Gamma ray source detection above 30 TeV is an encouraging approach for finding galactic cosmic ray sources. All sky survey for gamma ray sources using wide field of view detector is essential for population accumulati...Gamma ray source detection above 30 TeV is an encouraging approach for finding galactic cosmic ray sources. All sky survey for gamma ray sources using wide field of view detector is essential for population accumulation for various types of sources above 100 GeV. In order to target those goals, a large air shower particle detector array of 1 km^2 （the LHAASO project） at 4300 m a.s.l, is proposed, By adding two MagicⅡ- type telescopes in the array as proposed, LHAASO will be enhanced in source morphologic investigation power. The proposed array will be utilized also for energy spectrum measurement for individual cosmic ray species above 30 TeV. By re-configuring the wide field of view telescopes into fluorescence light detector array, the aperture of the detector array can be enlarged to cover an energy region above 100 PeV where the second knee is located. Cosmic ray spectrum and composition will be measured in order to transfer an energy scale to ultra high energy cosmic ray experiments.展开更多
Low thermal expansion superalloys have been used for a number of years in a variety of applications, including gas turbine engines. The low thermal expansion characteristics of the most widely used class of materials ...Low thermal expansion superalloys have been used for a number of years in a variety of applications, including gas turbine engines. The low thermal expansion characteristics of the most widely used class of materials are derived from the ferromagnetic characteristics of Ni, Fe, and Co-based austenitic matrices containing little or no Cr.Alloy developments have been aimed at improving the oxidation resistance and stress accelerated grain boundary oxygen (SAGBO) attack.INCONEL alloy 783 is an oxidation resistant, low coefficient of thermal expansion superalloy developed for gas turbine applications. Alloy 783 represents a culmination in the development, of an alloy system with very high alumtnum content that, in addition to forming γ′,causes βaluminide phase precipitation in the austenitic matrix.This type of structure can be processed to resist both SAGBO and general oxidation,while providing low thermal expansion and useful mechanical properties up to 700℃.Key aspects of the alloy's development are presented.展开更多
The characteristics of raindrop size distribution （DSD） over the Tibetan Plateau and southern China are studied in this paper, using the DSD data from April to August 2014 collected by HSC-PS32 disdrometers in Nagqu...The characteristics of raindrop size distribution （DSD） over the Tibetan Plateau and southern China are studied in this paper, using the DSD data from April to August 2014 collected by HSC-PS32 disdrometers in Nagqu and Yangjiang, com- prising a total of 9430 and 63661-rain raindrop spectra, respectively. The raindrop spectra, characteristics of parameter variations with rainfall rate, and the relationships between reflectivity factor （Z） and rainfall rate （R） are analyzed, as well as their DSD changes with precipitation type and rainfall rate. The results show that the average raindrop spectra appear to be one-peak curves, the number concentration for larger drops increase significantly with rainfall rate, and its value over southern China is much higher, especially in convective rain larger drops, especially for convective rain in southern China. Standardized Gamma distributions better describe DSD for All three Gamma parameters for stratiform precipitation over the Tibetan Plateau are much higher, while its shape parameter （,u） and mass-weighted mean diameter （Dm）, for convective precipitation, are less. In terms of parameter variation with rainfall rate, the normalized intercept parameter （Nw） over the Tibetan Plateau for stratiform rain increases with rainfall rate, which is opposite to the situation in convective rain. The/1 over the Tibetan Plateau for stratiform and convective precipitation types decreases with an increase in rainfall rate, which is opposite to the case for Dm variation. In Z-R relationships, like ＂Z = ARb＇＇, the coefficient A over the Tibetan Plateau is smaller, while its b is higher, when the rain type transfers from stratiform to convective ones. Furthermore, with an increase in rainfall rate, parameters A and b over southern China increase gradually, while A over the Tibetan Plateau decreases sub- stantially, which differs from the findings of previous studies. In terms of geographic location and climate over the Tibetan Plateau and southern China, the p展开更多
AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal ...AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.展开更多
BACKGROUND:Organ fibrosis has been viewed as one of the major medical problems, which can lead to progressive dysfunction of the liver, lung, kidney, skin, heart, and eventually death of patients. Fibrosis is initiate...BACKGROUND:Organ fibrosis has been viewed as one of the major medical problems, which can lead to progressive dysfunction of the liver, lung, kidney, skin, heart, and eventually death of patients. Fibrosis is initiated by a variety of pathological, physiological, biochemical, and physical factors. Regardless of their different etiologies, they all share a common pathogenetic process: excessive activation of the key profibrotic cytokine, transforming growth factor-β (TGF-β). Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor of the nuclear receptor superfamily, has received particular attention in recent years, because the activation of PPARγ by both natural and synthetic agonists could effectively inhibit TGF-β-induced profibrotic effects in many organs. DATA SOURCES: The English-language medical databases, PubMed, Elsevier and SpringerLink were searched for articles on PPARγ, TGF-β, and fibrosis, and related topics. RESULTS: TGF-β is recognized as a key profibrotic cytokine. Excessive activation of TGF-β increases synthesis of extracellular matrix proteins and decreases their degradation, associated with a gradual destruction of normal tissue architecture and function, whereas PPARγ agonists inhibit TGF-β signal transduction and are effective antifibrogenic agents in many organs including the liver, lung, kidney, skin and heart. CONCLUSIONS: The main antifibrotic activity of PPARγ agonists is to suppress the TGF-β signaling pathway by so-called PPARγ-dependent effect. In addition, PPARγ agonists, especially 15d-PGJ2, also exert potentially antifibrotic activity independent of PPARγ activation. TGF-β1/Smads signaling not only plays many essential roles in multiple developmental processes, butalso forms cross-talk networks with other signal pathways, and their inhibition by PPARγ agonists certainly affects the cytokine networks and causes non-suspected side-effects. Anti-TGF-β therapies with PPARγ agonists may have to be carefully tailored to be tissu展开更多
The effects of microstructure on the deformation and fracture behaviour of two-phase TiAl alloys were investjgated under monotonic and cyclical loading conditions, over a range of temperatu res.The tensile behaviour i...The effects of microstructure on the deformation and fracture behaviour of two-phase TiAl alloys were investjgated under monotonic and cyclical loading conditions, over a range of temperatu res.The tensile behaviour is analyzed for deformation temperatures between RT and 950℃, Fracture resistance behaviour and toughening mechanisms at RT and 800℃ are analyzed. and the inverse relationship botween ductility and toughness is explained using the crack initiation toughness. The preliminary results of load-controlled fatigue behaviour at 800℃ are interpreted using the tensile behaviour because deformation structure and fracture modes are similar under these two loading conditions展开更多
Finding the electromagnetic （EM） counterpart of binary compact star merger, especially the binary neutron star （BNS） merger, is critically important for gravitational wave （GW） astronomy, cosmology and fundament...Finding the electromagnetic （EM） counterpart of binary compact star merger, especially the binary neutron star （BNS） merger, is critically important for gravitational wave （GW） astronomy, cosmology and fundamental physics. On Aug. 17, 2017, Advanced LIGO and Fermi/GBM independently triggered the first BNS merger, GW170817, and its high energy EM counterpart, GRB 170817A, respectively, resulting in a global observation campaign covering gamma-ray, X-ray, UV, optical, IR, radio as well as neutrinos. The High Energy X-ray telescope （HE） onboard Insight-HXMT （Hard X-ray Modulation Telescope） is the unique high-energy gamma-ray telescope that monitored the entire GW localization area and especially the optical counterpart （SSS17a/AT2017gfo） with very large collection area （M000 cm2） and microsecond time resolution in 0.2-5 MeV. In addition, Insight-HXMT quickly implemented a Target of Opportunity （TOO） observation to scan the GW localization area for potential X-ray emission from the GW source. Although Insight-HXMT did not detect any significant high energy （0.2-5 MeV） radiation from GW170817, its observation helped to confirm the unexpected weak and soft nature of GRB 170817A. Meanwhile, Insight-HXMT/HE provides one of the most stringent constraints （-10-7 to 104 erg/cm2/s） for both GRB170817A and any other possible precursor or extended emissions in 0.2-5 MeV, which help us to better understand the properties of EM radiation from this BNS merger. Therefore the observation of Insight-HXMT constitutes an important chapter in the full context of multi-wavelength and multi-messenger observation of this historical GW event.展开更多
BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activa...BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma(PPAR-γ) on rat hepatic fibrosis. METHODS:Hepatic fibrosis in rats was induced by CCl4 for 2 weeks(early fibrosis)and 8 weeks(sustained fibrosis).The rats were randomly divided into four groups:normal control, fibrosis,blank vector,and PPAR-γ.They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene by portal vein injection.The liver of the rats was examined histologically and hydroxyproline was assessed.In vitro primary hepatic stellate cells(HSCs)were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene.The status of HSC proliferation was measured by the MTT assay.The protein levels of PPAR-γ,α-smooth muscle actin(α-SMA)and type I collagen expression were evaluated by the Western blotting method. RESULTS:In vitro studies revealed that expression of PPAR-γ inhibited expression ofα-SMA and type I collagen in activated HSCs(P<0.01)as well as HSC proliferation(P<0.01).In vivo experiments indicated that in the early hepatic fibrosis group,the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-γtransfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group;whereas the expressions of PPAR-γ andα-SMA were different compared to the hepatic fibrosis group(P<0.01).In the sustained hepatic fibrosis group,there were significant differences in the hydroxyproline content and the expression of PPAR-γ,α-SMA,and type I collagen between each group.CONCLUSION:PPAR-γcan inhibit HSC proliferation and hepatic fibrosis,and suppressα-SMA and type I collagen expression.展开更多
AIM:To investigate the effects of heme oxygenase(HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma(PPARγ) and nuclear factor-kappa B(NF-κB) in rats.METHODS:Sixty Wistar r...AIM:To investigate the effects of heme oxygenase(HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma(PPARγ) and nuclear factor-kappa B(NF-κB) in rats.METHODS:Sixty Wistar rats were used to construct liver fibrosis models and were randomly divided into 5 groups:group A(normal,untreated),group B(model for 4 wk,untreated),group C(model for 6 wk,untreated),group D [model for 6 wk,treated with zinc protoporphyrin Ⅸ(ZnPP-Ⅸ) from week 4 to week 6],group E(model for 6 wk,treated with hemin from week 4 to week 6).Next,liver injury was assessed by measuring serum alanine aminotransferase(ALT),aspartate aminotransferase(AST) and albumin levels.The degree of hepatic fibrosis was evaluated by measuring serum hyaluronate acid(HA),type Ⅳ collagen(Ⅳ-C) and by histological examination.Hydroxyproline(Hyp) content in the liver homogenate was determined.The expres-sion levels of alpha-smooth muscle actin(α-SMA) in liver tissue were measured by real-time quantitative polymerase chain reaction(RT-PCR).The expression levels of PPARγ and NF-κB were determined by RT-PCR and Western blotting.RESULTS:The expression of HO-1 increased with the development of fibrosis.Induction of HO-1 by hemin significantly attenuated the severity of liver injury and the levels of liver fibrosis as compared with inhibition of HO-1 by ZnPP-Ⅸ.The concentrations of serum ALT,AST,HA and Ⅳ-C in group E decreased compared with group C and group D(P < 0.01).Amount of Hyp and α-SMA in the liver tissues in group E decreased compared with group C(0.62 ± 0.14 vs 0.84 ± 0.07,1.42 ± 0.17 vs 1.84 ± 0.17,respectively,P < 0.01) and group D(0.62 ± 0.14 vs 1.11 ± 0.16,1.42 ± 0.17 vs 2.56 ± 0.37,respectively,P < 0.01).The expression of PPARγ at levels of transcription and translation decreased with the development of fibrosis especially in group D;and it increased in group E compared with groups C and D(0.88 ± 0.15 vs 0.56 ± 0.19,0.88 ± 0.15 vs 0.41 ± 0.11,respectively,P < 0.01).The expression of NF-κB 展开更多
A stochastic model for daily precipitation simulation in China was developedbased on the framework of a 'Richardson-type' weather generator that is an important tool instudying impacts of weather/climate on a ...A stochastic model for daily precipitation simulation in China was developedbased on the framework of a 'Richardson-type' weather generator that is an important tool instudying impacts of weather/climate on a variety of systems including ecosystem and risk assessment.The purpose of this work is to develop a weather generator for applications in China. The focus ison precipitation simulation since determination of other weather variables such as temperature isdependent on precipitation simulation. A framework of first order Markov Chain with GammaDistribution for daily precipitation is adopted in this work. Based on this framework, fourparameters of precipitation simulation for each month at 672 stations all over China were determinedusing daily precipitation data from 1961 to 2000. Compared with previous works, our estimation forthe parameters was made for more stations and longer observations, which makes the weather generatormore applicable and reliable. Spatial distributions of the four parameters are analyzed in aregional climate context. The seasonal variations of these parameters at five stations representingregional differences are discussed. Based on the estimated monthly parameters at 672 stations, dailyprecipitations for any period can be simulated. A 30-year simulation was made and compared withobservations during 1971-2000 in terms of annual and monthly statistics. The results aresatisfactory, which demonstrates the usefulness of the weather generator.展开更多
Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of r...Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium(RPE)cells in the equatorial region.Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length.Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye,most marked at the posterior pole.In any eye region,thickness of Bruch’s membrane(BM)is independent of axial length.BM opening,as the inner layer of the optic nerve head layers,is shifted in temporal direction in moderately elongated eyes(axial length<26.5 mm).It leads to an overhanging of BM into the intrapapillary compartment at the nasal optic disc side,and to an absence of BM at the temporal disc border.The lack of BM at the temporal disc side is the histological equivalent of parapapillary gamma zone.Gamma zone is defined as the parapapillary region without BM.In highly myopic eyes(axial length>26.5 mm),BM opening enlarges with longer axial length.It leads to a circular gamma zone.In a parallel manner,the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes.The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone,and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc.The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes.Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects,while thickness and density of the choriocapillaris,RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions.Conclusions:High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and RPE density in the equator展开更多
Introduction The Large High Altitude Air Shower Observatory plans to build a hybrid extensive air shower array with an area of about 1 km^(2) at an altitude of 4,410 m a.s.l.in Sichuan province,China,to explore the or...Introduction The Large High Altitude Air Shower Observatory plans to build a hybrid extensive air shower array with an area of about 1 km^(2) at an altitude of 4,410 m a.s.l.in Sichuan province,China,to explore the origin of high-energy cosmic rays.KM2A LHAASO-KM2A will detect gamma ray sources with a sensitivity of about 1%Crab Unit at 100 TeV.It covers an area of 1 km^(2) with a total of 5195 scintillation detectors.Its angular resolution reaches about 0.3 degrees,and the energy resolution is better than 25%.With the help of 1171 muon detectors,cosmic nuclei background will be rejected to a level of 10-4 at 50 TeV.The design and performances of the scintillation detectors and muon detectors are described in detail.WCDA LHAASO-WCDA focuses on surveying the northern sky for steady and transient sources from 100 GeV to 20 TeV,with a very high background rejection power and a good angular resolution.The WCDA consists of three water ponds with a total area of 78,000 m^(2),and the effective water depth is 4 m.Each water pond is divided into 5m×5m cells partitioned by black plastic curtains to prevent penetration of the light from neighboring cells.An 8-inch PMT sits at the bottom center of each cell,looking upward to collect Cherenkov light generated by shower secondary particles in water.WFCTA LHAASO-WFCTA is composed of 12 wide-field-of-view Cherenkov/fluorescence telescopes.Each telescope consists of a spherical light collector of about 4.7 m^(2) and focal plane camera of 32×32 pixels with a pixel size of 0.5 degree.LHAASO prototype arrays A prototype array about 1%of LHAASO has been constructed at Yangbajing Cosmic Ray Observatory and has been in operation for more than 2 years.Its performance fully meets the design requirements.Conclusion The LHAASO detectors are designed to fulfill the physical goals in gamma ray astronomy and cosmic ray physics.One-fourth of LHAASO will be constructed and put into operation to produce physical data by the end of 2018.The whole array will be finished in the beginning of 2021.展开更多
Despite great progress in the detection and treatment of prostate cancer, this disease remains an incredible health and economic burden. Although androgen receptor （AR） signaling plays a key role in the development ...Despite great progress in the detection and treatment of prostate cancer, this disease remains an incredible health and economic burden. Although androgen receptor （AR） signaling plays a key role in the development and progression of prostate cancer, aberrations in other molecular pathways also contribute to the disease, making it essential to identify and develop drugs against novel targets, both for the prevention and treatment of prostate cancer. One promising target is the peroxisome proliferator-activated receptor gamma （PPARy） protein. PPARy was originally thought to act as a tumor suppressor in prostate cells because agonist ligands inhibited the growth of prostate cancer cells; however, additional studies found that PPARy agonists inhibit cell growth independent of PPARy. Furthermore, PPARy expression increases with cancer grade/stage, which would suggest that it is not a tumor suppressor but instead that PPARy activity may play a role in prostate cancer development and/or progression. Indeed, two new studies, taking vastly different, unbiased approaches, have identified PPARy as a target in prostate cancer and suggest that PPARy inhibition might be useful in prostate cancer prevention and treatment. These findings could lead to a new therapeutic weapon in the fight against prostate cancer.展开更多
基金Supported by Knowledge Innovation Fund (U-526) of IHEP,China
文摘Gamma ray source detection above 30 TeV is an encouraging approach for finding galactic cosmic ray sources. All sky survey for gamma ray sources using wide field of view detector is essential for population accumulation for various types of sources above 100 GeV. In order to target those goals, a large air shower particle detector array of 1 km^2 （the LHAASO project） at 4300 m a.s.l, is proposed, By adding two MagicⅡ- type telescopes in the array as proposed, LHAASO will be enhanced in source morphologic investigation power. The proposed array will be utilized also for energy spectrum measurement for individual cosmic ray species above 30 TeV. By re-configuring the wide field of view telescopes into fluorescence light detector array, the aperture of the detector array can be enlarged to cover an energy region above 100 PeV where the second knee is located. Cosmic ray spectrum and composition will be measured in order to transfer an energy scale to ultra high energy cosmic ray experiments.
文摘Low thermal expansion superalloys have been used for a number of years in a variety of applications, including gas turbine engines. The low thermal expansion characteristics of the most widely used class of materials are derived from the ferromagnetic characteristics of Ni, Fe, and Co-based austenitic matrices containing little or no Cr.Alloy developments have been aimed at improving the oxidation resistance and stress accelerated grain boundary oxygen (SAGBO) attack.INCONEL alloy 783 is an oxidation resistant, low coefficient of thermal expansion superalloy developed for gas turbine applications. Alloy 783 represents a culmination in the development, of an alloy system with very high alumtnum content that, in addition to forming γ′,causes βaluminide phase precipitation in the austenitic matrix.This type of structure can be processed to resist both SAGBO and general oxidation,while providing low thermal expansion and useful mechanical properties up to 700℃.Key aspects of the alloy's development are presented.
基金supported jointly by the China Meteorological Administration Special Public Welfare Research Fund (Grant No. GYHY201406001)the National (Key) Basic Research and Development (973) Program of China (Grant No. 2012CB417202)the National Natural Science Foundation of China (Grant No. 41175038)
文摘The characteristics of raindrop size distribution （DSD） over the Tibetan Plateau and southern China are studied in this paper, using the DSD data from April to August 2014 collected by HSC-PS32 disdrometers in Nagqu and Yangjiang, com- prising a total of 9430 and 63661-rain raindrop spectra, respectively. The raindrop spectra, characteristics of parameter variations with rainfall rate, and the relationships between reflectivity factor （Z） and rainfall rate （R） are analyzed, as well as their DSD changes with precipitation type and rainfall rate. The results show that the average raindrop spectra appear to be one-peak curves, the number concentration for larger drops increase significantly with rainfall rate, and its value over southern China is much higher, especially in convective rain larger drops, especially for convective rain in southern China. Standardized Gamma distributions better describe DSD for All three Gamma parameters for stratiform precipitation over the Tibetan Plateau are much higher, while its shape parameter （,u） and mass-weighted mean diameter （Dm）, for convective precipitation, are less. In terms of parameter variation with rainfall rate, the normalized intercept parameter （Nw） over the Tibetan Plateau for stratiform rain increases with rainfall rate, which is opposite to the situation in convective rain. The/1 over the Tibetan Plateau for stratiform and convective precipitation types decreases with an increase in rainfall rate, which is opposite to the case for Dm variation. In Z-R relationships, like ＂Z = ARb＇＇, the coefficient A over the Tibetan Plateau is smaller, while its b is higher, when the rain type transfers from stratiform to convective ones. Furthermore, with an increase in rainfall rate, parameters A and b over southern China increase gradually, while A over the Tibetan Plateau decreases sub- stantially, which differs from the findings of previous studies. In terms of geographic location and climate over the Tibetan Plateau and southern China, the p
基金Supported by the Bavarian Ministry of Economy (Leitprojekt Medizintechnik) and the Hans L(o|¨)wel Foundation, Bamberg,Germany
文摘AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.
文摘BACKGROUND:Organ fibrosis has been viewed as one of the major medical problems, which can lead to progressive dysfunction of the liver, lung, kidney, skin, heart, and eventually death of patients. Fibrosis is initiated by a variety of pathological, physiological, biochemical, and physical factors. Regardless of their different etiologies, they all share a common pathogenetic process: excessive activation of the key profibrotic cytokine, transforming growth factor-β (TGF-β). Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor of the nuclear receptor superfamily, has received particular attention in recent years, because the activation of PPARγ by both natural and synthetic agonists could effectively inhibit TGF-β-induced profibrotic effects in many organs. DATA SOURCES: The English-language medical databases, PubMed, Elsevier and SpringerLink were searched for articles on PPARγ, TGF-β, and fibrosis, and related topics. RESULTS: TGF-β is recognized as a key profibrotic cytokine. Excessive activation of TGF-β increases synthesis of extracellular matrix proteins and decreases their degradation, associated with a gradual destruction of normal tissue architecture and function, whereas PPARγ agonists inhibit TGF-β signal transduction and are effective antifibrogenic agents in many organs including the liver, lung, kidney, skin and heart. CONCLUSIONS: The main antifibrotic activity of PPARγ agonists is to suppress the TGF-β signaling pathway by so-called PPARγ-dependent effect. In addition, PPARγ agonists, especially 15d-PGJ2, also exert potentially antifibrotic activity independent of PPARγ activation. TGF-β1/Smads signaling not only plays many essential roles in multiple developmental processes, butalso forms cross-talk networks with other signal pathways, and their inhibition by PPARγ agonists certainly affects the cytokine networks and causes non-suspected side-effects. Anti-TGF-β therapies with PPARγ agonists may have to be carefully tailored to be tissu
文摘The effects of microstructure on the deformation and fracture behaviour of two-phase TiAl alloys were investjgated under monotonic and cyclical loading conditions, over a range of temperatu res.The tensile behaviour is analyzed for deformation temperatures between RT and 950℃, Fracture resistance behaviour and toughening mechanisms at RT and 800℃ are analyzed. and the inverse relationship botween ductility and toughness is explained using the crack initiation toughness. The preliminary results of load-controlled fatigue behaviour at 800℃ are interpreted using the tensile behaviour because deformation structure and fracture modes are similar under these two loading conditions
基金supported by the National Program on Key Research and Development Project(Grant No.2016YFA0400800)from the Ministry of Science and Technology of China(MOST)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB23040400)the Hundred Talent Program of Chinese Academy of Sciences,the National Natural Science Foundation of China(Grant Nos.11233001,11503027,11403026,11473027,and11733009)
文摘Finding the electromagnetic （EM） counterpart of binary compact star merger, especially the binary neutron star （BNS） merger, is critically important for gravitational wave （GW） astronomy, cosmology and fundamental physics. On Aug. 17, 2017, Advanced LIGO and Fermi/GBM independently triggered the first BNS merger, GW170817, and its high energy EM counterpart, GRB 170817A, respectively, resulting in a global observation campaign covering gamma-ray, X-ray, UV, optical, IR, radio as well as neutrinos. The High Energy X-ray telescope （HE） onboard Insight-HXMT （Hard X-ray Modulation Telescope） is the unique high-energy gamma-ray telescope that monitored the entire GW localization area and especially the optical counterpart （SSS17a/AT2017gfo） with very large collection area （M000 cm2） and microsecond time resolution in 0.2-5 MeV. In addition, Insight-HXMT quickly implemented a Target of Opportunity （TOO） observation to scan the GW localization area for potential X-ray emission from the GW source. Although Insight-HXMT did not detect any significant high energy （0.2-5 MeV） radiation from GW170817, its observation helped to confirm the unexpected weak and soft nature of GRB 170817A. Meanwhile, Insight-HXMT/HE provides one of the most stringent constraints （-10-7 to 104 erg/cm2/s） for both GRB170817A and any other possible precursor or extended emissions in 0.2-5 MeV, which help us to better understand the properties of EM radiation from this BNS merger. Therefore the observation of Insight-HXMT constitutes an important chapter in the full context of multi-wavelength and multi-messenger observation of this historical GW event.
基金supported by a grant from the Science and Technology Commission of Shanghai Municipality(No.07JC14036)
文摘BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma(PPAR-γ) on rat hepatic fibrosis. METHODS:Hepatic fibrosis in rats was induced by CCl4 for 2 weeks(early fibrosis)and 8 weeks(sustained fibrosis).The rats were randomly divided into four groups:normal control, fibrosis,blank vector,and PPAR-γ.They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene by portal vein injection.The liver of the rats was examined histologically and hydroxyproline was assessed.In vitro primary hepatic stellate cells(HSCs)were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene.The status of HSC proliferation was measured by the MTT assay.The protein levels of PPAR-γ,α-smooth muscle actin(α-SMA)and type I collagen expression were evaluated by the Western blotting method. RESULTS:In vitro studies revealed that expression of PPAR-γ inhibited expression ofα-SMA and type I collagen in activated HSCs(P<0.01)as well as HSC proliferation(P<0.01).In vivo experiments indicated that in the early hepatic fibrosis group,the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-γtransfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group;whereas the expressions of PPAR-γ andα-SMA were different compared to the hepatic fibrosis group(P<0.01).In the sustained hepatic fibrosis group,there were significant differences in the hydroxyproline content and the expression of PPAR-γ,α-SMA,and type I collagen between each group.CONCLUSION:PPAR-γcan inhibit HSC proliferation and hepatic fibrosis,and suppressα-SMA and type I collagen expression.
文摘AIM:To investigate the effects of heme oxygenase(HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma(PPARγ) and nuclear factor-kappa B(NF-κB) in rats.METHODS:Sixty Wistar rats were used to construct liver fibrosis models and were randomly divided into 5 groups:group A(normal,untreated),group B(model for 4 wk,untreated),group C(model for 6 wk,untreated),group D [model for 6 wk,treated with zinc protoporphyrin Ⅸ(ZnPP-Ⅸ) from week 4 to week 6],group E(model for 6 wk,treated with hemin from week 4 to week 6).Next,liver injury was assessed by measuring serum alanine aminotransferase(ALT),aspartate aminotransferase(AST) and albumin levels.The degree of hepatic fibrosis was evaluated by measuring serum hyaluronate acid(HA),type Ⅳ collagen(Ⅳ-C) and by histological examination.Hydroxyproline(Hyp) content in the liver homogenate was determined.The expres-sion levels of alpha-smooth muscle actin(α-SMA) in liver tissue were measured by real-time quantitative polymerase chain reaction(RT-PCR).The expression levels of PPARγ and NF-κB were determined by RT-PCR and Western blotting.RESULTS:The expression of HO-1 increased with the development of fibrosis.Induction of HO-1 by hemin significantly attenuated the severity of liver injury and the levels of liver fibrosis as compared with inhibition of HO-1 by ZnPP-Ⅸ.The concentrations of serum ALT,AST,HA and Ⅳ-C in group E decreased compared with group C and group D(P < 0.01).Amount of Hyp and α-SMA in the liver tissues in group E decreased compared with group C(0.62 ± 0.14 vs 0.84 ± 0.07,1.42 ± 0.17 vs 1.84 ± 0.17,respectively,P < 0.01) and group D(0.62 ± 0.14 vs 1.11 ± 0.16,1.42 ± 0.17 vs 2.56 ± 0.37,respectively,P < 0.01).The expression of PPARγ at levels of transcription and translation decreased with the development of fibrosis especially in group D;and it increased in group E compared with groups C and D(0.88 ± 0.15 vs 0.56 ± 0.19,0.88 ± 0.15 vs 0.41 ± 0.11,respectively,P < 0.01).The expression of NF-κB
基金National Meteorological Center Project，Distinguished Overseas Scholar Foundation of CAS，科技部资助项目，Chinese Ministry of Water Resources, The Swedish Research Council fund
文摘A stochastic model for daily precipitation simulation in China was developedbased on the framework of a 'Richardson-type' weather generator that is an important tool instudying impacts of weather/climate on a variety of systems including ecosystem and risk assessment.The purpose of this work is to develop a weather generator for applications in China. The focus ison precipitation simulation since determination of other weather variables such as temperature isdependent on precipitation simulation. A framework of first order Markov Chain with GammaDistribution for daily precipitation is adopted in this work. Based on this framework, fourparameters of precipitation simulation for each month at 672 stations all over China were determinedusing daily precipitation data from 1961 to 2000. Compared with previous works, our estimation forthe parameters was made for more stations and longer observations, which makes the weather generatormore applicable and reliable. Spatial distributions of the four parameters are analyzed in aregional climate context. The seasonal variations of these parameters at five stations representingregional differences are discussed. Based on the estimated monthly parameters at 672 stations, dailyprecipitations for any period can be simulated. A 30-year simulation was made and compared withobservations during 1971-2000 in terms of annual and monthly statistics. The results aresatisfactory, which demonstrates the usefulness of the weather generator.
文摘Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium(RPE)cells in the equatorial region.Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length.Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye,most marked at the posterior pole.In any eye region,thickness of Bruch’s membrane(BM)is independent of axial length.BM opening,as the inner layer of the optic nerve head layers,is shifted in temporal direction in moderately elongated eyes(axial length<26.5 mm).It leads to an overhanging of BM into the intrapapillary compartment at the nasal optic disc side,and to an absence of BM at the temporal disc border.The lack of BM at the temporal disc side is the histological equivalent of parapapillary gamma zone.Gamma zone is defined as the parapapillary region without BM.In highly myopic eyes(axial length>26.5 mm),BM opening enlarges with longer axial length.It leads to a circular gamma zone.In a parallel manner,the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes.The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone,and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc.The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes.Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects,while thickness and density of the choriocapillaris,RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions.Conclusions:High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and RPE density in the equator
基金This work is supported in China by NSFC(Nos.11205165,11375210,11375224,11405181,11475190 and 11635011)the Chinese Academy of Sciences,Institute of High Energy Physics,the Key Laboratory of Particle Astrophysics,CAS.
文摘Introduction The Large High Altitude Air Shower Observatory plans to build a hybrid extensive air shower array with an area of about 1 km^(2) at an altitude of 4,410 m a.s.l.in Sichuan province,China,to explore the origin of high-energy cosmic rays.KM2A LHAASO-KM2A will detect gamma ray sources with a sensitivity of about 1%Crab Unit at 100 TeV.It covers an area of 1 km^(2) with a total of 5195 scintillation detectors.Its angular resolution reaches about 0.3 degrees,and the energy resolution is better than 25%.With the help of 1171 muon detectors,cosmic nuclei background will be rejected to a level of 10-4 at 50 TeV.The design and performances of the scintillation detectors and muon detectors are described in detail.WCDA LHAASO-WCDA focuses on surveying the northern sky for steady and transient sources from 100 GeV to 20 TeV,with a very high background rejection power and a good angular resolution.The WCDA consists of three water ponds with a total area of 78,000 m^(2),and the effective water depth is 4 m.Each water pond is divided into 5m×5m cells partitioned by black plastic curtains to prevent penetration of the light from neighboring cells.An 8-inch PMT sits at the bottom center of each cell,looking upward to collect Cherenkov light generated by shower secondary particles in water.WFCTA LHAASO-WFCTA is composed of 12 wide-field-of-view Cherenkov/fluorescence telescopes.Each telescope consists of a spherical light collector of about 4.7 m^(2) and focal plane camera of 32×32 pixels with a pixel size of 0.5 degree.LHAASO prototype arrays A prototype array about 1%of LHAASO has been constructed at Yangbajing Cosmic Ray Observatory and has been in operation for more than 2 years.Its performance fully meets the design requirements.Conclusion The LHAASO detectors are designed to fulfill the physical goals in gamma ray astronomy and cosmic ray physics.One-fourth of LHAASO will be constructed and put into operation to produce physical data by the end of 2018.The whole array will be finished in the beginning of 2021.
文摘Despite great progress in the detection and treatment of prostate cancer, this disease remains an incredible health and economic burden. Although androgen receptor （AR） signaling plays a key role in the development and progression of prostate cancer, aberrations in other molecular pathways also contribute to the disease, making it essential to identify and develop drugs against novel targets, both for the prevention and treatment of prostate cancer. One promising target is the peroxisome proliferator-activated receptor gamma （PPARy） protein. PPARy was originally thought to act as a tumor suppressor in prostate cells because agonist ligands inhibited the growth of prostate cancer cells; however, additional studies found that PPARy agonists inhibit cell growth independent of PPARy. Furthermore, PPARy expression increases with cancer grade/stage, which would suggest that it is not a tumor suppressor but instead that PPARy activity may play a role in prostate cancer development and/or progression. Indeed, two new studies, taking vastly different, unbiased approaches, have identified PPARy as a target in prostate cancer and suggest that PPARy inhibition might be useful in prostate cancer prevention and treatment. These findings could lead to a new therapeutic weapon in the fight against prostate cancer.
