Horizontal structure of convergent wind shear associated with sporadic E layers over East Asia

At present,the main detection instruments for observing sporadic E(Es)layers are ground-based radars,dense networks of ground-based global navigation satellite system(GNSS)receivers,and GNSS radio occultation,but they cannot capture the whole picture of the horizontal structure of Es layers.This study employs the Whole Atmosphere Community Climate Model with thermosphere and ionosphere eXtension model(WACCM-X 2.1)to derive the horizontal structure of the ion convergence region(HSICR)to explore the shapes of the large-scale Es layers over East Asia for the period from June 1 to August 31,2008.The simulation produced the various shapes of the HSICRs elongated in the northwest-southeast,northeast-southwest,or composed of individual small patches.The close connection between Es layer critical frequency(foEs)and vertical ion convergence indicates that the HSICR is a good candidate for revealing and explaining the horizontal structure of the large-scale Es layers.

Uncoupling protein 2 deficiency of non-cancerous tissues inhibits the progression of pancreatic cancer in mice

Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.

Regulation of hepatic blood flow:The hepatic arterial buffer response revisited

The interest in the liver dates back to ancient times when it was considered to be the seat of life processes. The liver is indeed essential to life,not only due to its complex functions in biosynthesis,metabolism and clearance,but also its dramatic role as the blood volume reservoir. Among parenchymal organs,blood flow to the liver is unique due to the dual supply from the portal vein and the hepatic artery. Knowledge of the mutual communication of both the hepatic artery and the portal vein is essential to understand hepatic physiology and pathophysiology. To distinguish the individual importance of each of these inflows in normal and abnormal states is still a challenging task and the subject of on-going research. A central mechanism that controls and allows constancy of hepatic blood flow is the hepatic arterial buffer response. The current paper reviews the relevance of this intimate hepatic blood flow regulatory system in health and disease. We exclusively focus on the endogenous interrelationship between the hepatic arterial and portal venous inflow circuits in liver resection and transplantation,as well as inflammatory and chronic liver diseases. We do not consider the hepatic microvascular anatomy,as this has been the subject of another recent review.

The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.METHODS: Human pancreatic cancer cell lines Capan-1^p53mut,Capan-2^p53wt, FAMPAC^p53mut, PANG1^p53mut, and rat pancreatic cancer cell lines AS^p53wt and DSL6A^p53null were used for in vitro studies. Following infection with different ratios of Adp53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivostudies.Tumor size, apoptosis (TUNEL) and survival were determined.RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitroand in vivoanalyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation

瞄准：在 thromboembolism 的开发在胰腺的癌症和它的角色学习织物因素(TF ) 的表示。方法：TF 表示被北污点和间接免疫荧光在八根人的胰腺的癌房间线学习。或者拼接的 TF (asTF ) 的表示被 RT-PCR 估计。另外， TF 表示被免疫荧光与胰腺的腺癌(PCa ) 在 19 个病人的胰腺的纸巾决定，有慢性胰炎(CP ) 的 9 个病人和 20 正常控制。血浆样品(30 PCa 病人， 13 CP 病人和 20 控制) 为可溶的 TF 层次和凝结激活标记被调查[thrombin-antithrombin III 建筑群(梭织) ，凝血素碎片 1 + 2 (F1 + 2 )] 。结果：所有胰腺的癌房间线表示了 TF (8/8 ) ，他们中的大多数表示了 asTF (6/8 ) 。在蛋白质水平的 TF 表示没与癌房间线的区别相关。几乎，二件胰腺的癌症组织样品染色了为 TF (17/19 ) 积极。在 CP 的所有样品，弱染色被限制为胰腺的管房间，而一些仅仅内皮下房间在正常控制的 9/20 是积极的。TF 并且在 PCa 病人梭织层次而 2 铺平的提高的 F1 + 没与控制相比到达统计意义，显著地与控制相比被提高。在病人们梭织的 CP 和 F1 + ， 2 个层次证明了显著地与控制相比被提高，尽管梭织举起少些比在 PCa 病人被读。结论：我们结束那除了起来房间膜上的 TF 的调整表示，可溶的 TF 可能在胰腺的癌症贡献凝结系统的激活。

Inhibitory effects of interferons on pancreatic stellate cell activation

瞄准：分析并且比较干扰素(IFN ) 的效果胰腺的星形的房间(PSC ) 上的 -alpha,IFN 贝它，和 IFN-gamma 激活在试管内并且阐明 IFN 的分子的基础行动。方法：PSC 与 recombinant 老鼠 IFN 从老鼠的胰腺的织物被孤立、有教养、刺激。房间增长和骨胶原合成被测量 5-bromo-2'-deoxyuridine (BrdU ) 的加入进 DNA 估计并且(3H ) 脯氨酸进醋性的酸可溶的蛋白质分别地。Apoptotic 房间被 FACS 分析(sub-G1 山峰方法) 决定。myofibroblastic PSC 显型的展览被 alpha 光滑的肌肉肌动朊(alpha- SMA ) 的免疫污点分析监视表示。估计信号变换器的激活和抄写(STAT ) 的使活跃之物，用 phospho-STAT-specific 抗体的西方的污点被执行。在 STAT1 功能上的研究，蛋白质的表示被 siRNA 禁止。结果：IFN 贝它和 IFN-gamma 然而并非 IFN-alpha 显著地减少了 PSC 增长和骨胶原合成。IFN-gamma 是清楚地禁止了 alpha-SMA 表示的唯一的 IFN。在使用的试验性的条件下面， apoptotic 细胞死亡的提高的率都没响应任何 IFN 处理被观察。IFN 贝它和 IFN-gamma 导致了 STAT1 和 STAT3 酷氨酸磷酸化的猛烈增加，当 IFN-alpha 的效果弱得多时。有 siRNA 的 STAT1 表示的抑制与 IFN-gamma 的显著地减少的生长禁止的效果被联系。结论：IFN 贝它并且特别地 IFN-gamma 在 PSC 激活在试管内上显示禁止的效果并且应该关于他们的在试管内效率被测试。由 IFN-gamma 行动的生长抑制要求 STAT1。

Mouse models of colorectal cancer: Past, present and future perspectives

Colorectal cancer(CRC)is the third most common diagnosed malignancy among both sexes in the United States as well as in the European Union.While the incidence and mortality rates in western,high developed countries are declining,reflecting the success of screening programs and improved treatment regimen,a rise of the overall global CRC burden can be observed due to lifestyle changes paralleling an increasing human development index.Despite a growing insight into the biology of CRC and many therapeutic improvements in the recent decades,preclinical in vivo models are still indispensable for the development of new treatment approaches.Since the development of carcinogen-induced rodent models for CRC more than 80 years ago,a plethora of animal models has been established to study colon cancer biology.Despite tenuous invasiveness and metastatic behavior,these models are useful for chemoprevention studies and to evaluate colitis-related carcinogenesis.Genetically engineered mouse models(GEMM)mirror the pathogenesis of sporadic as well as inherited CRC depending on the specific molecular pathways activated or inhibited.Although the vast majority of CRC GEMM lack invasiveness,metastasis and tumor heterogeneity,they still have proven useful for examination of the tumor microenvironment as well as systemic immune responses;thus,supporting development of new therapeutic avenues.Induction of metastatic disease by orthotopic injection of CRC cell lines is possible,but the so generated models lack genetic diversity and the number of suited cell lines is very limited.Patient-derived xenografts,in contrast,maintain the pathological and molecular characteristics of the individual patient's CRC after subcutaneous implantation into immunodeficient mice and are therefore most reliable for preclinical drug development–even in comparison to GEMM or cell line-based analyses.However,subcutaneous patient-derived xenograft models are less suitable for studying most aspects of the tumor microenvironment and anti-tumoral immune responses.The authors review the distinct mouse models of CRC with an emphasis on their clinical relevance and shed light on the latest developments in the field of preclinical CRC models.

Spatial Variability of Soil Properties and Rice Yield Along Two Catenas in Southeast China

In the light of an increasing demand for staple food, especially rice, in southeast China, investigations on the specific site potential expressed as the relationship between soil and crop yield parameters gain increasing importance. Soil texture and several soil chemical parameters as well as plant properties such as crop height, biomass and grain yield were investigated along two terraced catenas with contrasting soil textures cropped with wet rice. We were aiming at identifying correlative relationships between soil and crop properties. Data were analyzed both statistically and geostatistically on the basis of semivariograms. Statistical analysis indicated a significant influence of the relief position on the spatial distribution of soil texture, total carbon and total nitrogen contents. Significant correlations were found for the catena located in a sandstone area (Catena A) between rice yield and silt as well as total nitrogen content. Corresponding relationships were not detectable for paddy fields that developed from Quaternary clays (Catena B). As suggested by the nugget to sill ratio, spatial variability of soil texture, total carbon and nitrogen was mainly controlled by intrinsic factors, which might be attributed to the erosional transport of fine soil constituents, indicating the importance of the relief position and slope in soil development even in landscapes that are terraced. The crop parameters exhibited short ranges of influence and about one third of their variability was unexplained. Comparable ranges of selected crop and soil parameters, found only for Catena A, are indicative of close spatial interactions between rice yield and soil features. Our findings show that especially in sandstone-dominated areas, a site-specific management can contribute to an environmentally safe rice production increase.

Strength and compressibility behaviors of expansive soil treated with coffee husk ash

Various factors can affect the durability of roads, such as the strength of sub-grade, the quality of the subbase and base course, the environments and properties of the soil used. Particularly, roads built on expansive soil are susceptible to early damage due to the swelling and shrinkage characteristics of this kind of soil under changing moisture conditions. The most common technique used to improve the properties of problematic soil is stabilization with additives. Using waste materials to improve the properties of expansive soil is a recent trend in soil stabilization. This study deals with the treatment of expansive soil with coffee husk ash(CHA). Coffee husk is a by-product of coffee production, and CHA is the resulting ash after burning it. In this study, the bearing capacity and compressibility characteristics of expansive soil(specifically black cotton(BC) soil) stabilized with varying percentages of CHA(5%, 10%,15%, and 20%) are investigated. Then, scanning electron microscopy(SEM) and energy dispersive X-ray(EDX) were used to analyze the influence of CHA on surface morphology and chemical composition of the studied soil. The results showed that the soil treated with CHA is generally improved in terms of strength.Addition of 20% CHA increases the bearing capacity of the soil by three-fold. In addition, the morphological studies of the soil samples treated with 10% and 15% CHA indicated the formation of hydrated particles and cementitious compounds as a result of the reaction between the soil and CHA. This indicates the potential usage of CHA as a stabilization agent and subsequently, it can address the disposal and environmental concerns related to coffee husk.

Molecular determinants of the antitumor effects of trichostatin A in pancreatic cancer cells

AIM:To gain molecular insights into the action of the histone deacetylase inhibitor(HDACI) trichostatin-A(TSA) in pancreatic cancer(PC) cells.METHODS:Three PC cell lines,BxPC-3,AsPC-1 and CAPAN-1,were treated with various concentrations of TSA for def ined periods of time.DNA synthesis was assessed by measuring the incorporation of 5-bromo-2'deoxyuridine.Gene expression at the level of mRNA was quantif ied by real-time polymerase chain reaction.Expression and phosphorylation of proteins was monitored by immunoblotting,applying an infrared imaging technology.To study the role of p38 MAP kinase,the specif ic enzyme inhibitor SB202190 and an inactive control substance,SB202474,were employed.RESULTS:TSA most eff iciently inhibited BrdU incorporation in BxPC-3 cells,while CAPAN-1 cells displayed the lowest and AsPC-1 cells an intermediate sensitivity.The biological response of the cell lines correlated with the increase of histone H3 acetylation after TSA application.In BxPC-3 cells(which are wild-type for KRAS),TSA strongly inhibited phosphorylation of ERK 1/2 and AKT.In contrast,activities of ERK and AKT in AsPC-1 and CAPAN-1 cells(both expressing oncogenic KRAS) were not or were only modestly affected by TSA treatment.In all three cell lines,but most pronounced in BxPC-3 cells,TSA exposure induced an activation of the MAP kinase p38.Inhibition of p38 by SB202190 slightly but signif icantly diminished the antiproliferative effect of TSA in BxPC-3 cells.Interestingly,only BxPC-3 cells responded to TSA treatment by a signif icant increase of the mRNA levels of bax,a pro-apoptotic member of the BCL gene family.Finally,in BxPC-3 and AsPC-1 cells,but not in the cell line CAPAN-1,signif icantly higher levels of the cell cycle inhibitor protein p21Waf1 were observed after TSA application.CONCLUSION:The biological effect of TSA in PC cells correlates with the increase of acetyl-H3,p21Waf1,phospho-p38 and bax levels,and the decrease of phosphoERK 1/2 and phospho-AKT.

Bacteriolytic therapy of experimental pancreatic carcinoma

AIM:To investigate the effectiveness of Clostridium novyi(C.novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic,immunocompetent Panc02/C57Bl/6 model. METHODS:C.novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes.Systemic immune responses in peripheral blood and spleen were examined by flow cytometry.Supplementary,cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed. RESULTS:Application of spores identified,that(1) small tumors(<150 mm 3 )were completely unaffected (n=10);(2)very large tumors(>450 mm3)responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n=6);and(3)an optimal treatment window exists for tumors of approximately 250 mm 3 (n=21).In this latter group,all tumor-bearing animals had complete tu-mor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed(tumor volume at day 28:197.8±87.3 mm 3 vs 500.1±50.9 mm3,P<0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system. CONCLUSION:The observed complete tumor regression is encouraging and shows that immunotherapy with C.novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.

Cis-hydroxyproline-induced inhibition of pancreatic cancer cell growth is mediated by endoplasmic reticulum stress

瞄准：在老鼠上调查 cis-hydroxyproline (CHP ) 的生物效果，并且检验内在的分子的机制胰腺的癌房间线 DSL6A。方法：DSL6A 房间增长上的 CHP 的效果被使用 BrdU 加入估计。焦点的粘附激酶(FAK ) 的表示被西方的弄污和免疫荧光描绘。endoplasmic 感应(嗯) 应力被使用 RT-PCR 并且为葡萄糖相关的 protein-78 (GRP78 ) 和生长拘捕和 DNA 的西方的弄污调查可诱导的基因(GADD153 ) 。房间生存能力通过基于 DSL6A 房间的减小潜力测量新陈代谢的活动被决定。Apoptosis 被 caspase-3 激活的察觉和多形核白细胞(自动数据处理核糖) 的劈开分析象 DNA laddering 一样的聚合酶(PARP ) 。结果：除了增长的抑制，有 CHP 的孵化从焦点的粘附导致了 FAK 的解朊的劈开和酶的 delocalisation，由房间坚持的损失列在后面。同时，我们能显示出 GRP78 和 GADD153 的增加的表情，显示在 DSL6A 房间线的 ER 压力串联的调停 CHP 的激活。有 CHP 的 DSL6A 房间的延长孵化最后导致了 apoptotic 细胞死亡。在 L 脯氨酸旁边，由一个广谱朊酶禁止者的增加的细胞内部的解朊作用的抑制能在细胞的功能和分子的过程上废除 CHP 的效果。相反，阻碍执行 apoptosis caspases 的活动没在调停 CHP 的房间损坏上有影响。结论：我们的数据建议开始嗯由 CHP 的压力机械导致细胞内部的解朊的进程的激活包括 caspase 独立的 FAK 降级，导致损坏胰腺的癌房间。

Interleukin 4-induced neuroprotection and regulation of microglia activation as a therapeutic approach in the MPTP model of Parkinson's disease

Parkinson’s disease(PD)has been described as one of the most common neurodegenerative diseases affecting up to 2%of the worldwide population over 60 years of age.The hallmarks of PD are progressive loss of midbrain dopaminergic(m DA)neurons and a decrease in striatal dopamine levels,which result in typical clinical motor symptoms such as akinesia,resting tremor,rigidity,and gait impairments.Although the causes for PD are only partially understood and seem to be very heterogeneous,one of the common phenomenons observed in toxin-based animal models of PD as well as PD patients is a microglia-driven neuroinflammatory response,which is at least in part responsible for exacerbation of neuronal loss and worsening of

Medicinal uses,phytochemistry and pharmacology of Picralima nitida(Apocynaceae) in tropical diseases:A review

Picralima nitida Durand and Hook,(fam.Apocynaceae)is a West African plant with varied applications in African folk medicine.Various parts of the plant have been employed ethnomedicinally as remedy for fever,hypertension,jaundice,dysmenorrheal,gastrointestinal disorders and malaria.In order to reveal its full pharmacological and therapeutic potentials,die present review focuses on the current medicinal uses,phytochemistry,pharmacological and toxicological activities of this species.Literature survey on scientific journals,books as well as electronic sources have shown the isolation of alkaloids,tannins,polyphenols and steroids from different parts of the plant,pharmacological studies revealed that the extract or isolated compounds from this species posses analgesic,anti-inflammatory,hypoglyceamic,hypotensive,antiplasmodial,antimicrobial,antiulcer and antitumorigenic activities.Results from various scientific investigations to date have revealed the potential of the extract from the plant or isolated compounds for use in the treatment and prevention of various kinds of human diseases.However,further studies on the extracts and pure compounds from this species is required to completely assess its phytoc-hemical,pharmacological and toxicological profile as well as the mechanism of action behind these pharmacological activities exhibited by the compounds isolated from this species.

Modalities of testing Helicobacter pylori in patients with nonmalignant bile duct diseases

AIM: This paper describes the procedure of detection ofHelicobacter pylori ( H. pylori) in bile specimens in patientssuffering from benign diseases of biliary ducts (lithiasiswith/without nonspecific cholangitis).METHODS: The group of 72 patients entering the studyconsisted of 32 male and 40 female (45 % and 55 %,respectively). Bile was obtained during ERCP in 68 patients,and during cholecystectomy in 4 patients. A fast urease test(FUT) to determine the existence of H. pylori in gastricmucosa was carried out for all the patients during theendoscopic examination. The existence of genetic materialof H. pylori was determined by detection of ure A gene bythe method of nested PCR. The results of this reaction wereshown by electrophoresis on l0 g@ L-1 agarose gel in a bandof 256 bp.RESULTS: The majority of the patients included in our studyhad biliary lithiasis without signs of cholangitis (48 patients,67 %), whereas other patients were complicated bycholangitis (17 patients, 24 %). Seven patients (9 %) hadnormal ERCP, forming thus the control group. In the groupof patients with lithiasis 26 patients (54.2 %) had positivePCR of H. pylori in bile and among the patients withassociated cholangitis positive PCR was detected in 9patients (52.9 % ). Among the seven patients with nornalERCP only one (14 %) had positive PCR of H. pylori. Ahigh percentage of H. pylori infection of gastric mucosawas observed (57 patients, 79 % ) : It was also observed thatits slightly higher positivity was in the patients with distinctbile pathology: 81% FUT positive patients in the group withcholedocholithiasis alone and 76 % in the group withcholedocholithiasis associated with cholangitis. Seventy-onepercent of the patients with regular findings had positive FUT.CONCLUSION: The prevalence of H. pylori infection both inbile and in gastric mucosa in patients with benign diseasesof biliary ducts does not show a statistically significantdifference in relation to the prevalence of the same with thepatients with normal ERCP. The existence of H. pyloriinfection possibly does not play a role in pathogenesis ofbenign biliary diseases.

How do altitude and soil properties influence the taxonomic and phylogenetic structure and diversity of Brazilian páramo vegetation?

Altitude and environmental variables such as edaphic properties are considered determinants of species distribution and community composition in mountain ecosystems.Here,we aimed to outline the effects of distinct mountain peaks,altitude and soil properties on community composition,species density,phylogenetic structure and diversity of angiosperm páramo communities from the Serra do Brigadeiro State Park,Minas Gerais,southeastern Brazil.For that,we identified all angiosperm species found in 300 plots(1 m×1 m)from three mountain peaks,measured soil depth and analyzed soil fertility and texture in each plot.To reduce the number of soil variables and species composition,we computed principal coordinates based on soil properties and principal coordinates based on species-plot matrix for each plot.Furthermore,we computed the standard effect sizes of the mean phylogenetic pairwise distance and the mean nearest phylogenetic taxon distance for each plot to investigate differences in the degree of relatedness among coexisting species.We compared differences in response variables between peaks and modelled them in function of altitude and principle components of soil properties using mixed effect models.Species density and phylogenetic diversity differed between peaks,but,contrary to the previous findings,no relationships between species richness or phylogenetic diversity and altitude or soil properties were found,indicating that further investigations are necessary to understand the altitude-biodiversity relationship in Brazilian páramo vegetation.Community composition differed between peaks and depended on altitude,soil properties and interactions between them,indicating that upward shifting of bioclimatic conditions due to climate changes may alter communities of this ecosystem.Phylogenetic structure differed between peaks and was influenced by altitude and soil properties.As phylogenetic clustering increased with altitude,eventual upward movements of species in Brazilian páramo vegetation due to climate change may alter community composition and the degree of relatedness among coexisting species,increasing the risk of species from higher altitudes to disappear.Therefore,conservation priorities arise for higher landscape portions,where these high altitude species may find refuges.

Establishment,functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line

AIM To establish cell line and patient-derived xenograft(PDX) models for neuroendocrine carcinomas(NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research includingbiomarker testing and drug response prediction.METHODS Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue(HROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the HROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting(i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid cancers.RESULTS The established cell line HROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a Cp G island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS(wt), BRAF(mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC.

In situ differential scanning calorimetry analysis of dissolution and precipitation kinetics in Mg-Y-RE alloy WE43

Further development of our differential scanning calorimetry(DSC)method for the analysis of solid-solid phase transformations now also allows for its application in the kinetic analysis of age hardening in Mg alloys.As a result,the state-of-the-art for DSC on Mg alloys has been improved with respect to the accessible temperature range,zero-level accuracy and dynamic range.DSC analysis was performed on the example of Mg wrought alloy WE43.Heating DSC experiments on the initial condition T4 and even direct continuous cooling DSC analysis on the kinetics of quench induced precipitation during cooling from solution treatment were possible,covering a dynamic range of 0.01-3 K/s.The DSC findings are discussed with respect to literature knowledge and scanning electron microscopy analysis of the defined heat treatment states.

Molecular determinants of the profibrogenic effects of endothelin-1 in pancreatic stellate cells

AIM: To gain molecular insights into the expression and functions of endothelin-1 (ET-1) in pancreatic stellate cells (PSC). METHODS: PSCs were isolated from rat pancreas tissue, cultured, and stimulated with ET-1 or other extra-cellular mediators. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine into DNA and cell migration was studied in a transwell chamber assay. Gene expression at the level of mRNA was quantified by real-time polymerase chain reaction. Expression and phosphorylation of proteins were monitored by immunoblotting, applying an infrared imaging technology. ET-1 levels in cell culture supernatants were determined by an enzyme immunometric assay. To study DNA binding ofindividual transcription factors, electrophoretic mobility shift assays were performed. RESULTS: Among several mediators tested, transforming growth factor-β1 and tumour necrosis factor-α displayed the strongest stimulatory effects on ET-1 secretion. The cytokines induced binding of Smad3 and NF-κB, respectively, to oligonucleotides derived from the ET-1 promoter, implicating both transcription factors in the induction of ET-1 gene expression. In accordance with previous studies, ET-1 was found to stimulate migration but not proliferation of PSC. Stimulation of ET-1 receptors led to the activation of two distinct mitogen-activated protein kinases, p38 andextracellular signal-regulated kinases (ERK)1/2, as well as the transcription factor activator protein-1. At the mRNA level, enhanced expression of the PSC activation marker, α-smooth muscle actin and two proin· ammatory cytokines, interleukin (IL)-1β and IL-6, was observed. CONCLUSION: This study provides novel lines of evidence for profibrogenic and proin· ammatory actions of ET-1 in the pancreas, encouraging further studies with ET-1 inhibitors in chronic pancreatitis.

The cholera epidemic of 2004 in Douala, Cameroon: A lesson learned

Objective: To describe the outbreak of 2004 with a view of retrospectively identifying factors that might explain the low case fatality rate. Methods: Outbreak data from 4 915 Cholera patients from registers of the Regional Health Delegation in Douala were analyzed using SPSS. Chi-square test, univariate and multivariate analysis were applied. Results: The outbreak started January 2004, peaking at 187 cases per week in February. After a decrease in April, case numbers rose to 688 cases per week in June. The outbreak was over in September 2004( <10 cases per week). The case fatality rate was higher in treatment centers with fewer than one nurse per two patients, than in those with more nursing staff. A temporary staff reduction after the first wave of the epidemic was associated with the increase of the case fatality rate during the second wave. This increase was reversed after re-instating full staff capacity.Conclusions: Providing sufficient nursing staff helps to lower the case fatality rate of cholera. Besides a lack of staff, age above 40 years is a risk factor for death in this disease.