318 research outputs found
United States Air Force Academy get-away-special flexible beam experiment
The Department of Astronautics at the United States Air Force Academy is currently planning to fly an experiment in a NASA Get-Away-Special (GAS) canister. The experiment was named the flex beam experiment. The primary technical objective of the flex beam experiment is to measure the damping of a thin beam in the vacuum and zero G environment of space. By measuring the damping in space, it is hoped to determine the amount of damping the beam normally experiences due to the gravitational forces present on Earth. This will allow validation of models which predict the dynamics of thin beams in the space environment. The experiment will also allow the Academy to develop and improve its ability to perform experiments within the confines of a NASA GAS canister. Several experiments, of limited technical difficulty, were flown by the Academy. More complex experiments are currently planned and it is hoped to learn techniques with each space shuttle flight
13C n.m.r. isotopomer and computer-simulation studies of the non-oxidative pentose phosphate pathway of human erythrocytes
Accountability and responsibility: 'Rogue' school leaders and the induction of new teachers in England
This paper considers the professional responsibility of schools in England to provide effective induction practices in the context of a central government mandated policy. It looks at individual schools as ‘habitats’ for induction and the role of school leaders and LEAs as facilitators or inhibitors. Notions of professional responsibility and public accountability are used to analyse the small number of ‘rogue’ school leaders who, within the new legislative framework, treat new teachers unprofessionally and waste public resources. A typology of ‘rogue’ schools that are in some way deviant in transgressing induction requirements is developed and the various sanctions that can be deployed against such schools are examined. How LEAs handle their monitoring and accountability role and manage deviant schools is considered. Finally, suggestions are made for improvements, such as the need to clarify professional responsibility and refine systems of professional accountability
A TOMM40 poly-T variant modulates gene expression and is associated with vocabulary ability and decline in nonpathologic aging
The Translocase of Outer Mitochondrial Membrane 40 Homolog and Apolipoprotein E (TOMM40-APOE) locus has been associated with a number of age-related phenotypes in humans including nonpathologic cognitive aging, late-onset Alzheimer's disease, and longevity. Here, we investigate the influence of the TOMM40 intron 6 poly-T variant (rs10524523) on TOMM40 gene expression and cognitive abilities and decline in a cohort of 1613 community-dwelling elderly volunteers who had been followed for changes in cognitive functioning over a period of 14 years (range = 12–18 years). We showed that the shorter length poly-T variants were found to act as a repressor of luciferase gene expression in reporter gene constructs. Expression was reduced to approximately half of that observed for the very long variant. We further observed that the shorter poly-T variant was significantly associated with reduced vocabulary ability and a slower rate of vocabulary decline with age compared to the very long poly-T variants. No significant associations were observed for memory, fluid intelligence or processing speed, although the direction of effect, where the short variant was correlated with reduced ability and slower rate of decline was observed for all tests. Our results indicate that the poly-T variant has the ability to interact with transcription machinery and differentially modulate reporter gene expression and influence vocabulary ability and decline with age
Fatigue evaluation in maintenance and assembly operations by digital human simulation
Virtual human techniques have been used a lot in industrial design in order
to consider human factors and ergonomics as early as possible. The physical
status (the physical capacity of virtual human) has been mostly treated as
invariable in the current available human simulation tools, while indeed the
physical capacity varies along time in an operation and the change of the
physical capacity depends on the history of the work as well. Virtual Human
Status is proposed in this paper in order to assess the difficulty of manual
handling operations, especially from the physical perspective. The decrease of
the physical capacity before and after an operation is used as an index to
indicate the work difficulty. The reduction of physical strength is simulated
in a theoretical approach on the basis of a fatigue model in which fatigue
resistances of different muscle groups were regressed from 24 existing maximum
endurance time (MET) models. A framework based on digital human modeling
technique is established to realize the comparison of physical status. An
assembly case in airplane assembly is simulated and analyzed under the
framework. The endurance time and the decrease of the joint moment strengths
are simulated. The experimental result in simulated operations under laboratory
conditions confirms the feasibility of the theoretical approach
Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.
We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair
Psychological determinants of whole-body endurance performance
Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research.
Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research.
Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants.
Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance.
Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described
Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY
© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes
of Health, an American Heart Association Predoctoral Fellowship
(J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a
National Science Foundation Predoctoral Fellowship (B.B.)
The Role of Actin Turnover in Retrograde Actin Network Flow in Neuronal Growth Cones
The balance of actin filament polymerization and depolymerization maintains a steady state network treadmill in neuronal growth cones essential for motility and guidance. Here we have investigated the connection between depolymerization and treadmilling dynamics. We show that polymerization-competent barbed ends are concentrated at the leading edge and depolymerization is distributed throughout the peripheral domain. We found a high-to-low G-actin gradient between peripheral and central domains. Inhibiting turnover with jasplakinolide collapsed this gradient and lowered leading edge barbed end density. Ultrastructural analysis showed dramatic reduction of leading edge actin filament density and filament accumulation in central regions. Live cell imaging revealed that the leading edge retracted even as retrograde actin flow rate decreased exponentially. Inhibition of myosin II activity before jasplakinolide treatment lowered baseline retrograde flow rates and prevented leading edge retraction. Myosin II activity preferentially affected filopodial bundle disassembly distinct from the global effects of jasplakinolide on network turnover. We propose that growth cone retraction following turnover inhibition resulted from the persistence of myosin II contractility even as leading edge assembly rates decreased. The buildup of actin filaments in central regions combined with monomer depletion and reduced polymerization from barbed ends suggests a mechanism for the observed exponential decay in actin retrograde flow. Our results show that growth cone motility is critically dependent on continuous disassembly of the peripheral actin network
Receptor Sorting within Endosomal Trafficking Pathway Is Facilitated by Dynamic Actin Filaments
Early endosomes (EEs) are known to be a sorting station for internalized
molecules destined for degradation, recycling, or other intracellular
organelles. Segregation is an essential step in such sorting, but the molecular
mechanism of this process remains to be elucidated. Here, we show that actin is
required for efficient recycling and endosomal maturation by producing a motile
force. Perturbation of actin dynamics by drugs induced a few enlarged EEs
containing several degradative vacuoles and also interfered with their
transporting ability. Actin repolymerization induced by washout of the drug
caused the vacuoles to dissociate and individually translocate toward the
perinuclear region. We further elucidated that cortactin, an actin-nucleating
factor, was required for transporting contents from within EEs. Actin filaments
regulated by cortactin may provide a motile force for efficient sorting within
early endosomes. These data suggest that actin filaments coordinate with
microtubules to mediate segregation in EEs
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