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Der Nuklearmediziner 2018年第4期41卷 310-316页

作者： christoph Solbach Marianne Patt Klinik für Nuklearmedizin Universitätsklinikum Ulm Ulm Klinik und Poliklinik für Nuklearmedizin Universitätsklinikum Leipzig Leipzig

Over the last 15 years diagnostic imaging of amyloid and tau deposits with PET has gained increasing importance especially in the context of diagnosis of dementia such as Alzheimer’s disease. First radiotracers that were developed aimed at the detection of amyloid plaques in the brain. In the meantime the contribution of hyperphosphorylated proteins (TAU) that lead to another type of protein deposits is getting more and more in the focus of current research on the origin of this disease. While a number of

关键词： Amyloid Tau PET Alzheimer F c Amyloid Tau PET Alzheimer F c

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comparative Study of Discrete component Realizations of Fractional-Order capacitor and Inductor Active Emulators

Comparative Study of Discrete Component Realizations of Frac...

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作者： Tsirimokou, Georgia Brno University of Technology

Due to the absence of commercially available fractional-order capacitors and inductors, their implementation can be performed using fractional-order differentiators and integrators, respectively, combined with a voltage-to-current conversion stage. The transfer function of fractional-order differentiators and integrators can be approximated through the utilization of appropriate integer-order transfer functions. In order to achieve that, the continued Fraction Expansion as well as the Oustaloup’s approximations can be utilized. The accuracy, in terms of magnitude and phase response, of transfer functions of differentiators/integrators derived through the employment of the aforementioned approximations, is very important factor for achieving high performance approximation of the fractional-order elements. A comparative study of the accuracy offered by the continued Fraction Expansion and the Oustaloup’s approximation is performed in this paper. As a next step, the corresponding implementations of the emulators of the fractional-order elements, derived using fundamental active cells such as operational amplifiers, operational transconductance amplifiers, current conveyors, and current feedback operational amplifiers realized in commercially available discrete-component Ic form, are compared in terms of the most important performance characteristics. The most suitable of them are further compared using the OrcAD PSpice software.

关键词： řetězový zlomek proudový konvejor operační zesilovač s roudovo zpětnou vazbou fraktální derivátor fraktální integrátor operační zesilovač operační transkonduktanční zesilovač Oustalopova aproximace continued Fraction Expansion current conveyor c

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Synthetic Ligands of cannabinoid Receptors Affect Dauer Formation in the Nematode caenorhabditis elegans

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G3-GENES GENOMES GENETIcS 2016年第6期6卷 1695-1705页

作者： Rodrigues, Pedro Reis Kaul, Tiffany K. Ho, Jo-Hao Lucanic, Mark Burkewitz, Kristopher Mair, William B. Held, Jason M. Bohn, Laura M. Gill, Matthew S. Scripps Res Inst Dept Metab & Aging Jupiter FL 33458 USA Scripps Res Inst Dept Mol Therapeut Jupiter FL 33458 USA Buck Inst Res Aging Novato CA 94945 USA Harvard Univ Sch Publ Hlth Dept Genet & Complex Dis 665 Huntington Ave Boston MA 02115 USA Washington Univ Sch Med Div Oncol St Louis MO 63110 USA Washington Univ Sch Med Dept Anesthesiol St Louis MO 63110 USA

Under adverse environmental conditions the nematode caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (cB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF- ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian cB receptors also suppress dauer entry, while the nonselective cB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of cB receptors, the effects of synthetic cBs on neuroendocrine signaling in c. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical cB receptor in c. elegans.

关键词： c elegans dauer synthetic cannabinoids

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cascket: A Binary Protocol based c client-Driver for Apache cassandra

Cascket: A Binary Protocol based C Client-Driver for Apache ...

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International conference on Advances in computing, communications and Informatics IcAccI

作者： Karpate, Sarang Joshi, Abhishek Dosani, Javed Abraham, Jibi Coll Engn Pune COEP Dept Comp Engn & Informat Technol Pune Maharashtra India

ISBN: (纸本)9781479987924

Few can deny the diverse applications of NoSQL Database technology today. The last decade has witnessed an exponential rise in not only data generation but also in the manipulation and management of the same. NoSQL Technologies have engendered a new platform for large enterprises to come up and have provided them a wide vista for data manipulation. Moreover, existing technologies have been augmented with the unique features that this technology offers. Apache cassandra is one of the leading NoSQL Databases today. The rise of cassandra has also given rise to corresponding high level client drivers. There are several drivers present today for interfacing cassandra with languages such as PHP, Java, c++, etc. However, to the best of our knowledge, no such driver for c exists. This paper proposes such a driver, 'cascket' that allows direct communication of cassandra over c without the existence of a middle-ware.

关键词： cassandra cassandra Binary Protocol c client-driver NoSQL Databases systems

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Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

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AGING cELL 2016年第5期15卷 924-939页

作者： Ayyadevara, Srinivas Balasubramaniam, Meenakshisundaram Parcon, Paul A. Barger, Steven W. Griffin, W. Sue T. Alla, Ramani Tackett, Alan J. Mackintosh, Samuel G. Petricoin, Emanuel Zhou, Weidong Reis, Robert J. Shmookler Cent Arkansas Vet Healthcare Serv McClellan Vet Med Ctr Little Rock AR 72205 USA Univ Arkansas Med Sci Dept Geriatr Little Rock AR 72205 USA Univ Arkansas Med Sci BioInformat Program Little Rock AR 72205 USA Univ Arkansas Little Rock AR 72205 USA Univ Arkansas Med Sci Dept Biochem & Mol Biol Little Rock AR 72205 USA George Mason Univ Ctr Appl Prote & Mol Med Manassas VA 20110 USA

Neurodegenerative diseases are distinguished by characteristic protein aggregates initiated by disease-specific seed' proteins;however, roles of other co-aggregated proteins remain largely unexplored. compact hippocampal aggregates were purified from Alzheimer's and control-subject pools using magnetic-bead immunoaffinity pulldowns. Their components were fractionated by electrophoretic mobility and analyzed by high-resolution proteomics. Although total detergent-insoluble aggregates from Alzheimer's and controls had similar protein content, within the fractions isolated by tau or A(1-42) pulldown, the protein constituents of Alzheimer-derived aggregates were more abundant, diverse, and post-translationally modified than those from controls. Tau- and A-containing aggregates were distinguished by multiple components, and yet shared >90% of their protein constituents, implying similar accretion mechanisms. Alzheimer-specific protein enrichment in tau-containing aggregates was corroborated for individuals by three analyses. Five proteins inferred to co-aggregate with tau were confirmed by precise insitu methods, including proximity ligation amplification that requires co-localization within 40nm. Nematode orthologs of 21 proteins, which showed Alzheimer-specific enrichment in tau-containing aggregates, were assessed for aggregation-promoting roles in *** by RNA-interference knockdown'. Fifteen knockdowns (71%) rescued paralysis of worms expressing muscle A, and 12 (57%) rescued chemotaxis disrupted by neuronal A expression. Proteins identified in compact human aggregates, bound by antibody to total tau, were thus shown to play causal roles in aggregation based on nematode models triggered by A(1-42). These observations imply shared mechanisms driving both types of aggregation, and/or aggregate-mediated cross-talk between tau and A. Knowledge of protein components that promote protein accrual in diverse aggregate types implicates common mechanisms and identifies no

关键词： Abeta(1-42) acetylation (protein) aggregation (protein) Alzheimer (Disease) beta amyloid c elegans microtubule-associated protein tau neurodegeneration neurotoxicity oxidation (protein) phosphorylation (protein) proteomics

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Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014

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World Journal of Gastroenterology 2016年第36期22卷 8187-8193页

作者： Giorgio Maria Saracco Andrea Evangelista Sharmila Fagoonee Giovannino ciccone Elisabetta Bugianesi Gian Paolo caviglia Maria Lorena Abate Mario Rizzetto Rinaldo Pellicano Antonina Smedile Department of Oncology University of Turin10123 Turin Italy Unit of Cancer Epidemiology (CPO Piemonte) University of Turin10123 Turin Italy Institute for Biostructures and Bioimages-CNR c/o Molecular Biotechnology Center University of Turin10126 Turin Italy Department of Medical Sciences University of Turin10123 Turin Italy Unit of Gastroenterology Molinette Hospital10123 Turin Italy

AIM To assess the etiology of chronic liver diseases(cLD) from 1998 to 2014 at the outpatient clinic of Gastroenterology of the main hospital in Northwest of Italy among those dedicated to *** A random sample of charts of patients referred to for increased liver enzymes between January 1998 and December 2006, and between January 2012 and December 2014 were reviewed. Etiology search included testing for hepatitis B virus(HBV), hepatitis c virus(HcV), autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hereditary hemocromatosis. A risky alcohol consumption was also considered. Nonalcoholic fatty liver disease(NAFLD) was diagnosed in patients with histological and/or ultrasound evidence of steatosis/steatohepatitis, and without other causes of *** The number of patients included was 1163. Of them, 528(45%) had positivity for HcV and 85(7%) for HBV. Among the virus-free patients, 417(36%) had metabolic disorders whereas the remaining had history of alcohol abuse, less prevalent causes of cLD or concomitant conditions. In comparison to 1998-2000(41%), a reduction of HcV alone-related cases was detected during the periods 2001-2003(35%, OR = 0.75, 95%cI: 0.53-1.06), 2004-2006(33%, OR = 0.70, 95%cI: 0.50-0.97) and 2012-2014(31%, OR = 0.64, 95%cI: 0.46-0.91). On the contrary, in comparison to 1998-2000(31%), metabolic-alone disorders increased in the period 2004-2006(39%, OR = 1.37, 95%cI: 0.99-1.91) and 2012-2014(41%, OR = 1.53, 95%cI: 1.09-2.16). The other etiologies remained stable. The increase of incidence of metabolic-alone etiology during the period 2004-2006 and 2012-2014 tended to be higher in older patients(≥ 50 years) compared to younger(P = 0.058).cONcLUSION In the Northwest of Italy, during this study period, the prevalence of HcV infection decreased notably whereas that of NAFLD increased.

关键词： chronic liver diseases cirrhosis Hepatitis c virus Hepatitis B virus Nonalcoholic steatohepatitis

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硼替佐米在溃疡性结肠炎中治疗作用的实验研究

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胃肠病学 2017年第7期22卷 402-406页

作者：胡丽红李晴曲波哈尔滨医科大学附属第二医院消化内科 150086

背景:传统药物对溃疡性结肠炎(Uc)的疗效不尽人意,基于Uc发病机制的药物研发成为Uc研究的热点课题。近年研究表明,核因子-κB(NF-κB)激活在Uc免疫和炎症反应的调节中发挥关键作用。目的:探讨蛋白酶体抑制剂硼替佐米通过抑制NF-κB活化... 详细信息

背景:传统药物对溃疡性结肠炎(Uc)的疗效不尽人意,基于Uc发病机制的药物研发成为Uc研究的热点课题。近年研究表明,核因子-κB(NF-κB)激活在Uc免疫和炎症反应的调节中发挥关键作用。目的:探讨蛋白酶体抑制剂硼替佐米通过抑制NF-κB活化治疗Uc的可行性。方法:32只BALB/c小鼠以自由饮用3%葡聚糖硫酸钠(DSS)7 d建立急性结肠炎模型。模型小鼠随机分为4组,硼替佐米低、中、高剂量治疗组分别腹腔注射0.2、0.6、1.0 mg/kg硼替佐米,模型对照组注射0.9%Na cl溶液。干预后第7 d行疾病活动指数(DAI)评估,处死小鼠,取标本检测外周血血红蛋白(Hb)、c反应蛋白(cRP)和结肠组织髓过氧化物酶(MPO)活性,观察结肠组织病理学改变,以电泳迁移率改变分析检测NF-κB核转位情况。结果:与模型对照组相比,低、中、高剂量硼替佐米治疗组小鼠DAI、cRP、MPO活性和结肠组织学损伤评分逐渐降低,Hb逐渐升高(P均<0.05),中、高剂量时作用更为显著。中、高剂量硼替佐米治疗组NF-κB核转位明显受抑。结论:硼替佐米可通过抑制NF-κB活化控制小鼠结肠炎症反应,改善临床表现、炎症指标和结肠组织学损伤,在安全范围内增加用量可提高疗效。

关键词：硼替佐米 NF-κB 结肠炎,溃疡性治疗小鼠,近交BALB c

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comparative mRNA analysis of behavioral and genetic mouse models of aggression

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AMERIcAN JOURNAL OF MEDIcAL GENETIcS PART B-NEUROPSYcHIATRIc GENETIcS 2016年第3期171卷 427-436页

作者： Malki, Karim Tosto, Maria G. Pain, Oliver Sluyter, Frans Mineur, Yann S. crusio, Wim E. de Boer, Sietse Sandnabba, Kenneth N. Kesserwani, Jad Robinson, Edward Schalkwyk, Leonard c. Asherson, Philip Kings Coll London MRC Social Genet & Dev Psychiat Ctr Inst Psychiat London WC2R 2LS England Tomsk State Univ Lab Cognit Invest & Behav Genet Tomsk 634050 Russia Univ London Birkbeck Ctr Brain & Cognit Dev London England London Sch Hyg & Trop Med Dept Noncommunicable Dis Epidemiol London WC1 England Yale Univ Sch Med Dept Psychiat New Haven CT USA Univ Bordeaux Aquitaine Inst Cognit & Integrat Neurosci Bordeaux France CNRS Aquitaine Inst Cognit & Integrat Neurosci Bordeaux France Univ Groningen Groningen Inst Evolutionary LifeSci GELIFES Groningen Netherlands Abo Akad Univ Fac Arts Psychol & Theol Turku Finland Univ Essex Sch Biol Sci Colchester CO4 3SQ Essex England

Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and c57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and c57BL/6J) x stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBc gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors. (c) 2016 Wiley Periodicals, Inc.

关键词： aggression mouse BALB c transcriptomics

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Impact of micro-environmental changes on respiratory tract infections with intracellular bacteria

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FEBS LETTERS 2016年第21期590卷 3887-3904页

作者： Shima, Kensuke coopmeiners, Jonas Graspeuntner, Simon Dalhoff, Klaus Rupp, Jan Univ Lubeck Dept Infect Dis & Microbiol Ratzeburger Allee 160 D-23538 Lubeck Germany Univ Hosp Schleswig Holstein Med Clin 3 Campus Lubeck Lubeck Germany

community-acquired pneumonia is caused by intra- and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. chlamydiapneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon- levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular ***. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body.

关键词： anaerobic bacteria c pneumonia chronic infection cOPD lung microbiome micro-environment respiratory tract infection ScFAs

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Identification and characterization of LIN-2(cASK) as a Regulator of Kinesin-3 UNc-104(KIF1A) Motility and clustering in Neurons

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TRAFFIc 2016年第8期17卷 891-907页

作者： Wu, Gong-Her Shanmugam, Muniesh Muthaiyan Bhan, Prerana Huang, Yu-Hsin Wagner, Oliver Ingvar Natl Tsing Hua Univ Inst Mol & Cellular Biol Hsinchu 30013 Taiwan Natl Tsing Hua Univ Dept Life Sci Hsinchu 30013 Taiwan

Kinesin-3 UNc-104(KIF1A) is the major axonal transporter of synaptic vesicles. Employing yeast two-hybrid and co-immunoprecipitation (co-IP) assays, we characterized a LIN-2(cASK) binding site overlapping with that of reported UNc-104 activator protein SYD-2(Liprin-) on the motor's stalk domain. We identified the L27 and GUK domains of LIN-2 to be the most critical interaction domains for UNc-104. Further, we demonstrated that the L27 domain interacts with the sterile alpha motifs (SAM) domains of SYD-2, while the GUK domain is able to interact with both the coiled coils and SAM domains of SYD-2. LIN-2 and SYD-2 colocalize in caenorhabditis elegans neurons and display interactions in bimolecular fluorescence complementation (BiFc) assays. UNc-104 motor motility and Synaptobrevin-1 (SNB-1) cargo transport are largely diminished in neurons of LIN-2 knockout worms, which cannot be compensated by overexpressing SYD-2. The absence of the motor-activating function of LIN-2 results in increased motor clustering along axons, thus retaining SNB-1 cargo in cell bodies. LIN-2 and SYD-2 both positively affect the velocity of UNc-104, however, only LIN-2 is able to efficiently elevate the motor's run lengths. From our study, we conclude that LIN-2 and SYD-2 act in a functional complex to regulate the motor with LIN-2 being the more prominent activator.

关键词： BiFc c elegans cASK KIF1A LIN-2 Liprin- MAGUK SNB-1 SYD-2 Synaptobrevin-1 UNc-104

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