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921.
Purpose

New-generation wide-base tire (NG-WBT) is known for improving fuel economy and at the same time for potentially causing a greater damage to pavement. No study has been conducted to evaluate the net environmental saving of the combined system of pavements and NG-WBT. This study adopted a holistic approach (life cycle assessment [LCA] and life cycle costing [LCC]) to quantitatively evaluate the environmental and economic impact of using NG-WBT.

Methods

The net effect of different levels of market penetration of NG-WBT on energy consumption, global warming potential (GWP), and cost based on the fatigue cracking and rutting performance of two different asphalt concrete (AC) pavement structures was evaluated. The performance of pavements was determined based on pavement design lives; pavement surface characteristics, and pavement critical strain responses obtained from the artificial neural network (ANN) based on finite element (FE) simulations were used to calculate design lives of pavements. Based on the calculated design lives, life cycle inventory (LCI) and cost databases, and rolling resistance (RR) models previously developed by the University of Illinois at Urbana-Champaign (UIUC) were used to calculate the environmental and economic impact of the combined system.

Results and discussion

The fuel economy improvement using NG-WBT is 1.5% per axle. Scenario-based case studies were conducted. Considering 0% NG-WBT market penetration (or 100% standard dual tire assembly [DTA]) as a baseline, scenario 1 assumed the same fatigue and rutting potential between NG-WBT and DTA; therefore, the only difference came from fuel economy improvement of using NG-WBT. In scenario 2, pavement fatigue cracking potential determined the pavement design life; both thick and thin AC overlay sections experienced positive net environmental savings, but mixed net economic savings. In scenario 3, pavement rutting potential determined the pavement design life; the thick AC overlay section experienced positive net environmental savings, but mixed net economic savings. The thin section experienced negative net environmental and economic savings.

Conclusions

The outcomes of scenario-based case studies indicated that NG-WBT can result in significant savings in life cycle energy consumption and cost, and GWP; however, these benefits were sensitive to the method used to determine the pavement performance; especially, a small change in pavement strain can result in significant change in pavement life. In addition, the effect of fuel price/economy improvement, discount rate, and International Roughness Index (IRI) threshold values was studied in the sensitivity analyses.

  相似文献   
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N-Aliphatic ester analogues of the non-opioid ketamine (1) retain effective anaesthetic/analgesic properties while minimising ketamine’s psychomimetic side-effects. We show that the anaesthetic/analgesic properties of these ester analogues depend critically on the length (from 2 to 4 carbons), polarity and steric cross-section of the aliphatic linker chain. More stable amide and ethylsulfone analogues generally showed weaker anaesthetic/analgesic activity. There was no correlation between the anaesthetic/analgesic properties of the compounds and their binding affinities for the N-methyl-d-aspartate (NMDA) receptor.  相似文献   
924.
Cardiovascular cell-based regenerative medicine has enjoyed a brief but exciting history. In little over a decade, multiple hypotheses have risen and fallen, and this work has now triggered a critical reconsideration of several long-held cardiovascular paradigms. These and other issues were the focus of the second Symposium on Cardiovascular Regenerative Medicine, recently held at the NIH-NHLBI in Bethesda, MD, USA. The meeting served to showcase some of the highlights of the past decade but, at the same time, sharply underlined the enormity of the task ahead. Collectively, a sense emerged that researchers in this field are "digging in for the long haul."  相似文献   
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928.
Ribosome biogenesis is a ubiquitous and essential process in cells. Defects in ribosome biogenesis and function result in a group of human disorders, collectively known as ribosomopathies. In this study, we describe a zebrafish mutant with a loss-of-function mutation in nol9, a gene that encodes a non-ribosomal protein involved in rRNA processing. nol9 sa1022/sa1022 mutants have a defect in 28S rRNA processing. The nol9 sa1022/sa1022 larvae display hypoplastic pancreas, liver and intestine and have decreased numbers of hematopoietic stem and progenitor cells (HSPCs), as well as definitive erythrocytes and lymphocytes. In addition, ultrastructural analysis revealed signs of pathological processes occurring in endothelial cells of the caudal vein, emphasizing the complexity of the phenotype observed in nol9 sa1022/sa1022 larvae. We further show that both the pancreatic and hematopoietic deficiencies in nol9 sa1022/sa1022 embryos were due to impaired cell proliferation of respective progenitor cells. Interestingly, genetic loss of Tp53 rescued the HSPCs but not the pancreatic defects. In contrast, activation of mRNA translation via the mTOR pathway by L-Leucine treatment did not revert the erythroid or pancreatic defects. Together, we present the nol9 sa1022/sa1022 mutant, a novel zebrafish ribosomopathy model, which recapitulates key human disease characteristics. The use of this genetically tractable model will enhance our understanding of the tissue-specific mechanisms following impaired ribosome biogenesis in the context of an intact vertebrate.  相似文献   
929.

Background

Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging.

Results

We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21–1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775).

Conclusions

Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9090-9) contains supplementary material, which is available to authorized users.  相似文献   
930.
For the past fifty-five years, much of my research has focused on the function and biogenesis of red blood cells, including the cloning and study of many membrane proteins such as glucose and anion transporters and the erythropoietin receptor. We have also elucidated the mechanisms of membrane insertion, folding, and maturation of many plasma membrane and secreted proteins. Despite all of this work and more, I remain extremely proud of our very early work on the regulation of mRNA translation: work on bacteriophage f2 RNA in the 1960s and on translation of α- and β-globin mRNAs in the early 1970s. Using techniques hopelessly antiquated by today''s standards, we correctly elucidated many important aspects of translational control, and I thought readers would be interested in learning how we did these experiments.  相似文献   
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