944 resultados para Ran GTPase


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Yuanmou area lies on the southeastern edge of the Tibetan Plateau, the middlesegment of Yunnan-Sichuan North-South Extending Tectonic Belt and the upper reaches of the Yangztze River, which is renowned for its thick late Cenozoic fluvial-lacustrine sequences that yield rich mammalian fossils including hominoid and early human. The sediments provides great potentials for understanding the relationships between uplift of the Tibetan Plateau, evolution of hominoids and other mammalian and evolution and formation of basins in Southwest China since late Miocene. However, lithostratigrphic and chronologic views on them are controversial and hinder further discussion of the relationships of them. To this end, we selected the Baozidongqing section and the Dapoqing section to carry out systematic lithostratigraphic, magnetostratlgraphic and environmental magnetism researches in this area.The Baozidongqing section was dated to about 10.95-7.17 Ma. The age estimation of the topmost hominoid-bearing layer was about 7.43-7.17 Ma. Rock magnetic results show that the dominant magnetic carrier is hematite, with minor amount of magnetite. Both the composition and concentration of magnetic minerals strongly correlate with the lithostratigraphy, indicating that Yuanmou basin is characterized by alternating of long-term torrid-humid climate and short-term dry-hot climate. But the pattern of these short-term hot-dry events, including both the lasting time and the frequency of their occurrence dramatically changed since -8.1 Ma. Our results infer that the drying process of the Asian west interior and a significant uplift of the Tibetan Plateau would have probably caused jointly the extinction of hominoids, or the emigration of hominoids from Yuanmou to adjacent relatively torrid-humid areas.The strata between the upper of the Dapoqing section, the Niujianbao Hill and Shangnabang area can be linked by three mark layers of conglomerate, which is rather continuous and coherent than physical disturbance by new tectonic activities. Rock magnetic studies indicate that hematite is the main magnetic carriers. The section is dated back to about 2.8-1.37 Ma. Its paleocurrent flowed northeastward, which was a close and stagnant river and swamp environment about 2.2 Ma ago. Then it ran northwestward and turned into an open overflown and braid river sedimentary face during 2.2 to 1.57 Ma. Since 1.57 Ma, the paleocurrent flowed intensely northwestern and about 1.37 Ma ago, it ended the basically continuous fluvial-lacustrine deposition.

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An in-situ modified sol-gel method for the preparation of a Ni-based monolith-supported catalyst is reported. With the presence of a proper amount of plasticizer and binder, and at an optimized pH value, the stable boehmite sol was modified with metal ions (Ni, Li, La) successfully without distinct growth of the particle size. Monolith-supported Ni-based/gamma-Al2O3 catalysts were obtained using the modified sol as the coating medium with several cycles of dip-coating and calcination. Combined BET, SEM-EDS, XRD and H-2-TPR investigations demonstrated that the derived monolith catalysts had a high specific surface area, a relatively homogeneous surface composition, and a high extent of interaction between the active component and the support. These catalysts showed relatively stable catalytic activities for partial oxidation of methane (POM) to syngas under atmospheric pressure. The monolith catalysts prepared by this sol-gel method also demonstrated an improved resistance to sintering and loss of the active component during the reaction process.

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Five hydrotalcites with Mg/Al molar ratio range of 3-15 were prepared. The structure and basicity of Mg-Al mixed oxides (Mg(Al)O) transformed from hydrotalcites were investigated by TPD, XPS, XRD, FT-IR and NMR techniques. The results of elemental analysis and XPS indicate that Al is enriched in the surface regions of Mg(Al)O, and its amount increases with the Mg/Al molar ratio and, the calcination temperature. Al-27-MAS-NMR results show that Al exists in two chemical environments: tetrahedral aluminium (Al(t)) and octahedral aluminium (Al(o)) in Mg(AI)O. The amount of Al(t) increases with the Mg/Al molar ratio and the calcination temperature. It is assumed that Al(t) may be mainly from the surface Al. Temperature-programmed desorption (TPD) of CO2 shows that the number of basic sites of Mg(Al)O samples increases with the Mg/Al molar ratio, and the maximum number of basic sites is obtained for hydrotalcite calcined at 773 K. Infrared spectra of adsorbed CO2 and B(OCH3)(3) reveal that there are two kinds of basic sites: weak basic OH- sites and strong basic O2- sites on the Mg(AI)O samples, the base strength depends on the Mg/Al molar ratio and calcination temperature.

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The creative industries sector faces a constantly changing context characterised by the speed of the development and deployment of digital information systems and Information Communications Technologies (ICT) on a global scale. This continuous digital disruption has had significant impact on the whole value chain of the sector: creation and production; discovery and distribution; and consumption of cultural goods and services. As a result, creative enterprises must evolve business and operational models and practices to be sustainable. Enterprises of all scales, type, and operational model are affected, and all sectors face ongoing digital disruption. Management consultancy practitioners and business strategy academics have called for new strategy development frameworks and toolkits, fit for a continuously changing world. This thesis investigates a novel approach to organisational change appropriate to the digital age, in the context of the creative sector in Scotland. A set of concepts, methods, tools, and processes to generate theoretical learning and practical knowing was created to support enterprises to digitally adapt through undertaking journeys of change and organisational development. The framework is called The AmbITion Approach. It was developed by blending participatory action research (PAR) methods and modern management consultancy, design, and creative practices. Empirical work also introduced to the framework Coghlan and Rashford’s change categories. These enabled the definition and description of the extent to which organisations developed: whether they experienced first order (change), second order (adaptation) or third order (transformation) change. Digital research tools for inquiry were tested by a pilot study, and then embedded in a longitudinal study over two years of twentyone participant organisations from Scotland’s creative sector. The author applied and investigated the novel approach in a national digital development programme for Scotland’s creative industries. The programme was designed and delivered by the author and ran nationally between 2012-14. Detailed grounded thematic analysis of the data corpus was undertaken, along with analysis of rich media case studies produced by the organisations about their change journeys. The results of studies on participants, and validation criteria applied to the results, demonstrated that the framework triggers second (adaptation) and third order change (transformation) in creative industry enterprises. The AmbITion Approach framework is suitable for the continuing landscape of digital disruption within the creative sector. The thesis contributes to practice the concepts, methods, tools, and processes of The AmbITion Approach, which have been empirically tested in the field, and validated as a new framework for business transformation in a digital age. The thesis contributes to knowledge a theoretical and conceptual framework with a specific set of constructs and criteria that define first, second, and third order change in creative enterprises, and a robust research and action framework for the analysis of the quality, validity and change achieved by action research based development programmes. The thesis additionally contributes to the practice of research, adding to our understanding of the value of PAR and design thinking approaches and creative practices as methods for change.

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In this reported clinical case, a healthy and well-trained male subject [aged 37 years, maximal oxygen uptake (V[Combining Dot Above]O2max) 64 mL·kg·min] ran for 23 hours and 35 minutes covering 160 km (6.7 km/h average running speed). The analysis of hematological and biochemical parameters 3 days before the event, just after termination of exercise, and after 24 and 48 hours of recovery revealed important changes on muscle and liver function, and hemolysis. The analysis of urine sediments showed an increment of red and white blood cells filtrations, compatible with transient nephritis. After 48 hours, most of these alterations were recovered. Physicians and health professionals who monitor such athletic events should be aware that these athletes could exhibit transient symptoms compatible with severe pathologies and diseases, although the genesis of these blood and urinary abnormalities are attributable to transient physiological adaptations rather to pathological status.

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Haycock, Marged. 'Defnydd hyd Ddydd Brawd: rhai agweddau ar y ferch ym marddoniaeth yr oesoedd canol', In: 'Cymru a'r Cymry 2000-Wales and the Welsh 2000', Geraint H. Jenkins (ed.), (Canolfan Uwchefrydiau Cymreig a Cheltaidd Prifysgol Cymru), pp.41-70, 2002

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Niniejsze badanie koncentruje się na księgach powstałych w wyniku działalności organizacji cechowych na Pomorzu Zachodnim. Jest to specyficzny rodzaj zabytków, w których odzwierciedla się życie zarówno zawodowe, jak i społeczne oraz towarzyskie korporacji. Pisane były niejednokrotnie przez kolejne pokolenia, obejmują nawet kilka stuleci, przez co stanowią cenne źródło historyczne. Księgi dzieliły się na urzędowe, obejmujące całokształt działalności (Amtsbuch), oraz wyspecjalizowane – księgi protokołów (Protokollbuch), księgi mistrzów, czeladników i uczniów (Meister-, Gesellen- i Lehrjungenbuch), księgi rachunkowe (Rechnungsbuch) i księgi normatywne. Tekst ukazuje znaczną różnorodność kwestii poruszanych w poszczególnych rodzajach ksiąg, a także ich formę zewnętrzną. Podstawę do badań stanowią obiekty przechowywane w Archiwum Państwowym w Szczecinie. Daleko posunięte podobieństwo w funkcjonowaniu cechów poza granicami Pomorza pozwala na przeniesienie wniosków również na inne organizacje cechowe.

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Sonic boom propagation in a quiet) stratified) lossy atmosphere is the subject of this dissertation. Two questions are considered in detail: (1) Does waveform freezing occur? (2) Are sonic booms shocks in steady state? Both assumptions have been invoked in the past to predict sonic boom waveforms at the ground. A very general form of the Burgers equation is derived and used as the model for the problem. The derivation begins with the basic conservation equations. The effects of nonlinearity) attenuation and dispersion due to multiple relaxations) viscosity) and heat conduction) geometrical spreading) and stratification of the medium are included. When the absorption and dispersion terms are neglected) an analytical solution is available. The analytical solution is used to answer the first question. Geometrical spreading and stratification of the medium are found to slow down the nonlinear distortion of finite-amplitude waves. In certain cases the distortion reaches an absolute limit) a phenomenon called waveform freezing. Judging by the maturity of the distortion mechanism, sonic booms generated by aircraft at 18 km altitude are not frozen when they reach the ground. On the other hand, judging by the approach of the waveform to its asymptotic shape, N waves generated by aircraft at 18 km altitude are frozen when they reach the ground. To answer the second question we solve the full Burgers equation and for this purpose develop a new computer code, THOR. The code is based on an algorithm by Lee and Hamilton (J. Acoust. Soc. Am. 97, 906-917, 1995) and has the novel feature that all its calculations are done in the time domain, including absorption and dispersion. Results from the code compare very well with analytical solutions. In a NASA exercise to compare sonic boom computer programs, THOR gave results that agree well with those of other participants and ran faster. We show that sonic booms are not steady state waves because they travel through a varying medium, suffer spreading, and fail to approximate step shocks closely enough. Although developed to predict sonic boom propagation, THOR can solve other problems for which the extended Burgers equation is a good propagation model.

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Rab4 is a member of the Rab superfamily of small GTPases. It is localized to the early sorting endosome and plays a role in regulating the transport from this compartment to the recycling and degradative pathways. In order to further our understanding of the role Rab4 plays in endocytosis, a yeast two-hybrid screen was performed to identify putative Rab4 effectors. A constitutively active mutant of Rab4, Rab4Q67L, when used as bait to screen a HeLa cDNA library, identified a novel 80kDa protein that interacted with Rab4-GTP. This protein was called Rab Coupling Protein (RCP). RCP interacts preferentially with the GTP-bound form of Rab4. Subsequent work demonstrated that RCP also interacts with Rab11, and that this interaction is not nucleotide-depenedent. RCP is predominantly membrane-bound and localised to the perinuclear recycling compartment. Expression of a truncation mutant of RCP, that contains the Rab binding domain, in HeLa cells, results in the formation of an extensive tubular network that can be labelled with transferrin. These tubules are derived from the recycling compartment since they are inaccessible to transferrin when the ligand is internalised at 18oC. The truncation mutant-induced morphology can be rescued by overexpression of active Rab11, but not active Rab4. This suggests that RCP functions between Rab4 and Rab11 in the receptor recycling pathway, and may act as a ‘molecular bridge’ between these two sequentially acting small GTPases. Quantitative assays demonstrated that overexpression of the truncation mutant results in a dramatic inhibition in the rate of receptor recycling. Database analysis revealed that RCP belongs to a family of Rab interacting proteins, each characterised by a carboxy-terminal coiled-coil domain and an amino-terminal phospholipid-binding domain. KIAA0941, an RCP homologue, interacts with Rab11, but not with Rab4. Overexpression of its Rab binding domain also results in a tubular network, however, this tubulation cannot be rescued by active Rab11.

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Technology boosters, such as strain, HKMG and FinFET, have been introduced into semiconductor industry to extend Moore’s law beyond 130 nm technology nodes. New device structures and channel materials are highly demanded to keep performance enhancement when the device scales beyond 22 nm. In this work, the properties and feasibility of the proposed Junctionless transistor (JNT) have been evaluated for both Silicon and Germanium channels. The performance of Silicon JNTs with 22 nm gate length have been characterized at elevated temperature and stressed conditions. Furthermore, steep Subthreshold Slopes (SS) in JNT and IM devices are compared. It is observed that the floating body in JNT is relatively dynamic comparing with that in IM devices and proper design of the device structure may further reduce the VD for a sub- 60 mV/dec subthreshold slope. Diode configuration of the JNT has also been evaluated, which demonstrates the first diode without junctions. In order to extend JNT structure into the high mobility material Germanium (Ge), a full process has been develop for Ge JNT. Germanium-on-Insulator (GeOI) wafers were fabricated using Smart-Cut with low temperature direct wafer bonding method. Regarding the lithography and pattern transfer, a top-down process of sub-50-nm width Ge nanowires is developed in this chapter and Ge nanowires with 35 nm width and 50 nm depth are obtained. The oxidation behaviour of Ge by RTO has been investigated and high-k passivation scheme using thermally grown GeO2 has been developed. With all developed modules, JNT with Ge channels have been fabricated by the CMOScompatible top-down process. The transistors exhibit the lowest subthreshold slope to date for Ge JNT. The devices with a gate length of 3 μm exhibit a SS of 216 mV/dec with an ION/IOFF current ratio of 1.2×103 at VD = -1 V and DIBL of 87 mV/V.

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The Pulitzer Prize in Music, established in 1943, is one of America's most prestigious awards. It has been awarded to fifty-three composers for a "distinguished musical composition of significant dimension by an American that has had its first performance in the United States during the year." Composers who have won the Pulitzer Prize are considered to be at the pinnacle of their creativity and have provided the musical world with classical music compositions worthy of future notice. By tracing the history of Pulitzer Prize-winning composers and their compositions, researchers and musicians enhance their understanding of the historical evolution of American music, and its impact on American culture. Although the clarinet music of some of these composers is rarely performed today, their names will be forever linked to the Pulitzer, and because of that, their compositions will enjoy a certain sense of immortality. Of the fifty-four composers who have won the award, forty-seven have written for the clarinet in a solo or chamber music setting (five or less instruments). Just as each Pulitzer Prize-winning composition is a snapshot of the state of American music at that time, these works trace the history of American clarinet musical development, and therefore, they are valuable additions to the clarinet repertoire and worthy of performance. This dissertation project consists of two recitals featuring the solo and chamber clarinet music of sixteen Pulitzer Prize-winning composers, extended program notes containing information on each composer's life, their music, the Pulitzer Prize-winning composition and the recital selection, and a complete list of all Pulitzer Prize-winning composers and their solo and chamber clarinet music. Featured Composers Dominick Argento, To Be Sung Upon the Water Leslie Bassett, Soliloquies William Bolcom, Little Suite of Four Dances Aaron Copland, As it Fell Upon a Day John Corigliano, Soliloquy Norman Dello Joio, Concertante Morton Gould, Benny's Gig Charles Ives, Largo Douglas Moore, Quintet for Clarinet and Strings George Perle, Three Sonatas Quincy Porter, Quintet for Clarinet and Strings Mel Powell, Clarinade Shulamit Ran, Private Game Joseph Schwantner, Entropy Leo Sowerby, Sonata Ernst Toch, Adagio elegiaco

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The relationship of mitochondrial dynamics and function to pluripotency are rather poorly understood aspects of stem cell biology. Here we show that growth factor erv1-like (Gfer) is involved in preserving mouse embryonic stem cell (ESC) mitochondrial morphology and function. Knockdown (KD) of Gfer in ESCs leads to decreased pluripotency marker expression, embryoid body (EB) formation, cell survival, and loss of mitochondrial function. Mitochondria in Gfer-KD ESCs undergo excessive fragmentation and mitophagy, whereas those in ESCs overexpressing Gfer appear elongated. Levels of the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) are highly elevated in Gfer-KD ESCs and decreased in Gfer-overexpressing cells. Treatment with a specific inhibitor of Drp1 rescues mitochondrial function and apoptosis, whereas expression of Drp1-dominant negative resulted in the restoration of pluripotency marker expression in Gfer-KD ESCs. Altogether, our data reveal a novel prosurvival role for Gfer in maintaining mitochondrial fission-fusion dynamics in pluripotent ESCs.

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Wg/Wnt signals specify cell fates in both invertebrate and vertebrate embryos and maintain stem-cell populations in many adult tissues. Deregulation of the Wnt pathway can transform cells to a proliferative fate, leading to cancer. We have discovered that two Drosophila proteins that are crucial for cytokinesis have a second, largely independent, role in restricting activity of the Wnt pathway. The fly homolog of RacGAP1, Tumbleweed (Tum)/RacGAP50C, and its binding partner, the kinesin-like protein Pavarotti (Pav), negatively regulate Wnt activity in fly embryos and in cultured mammalian cells. Unlike many known regulators of the Wnt pathway, these molecules do not affect stabilization of Arm/beta-catenin (betacat), the principal effector molecule in Wnt signal transduction. Rather, they appear to act downstream of betacat stabilization to control target-gene transcription. Both Tum and Pav accumulate in the nuclei of interphase cells, a location that is spatially distinct from their cleavage-furrow localization during cytokinesis. We show that this nuclear localization is essential for their role in Wnt regulation. Thus, we have identified two modulators of the Wnt pathway that have shared functions in cell division, which hints at a possible link between cytokinesis and Wnt activity during tumorigenesis.

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This study, "Civil Rights on the Cell Block: Race, Reform, and Violence in Texas Prisons and the Nation, 1945-1990," offers a new perspective on the historical origins of the modern prison industrial complex, sexual violence in working-class culture, and the ways in which race shaped the prison experience. This study joins new scholarship that reperiodizes the Civil Rights era while also considering how violence and radicalism shaped the civil rights struggle. It places the criminal justice system at the heart of both an older racial order and within a prison-made civil rights movement that confronted the prison's power to deny citizenship and enforce racial hierarchies. By charting the trajectory of the civil rights movement in Texas prisons, my dissertation demonstrates how the internal struggle over rehabilitation and punishment shaped civil rights, racial formation, and the political contest between liberalism and conservatism. This dissertation offers a close case study of Texas, where the state prison system emerged as a national model for penal management. The dissertation begins with a hopeful story of reform marked by an apparently successful effort by the State of Texas to replace its notorious 1940s plantation/prison farm system with an efficient, business-oriented agricultural enterprise system. When this new system was fully operational in the 1960s, Texas garnered plaudits as a pioneering, modern, efficient, and business oriented Sun Belt state. But this reputation of competence and efficiency obfuscated the reality of a brutal system of internal prison management in which inmates acted as guards, employing coercive means to maintain control over the prisoner population. The inmates whom the prison system placed in charge also ran an internal prison economy in which money, food, human beings, reputations, favors, and sex all became commodities to be bought and sold. I analyze both how the Texas prison system managed to maintain its high external reputation for so long in the face of the internal reality and how that reputation collapsed when inmates, inspired by the Civil Rights Movement, revolted. My dissertation shows that this inmate Civil Rights rebellion was a success in forcing an end to the existing system but a failure in its attempts to make conditions in Texas prisons more humane. The new Texas prison regime, I conclude, utilized paramilitary practices, privatized prisons, and gang-related warfare to establish a new system that focused much more on law and order in the prisons than on the legal and human rights of prisoners. Placing the inmates and their struggle at the heart of the national debate over rights and "law and order" politics reveals an inter-racial social justice movement that asked the courts to reconsider how the state punished those who committed a crime while also reminding the public of the inmates' humanity and their constitutional rights.

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Lymphocyte chemotaxis is a complex process by which cells move within tissues and across barriers such as vascular endothelium and is usually stimulated by chemokines such as stromal cell-derived factor-1 (CXCL12) acting via G protein-coupled receptors. Because members of this receptor family are regulated ("desensitized") by G protein-coupled receptor kinase (GRK)-mediated receptor phosphorylation and beta-arrestin binding, we examined signaling and chemotactic responses in splenocytes derived from knockout mice deficient in various beta-arrestins and GRKs, with the expectation that these responses might be enhanced. Knockouts of beta-arrestin2, GRK5, and GRK6 were examined because all three proteins are expressed at high levels in purified mouse CD3+ T and B220+ B splenocytes. CXCL12 stimulation of membrane GTPase activity was unaffected in splenocytes derived from GRK5-deficient mice but was increased in splenocytes from the beta-arrestin2- and GRK6-deficient animals. Surprisingly, however, both T and B cells from beta-arrestin2-deficient animals and T cells from GRK6-deficient animals were strikingly impaired in their ability to respond to CXCL12 both in transwell migration assays and in transendothelial migration assays. Chemotactic responses of lymphocytes from GRK5-deficient mice were unaffected. Thus, these results indicate that beta-arrestin2 and GRK6 actually play positive regulatory roles in mediating the chemotactic responses of T and B lymphocytes to CXCL12.