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Significance of hepatitis virus infection in the oncogenicinitiation of hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第4期22卷 1497-1512页

作者： Caecilia hC Sukowati Korri E El-Khobar Susan I Ie Beatrice Anfuso david h muljono Claudio Tiribelli Fondazione Italiana Fegato ONLUS AREA Science Park Basovizza34149 TriesteItaly Department of Medicine Surgeryand Health SciencesUniversity of TriesteTeaching Hospital Cattinara34149 TriesteItaly Laboratory of hepatitis and Emerging Disease Eijkman Institute for Molecular BiologyJakarta 10430Indonesia Storr Liver Centre The Westmead Institute for Medical ResearchThe University of Sydney at Westmead HospitalWestmead NSW 2145Australia

hepatocellular carcinoma(hCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(hBV) and/or hepatitis C virus(hCV) is a major risk factor in the development of the hCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of hBV and hCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally hCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of hBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of hBV and hCV in the early initiation of hCC.

关键词： hepatocellular carcinoma hepatitis B virus hepatitis C virus Oncogenicity Viral pathogenicity

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina hromada Patrick heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.heinzel Antal Nógrádi Andreas h.Teuschl-Woller david hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). however, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

The Katanin Microtubule Severing Protein in Plants

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Journal of Integrative Plant Biology 2007年第8期49卷 1174-1182页

作者： david h.Burk Department of Plant Biology University of GeorgiaAthensGeorgia 30602USA

Katanin is a heterodimeric microtubule （MT） severing protein that uses energy from ATP hydrolysis to generate internal breaks along MTs. Katanin p60, one of the two subunits, possesses ATPase and MT-binding/severing activities, and the p 80 subunit is responsible for targeting of katanin to certain subcellular locations. In animals, katanin plays an important role in the release of MTs from their nucleation sites in the centrosome. It is also involved in severing MTs into smaller fragments which can serve as templates for further polymerization to increase MT number during meiotic and mitotic spindle assembly. Katanin homologs are present in a wide variety of plant species. The Arabidopsis katanin homolog has been shown to possess ATP-dependent MT severing activity in vitro and exhibit a punctate localization pattern at the cell cortex and the perinuclear region. Disruption of katanin functions by genetic mutations causes a delay in the disappearance of the perinuclear MT array and results in an aberrant organization of cortical MTs in elongating cells. Consequently, katanin mutations lead to defects in cell elongation, cellulose microfibril deposition, and hormonal responses. Studies of katanin in plants provide new insights into our understanding of its roles in cellular functions.

关键词： katanin microtubules microtubule severing protein.

A Short-Range Quantitative Precipitation Forecast Algorithm Using Back-Propagation Neural Network Approach

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Advances in Atmospheric Sciences 2006年第3期23卷 405-414页

作者：冯业荣 david h.KITZMILLER Department of Atmospheric Science hydrology Laboratory

A back-propagation neural network （BPNN） was used to establish relationships between the shortrange （0-3-h） rainfall and the predictors ranging from extrapolative forecasts of radar reflectivity, satelliteestimated cloud-top temperature, lightning strike rates, and Nested Grid Model （NGM） outputs. Quan- titative precipitation forecasts （QPF） and the probabilities of categorical precipitation were obtained. Results of the BPNN algorithm were compared to the results obtained from the multiple linear regression algorithm for an independent dataset from the 1999 warm season over the continental United States. A sample forecast was made over the southeastern United States. Results showed that the BPNN categorical rainfall forecasts agreed well with Stage Ⅲ observations in terms of the size and shape of the area of rainfall. The BPNN tended to over-forecast the spatial extent of heavier rainfall amounts, but the positioning of the areas with rainfall ≥25.4 mm was still generally accurate. It appeared that the BPNN and linear regression approaches produce forecasts of very similar quality, although in some respects BPNN slightly outperformed the regression.

关键词： quantitative precipitation forecast BP neural network WSR-88D Doppler radar lightning strike rate infrared satellite data NGM model

CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40-induced RAG expression

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Cellular & Molecular Immunology 2013年第6期10卷 483-489页

作者： Gisela M Vaitaitis david h Wagner Jr Department of Medicine and Webb-Waring Center University of Colorado Denver Aurora CO USA

CD4＋ T cells expressing CD40 （Th40 cells） constitute a pathogenic T-cell subset that is necessary and sufficient to transfer autoimmune disease. We have previously demonstrated that CD40 signals peripheral Th40 cells to induce RAG1 and RAG2 expression, proteins necessary for the expression of T-cell receptor （TCR）, leading to TCR revision. The dependency of TCR expression in the thymus on RAG proteins has long been known. however, despite numerous publications, there is controversy as to whether TCR expression can be altered in the periphery, post-thymic selective pressures. Therefore, a better understanding of TCR expression in primary peripheral cells is needed. We now show that the CD40 protein itself interacts with RAG1 and RAG2 as well as with Ku70 and translocates to the nucleus in Th40 cells. This indicates that the CD40 molecule is closely involved in the mechanism of TCR expression in the periphery. In addition, Fas signals act as a silencing mechanism for CD40-induced RAGs and prevent CD40 translocation to the nucleus. It will be important to further understand the involvement of CD40 in peripheral TCR expression and how TCR revision impacts auto-antigen recognition in order to effectively target and tolerize autoaggressive T cells in autoimmune disease.

关键词： autoimmunity CD40 Fas RAG T-cell receptor

EXTRACTING BEhAVIOURAL MODELS FROM 2010FIFA WORLD CUP

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Journal of Systems Science & Complexity 2013年第1期26卷 43-61页

作者： MENNDEZ héctor BELLO-ORGAZ Gema CAMAChO david Department of Computer Science Universidad Autnoma de Madrid

The FIFA World Cup^(TM) is the most profitable worldwide *** FIFA publishes global statistics of this competition which provide global data about the players and teams during the *** work is focused on the extraction of behavioural patterns for both,players and teams strategies,through the automated analysis of this *** knowledge and models extracted in this work could be applied to soccer leagues or even it could be oriented to sport ***,the main contribution is related to the study on several automatic knowledge extraction techniques,such as clustering methods,and how these techniques can be used to obtain useful behavioural models from a global statistics *** information provided by the clustering algorithms shows similar properties which have been combined to define the models,making the human interpretation of these statistics ***,the most successful teams strategies have been analysed and compared.

关键词： Behavioural patterns clustering FIFA World Cup football soccer web mining.

hepatic expression and cellular distribution of the glucose transporter family

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World Journal of Gastroenterology 2012年第46期18卷 6771-6781页

作者： Sumera Karim david h Adams Patricia F Lalor Centre for Liver Research and NIhR Biomedical Research Unit Institute of Biomedical Research University of Birmingham

Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. however there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required.

关键词： hepatic Liver Glucose transporters Glucose Transport hepatocyte

Modeling of cable vibration effects of cable-stayed bridges

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Earthquake Engineering and Engineering Vibration 2002年第1期1卷 74-85页

作者： S.h.Cheng david T.Lau Department of Civil and Environmental Engineering Carleton UniversityOttawaOntarioCanadaPost-doctoral fellow Department of Civil and Environmental Engineering Carleton UniversityOttawaOntarioCanada Professor

The analysis of dynamic responses of cable-stayed bridges subjected to wind and earthquake loads generally considers only the motions of the bridge deck and *** influence of the stay cable vibration on the responses of the bridge is either ignored or considered by approximate *** transverse vibration of the stay cables,which can be significant in some cases,are usually neglected in previous *** the present study,a new three-node cable element has been developed to model the transverse motions of the *** interactions between the cable behavior and the other parts of the bridge superstructure are considered by the concept of dynamic *** nonlinear effect of the cable caused by its self-weight is included in the *** examples are presented to demonstrate the accuracy and efficiency of the proposed model. The impact of cable vibration behavior on the dynamic characteristics of cable-stayed bridges is discussed.

关键词： cable-stayed bridges cable vibration dynamics finite elements long-span structures

Mantle-derived magmas:intraplate,hot-spots and mid-ocean ridges

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Science Bulletin 2015年第22期60卷 1873-1900页

作者： david h.Green Trevor J.Falloon Earth Sciences School of Physical Sciences University of Tasmania

Primary or parental magmas act as probes to infer eruption and source temperatures for both mid-ocean ridge （MOR） and‘hot-spot＇ magmas （tholeiitic picrites）. The experimental petrogenetic constraints （＇inverse＇ experiments） argue for no significant temperature differences between them. however, there are differences in major, minor and trace elements which characterise geochemical, not thermal, anomalies beneath ‘hot-spots＇. We suggest that diapiric upwelling from interfaces （redox contrasts） between old subducted slab and normal MOR basalt source mantle is the major reason for the observed characteristics of island chain or ‘hot-spot＇ volcanism. Intraplate basalts also include widely distributed volcanic centres containing lherzolite xenoliths, i.e. mantle-derived magmas. Inverse experiments on olivine basalt, alkali oli- vine basalt, olivine basanite, olivine nephelinite, olivine melilitite and olivine leucitite （lamproite） determined liquidus phases as a function of pressure, initially under anhydrous and CO2-absent conditions. Under C- and h-absent conditions, only tholeiites to alkali olivine basalts had O1 ＋ Opx 4-Cpx as high-pressure liquidus phases. Addition of h20 accessed olivine basanites at 2.5-3 GPa, ,- 1,200 ℃, but both CO2 and h20 were necessary to obtain saturation with O1, Opx, Cpx and Ga at 2.5-3.5 GPa for olivine nephelinite and olivine melilitite. The forward and inverse experimental studies are combined to formulate a petrogenetic grid for intraplate, ‘hot-spot＇ and MOR magmatism within the plate tectonics paradigm. The asthenosphere is geochemically zoned by slow upward migration of incipient melt. The solidus and phasestabilities of lherzolite with very small water contents （〈3,000 ppm） determine the thin plate behaviour of the oceanic lithosphere and thus the Earth＇s convection in the form of plate tectonics. There is no evidence from the parental magmas of MOR and ‘hot-spots＇ to support the ＇deep mantle thermal plume＇ hypothesis. The preferr

关键词： experimentsMantle-derived magmas ·high-pressureC-h-O · Asthenosphere - hot-spotsPlate tectonics