We present atmospheric sulfur hexafluoride (SF6 ) mole fractions and emissions estimates from the 1970s to 2008. Measurements were made of archived air samples starting from 1973 in the Northern ...Hemisphere and from 1978 in the Southern Hemisphere, using the Advanced Global Atmospheric Gases Experiment (AGAGE) gas chromatographic-mass spectrometric (GC-MS) systems. These measurements were combined with modern high-frequency GC-MS and GC-electron capture detection (ECD) data from AGAGE monitoring sites, to produce a unique 35-year atmospheric record of this potent greenhouse gas. Atmospheric mole fractions were found to have increased by more than an order of magnitude between 1973 and 2008. The 2008 growth rate was the highest recorded, at 0.29 ± 0.02 pmolmol-1 yr-1 . A three-dimensional chemical transport model and a minimum variance Bayesian inverse method was used to estimate annual emission rates using the measurements, with a priori estimates from the Emissions Database for Global Atmospheric Research (EDGAR, version 4). Consistent with the mole fraction growth rate maximum, global emissions during 2008 were also the highest in the 1973-2008 period, reaching 7.4 ± 0.6 Gg yr-1 (1-σ uncertainties) and surpassing the previous maximum in 1995. The 2008 values follow an increase in emissions of 48 ± 20% since 2001. A second global inversion which also incorporated National Oceanic and Atmospheric Administration (NOAA) flask measurements and in situ monitoring site data agreed well with the emissions derived using AGAGE measurements alone. By estimating continent-scale emissions using all available AGAGE and NOAA surface measurements covering the period 2004-2008, with no pollution filtering, we find that it is likely that much of the global emissions rise during this five-year period originated primarily from Asian developing countries that do not report detailed, annual emissions to the United Nations Framework Convention on Climate Change (UNFCCC). We also find it likely that SF6 emissions reported to the UNFCCC were underestimated between at least 2004 and 2005.
Tripartite multidrug efflux systems of Gram-negative bacteria are composed of an inner membrane transporter, an outer membrane channel and a periplasmic adaptor protein. They are assumed to form ...ducts inside the periplasm facilitating drug exit across the outer membrane. Here we present the reconstitution of native Pseudomonas aeruginosa MexAB-OprM and Escherichia coli AcrAB-TolC tripartite Resistance Nodulation and cell Division (RND) efflux systems in a lipid nanodisc system. Single-particle analysis by electron microscopy reveals the inner and outer membrane protein components linked together via the periplasmic adaptor protein. This intrinsic ability of the native components to self-assemble also leads to the formation of a stable interspecies AcrA-MexB-TolC complex suggesting a common mechanism of tripartite assembly. Projection structures of all three complexes emphasize the role of the periplasmic adaptor protein as part of the exit duct with no physical interaction between the inner and outer membrane components.
This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic ...radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials.
Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared.
PCI patients survived significantly longer than non-PCI patients {hazard ratio HR = 0.61 95% confidence interval (CI): 0.52–0.72; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018).
PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.
Many consider femoral nerve block the gold standard in pain management following knee arthroplasty. Local infiltration analgesia is an alternate approach that applies the concept of surgical wound ...infiltration with local anaesthetics. This meta-analysis aims to compare both analgesic treatments for analgesia and functional outcomes after total knee arthroplasty. This meta-analysis was performed according to the PRISMA statement guidelines. The primary outcomes were cumulative i.v. morphine consumption, pain scores at rest and on movement on postoperative day one (analogue scale,0–10). Secondary outcomes included range of motion, quadriceps muscle strength, length of stay and rates of complications (neurologic events, cardiovascular events, falls and knee infections). Fourteen trials, including 1122 adult patients were identified. There was no difference in i.v. morphine consumption (mean difference: −2.0 mg; 95% CI: −4.9, 0.9 mg; I2+69%; P+0.19), pain scores at rest (mean difference: −0.1; 95% CI: −0.4, 0.3; I2+72%; P+0.80) and pain scores on movement (mean difference: 0.2; 95% CI: −0.5, 0.8; I2+80%; P+0.64) on postoperative day one (a negative mean difference favours local infiltration analgesia). The qualities of evidence for our primary outcomes were moderate according to the GRADE system. There were no clinical differences in functional outcomes or rates of complications. Complication rates were captured by three trials or fewer with exception of knee infection, which was sought by eight trials. Local infiltration analgesia provides similar postoperative analgesia after total knee arthroplasty to femoral nerve block. Although this meta-analysis did not capture any difference in rates of complications, the low number of trials that specifically sought these outcomes dictates caution.
Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such ...peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for accurate de novo design of conformationally restricted peptides, and the use of these methods to design 18-47 residue, disulfide-crosslinked peptides, a subset of which are heterochiral and/or N-C backbone-cyclized. Both genetically encodable and non-canonical peptides are exceptionally stable to thermal and chemical denaturation, and 12 experimentally determined X-ray and NMR structures are nearly identical to the computational design models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs.
Low back pain is a leading cause of disability and is frequently associated with whole-body vibration exposure in industrial workers and military personnel. While the pathophysiological mechanisms by ...which whole-body vibration causes low back pain have been studied in vivo, there is little data to inform low back pain diagnosis. Using a rat model of repetitive whole-body vibration followed by recovery, our objective was to determine the effects of vibration frequency on hind paw withdrawal threshold, circulating nerve growth factor concentration, and intervertebral disc degeneration.
Male Sprague-Dawley rats were vibrated for 30 min at an 8 Hz or 11 Hz frequency every other day for two weeks and then recovered (no vibration) for one week. Von Frey was used to determine hind paw mechanical sensitivity every two days. Serum nerve growth factor concentration was determined every four days. At the three-week endpoint, intervertebral discs were graded histologically for degeneration.
The nerve growth factor concentration increased threefold in the 8 Hz group and twofold in the 11 Hz group. The nerve growth factor concentration did not return to baseline by the end of the one-week recovery period for the 8 Hz group. Nerve growth factor serum concentration did not coincide with intervertebral disc degeneration, as no differences in degeneration were observed among groups. Mechanical sensitivity generally decreased over time for all groups, suggesting a habituation (desensitization) effect.
This study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.
•Rats were subjected to repeated whole-body vibration at 8 Hz or 11 Hz.•Serum nerve growth factor concentration increased more following vibration at 8 Hz.•Increased nerve growth factor did not result in intervertebral disc degeneration.•Nerve growth factor could be used to diagnose low back pain from whole-body vibration.
PERSIANN-CDR Ashouri, Hamed; Hsu, Kuo-Lin; Sorooshian, Soroosh ...
Bulletin of the American Meteorological Society,
01/2015, Letnik:
96, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A new retrospective satellite-based precipitation dataset is constructed as a climate data record for hydrological and climate studies. Precipitation Estimation from Remotely Sensed Information using ...Artificial Neural Networks–Climate Data Record (PERSIANN-CDR) provides daily and 0.25° rainfall estimates for the latitude band 60°S–60°N for the period of 1 January 1983 to 31 December 2012 (delayed present). PERSIANN-CDR is aimed at addressing the need for a consistent, long-term, high-resolution, and global precipitation dataset for studying the changes and trends in daily precipitation, especially extreme precipitation events, due to climate change and natural variability. PERSIANN-CDR is generated from the PERSIANN algorithm using GridSat-B1 infrared data. It is adjusted using the Global Precipitation Climatology Project (GPCP) monthly product to maintain consistency of the two datasets at 2.5° monthly scale throughout the entire record. Three case studies for testing the efficacy of the dataset against available observations and satellite products are reported. The verification study over Hurricane Katrina (2005) shows that PERSIANN-CDR has good agreement with the stage IV radar data, noting that PERSIANN-CDR has more complete spatial coverage than the radar data. In addition, the comparison of PERSIANN-CDR against gauge observations during the 1986 Sydney flood in Australia reaffirms the capability of PERSIANN-CDR to provide reasonably accurate rainfall estimates. Moreover, the probability density function (PDF) of PERSIANN-CDR over the contiguous United States exhibits good agreement with the PDFs of the Climate Prediction Center (CPC) gridded gauge data and the Tropical Rainfall Measuring Mission (TRMM) Multi-Satellite Precipitation Analysis (TMPA) product. The results indicate high potential for using PERSIANN-CDR for long-term hydroclimate studies in regional and global scales.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The impact of genetic regulatory variation active in early pancreatic development on adult pancreatic disease and traits is not well understood. Here, we generate a panel of 107 fetal-like ...iPSC-derived pancreatic progenitor cells (iPSC-PPCs) from whole genome-sequenced individuals and identify 4065 genes and 4016 isoforms whose expression and/or alternative splicing are affected by regulatory variation. We integrate eQTLs identified in adult islets and whole pancreas samples, which reveal 1805 eQTL associations that are unique to the fetal-like iPSC-PPCs and 1043 eQTLs that exhibit regulatory plasticity across the fetal-like and adult pancreas tissues. Colocalization with GWAS risk loci for pancreatic diseases and traits show that some putative causal regulatory variants are active only in the fetal-like iPSC-PPCs and likely influence disease by modulating expression of disease-associated genes in early development, while others with regulatory plasticity likely exert their effects in both the fetal and adult pancreas by modulating expression of different disease genes in the two developmental stages.
•Experimental validation of electrical efficiency PVT water collector has been done.•Annual performance has been studied considering all types of weather conditions.•Carbon credit earned in a year ...and annualized uniform cost has been determined.
In present communication, an experimental study has been carried out to evaluate the performance of series connected photovoltaic thermal (PVT) water collector in terms of overall thermal energy gain and overall exergy gain. Earlier developed theoretical model has been validated by performing the experiment in a clear sky day, hazy day and partially cloudy day for New Delhi climatic condition. It was found that theoretical results were in good agreement with experimental results. The annual energy gain, exergy gains, CO2 mitigation, energy matrices and carbon credit of the system have also been discussed. The energy pay-back time was found to be 1.50 and 14.19years on overall thermal energy and exergy basis respectively. Carbon credits earned in a year were Rs. 6321.70 for overall thermal energy gain and Rs. 667.30 for overall exergy gain. For 30years of life time, cost of one unit of electricity was estimated to be Rs. 1.53 on overall thermal energy basis however it was Rs. 14.45 on overall exergy basis.
Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities ...between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3–6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis‐associated occlusion of the bronchiolar airways in all allografts of long‐term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long‐term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long‐term survivors develop histologic changes in the allografts that are hallmarks of OB.
The authors developed an orthotopic model of lung transplantation in the ferret that develops the entire spectrum of lung allograft pathology similar to humans, including acute rejection, lymphocytic bronchiolitis and obliterative bronchiolitis.
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