Genetinių veiksnių, lemiančių žmogaus fizinį pajėgumą, analizė Tapimas didelio meistriškumo sportininku yra sudėtingas procesas, kuriam įtakos turi ne tik aplinkos ar psichologiniai veiksniai, tačiau ir genetiškai nulemtos fizinio pajėgumo savybės. Fizinis pajėgumas- sudėtinė kiekybinė paveldima savybė, kurios fenotipus įtakoja daug genų bei aplinkos veiksnių. Daugeliu atvejų morfologinės ir funkcinės sportininko savybės yra siejamos su vieno nukleotido polimorfizmais tam tikrame gene. Skirtingi to paties geno aleliai gali turėti skirtingą poveikį asmens fiziniam vystymuisi ir darbingumui. Maksimalus deguonies suvartojimas (MDS) apibūdina žmogaus fizinį pajėgumą tai yra didžiausią žmogaus kūno gebėjimą transportuoti ir panaudoti deguonį didėjant krūviui treniruočių metu. MDS yra lemiamas daugelio fiziologinių veiksnių vieni svarbiausių iš jų yra širdies ir kraujagyslių, kvepavimo sistemų veikla bei ją įtakojantys genetiniai veiksniai. Šio darbo tikslas- parinkti ir įvertinti AGTR1, AGTR2, AGT, AMPD1, MB, ACTN3 genų žymenų įtaką žmogaus fiziniam pajėgumui remiantis Lietuvos didelio meistriškumo sportininkų ir kontrolinės grupės analize. Buvo pasirinkti AGTR1 c.1166A>C, AGTR2 c.*501A>C, AGT c.620C>T, AMPD1 c.34C>T, MB c.174G>A, ACTN3 c.1747C>T polimorfizmai. Darbe ištirta kontrolinė grupė, sudaryta iš 250 gimininiais ryšiais nesusijusių asmenų bei didelio meistriškumo Lietuvos sportininkų grupės (149 sportininkai) sudarytos pagal sportininkų kvalifikaciją ir jų propaguojamą... [toliau žr. visą tekstą] / The analysis of the genetic factors that influence human physical capacity Although the making of an elite athlete is complex and includes a range of environmental and behavioral factors, genetic predisposition to athleticism is also important. Physical capacity is a typical quantitative complex inheritable, the phenotypes of which are influenced by multiple genes as well as environmental factors. In most of the cases the morphological and functional parameters of an athlete are associated with single nucleotide polymorphisms of a particular gene. Different alleles of the same gene can have distinct effect on a person’s physical development and working capacity. VO2 max (also maximal oxygen consumption, aerobic capacity) is the maximum capacity of an individual's body to transport and utilize oxygen during incremental exercise, which reflects the physical fitness of the individual. There are many physiological factors that combine to determine VO2max among the most important of which are the functions of the cardiovascular, pulmonary systems and the underlying genetic factors. The aim of this study was to choose and asses the influence of the AGT, AGTR1, AGTR2, AMPD and ACTN3 genetic variants on human physical performance by the analysis of Lithuanian elite athletes and the control group. The AGTR1 c.1166A>C, AGTR2 c.*501A>C, AGT c.620C>T, AMPD1 c.34C>T, MB c.174G>A, ACTN3 c.1747C>T polymorphisms were chosen for the research. The study involved the analysis of the elite... [to full text]

RAID-6 is widely used to tolerate concurrent failures of any two disks to provide a higher level of reliability with the support of erasure codes. Among many implementations, one class of codes called Maximum Distance Separable (MDS) codes aims to offer data protection against disk failures with optimal storage efficiency. Typical MDS codes contain horizontal and vertical codes. However, because of the limitation of horizontal parity or diagonal/anti-diagonal parities used in MDS codes, existing RAID-6 systems suffer several important problems on performance and scalability, such as low write performance, unbalanced I/O, and high migration cost in the scaling process. To address these problems, in this dissertation, we design techniques for high performance and scalable RAID-6 systems. It includes high performance and load balancing erasure codes (H-Code and HDP Code), and Stripe-based Data Migration (SDM) scheme. We also propose a flexible MDS Scaling Framework (MDS-Frame), which can integrate H-Code, HDP Code and SDM scheme together. Detailed evaluation results are also given in this dissertation.

The aim of this study was to map the intellectual base at the Swedish School of Library and Information Science (SSLIS) at the University Collage of Borås, and to compare this intellectual base to the intellectual base of the research area Library and Information Science. This was done by analysing the citations in publications published, between the year of 2001 to the first quarter of 2006, by researchers at the institution, using the technique of author cocitation analysis. Cluster analysis and multidimensional scaling, statistical techniques that are traditional i the author cocitation analysis, formed an objective map of the intellectual base at the SSLIS. This map was then compared with three prior studies, that used the same technique to map the intellectual base of the research area. The result shows that the map of the intellectual base at the SSLIS consists of the specialities: user studies, library studies, culture/cultural policy, information retrieval, bibliometrics and information in organisations. The comparison to the prior studies shows that the intellectual base at the SSLIS is somewhat different to the intellectual base of the research area. The main differences between the two intellectual bases are: culture/cultural policy and library studies are not represented in the intellectual base of the research area, bibliometrics is not as obvious in the intellectual base of SSLIS as in the intellectual base of the research area. / Uppsatsnivå: D

The purpose with this study is to map the research front and the research base in information science, by using the bibliometric methods bibliographic coupling and author-co citation analysis. The research questions are: 1. What is the nature of the research front in information science, regarding which areas that are being studied? 2. What is the nature of the research base in information science, regarding which authors who are most cited, and how they can be grouped? The data used in the study were gathered from articles published in the journal Journal of the American society for information science and technology, published between 2004-2006, respectively 1986-2006. The result was presented by using cluster analysis and MDS-maps. The study shows that the research front can be divided in to three areas: 1. Information searching and information retrieval from the World Wide Web. 2. Bibliometrics. 3. Information searching and information retrieval, not from the World Wide Web. The 50 most cited authors was identified, and could be grouped into three areas: 1. Bibliometrics, 2. General, 3. Hard-IR/Soft-IR. / Uppsatsnivå: D

L’érythropoïèse est le processus aboutissant à la production des hématies à partir d’une cellule souche hématopoïétique. La différenciation érythroïde implique des changements morphologiques en partie liés à la perte d’expression membranaire du récepteur à activité tyrosine kinase de classe III, c-Kit. En réponse à son ligand, le SCF, c-Kit est activé puis internalisé et dégradé par la voie du protéasome, via l’ubiquitine E3-ligase c-Cbl, ou par la voie lysosomale suite à une endocytose. Dans la première partie de ce travail, nous avons pu mettre en évidence qu’en absence de SCF et en réponse à un inhibiteur de tyrosine kinase, l’imatinib, les érythroblastes cultivés ex vivo perdent l’expression membranaire de c-Kit et accélèrent leur entrée en différenciation terminale. Au vu de ces observations, nous avons cherché à comprendre les mécanismes impliqués. Sur un modèle de cellules érytholeucémiques dépendantes de l’érythropoïétine, mais exprimant de manière endogène c-Kit, nous avons montré que l’imatinib induit une internalisation du récepteur ainsi que sa dégradation par la voie lysosomale et de manière indépendant de c-Cbl. De plus, nous avons montré que cet effet est réversible et que l’imatinib ne bloque pas la réexpression de c-Kit après son internalisation en réponse au SCF. Des marquages métaboliques ont permis de montrer que l’imatinib ne modifie ni la synthèse ni la maturation de c-Kit et que le profil phospho-tyrosine des cellules traitées à l’imatinib est globalement inchangé. Enfin, nous avons montré que la fixation de l’imatinib à la poche catalytique de c-Kit est indispensable à son internalisation, et par conséquent à sa dégradation. Il apparait donc que l’imatinib lève l’auto-inhibition de c-Kit, qui semble nécessaire pour son maintien à la membrane. Dans la seconde partie de ce travail, nous nous sommes intéressés aux changements morphologiques subis par les nucléoles, lieu de la biogenèse des ribosomes, au cours de différenciation des érythroblastes. L’étude de la taille et du potentiel prolifératif des cellules, ainsi que l’analyse morphologique des nucléoles, nous a permis de confirmer que la réduction de taille des cellules est contemporaine d’un ralentissement de leur prolifération ainsi que de la réduction du volume et de la surface du composé granulaire (CG), « matrice » du nucléole. En microscopie électronique, nous montrons la persistance des CG en fin de maturation. Enfin, nous avons également étudié l’évolution des nucléoles dans un contexte pathologique de syndromes myélodysplasiques de faible risque, qui se caractérisent par une hématopoïèse inefficace. Nous observons que les cellules pathologiques immatures ont des CG plus volumineux que les cellules normales immatures, et qu’au cours de la différenciation, la morphologie des nucléoles est identique entre les cellules normales et pathologiques. En conclusion, ce travail a permis de décrire 1) le mécanisme d’internalisation d’un récepteur à activité tyrosine kinase de classe III, c-Kit par l’imatinib et 2) la morphologie du nucléole au cours de la différenciation érythroïde normale et pathologique des syndromes myélodysplasiques de faible risque. / Erythropoiesis is the process leading to the production of red blood cells from hematopoietic stem cell. The erythroid differentiation involves morphological cell changes, in part related to the loss of membrane expression of the type III receptor tyrosine kinase, c-Kit. In response to its ligand SCF, c-Kit is activated, then internalized and degraded by the proteasome pathway via the E3 ubiquitin ligase c-Cbl, or by the lysosomal pathway, after endocytosis. In the first part of this work, we demonstrated that in the absence of SCF and in response to tyrosine kinase inhibitor, imatinib, erythroblasts cultured ex vivo, lose membrane expression of c-Kit and accelerate their terminal differentiation. In view of these observations, we sought to understand the mechanisms involved. On an erythropoietin dependent cell line expressing c-Kit at the membrane, we showed that imatinib induces receptor internalization and degradation by the lysosomal pathway, independently of c -Cbl. Furthermore, we showed that this effect is reversible and that imatinib does not block the c-Kit re-expression after its internalization, in response to SCF. Metabolic labelling showed that imatinib does not alter synthesis or maturation of c -Kit and that the phospho-tyrosine profile of cells treated with imatinib is generally unchanged. Finally, we showed that the binding of imatinib to the catalytic pocket of c-Kit is essential for its internalization, and therefore its degradation. So, it appears that imatinib removes c-Kit self-inhibition, which seems necessary to its retention at the membrane. In the second part of this work, we studied the morphological changes of nucleoli, the site of ribosome biogenesis, during erythroid differentiation. We showed that the reduction of cell size takes place at the same time than reduction of cell proliferation and reduction of surface and volume of the Granular Compound (GC), the “matrix” of the nucleolus. Moreover, we showed by electronic microscopy, the persistence of GC at the end of maturation. Finally, we also studied the evolution of nucleoli in a pathological context of low risk myelodysplastic syndromes, which are characterized by ineffective hematopoiesis. We observed that immature pathological cells have larger GC than immature normal cells, but that during differentiation, the morphology of nucleoli is identical between normal and pathological cells. In conclusion, this work has allowed us to describe 1) the mechanisms of internalization of a class III receptor tyrosine kinase, c-Kit by imatinib and 2) the morphology of the nucleolus during normal and pathological low risk myelodysplastic syndromes of erythroid differentiation.

No description available.

Hematopoietic stem cells (HSCs) that function to maintain the hematopoietic compartment through self-renewal and differentiation capacities, as well as their downstream progeny, are susceptible to transformation resulting in the generation of the leukemic stem cell (LSC). Chief in the factors that control HSC regulation and protection of the HSC compartment is the cellular redox environment. Deregulation of the Hematopoietic Stem/Progenitor Cell (HSPC) redox environment results in loss of HSPC function and exhaustion. The characteristic developments of HSPC exhaustion via exposure to redox stress closely mirror phenotypic traits of hematopoietic malignancies, presenting the HSPC/LSC redox environment as a potential therapeutic target. While myelosuppression and HSPC exhaustion are detrimental side effects of classical chemotherapies, new approaches that differentially modify the HSPC/LSC redox environment may demonstrate LSC cytotoxicity while offering protection of normal HSPC function via differential activation of internal signaling pathways. Precisely how the redox environment and downstream signaling events are affected by these treatments remains unclear; thus highlighting the need for robust methods that evaluate the HSPC/LSC redox state. Because the glutathione (GSH), glutathione disulfide (GSSG) redox couple heavily contributes to the management of HSPC function and redox environment, characterizing the GSH/GSSG redox potential at the HSPC level would provide great insight for therapeutic opportunities. However, accurate measurement the GSH/GSSG redox potential within HSPCs/LSCs has been difficult due to their inherently low numbers. Here, we describe the development and validation of a sensitive method used for the direct and simultaneous quantitation of both oxidized and reduced GSH via LC-MS/MS. We use these methodologies to establish a difference in GSH-GSSG half-cell reduction potentials between normal and malignant HSPCs and examine the therapeutic effect of a redox active MnSOD mimetic, Mn(III) mesotetrakis (N-n-butoxyethylpyridinium-2yl) porphyrin, MnTnBuOE-2-PyP5+ (MnP), within these populations in vitro as well as within a human xenograft model in vivo. MnP demonstrates significant cytotoxic effects in several malignant models, while inducing an opposite cytoprotective effect in normal HSPC populations. The GSH/GSSG redox balance, specifically managed by glutathione reductase activity, is identified as a determining factor of MnP efficacy in various malignant populations. Treatment of the human myelodysplastic cell line (MDSL) offers mechanistic insights into MnP efficacy through hydrogen peroxide mediated activation of activator protein 1 (AP-1) signaling. We identify the redox dependent activation of JunB, a known regulator of normal myeloid lineage HSC proliferation, as a transcriptional mechanistic mediator of MnP treatment induced AP-1 signaling resulting in malignant cytotoxicity. The development of this novel method allowing for the identification of targetable differences between normal and malignant cell populations has provided insight to the underpinnings of potential redox based therapies. Additionally, the finding that MnP can target varying cellular redox states and exert selective cytotoxicity in malignant over normal populations by re-gaining lost control of AP-1 signaling demonstrates the potential for development of safe therapeutics within a variety of clinical applications.

Many geological deposits contain nonlinear anisotropic features such as veins, channels, folds or local changes in orientation; numerical property modeling must account for these features to be reliable and predictive. This work incorporates locally varying anisotropy into inverse distance estimation, kriging and sequential Gaussian simulation. The methodology is applicable to a range of fields including (1) mining-mineral grade modeling (2) petroleum-porosity, permeability, saturation and facies modeling (3) environmental-contaminate concentration modeling. An exhaustive vector field defines the direction and magnitude of anisotropy and must be specified prior to modeling. Techniques explored for obtaining this field include: manual; moment of inertia of local covariance maps; direct estimation and; automatic feature interpolation. The methodology for integrating locally varying anisotropy into numerical modeling is based on modifying the distance/covariance between locations in space. Normally, the straight line path determines distance but in the presence of nonlinear features the appropriate path between locations traces along the features. These paths are calculated with the Dijkstra algorithm and may be nonlinear in the presence of locally varying anisotropy. Nonlinear paths do not ensure positive definiteness of the required system of equations when used with kriging or sequential Gaussian simulation. Classical multidimensional scaling is applied to ensure positive definiteness but is found to be computationally infeasible for large models, thus, landmark points are used for efficiency with acceptable losses in precision. The methodology is demonstrated on two data sets (1) net thickness of the McMurray formation in northern Alberta and (2) gold grade in a porphyry copper deposit. Integrating LVA into numerical modeling increases local accuracy and improves leave-one-out cross validation analysis results in both case studies. / Mining Engineering

People¡¦s individual personality and aesthetics tastes regarding living milieu can be examined and understood through their preferences on designs of living-room furnishing. The current research investigated college students¡¦ needs and cognition about living-room furnishing, sifted out various factors for living-room functionality demands, and understood cluster analysis among the groups derived from the factors. Additionally, the current study analyzed the relationships between functionality demands and furnishings of living-room, as well as the cognition situation of the students in the different groups regarding designs of living room. Forty-five (45) students of the National Sun Yat-San University were recruited as participants in the quasi-experiment for similarity of living room designs. In addition, one hundred and fifty (150) were collected for the questionnaire of living room needs and preferences. The methods for the data analysis in the current research included factor analysis, cluster analysis, MDS, and association and preference analysis. The major findings are listed as the followings. 1. The people¡¦s needs of living room functionality have three factors: family gathering, aesthetic taste, and sociableness. 2. The higher education level, the more demanding on the functions of ¡§family gathering and aesthetic taste¡¨. The higher monthly living budget, the more inclining for the function of ¡§sociableness¡¨. 3. Each group has different cognition dimensions and preference patterns about living designs.

Product semantics is an important concept in the contemporary product design. The current thesis research, applying separately the ¡§Semantic Differential (SD)¡¨ approach and the ¡§Multidimensional Scaling (MDS)¡¨ method, parallel tested the dimensions of symbolic communication between products and consumers. While taking the rational dimension in the traditional product consideration as the base-lines to contrast, the present study explored, reviewed, and tested with empirical data the constructs of affective aspects in product design and the possible dimensions. The testing products included: desk lamp and sofa coach, each involving 10 product design in various styles or attributes. Participants in the empirical data collection were 120 undergraduate and master students at National Sun Yat-Sen University, Kaohsiung, Taiwan; 60 in the experiment for MDS data and other 120 for the survey questionnaire of the SD scales. The results in SD data analysis, through the factor analysis and the reliability checking, confirmed existence of three affective dimensions¡Xaesthetic design, mood expression, and ideology assertion¡Xwith good statistical significances. On the other hand, the MDS data, via clustering the subjects into homogenous groups and the dimensional plots, partly revealed some of the affective aspects, while also demonstrated the rational perception in traditional consideration. The statistical checking figures all were controlled within the acceptable levels.