Glassiness in a model without energy barriers

We propose a microscopic model without energy barriers in order to explain some generic features observed in structural glasses. The statics can be exactly solved while the dynamics has been clarified using Monte Carlo calculations. Although the model has no thermodynamic transition it captures some of the essential features of real glasses, i.e., extremely slow relaxation, time dependent hysteresis effects, anomalous increase of the relaxation time and aging. This suggests that the effect of entropy barriers can be an important ingredient to account for the behavior observed in real glasses.Comment: 11 Pages + 3 Figures, Revtex, uufiles have been replaced since figure 2 was corrupted in the previous submissio

Advancing Scientific Understanding of the Global Methane Budget in Support of the Paris Agreement

The 2015 Paris Agreement of the United Nations Framework Convention on Climate Change aims to keep global average temperature increases well below 2 °C of preindustrial levels in the Year 2100. Vital to its success is achieving a decrease in the abundance of atmospheric methane (CH4), the second most important anthropogenic greenhouse gas. If this reduction is to be achieved, individual nations must make and meet reduction goals in their nationally determined contributions, with regular and independently verifiable global stock taking. Targets for the Paris Agreement have been set, and now the capability must follow to determine whether CH4 reductions are actually occurring. At present, however, there are significant limitations in the ability of scientists to quantify CH4 emissions accurately at global and national scales and to diagnose what mechanisms have altered trends in atmospheric mole fractions in the past decades. For example, in 2007, mole fractions suddenly started rising globally after a decade of almost no growth. More than a decade later, scientists are still debating the mechanisms behind this increase. This study reviews the main approaches and limitations in our current capability to diagnose the drivers of changes in atmospheric CH4 and, crucially, proposes ways to improve this capability in the coming decade. Recommendations include the following: (i) improvements to process‐based models of the main sectors of CH4 emissions—proposed developments call for the expansion of tropical wetland flux measurements, bridging remote sensing products for improved measurement of wetland area and dynamics, expanding measurements of fossil fuel emissions at the facility and regional levels, expanding country‐ specific data on the composition of waste sent to landfill and the types of wastewater treatment systems implemented, characterizing and representing temporal profiles of crop growing seasons, implementing parameters related to ruminant emissions such as animal feed, and improving the detection of small fires associated with agriculture and deforestation; (ii) improvements to measurements of CH4 mole fraction and its isotopic variations—developments include greater vertical profiling at background sites, expanding networks of dense urban measurements with a greater focus on relatively poor countries, improving the precision of isotopic ratio measurements of 13CH4, CH3D, 14CH4, and clumped isotopes, creating isotopic reference materials for international‐scale development, and expanding spatial and temporal characterization of isotopic source signatures; and (iii) improvements to inverse modeling systems to derive emissions from atmospheric measurements—advances are proposed in the areas of hydroxyl radical quantification, in systematic uncertainty quantification through validation of chemical transport models, in the use of source tracers for estimating sector‐level emissions, and in the development of time and spaceresolved national inventories. These and other recommendations are proposed for the major areas of CH4 science with the aim of improving capability in the coming decade to quantify atmospheric CH4 budgets on the scales necessary for the success of climate policies. Plain Language Summary Methane is the second largest contributor to climate warming from human activities since preindustrial times. Reducing human‐made emissions by half is a major component of the 2015 Paris Agreement target to keep global temperature increases well below 2 °C. In parallel to the methane emission reductions pledged by individual nations, new capabilities are needed to determine independently whether these reductions are actually occurring and whether methane concentrations in the atmosphere are changing for reasons that are clearly understood. At present significant challenges limit the ability of scientists to identify the mechanisms causing changes in atmospheric methane. This study reviews current and emerging tools in methane science and proposes major advances needed in the coming decade to achieve this crucial capability. We recommend further developing the models that simulate the processes behind methane emissions, improving atmospheric measurements of methane and its major carbon and hydrogen isotopes, and advancing abilities to infer the rates of methane being emitted and removed from the atmosphere from these measurements. The improvements described here will play a major role in assessing emissions commitments as more cities, states, and countries report methane emission inventories and commit to specific emission reduction targets. </div

Study of the daily and seasonal atmospheric CH₄ mixing ratio variability in a rural Spanish region using 222Rn tracer

Unidad de excelencia María de Maeztu MdM-2015-0552Atmospheric concentrations of the two main greenhouse gases (GHGs), carbon dioxide (CO₂) and methane (CH₄), are continuously measured since November 2012 at the Spanish rural station of Gredos (GIC3), within the climate network ClimaDat, together with atmospheric radon (²²²Rn) tracer and meteorological parameters. The atmospheric variability of CH₄ concentrations measured from 2013 to 2015 at GIC3 has been analyzed in this study. It is interpreted in relation to the variability of measured 222Rn concentrations, modelled ²²²Rn fluxes and modelled heights of the planetary boundary layer (PBLH) in the same period. In addition, nocturnal fluxes of CH4 were estimated using two methods: the Radon Tracer Method (RTM) and one based on the EDGARv4.2 bottom-up emission inventory. Both previous methods have been applied using the same footprints, calculated with the atmospheric transport model FLEXPARTv6.2. Results show that daily and seasonal changes in atmospheric concentrations of ²²²Rn (and the corresponding fluxes) can help to understand the atmospheric CH₄ variability. On daily basis, the variation in the PBLH mainly drives changes in ²²²Rn and CH₄ concentrations while, on monthly basis, their atmospheric variability seems to depend on changes in their emissions. The median value of RTM based methane fluxes (FR_CH₄) is 0.17 mg CH₄ m−2 h−1 with an absolute deviation of 0.08 mg CH₄ m⁻² h⁻¹. Median methane fluxes based on bottom-up inventory (FE_CH₄) is of 0.32 mg CHv m⁻² h⁻¹ with an absolute deviation of 0.06 mg CH₄ m⁻² h⁻¹. Monthly FR_CH₄ flux shows a seasonality which is not observed in the monthly FE_CH₄ flux. During January-May FR_CH₄ fluxes present a median value of 0.08 mg CH₄ m⁻² h⁻¹ with an absolute deviation of 0.05 mg CH₄ m⁻² h⁻¹ and a median value of 0.19 mg CH₄ m⁻² h⁻¹ with an absolute deviation of 0.06 mg CH₄ m⁻² h⁻¹ during June-December. This seasonal doubling of the median methane fluxes calculated by RTM at the GIC3 area seems to be mainly related to the alternate presence of transhumant livestock in the GIC3 area. The results obtained in this study highlight the benefit of applying independent RTM to improve the seasonality of the emission factors from bottom-up inventories

The rs429358 locus in apolipoprotein E is associated with hepatocellular carcinoma in patients with cirrhosis

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P=2.9×10−5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P=3.1×10−6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P=0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P=0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion

<p>Abstract</p> <p>Background</p> <p>Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion.</p> <p>Methods</p> <p>Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode.</p> <p>Results</p> <p>In group 1 the Pw/Pa ratio decreased by 10 ± 22% from 0.20 ± 0.09 to 0.19 ± 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 ± 15% from 0.22 ± 0.09 to 0.24 ± 0.10 (p = 0.001) when electrical neurostimulation was activated.</p> <p>Conclusion</p> <p>Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.</p

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.</p

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.</p