1,135 research outputs found
Rutherford cables with anisotropic transverse resistance
Putting a resistive core into the center of a Rutherford cable increases resistance between strands in the crossover direction, which greatly reduces the coupling currents, even when the resistance to adjacent turns remains small. This allows one to improve stability by soldering strands together or using porous metal, without incurring a penalty of increased coupling. We describe our manufacturing methods and an experimental measurement of coupling
The transformative potential of reflective diaries for elite English cricketers
The sport of cricket has a history of its players suffering from mental health issues. The psychological study of cricket and, in particular, the attendant demands of participating at an elite level has not previously received rigorous academic attention. This study explored ten elite male cricketers’ experiences of keeping a daily reflective diary for one month during the competitive season. The aim was to assess how valuable qualitative diaries are in this field. Participants were interviewed regarding their appraisal of the methodology as a self‐help tool that could assist coping with performance pressures and wider life challenges. Three outcomes were revealed: first, that diary keeping was an effective opportunity to reflect upon the past and enhance one’s self (both as an individual and a performer); second, that diary keeping acted as a form of release that allowed participants to progress; and third, that diary keeping allowed participants to discover personal patterns of success that increased the likeliness of optimum performance
Elasticity near the vulcanization transition
Signatures of the vulcanization transition--amorphous solidification induced
by the random crosslinking of macromolecules--include the random localization
of a fraction of the particles and the emergence of a nonzero static shear
modulus. A semi-microscopic statistical-mechanical theory is presented of the
latter signature that accounts for both thermal fluctuations and quenched
disorder. It is found (i) that the shear modulus grows continuously from zero
at the transition, and does so with the classical exponent, i.e., with the
third power of the excess cross-link density and, quite surprisingly, (ii) that
near the transition the external stresses do not spoil the spherical symmetry
of the localization clouds of the particles.Comment: REVTEX, 5 pages. Minor change
Aerostructural Optimization of Long Span Bridges: Current Advances and Challenges
Structures Congress 2020. 5-8 abril, 2020. St. Louis, Missouri[Abstract] This paper describes the evolution of deck shape of long span bridges since the Tacoma Narrows collapse trying to avoid undesirable aerodynamic behavior under wind flow and the trend in the last decades to increase the length of the main span of suspension and cable stayed bridges. The necessity to use advanced technologies to help the engineer to obtain the best possible design is highlighted and the advantages of applying optimization methodologies is encouraged. It is explained that this approach requires to use only numerical tools and hence to eliminate experimental studies, as wind tunnel tests using reduced models of full bridge of a segment of the deck, and their substitution by computational fluid dynamics (CFD) simulations. After doing so, the current capabilities of this approach are presented and, finally, the problems that need to be solved to have a fully operational methodology able to be implemented in real structures are outlined.This research has been funded by the Spanish Ministry of Economy and Competitiveness in the frame of the research project BIA2016-76656-R and the Galician regional government (including FEDER Funding) reference ED431C 2017/72. M. Cid Montoya has been funded by the Galician regional government (Xunta de Galicia) with reference ED481B 2018/053 and the Fulbright postdoctoral scholarship programXunta de Galicia; ED431C 2017/72Xunta de Galicia; ED481B 2018/05
MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4
Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically
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