difference between our derived values and the Wetlands Supplement value is due to differences in peat quality and, consequently, decomposition rates. Emissions from burning of the peat (g kg-1 dry fuel burned) were estimated to be approximately 1346 CO2, 8.35 methane (CH4), 218 carbon monoxide (CO), 1.53 ethane (C2H6), 1.74 ethylene (C2H4), 0.60 methanol (CH3OH), 2.21 hydrogen cyanide (HCN) and 0.73 ammonia (NH3), and this emphasises the importance of understanding the full suite of trace gas emissions from biomass burning. Our results highlight the importance of generating reliable Tier 2 values for different regions and land use categories. Furthermore, given that the IPCC Tier 1 EF was only based on 20 sites (all from Canada and Fennoscandia), we suggest that data from another 9 sites significantly expand the global data set, as well as adding a new region.
Prolonged ileus-the failure of postoperative ileus to resolve within a few days after major abdominal surgery-leads to significant medical consequences for the patient and costs to the hospital ...system. The aim of this retrospective analysis of prospectively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer.
Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995-2009. Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression.
Prolonged ileus occurred in 14.0% of patients. Statistically significant independent predictors of prolonged ileus were male sex (OR: 1.7, P < 0.001), peripheral vascular disease (OR: 1.8, P < 0.001), respiratory comorbidity (OR: 1.6, P < 0.001), resection at urgent operation (OR: 2.2, P < 0.001), perioperative transfusion (OR: 1.6, P < 0.010), stoma constructed (OR: 1.4, P < 0.001), and operation lasting ≥3 hours (OR: 1.6, P < 0.001).
These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them. These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment.
We examine the ozone production from boreal forest fires based on a case study of wildfires in Alaska and Canada in summer 2004. The model simulations were performed with the chemistry transport ...model, MOZART‐4, and were evaluated by comparison with a comprehensive set of aircraft measurements. In the analysis we use measurements and model simulations of carbon monoxide (CO) and ozone (O3) at the PICO‐NARE station located in the Azores within the pathway of North American outflow. The modeled mixing ratios were used to test the robustness of the enhancement ratio ΔO3/ΔCO (defined as the excess O3 mixing ratio normalized by the increase in CO) and the feasibility for using this ratio in estimating the O3 production from the wildfires. Modeled and observed enhancement ratios are about 0.25 ppbv/ppbv which is in the range of values found in the literature and results in a global net O3 production of 12.9 ± 2 Tg O3 during summer 2004. This matches the net O3 production calculated in the model for a region extending from Alaska to the east Atlantic (9–11 Tg O3) indicating that observations at PICO‐NARE representing photochemically well aged plumes provide a good measure of the O3 production of North American boreal fires. However, net chemical loss of fire‐related O3 dominates in regions far downwind from the fires (e.g., Europe and Asia) resulting in a global net O3 production of 6 Tg O3 during the same time period. On average, the fires increased the O3 burden (surface −300 mbar) over Alaska and Canada during summer 2004 by about 7–9% and over Europe by about 2–3%.
Aerosols in Titan's atmosphere play an important role in determining its thermal structure. They also serve as sinks for organic vapours and can act as condensation nuclei for the formation of ...clouds, where the condensation efficiency will depend on the chemical composition of the aerosols. So far, however, no direct information has been available on the chemical composition of these particles. Here we report an in situ chemical analysis of Titan's aerosols by pyrolysis at 600 °C. Ammonia (NH3) and hydrogen cyanide (HCN) have been identified as the main pyrolysis products. This clearly shows that the aerosol particles include a solid organic refractory core. NH3 and HCN are gaseous chemical fingerprints of the complex organics that constitute this core, and their presence demonstrates that carbon and nitrogen are in the aerosols.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prior to ~1 million years ago (Ma), variations in global ice volume were dominated by changes in obliquity; however, the role of precession remains unresolved. Using a record of North Atlantic ice ...rafting spanning the past 1.7 million years, we find that the onset of ice rafting within a given glacial cycle (reflecting ice sheet expansion) consistently occurred during times of decreasing obliquity whereas mass ice wasting (ablation) events were consistently tied to minima in precession. Furthermore, our results suggest that the ubiquitous association between precession-driven mass wasting events and glacial termination is a distinct feature of the mid to late Pleistocene. Before then (increasing), obliquity alone was sufficient to end a glacial cycle, before losing its dominant grip on deglaciation with the southward extension of Northern Hemisphere ice sheets since ~1 Ma.
The aim of this study was to determine whether anastomotic leakage has an independent association with overall survival and cancer-specific survival.
There are many known prognostic indicators ...following surgery for colorectal cancer (CRC). However, the impact of anastomotic leakage has not been adequately assessed.
Consecutive patients undergoing resection between 1971 and 1999 were recorded prospectively in the Concord Hospital CRC database. Total anastomotic leakage was defined as any leak, whether local, general, or radiologically diagnosed. Patients were followed until death or to December 31, 2002. The association between anastomotic leakage and both overall survival and cancer-specific survival was examined by proportional hazards regression with adjustment for other patient and tumor characteristics influencing survival. Confidence intervals (CI) were set at the 95% level.
From an initial 2980 patients, 1722 remained after exclusions. The total leak rate was 5.1% (CI 4.1-6.2%). In patients with a leak, the 5-year overall survival rate was 44.3% (CI 33.5-54.6%) compared to 64.0% (CI 61.5-66.3%) in those without leak. In proportional hazards regression-after adjustment for age, gender, urgent resection, site, size, stage, grade, venous invasion, apical node metastasis and serosal surface involvement-anastomotic leakage had an independent negative association with overall survival (hazard ratio HR 1.6, CI 1.2-2.0) and cancer-specific survival (HR 1.8, CI 1.2-2.6).
Apart from its immediate clinical consequences, anastomotic leakage also has an independent negative association with survival.
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