Fall-Protection Harness Training: Donning Skill Improves with Up to Four Repetitions

Injuries and fatalities from falling remain a major occupational safety concern. Among the multiple tactics for preventing fatal falls is the use of personal fall protection involving wearing a harness connected to a secure anchor point. This requires training to ensure trainees understand the importance of fall protection and have the skill to implement it correctly. One important skill is donning a fall protection harness and adjusting the straps. Those who conduct training on fall protection need to coach trainees through the steps involved in donning a harness. This study was undertaken to learn the benefits of practicing with the guidance of a coach. The experiment had university student volunteers watch a training video twice and then don a harness four times while being coached. Times for each of the five steps involved in donning and adjusting a harness were obtained for the 22 subjects who completed all steps. Time was used as the measure of skill level. The step of adjusting the leg straps accounted for the most time in all of the four repetitions. Total time to don fall protection was reduced with practice. The reduction followed a learning curve function based on a power model. According to this model, each doubling of the number of repetitions results in a 22.1% reduction in total time to don the harness

Collective Antenna Effects in the Terahertz and Infrared Response of Highly Aligned Carbon Nanotube Arrays

We study macroscopically-aligned single-wall carbon nanotube arrays with uniform lengths via polarization-dependent terahertz and infrared transmission spectroscopy. Polarization anisotropy is extreme at frequencies less than $\sim$3 THz with no sign of attenuation when the polarization is perpendicular to the alignment direction. The attenuation for both parallel and perpendicular polarizations increases with increasing frequency, exhibiting a pronounced and broad peak around 10 THz in the parallel case. We model the electromagnetic response of the sample by taking into account both radiative scattering and absorption losses. We show that our sample acts as an effective antenna due to the high degree of alignment, exhibiting much larger radiative scattering than absorption in the mid/far-infrared range. Our calculated attenuation spectrum clearly shows a non-Drude peak at $\sim$10 THz in agreement with the experiment.Comment: 5 pages, 5 figure

Synaptic abnormalities in the infralimbic cortex of a model of congenital depression

Multiple lines of evidence suggest that disturbances in excitatory transmission contribute to depression. Whether these defects involve the number, size, or composition of glutamatergic contacts is unclear. This study used recently introduced procedures for fluorescence deconvolution tomography in a well-studied rat model of congenital depression to characterize excitatory synapses in layer I of infralimbic cortex, a region involved in mood disorders, and of primary somatosensory cortex. Three groups were studied: (1) rats bred for learned helplessness (cLH); (2) rats resistant to learned helplessness (cNLH); and (3) control Sprague Dawley rats. In fields within infralimbic cortex, cLH rats had the same numerical density of synapses, immunolabeled for either the postsynaptic density (PSD) marker PSD95 or the presynaptic protein synaptophysin, as controls. However, PSD95 immunolabeling intensities were substantially lower in cLH rats, as were numerical densities of synapse-sized clusters of the AMPA receptor subunit GluA1. Similar but less pronounced differences (comparable numerical densities but reduced immunolabeling intensity for PSD95) were found in the somatosensory cortex. In contrast, non-helpless rats had 25% more PSDs than either cLH or control rats without any increase in synaptophysin-labeled terminal frequency. Compared with controls, both cLH and cNLH rats had fewer GABAergic contacts. These results indicate that congenital tendencies that increase or decrease depression-like behavior differentially affect excitatory synapses

Conformational transition of FGFR kinase activation revealed by site-­specific unnatural amino acid reporter and single molecule FRET

Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo

Projected sea level rise and changes in extreme storm surge and wave events during the 21st century in the region of Singapore

Singapore is an island state with considerable population, industries, commerce and transport located in coastal areas at elevations less than 2 m making it vulnerable to sea-level rise. Mitigation against future inundation events requires a quantitative assessment of risk. To address this need, regional projections of changes in (i) long-term mean sea level and (ii) the frequency of extreme storm surge and wave events have been combined to explore potential changes to coastal flood risk over the 21st century. Local changes in time mean sea level were evaluated using the process-based climate model data and methods presented in the IPCC AR5. Regional surge and wave solutions extending from 1980 to 2100 were generated using ~ 12 km resolution surge (Nucleus for European Modelling of the Ocean – NEMO) and wave (WaveWatchIII) models. Ocean simulations were forced by output from a selection of four downscaled (~ 12 km resolution) atmospheric models, forced at the lateral boundaries by global climate model simulations generated for the IPCC AR5. Long-term trends in skew surge and significant wave height were then assessed using a generalised extreme value model, fit to the largest modelled events each year. An additional atmospheric solution downscaled from the ERA-Interim global reanalysis was used to force historical ocean model simulations extending from 1980–2010, enabling a quantitative assessment of model skill. Simulated historical sea surface height and significant wave height time series were compared to tide gauge data and satellite altimetry data respectively. Central estimates of the long-term mean sea level rise at Singapore by 2100 were projected to be 0.52 m (0.74 m) under the RCP 4.5 (8.5) scenarios respectively. Trends in surge and significant wave height 2 year return levels were found to be statistically insignificant and/or physically very small under the more severe RCP8.5 scenario. We conclude that changes to long-term mean sea level constitute the dominant signal of change to the projected inundation risk for Singapore during the 21st century. We note that the largest recorded surge residual in the Singapore Strait of ~ 84 cm lies between the central and upper estimates of sea level rise by 2100, highlighting the vulnerability of the region

Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET

Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo

CRY2 Is Associated with Depression

Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated.We observed a marked diurnal variation in human CRY2 mRNA levels from peripheral blood mononuclear cells and a significant up-regulation (P = 0.020) following one-night total sleep deprivation, a known antidepressant. In depressed bipolar patients, levels of CRY2 mRNA were decreased (P = 0.029) and a complete lack of increase was observed following sleep deprivation. To investigate a possible genetic contribution, we undertook SNP genotyping of the CRY2 gene in two independent population-based samples from Sweden (118 cases and 1011 controls) and Finland (86 cases and 1096 controls). The CRY2 gene was significantly associated with winter depression in both samples (haplotype analysis in Swedish and Finnish samples: OR = 1.8, P = 0.0059 and OR = 1.8, P = 0.00044, respectively).We propose that a CRY2 locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of CRY2 expression

Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3β antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies

PVP2008-61762 DESIGN AND MANUFACTURE OF WELDED PLATE SPECIMENS FOR RESIDUAL STRESS EXPERIMENTS

ABSTRACT A long-term UK research programme has been established in order to improve the understanding of thermo-mechanical behaviour and residual stresses generated in pressure vessel steel welds as well as developing finite element (FE) welding simulation methods. The production of representative test specimens is an important element of this research project, since quality measurement data are needed to validate FE models. This paper describes the design, development and manufacture of welded plate specimens used for residual stress (RS) experiments. To date, research has focused mainly on developing the understanding of SA508 pressure vessel steel welds. Specimen dimensions were selected to facilitate stress measurements using a range of techniques. The philosophy adopted was to start with relatively simple 1-pass weld specimens and gradually increase the complexity to multi-pass groove welds in plates. Simple 1-pass weld specimens were generally designed to investigate the effect of welding parameters on thermomechanical behaviour, such as heat-affected zone (HAZ) microstructures and phase transformations. Later specimens are more representative of multi-pass power plant welds. They are being used to study material thermal cyclic hardening/softening behaviour. Other issues of concern are also being investigated, such as the effect of restraint during welding on RS and the effectiveness of post weld heat treatment (PWHT). Specimens were also designed to study peak stresses arising at bead stop/start positions and whether such peak stresses are annealed in overlaying additional weld metal. These investigations were performed on multi-pass groove welds in both austenitic and ferritic steel plates. Practical issues encountered during welding trials are discussed, including plate distortion and magnetisation of the ferritic steel plates. Information is also provided about welding temperature measurements and metallurgical examinations