991 resultados para 187-1161
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2006
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2016
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The extremes of exercise capacity and health are considered a complex interplay between genes and the environment. In general, the study of animal models has proven critical for deep mechanistic exploration that provides guidance for focused and hypothesis driven discovery in humans. Hypotheses underlying molecular mechanisms of disease, and gene/tissue function can be tested in rodents in order to generate sufficient evidence to resolve and progress our understanding of human biology. Here we provide examples of three alternative uses of rodent models that have been applied successfully to advance knowledge that bridges our understanding of the connection between exercise capacity and health status. Firstly we review the strong association between exercise capacity and all-cause morbidity and mortality in humans through artificial selection on low and high exercise performance in the rat and the consequent generation of the "energy transfer hypothesis". Secondly we review specific transgenic and knock-out mouse models that replicate the human disease condition and performance. This includes human glycogen storage diseases (McArdle and Pompe) and α-actinin-3 deficiency. Together these rodent models provide an overview of the advancements of molecular knowledge required for clinical translation. Continued study of these models in conjunction with human association studies will be critical to resolving the complex gene-environment interplay linking exercise capacity, health, and disease.
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Rowland, J.J. (2003) Model Selection Methodology in Supervised Learning with Evolutionary Computation. BioSystems 72, 1-2, pp 187-196, Nov
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Tedd, L.A. (2003). Library co-operation and ICT in the UK: an overview. Information Services and Use, 23(4), 199-210
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McInnes, Colin, Spectator Sport War: The West and Contemporary Conflict (Boulder, CO: Lynne Rienner, 2002) pp.vii+187 RAE2008
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Watt, D. (2006). Faith in the Landscape: Overseas Pilgrimages in 'The Book of Margery Kempe'. In C. Lees and G. Overing (Eds.), A Place to Believe In: Locating Medieval Landscapes (pp.170-187). University Park (PA): Pennsylvania State University Press. RAE2008
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Griffiths, L.; and O'Malley, T. (2007). Media Literacy in Wales: a Critical Review of Industry and Education Policies. Cyfrwng. 4, pp.7-23. RAE2008
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Langstaff, David; Bushell, A.; Chase, T.; Evans, D.A., (2005) 'A fully integrated multi-channel detector for electron spectroscopy', Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 238 pp.219-223 RAE2008 Synchrotron Radiation in Materials Science ? Proceedings of the 4th Conference on Synchrotron Radiation in Materials Science 4th Conference on Synchrotron Radiation in Materials Science
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STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.
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Treścią publikacji jest przedstawienie wybranych problemów prognozowania w naukach społecznych. W artykule skoncentrowano się na metodzie gier decyzyjnych/symulacyjnych, które – zwłaszcza wraz z rozwojem teorii gier oraz komputerów – są coraz częściej wykorzystywane w wielu dziedzinach. Na wybranych przykładach gier decyzyjnych/symulacyjnych – Poznań International Model United Nations 2013/POZiMUN; S.E.N.S.E. a także gry sieciowej EVE Online – wskazano jak ważne są takie ćwiczenia, by móc precyzyjniej przewidywać przyszłość. Zwrócono także szczególną uwagę na kwestię przypadku oraz czynników zakłócających, które mogą destabilizować proces przewidywania. Poruszono ponadto problem podejmowania decyzji w aspekcie klasycznej oraz kwantowej logiki.
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sermon text; MS Word document
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Along with the growing demand for cryptosystems in systems ranging from large servers to mobile devices, suitable cryptogrophic protocols for use under certain constraints are becoming more and more important. Constraints such as calculation time, area, efficiency and security, must be considered by the designer. Elliptic curves, since their introduction to public key cryptography in 1985 have challenged established public key and signature generation schemes such as RSA, offering more security per bit. Amongst Elliptic curve based systems, pairing based cryptographies are thoroughly researched and can be used in many public key protocols such as identity based schemes. For hardware implementions of pairing based protocols, all components which calculate operations over Elliptic curves can be considered. Designers of the pairing algorithms must choose calculation blocks and arrange the basic operations carefully so that the implementation can meet the constraints of time and hardware resource area. This thesis deals with different hardware architectures to accelerate the pairing based cryptosystems in the field of characteristic two. Using different top-level architectures the hardware efficiency of operations that run at different times is first considered in this thesis. Security is another important aspect of pairing based cryptography to be considered in practically Side Channel Analysis (SCA) attacks. The naively implemented hardware accelerators for pairing based cryptographies can be vulnerable when taking the physical analysis attacks into consideration. This thesis considered the weaknesses in pairing based public key cryptography and addresses the particular calculations in the systems that are insecure. In this case, countermeasures should be applied to protect the weak link of the implementation to improve and perfect the pairing based algorithms. Some important rules that the designers must obey to improve the security of the cryptosystems are proposed. According to these rules, three countermeasures that protect the pairing based cryptosystems against SCA attacks are applied. The implementations of the countermeasures are presented and their performances are investigated.
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This Portfolio of Exploration outlines the course of learning by a practitioner on a personal leadership journey. It constructs a functional examination of ideas around leadership. It explores the belief system which underpins leadership practice and it also explores to what extent the increased participation of women can lead to a qualitatively different type of leadership. Different models of leadership are explored to find the model which can best fit with the author’s perception of leadership. The Women’s Intercultural Leadership Model is discussed. This model conceptualises leadership as the envisioning of oneself and others as potential leaders. It seeks to promote that recognition whilst at the same time encouraging personal transformation. The promotion of a values based leadership is examined. The value of fairness is examined as an element of functional leadership. The extent to which increasing the number of women in leadership can lead to a qualitatively different type of leadership is explored. Drucker’s assertion that every practice rests on theory is used to unearth the underlying assumptions of this reflective practitioner doctorate. Kegan’s Theory of Adult Mental Development and Subject-Object separation is used to explicitly examine knowledge construction. Myers Briggs Type Indicator (MBTI) and Assumption/Commitment/Behaviour/Outcome (ACBO) template are used to promote practice change.