In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue rem...In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.展开更多
The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ J/ψ pK-（-B/0→ J/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse mome...The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ J/ψ pK-（-B/0→ J/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse momentum, PT, and rapidity, y. The kinematic region of the measurements is pT〈20 GeV/c and 2.0 〈g〈4.5.The measurements use a data sample corresponding to an integrated luminosity of 3fb-1 collected by the LHCb detector in pp collisions at centre-of-mass energies √s=7 TeV in 2011 and √s=8 TeV in 2012. Based on previous LHCb results of the fragmentation fraction ratio,f∧0/b/fd,the branching fraction of the decay ∧0/b→ J/ψ pK-is measured to be B（∧0/b→ J/ψ pK-）=（3.17±0.04±0.07±0.34＋0.45/-0.28）×10-4,where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay -B/0 →J/ψ-K＊（892）0,and the fourth is due to the knowledge of f∧0/b/fd.The sum of the asymmetries in the production and decay between ∧0/b and ∧0/bis also measured as a function of PT and y.The previously published branching fraction of ∧0/b→ J/ψ pπ-,relative to that of ∧0/b→ J/ψ pK-,is updated. The branching fractions of ∧0/b→P＋c（→ J/ψp）K-are determined.展开更多
The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. Enhanced inflammation in the liver during ethanol exposure is an important c...The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. Enhanced inflammation in the liver during ethanol exposure is an important contributor to injury. Kupffer cells, the resident macrophages in liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharide via Toll-like receptor 4. This sensitization enhances production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species, that contribute to hepatocyte dysfunction, necrosis, apoptosis, and fibrosis. Impaired resolution of the inflammatory process probably also contributes to ALD. The resolution of inflammation is an active, highly coordinated response that can potentially be manipulated via therapeutic interventions to treat chronic inflammatory diseases. Recent studies have identif ied an adiponectin/interleukin-10/heme oxygenase-1 (HO-1) pathway that is profoundly effective in dampening the enhanced activation of innate immune responses in primary cultures of Kupffer cells, as well as in an in vivo mouse model of chronic ethanol feeding. Importantly, induction of HO-1 also reduces ethanol-induced hepatocellular apoptosis in this in vivo model. Based on these data, we hypothesize that the development of therapeutic agents to regulate HO-1 and its downstream targets could be useful in enhancing the resolution of inflammation during ALD and preventing progression of early stages of liver injury.展开更多
AIM:To assess the relationship between preoperative computed tomography(CT)and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS:A retro...AIM:To assess the relationship between preoperative computed tomography(CT)and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS:A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy.Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens.Inter-and intra-observer variations in CT measurements were assessed.Survival data were collected.RESULTS:There was a weak correlation between CT and pathological tumor length(r=0.30,P=0.025).CT lengths were longer than pathological lengths in 68%(38/56)of patients with a mean difference of 1.67 cm(95%CI:1.18-2.97).The mean difference in measurements by two radiologists was 0.39 cm(95% CI:-0.59-1.44).The mean difference between repeat CT measured tumor length(intra-observer variation) were 0.04 cm(95%CI:-0.59-0.66)and 0.47 cm (95%CI:-0.53-1.47).When stratified,patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length(r =0.69,P=0.0014,n=37)than patients that did(r= 0.13,P=0.43,n=19).Median survival with CT tumor length>5.6 cm was poorer than with smaller tumors,but the difference was not statistically significant.CONCLUSION:Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions,particularly for planning radiotherapy.展开更多
Knowledge of the airflow patterns and methane distributions at a continuous miner face under different ventilation conditions can minimize the risks of explosion and injury to miners by accurately forecasting potentia...Knowledge of the airflow patterns and methane distributions at a continuous miner face under different ventilation conditions can minimize the risks of explosion and injury to miners by accurately forecasting potentially hazardous face methane levels. This study focused on validating a series of computational fluid dynamics(CFD) models using full-scale ventilation gallery data that assessed how curtain setback distance impacted airflow patterns and methane distributions at an empty mining face(no continuous miner present). Three CFD models of face ventilation with 4.6, 7.6 and 10.7 m(15, 25, and 35 ft) blowing curtain setback distances were constructed and validated with experimental data collected in a full-scale ventilation test facility. Good agreement was obtained between the CFD simulation results and this data.Detailed airflow and methane distribution information are provided. Elevated methane zones at the working faces were identified with the three curtain setback distances. Visualization of the setback distance impact on the face methane distribution was performed by utilizing the post-processing capability of the CFD software.展开更多
Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases....Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in E/f3 （homologous to human ESE-1） knockout mice, the expression of the inflammatory cytokine interleukin-6 （IL-6） is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.展开更多
Lateritic soils are frequently utilised in tropical areas of the developing world as an engineering material in the construction of rural earth roads, usually in the form of engineered natural surface (ENS) roads. The...Lateritic soils are frequently utilised in tropical areas of the developing world as an engineering material in the construction of rural earth roads, usually in the form of engineered natural surface (ENS) roads. The heavy, seasonal rainfalls common to the tropics results in ENS roads becoming quickly saturated with rainwater, and no longer accessible to motorised transportation. Microbially induced calcite precipitation (MICP) has been successfully used as a treatment process to decrease the permeability of clean, cohesionless sands by studies trying to impede the movement of groundwater, and any pollutants they may contain. In order to see if MICP treatment can also reduce the susceptibility of ENS road lateritic soils to rainwater saturation, this study has treated a Brazilian sample extracted from an ENS road in Espirito do Santo, Brazil, using the MICP bacterium Sporosarcina pasteurii contained within a urea-calcium chloride solution inoculum. Investigation, by means of a Rowe cell, of the post-treatment permeability, to untreated control samples, has shown an average decrease in the vertical coefficient of permeability of 83%, from 1.15 × 10-7 m/s for the untreated control samples, to 1.92 × 10-8 m/s in treated samples.展开更多
Conventional fusion arc welding of high-strength quenched and tempered steel can be improved through the use of non-conventional laser beam welding. This article presents the investigations of autogenous bead on plate...Conventional fusion arc welding of high-strength quenched and tempered steel can be improved through the use of non-conventional laser beam welding. This article presents the investigations of autogenous bead on plate and butt CO<sub>2</sub> Laser Welding (LW) of 7 mm thick high-strength quenched and tempered low alloy SM570 (JIS) steel plates. The influence of laser welding parameters, mainly welding speed, defocusing distance and shielding gas flow rate on the weld profile, i.e., weld zone penetration depth and width, microstructure and mechanical properties of welded joints was determined. All welded joints showed smooth and uniform weld beads free from superficial porosity and undercuts. The selected best welding conditions were a laser power of 5.0 kW, welding speed of 500 mm/min, argon gas shielding flow rate of 30 L/min and a defocusing distance of -0.5 mm. It was observed that these conditions gave complete penetration and minimized the width of the weld bead. The microstructure of the welded joints was evaluated by light optical microscopy. The weld metal (WM) and heat-affected zone (HAZ) near weld metal achieved maximum hardness (355 HV). The tensile fractured samples showed the ductile mode of failure and ultimate tensile strength of 580 MPa.展开更多
<strong>Background:</strong> The IMF fears the COVID-19 pandemic will create an economic down-turn matching the Great Depression. More recent recessions have led to physical and mental health problems incl...<strong>Background:</strong> The IMF fears the COVID-19 pandemic will create an economic down-turn matching the Great Depression. More recent recessions have led to physical and mental health problems including suicide deaths of young adults (15 - 34). We aim to identify risk patterns of mortality by age from influenza and suicide mortality in peak years from 1979 to 2016 to see if there are lessons to be learned for policy makers and psychiatric services.<strong> Method:</strong> Using WHO mortality data for 1979-2016 peak years of influenza deaths and suicides are identified in ten Western countries. Death rates per million in each age-band are calculated for both sexes and the percentage of the total deaths accruing in each of five age-bands for influenza and suicides. Ratios of influenza to suicide by age in regard to rates and percentages of deaths indicate differential risk mortality and morbidity patterns.<strong> Results: </strong>Of the ten country’s average Influenza deaths, 95% occurred in people over 55, including 80% - 85% for the over 75’s. Conversely it was 59% of suicides occurred in peoples aged <55 years. Young adults (15 - 34) influenza to suicide ratios were 1:12.1 and 35 - 54 years ratio 1:9.3. <strong>Discussion:</strong> IMF predicts major unemployment, which is likely to create mental health problems, including suicide as well as worsening child health outcomes linked to relative poverty. These wider inter-related factors should be considered by policy-makers and mental health services. The age patterns of risk of mortality point towards a cumulative summation of morbidity and mortality risks of the socio-economic consequences of the COVID pandemic.展开更多
Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phos-phorylation(OxPhos)and increases mitochondrial production of reactive oxygen species(ROS).In primary tu-mors thi...Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phos-phorylation(OxPhos)and increases mitochondrial production of reactive oxygen species(ROS).In primary tu-mors this provokes metabolic reprogramming of both tumor cells and cancer stem cells and emergence of highly metastatic cancer cells.Tumor reprogramming is initiated by activating nuclear respiratory factors and hypoxia-inducible factors in response to changes in oxygen and ROS levels.Hence,hypoxia-induced pro-oxidative stress drives invasion and metastasis.However,it is also the Achilles’heel of metastatic cancer cells because pro-oxi-dative agents further overload the mitochondria and intracellular milieu with excessive ROS to trigger apoptosis,whereas antioxidant agents promote their survival and tumor progression.Herein lies the metastatic tumor cell sensitivity to non-steroidal anti-inflammatory drugs(NSAIDs)and we and others have shown that the NSAID celecoxib exerts powerful pro-oxidative anticancer effects by directly targeting mitochondria to increase ROS production and trigger cancer cell death,including metastatic cancer cells and cancer stem cells.This review highlights the considerable benefits from appropriate NSAID use in humans against post-diagnosis metastatic tumors and the need to further develop their use as adjuvant therapy for advanced stage metastatic disease where they are already showing significantly improved clinical outcomes.展开更多
The purpose of this study was to report the adjusted effect sizes of mid trimester sonographic findings that are associated with Down syndrome in a sonographically screened population. A large prospective single- cent...The purpose of this study was to report the adjusted effect sizes of mid trimester sonographic findings that are associated with Down syndrome in a sonographically screened population. A large prospective single- center cohort study was conducted between March 1993 and December 2002 in South- East Queensland with women who were first scanned between 15 to 22 weeks of gestation. Univariate and multivariable logistic regression modeling was used to relate karyotypically ascertained Down syndrome fetuses and their control counterparts against routinely collected demographic and sonographic findings. Data were available for 73 Down- affected and 16,891 unaffected pregnancies. Strong colinearity existed between short humerus and short femurs that necessitated the removal of FL in pursuant multivariable models. In the most parsimonious model, which was adjusted for maternal age and gestational age, pregnancies with thick nuchal skinfold (regression coefficient β .[± .SE], 2.100 ± 0.545), short humerus length (regression coefficient β , 2.304 ± 0.314), presence of echogenic bowel (regression coefficient β , 1.602 ± 0.412), presence of echogenic intracardiac focus (regression coefficient β , 1.975 ± 0.308)- , presence of renal pelvic dilation (regression coefficient β , 1.281 ± 0.420), presence of aneuploid associated anomalies (regression coefficient β , 4.473 ± 0.535), the interaction between gestational age and thick nuchal skinfold (regression coefficient β , 0.465 ± 0.210), and the interaction between short humerus length and the presence of aneuploid associated anomalies (regression coefficient β , - 1.693 ± 0.811) all were associated significantly with Down syndrome risk (all P<.05). Adjusted relative risk estimates were substantially different from their crude estimates. Routinely collected mid trimester sonographic findings are associated significantly with Down syndrome risk in a sonographically screened population after accounting for maternal age and gestational age. Because of dependencies b展开更多
基金Supported by Wellcome Trust Clinical Research Training Fellowship to MDB
文摘In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.
基金Supported by CERN and national agencies:CAPES,CNPq,FAPERJ and FINEP(Brazil)NSFC(China)+17 种基金CNRS/IN2P3(France)BMBF,DFG,HGF and MPG(Germany)INFN(Italy)FOM and NWO(The Netherlands)MNi SW and NCN(Poland)MEN/IFA(Romania)Min ES and FANO(Russia)Min ECo(Spain)SNSF and SER(Switzerland)NASU(Ukraine)STFC(United Kingdom)NSF(USA)supported by IN2P3(France),KIT and BMBF(Germany),INFN(Italy),NWOSURF(The Netherlands),PIC(Spain),Grid PP(United Kingdom)support from EPLANET,Marie Sk lodowska-Curie ActionsERC(European Union),Conseil général de Haute-Savoie,Labex ENIGMASS and OCEVU,RégionAuvergne(France),RFBR(Russia),Xunta GalGENCAT(Spain),Royal Society and Royal Commission for the Exhibition of 1851(United Kingdom)
文摘The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ J/ψ pK-（-B/0→ J/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse momentum, PT, and rapidity, y. The kinematic region of the measurements is pT〈20 GeV/c and 2.0 〈g〈4.5.The measurements use a data sample corresponding to an integrated luminosity of 3fb-1 collected by the LHCb detector in pp collisions at centre-of-mass energies √s=7 TeV in 2011 and √s=8 TeV in 2012. Based on previous LHCb results of the fragmentation fraction ratio,f∧0/b/fd,the branching fraction of the decay ∧0/b→ J/ψ pK-is measured to be B（∧0/b→ J/ψ pK-）=（3.17±0.04±0.07±0.34＋0.45/-0.28）×10-4,where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay -B/0 →J/ψ-K＊（892）0,and the fourth is due to the knowledge of f∧0/b/fd.The sum of the asymmetries in the production and decay between ∧0/b and ∧0/bis also measured as a function of PT and y.The previously published branching fraction of ∧0/b→ J/ψ pπ-,relative to that of ∧0/b→ J/ψ pK-,is updated. The branching fractions of ∧0/b→P＋c（→ J/ψp）K-are determined.
基金Supported by (in part) NIH Grants No. RO1AA0011975Supported by (in part) NIH Grants No. R56AA001975Supported by (in part) NIH Grants No. RO1AA011876
文摘The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. Enhanced inflammation in the liver during ethanol exposure is an important contributor to injury. Kupffer cells, the resident macrophages in liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharide via Toll-like receptor 4. This sensitization enhances production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species, that contribute to hepatocyte dysfunction, necrosis, apoptosis, and fibrosis. Impaired resolution of the inflammatory process probably also contributes to ALD. The resolution of inflammation is an active, highly coordinated response that can potentially be manipulated via therapeutic interventions to treat chronic inflammatory diseases. Recent studies have identif ied an adiponectin/interleukin-10/heme oxygenase-1 (HO-1) pathway that is profoundly effective in dampening the enhanced activation of innate immune responses in primary cultures of Kupffer cells, as well as in an in vivo mouse model of chronic ethanol feeding. Importantly, induction of HO-1 also reduces ethanol-induced hepatocellular apoptosis in this in vivo model. Based on these data, we hypothesize that the development of therapeutic agents to regulate HO-1 and its downstream targets could be useful in enhancing the resolution of inflammation during ALD and preventing progression of early stages of liver injury.
基金Supported by The local departmental research fund
文摘AIM:To assess the relationship between preoperative computed tomography(CT)and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS:A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy.Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens.Inter-and intra-observer variations in CT measurements were assessed.Survival data were collected.RESULTS:There was a weak correlation between CT and pathological tumor length(r=0.30,P=0.025).CT lengths were longer than pathological lengths in 68%(38/56)of patients with a mean difference of 1.67 cm(95%CI:1.18-2.97).The mean difference in measurements by two radiologists was 0.39 cm(95% CI:-0.59-1.44).The mean difference between repeat CT measured tumor length(intra-observer variation) were 0.04 cm(95%CI:-0.59-0.66)and 0.47 cm (95%CI:-0.53-1.47).When stratified,patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length(r =0.69,P=0.0014,n=37)than patients that did(r= 0.13,P=0.43,n=19).Median survival with CT tumor length>5.6 cm was poorer than with smaller tumors,but the difference was not statistically significant.CONCLUSION:Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions,particularly for planning radiotherapy.
文摘Knowledge of the airflow patterns and methane distributions at a continuous miner face under different ventilation conditions can minimize the risks of explosion and injury to miners by accurately forecasting potentially hazardous face methane levels. This study focused on validating a series of computational fluid dynamics(CFD) models using full-scale ventilation gallery data that assessed how curtain setback distance impacted airflow patterns and methane distributions at an empty mining face(no continuous miner present). Three CFD models of face ventilation with 4.6, 7.6 and 10.7 m(15, 25, and 35 ft) blowing curtain setback distances were constructed and validated with experimental data collected in a full-scale ventilation test facility. Good agreement was obtained between the CFD simulation results and this data.Detailed airflow and methane distribution information are provided. Elevated methane zones at the working faces were identified with the three curtain setback distances. Visualization of the setback distance impact on the face methane distribution was performed by utilizing the post-processing capability of the CFD software.
文摘Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in E/f3 （homologous to human ESE-1） knockout mice, the expression of the inflammatory cytokine interleukin-6 （IL-6） is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0603)the National Natural Science Foundation of China(41971153 and 42171086)+1 种基金the Science and Technology Department of Tibet Program(XZ202301ZY0016G)the Chinese Committee on International Centre for Integrated Mountain Development(CNICIMOD)。
文摘Lateritic soils are frequently utilised in tropical areas of the developing world as an engineering material in the construction of rural earth roads, usually in the form of engineered natural surface (ENS) roads. The heavy, seasonal rainfalls common to the tropics results in ENS roads becoming quickly saturated with rainwater, and no longer accessible to motorised transportation. Microbially induced calcite precipitation (MICP) has been successfully used as a treatment process to decrease the permeability of clean, cohesionless sands by studies trying to impede the movement of groundwater, and any pollutants they may contain. In order to see if MICP treatment can also reduce the susceptibility of ENS road lateritic soils to rainwater saturation, this study has treated a Brazilian sample extracted from an ENS road in Espirito do Santo, Brazil, using the MICP bacterium Sporosarcina pasteurii contained within a urea-calcium chloride solution inoculum. Investigation, by means of a Rowe cell, of the post-treatment permeability, to untreated control samples, has shown an average decrease in the vertical coefficient of permeability of 83%, from 1.15 × 10-7 m/s for the untreated control samples, to 1.92 × 10-8 m/s in treated samples.
文摘Conventional fusion arc welding of high-strength quenched and tempered steel can be improved through the use of non-conventional laser beam welding. This article presents the investigations of autogenous bead on plate and butt CO<sub>2</sub> Laser Welding (LW) of 7 mm thick high-strength quenched and tempered low alloy SM570 (JIS) steel plates. The influence of laser welding parameters, mainly welding speed, defocusing distance and shielding gas flow rate on the weld profile, i.e., weld zone penetration depth and width, microstructure and mechanical properties of welded joints was determined. All welded joints showed smooth and uniform weld beads free from superficial porosity and undercuts. The selected best welding conditions were a laser power of 5.0 kW, welding speed of 500 mm/min, argon gas shielding flow rate of 30 L/min and a defocusing distance of -0.5 mm. It was observed that these conditions gave complete penetration and minimized the width of the weld bead. The microstructure of the welded joints was evaluated by light optical microscopy. The weld metal (WM) and heat-affected zone (HAZ) near weld metal achieved maximum hardness (355 HV). The tensile fractured samples showed the ductile mode of failure and ultimate tensile strength of 580 MPa.
文摘<strong>Background:</strong> The IMF fears the COVID-19 pandemic will create an economic down-turn matching the Great Depression. More recent recessions have led to physical and mental health problems including suicide deaths of young adults (15 - 34). We aim to identify risk patterns of mortality by age from influenza and suicide mortality in peak years from 1979 to 2016 to see if there are lessons to be learned for policy makers and psychiatric services.<strong> Method:</strong> Using WHO mortality data for 1979-2016 peak years of influenza deaths and suicides are identified in ten Western countries. Death rates per million in each age-band are calculated for both sexes and the percentage of the total deaths accruing in each of five age-bands for influenza and suicides. Ratios of influenza to suicide by age in regard to rates and percentages of deaths indicate differential risk mortality and morbidity patterns.<strong> Results: </strong>Of the ten country’s average Influenza deaths, 95% occurred in people over 55, including 80% - 85% for the over 75’s. Conversely it was 59% of suicides occurred in peoples aged <55 years. Young adults (15 - 34) influenza to suicide ratios were 1:12.1 and 35 - 54 years ratio 1:9.3. <strong>Discussion:</strong> IMF predicts major unemployment, which is likely to create mental health problems, including suicide as well as worsening child health outcomes linked to relative poverty. These wider inter-related factors should be considered by policy-makers and mental health services. The age patterns of risk of mortality point towards a cumulative summation of morbidity and mortality risks of the socio-economic consequences of the COVID pandemic.
基金This work was partially supported by CONACyT-Mexico grants No.239930 and 281428 to RMS and 283144 to SRE.Rhys Pritchard was supported by an Australian postgraduate research award(APRA).
文摘Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phos-phorylation(OxPhos)and increases mitochondrial production of reactive oxygen species(ROS).In primary tu-mors this provokes metabolic reprogramming of both tumor cells and cancer stem cells and emergence of highly metastatic cancer cells.Tumor reprogramming is initiated by activating nuclear respiratory factors and hypoxia-inducible factors in response to changes in oxygen and ROS levels.Hence,hypoxia-induced pro-oxidative stress drives invasion and metastasis.However,it is also the Achilles’heel of metastatic cancer cells because pro-oxi-dative agents further overload the mitochondria and intracellular milieu with excessive ROS to trigger apoptosis,whereas antioxidant agents promote their survival and tumor progression.Herein lies the metastatic tumor cell sensitivity to non-steroidal anti-inflammatory drugs(NSAIDs)and we and others have shown that the NSAID celecoxib exerts powerful pro-oxidative anticancer effects by directly targeting mitochondria to increase ROS production and trigger cancer cell death,including metastatic cancer cells and cancer stem cells.This review highlights the considerable benefits from appropriate NSAID use in humans against post-diagnosis metastatic tumors and the need to further develop their use as adjuvant therapy for advanced stage metastatic disease where they are already showing significantly improved clinical outcomes.
文摘The purpose of this study was to report the adjusted effect sizes of mid trimester sonographic findings that are associated with Down syndrome in a sonographically screened population. A large prospective single- center cohort study was conducted between March 1993 and December 2002 in South- East Queensland with women who were first scanned between 15 to 22 weeks of gestation. Univariate and multivariable logistic regression modeling was used to relate karyotypically ascertained Down syndrome fetuses and their control counterparts against routinely collected demographic and sonographic findings. Data were available for 73 Down- affected and 16,891 unaffected pregnancies. Strong colinearity existed between short humerus and short femurs that necessitated the removal of FL in pursuant multivariable models. In the most parsimonious model, which was adjusted for maternal age and gestational age, pregnancies with thick nuchal skinfold (regression coefficient β .[± .SE], 2.100 ± 0.545), short humerus length (regression coefficient β , 2.304 ± 0.314), presence of echogenic bowel (regression coefficient β , 1.602 ± 0.412), presence of echogenic intracardiac focus (regression coefficient β , 1.975 ± 0.308)- , presence of renal pelvic dilation (regression coefficient β , 1.281 ± 0.420), presence of aneuploid associated anomalies (regression coefficient β , 4.473 ± 0.535), the interaction between gestational age and thick nuchal skinfold (regression coefficient β , 0.465 ± 0.210), and the interaction between short humerus length and the presence of aneuploid associated anomalies (regression coefficient β , - 1.693 ± 0.811) all were associated significantly with Down syndrome risk (all P<.05). Adjusted relative risk estimates were substantially different from their crude estimates. Routinely collected mid trimester sonographic findings are associated significantly with Down syndrome risk in a sonographically screened population after accounting for maternal age and gestational age. Because of dependencies b
