Understanding standing

Research objectives. Psychophysical acceleration threshold is a tool for detecting deficits in dynamic postural control. Our lab has shown differences in the acceleration threshold among young adults, elderly adults, and elderly adults with diabetes. Electromyography, Semmes-Weinstein monofilaments, and hearing tests investigate the underlying physiological mechanisms for the detriments in postural control. Due to peri-sway perturbations, the motion of a person\u27s sway affects the signal to noise ratio for perturbed stance. Since increases in sway range accompany postural instabilities, sway entrainment will allow us to investigate changes in acceleration threshold at different points in sway. The center of pressure, observed for entrainment, only changes due to rotations about joints, specifically the ankle. The current method to model rotation about the ankle is a single orthogonal joint, and therefore inaccurate. Methods. The SLIP-FALLS-STEPm Platform has lead to the ability to accurately measure and observe interactions in the range of postural sway. The combination of the platform with other testing modalities such as camera tracking systems, force mats, and accelerometers will allow for a comprehensive testing scheme. The new scheme can be combined with the induced sway produced by a sub-threshold sinusoidal entrainment process. The nonorthogonal modelling is programmed in Matlab®. Results. For constant displacements, anterior accelerations thresholds via two-alternate forced choice (2AFC) showed differences in postural stability in mature, diabetic individuals with peripheral neuropathy (DPN) and those who are neurally intact (DNI) compared to healthy mature adults (HMA), which corresponded with previous results of lateral perturbations. Both DNI and DPN had significantly higher thresholds for acceleration via 2AFC than HMA at 1 and 4 mm displacements (p \u3c 0.01 and p Conclusion. The anterior acceleration thresholds show that peripheral neuropathy is not the sole cause for postural instability with diabetes. The ability to control the motion of sway will allow us to describe acceleration threshold throughout the range of sway. With a realistic ankle model, we will be able to better simulate postural dynamics

The Development a Polymerase Chain Reaction (PCR) to detect C.Pneumoniae and C.Psittaci

     C.pneumoniae and C.psittaci both cause respiratory infections in human. detection  of  these  organisms  in  tissue  culture  is  difficult  and serological  testing  is unreliable. There  are  no  sensitive  and  reliable  tests  for  the  detection  of  these  organisms. The  polymerase  chain reaction  (PCR  )  has  provided  an alternative  diagnostic  method  for the detection of these fastidious  organisms. The aim of this study was to develop a PCR to detect C.pneumoniae and C.psittaci from clinical samples. The PCR was optimized in a series of experiments. To determine  if  the  optimized  PCR  could  be applied  to  clinical samples, mock  positive specimen  were  produced by  adding  chlamydiae  to  throat  swab  from  healthy  adults. The DNA was extracted by phenol/chloroform. When tested by PCR all the throat swabs were negative. However,  when  diluted  and  retested,  many  of the  swabs  were  positive  and 10 IFU  of C.psittaci  and  100  IFU  of C.pneumoniae  could  be   detected.  This  experiment  indicates  that  inhibitor  to  PCR  are  found  in  throat  swab  and  further  work  is  needed   on  specimen  preparation.   The PCR was optimized in a series of experiments.    The  optimal  conditions  were  to  use  a two  segment  PCR  with  68°c  annealing  and  polymerization  temperature, 2.0mM  Mgcl2,  0.2μM  primers  and  40  cycles. The  PCR   was  highly  sensitive  and  could  detect  one  inclusion  forming  unit  with  both  C.pneumoniae   and  C.psittaci  strains.  Two  human  strains  and  one   nonhuman   strain  of  C.pneumoniae   and   two  avian   strains   and  three  mammalian   strains   of C.psittaci   were   used   to  determine   the specificity  of PCR. The PCR detected all these different strains.   C.trachomatis   strains   were not detected.  Various bacterial  strains, fungi  DNA,  and  human  DNA  were  negative  in  PCR  and no  amplification  DNA  was  found   in  negative  controls

Regulation of 5'-adenosine monophosphate deaminase in the freeze tolerant wood frog, Rana sylvatica

<p>Abstract</p> <p>Background</p> <p>The wood frog, <it>Rana sylvatica</it>, is one of a few vertebrate species that have developed natural freeze tolerance, surviving days or weeks with 65–70% of its total body water frozen in extracellular ice masses. Frozen frogs exhibit no vital signs and their organs must endure multiple stresses, particularly long term anoxia and ischemia. Maintenance of cellular energy supply is critical to viability in the frozen state and in skeletal muscle, AMP deaminase (AMPD) plays a key role in stabilizing cellular energetics. The present study investigated AMPD control in wood frog muscle.</p> <p>Results</p> <p>Wood frog AMPD was subject to multiple regulatory controls: binding to subcellular structures, protein phosphorylation, and effects of allosteric effectors, cryoprotectants and temperature. The percentage of bound AMPD activity increased from 20 to 35% with the transition to the frozen state. Bound AMPD showed altered kinetic parameters compared with the free enzyme (<it>S</it>_0.5AMP was reduced, Hill coefficient fell to ~1.0) and the transition to the frozen state led to a 3-fold increase in <it>S</it>_0.5AMP of the bound enzyme. AMPD was a target of protein phosphorylation. Bound AMPD from control frogs proved to be a low phosphate form with a low <it>S</it>_0.5AMP and was phosphorylated in incubations that stimulated PKA, PKC, CaMK, or AMPK. Bound AMPD from frozen frogs was a high phosphate form with a high <it>S</it>_0.5AMP that was reduced under incubation conditions that stimulated protein phosphatases. Frog muscle AMPD was activated by Mg·ATP and Mg·ADP and inhibited by Mg·GTP, KCl, NaCl and NH₄Cl. The enzyme product, IMP, uniquely inhibited only the bound (phosphorylated) enzyme from muscle of frozen frogs. Activators and inhibitors differentially affected the free versus bound enzyme. <it>S</it>_0.5AMP of bound AMPD was also differentially affected by high versus low assay temperature (25 vs 5°C) and by the presence/absence of the natural cryoprotectant (250 mM glucose) that accumulates during freezing.</p> <p>Conclusion</p> <p>Maintenance of long term viability under the ischemic conditions in frozen muscle requires attention to the control of cellular energetics. Differential regulatory controls on AMPD by mechanisms including binding to muscle proteins, actions allosteric effectors, glucose and temperature effects and reversible phosphorylation adjust enzyme function for an optimal role in controlling cellular adenylate levels in ischemic frozen muscle. Stable modification of AMPD properties via freeze-responsive phosphorylation may contribute both to AMPD control and to coordinating AMPD function with other enzymes of energy metabolism in cold ischemic muscle.</p

Can routinely collected hospital admission data be used to study temporal morbidity and mortality trends in maintenance renal replacement patients? Analyses from the Oxford Record Linkage Study and all England Hospital Episode Statistics, 1965 2011

Maintenance dialysis programmes for end-stage renal disease (ESRD) began in the United Kingdom in the 1960s. Until the 1980s, renal replacement therapy (RRT, i.e., dialysis or kidney transplantation) was restricted to ESRD patients who were considered the most economically active and those with diabetes or other comorbidities were often not referred or treated. This contrasts with the situation 50 years later when the median age of patients starting maintenance RRT is 65 years and diabetes is the leading cause of ESRD. Examining long-term temporal mortality trends helps describe past and current serious health risks. Their interpretation is difficult in RRT populations as comparisons between treated ESRD and other populations need to take account of the substantial secular changes in the prevalence of comorbid illnesses which influence both mortality and the likelihood of receiving RRT. To date, no large study has standardized mortality rates in treated ESRD and general population cohorts to the same comorbidity as well as age/sex structure. Therefore, although data from ESRD registries in the United States 1977-2007, Europe 1998-2007, Australasia 1992-2005,and UK 2002-2011 have all shown modest improvements in mortality for people with treated ESRD, it is unclear whether the magnitude of this change is comparable to those observed in the general population during the same period. The Oxford Record Linkage Study (ORLS) was established in 1963 and recorded information about all hospital inpatient admissions in Oxfordshire and the surrounding counties. Hospital Episode Statistics (HES) succeeded ORLS and established nationwide coverage from 1998. Mortality trends among new maintenance RRT patients and a set of general population controls, extracted from these two datasets were performed. Novel approaches ensured that both cohorts could be corrected for changes in prior comorbidity over time and the effects of transplantation, and stratified analyses in patients with and without diabetes could be performed.   Key aims of thesis 1) Derive and validate a cohort of end-stage renal disease (ESRD) patients exclusively from anonymised, individually-linked prospectively collected hospital inpatients datasets 2) Analyse the temporal trends of age, sex and comorbidity adjusted mortality rates in the ESRD cohort 3) Concurrently derive a comparative general population to provide an opportunity to compare trends between the ESRD and general populations 4) Demonstrate other uses of routinely collected hospital inpatients datasets in renal epidemiolog

Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease

Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD

How Racist Violence Becomes a Virtue: An Application of Discourse Analysis

This discourse analytic study examines how violence can be constructed as an honourable course of action, using the example of a leaflet circulated in the loyalist Donegall Pass area of Belfast urging the removal of the minority Chinese population. Starting from the assumptions that racism is an ideological practice that naturalises social categories and devalues members of some of them so that their subjugation and exclusion is legitimised (Miles and Brown 2003; Billig 2002), and that violence is a human activity imbued with meaning through discourse, we applied guidelines set out by Parker (1992) to consider language as a social practice that achieves specific discursive effects by constructing its objects in a particular way. Two interrelated discourses were identified: a community-focused discourse construed the Chinese immigrants as morally and culturally bereft and negated their worth, while a martial discourse focused on defending the locality against foreign invasion. An examination of themes in loyalist culture revealed ways in which the text reconstructed resonant fears, and we argue that the way the in-group constructs its character defines the racist construction of the other

ORFEUS II and IUE Spectroscopy of EX Hydrae

Using ORFEUS-SPAS II FUV spectra, IUE UV spectra, and archival EUVE deep survey photometry, we present a detailed picture of the behavior of the magnetic cataclysmic variable EX Hydrae. Like HUT spectra of this source, the FUV and UV spectra reveal broad emission lines of He II, C II-IV, N III and V, O VI, Si III-IV, and Al III superposed on a continuum which is blue in the UV and nearly flat in the FUV. Like ORFEUS spectra of AM Her, the O VI doublet is resolved into broad and narrow emission components. Consistent with its behavior in the optical, the FUV and UV continuum flux densities, the FUV and UV broad emission line fluxes, and the radial velocity of the O VI broad emission component all vary on the spin phase of the white dwarf, with the maximum of the FUV and UV continuum and broad emission line flux light curves coincident with maximum blueshift of the broad O VI emission component. On the binary phase, the broad dip in the EUV light curve is accompanied by strong eclipses of the UV emission lines and by variations in both the flux and radial velocity of the O VI narrow emission component. The available data are consistent with the accretion funnel being the source of the FUV and UV continuum and the O VI broad emission component, and the white dwarf being the source of the O VI narrow emission component.Comment: 21 pages, 10 Postscript figures; LaTeX format, uses aaspp4.sty; table2.tex included separately because it must be printed sideways - see instructions in the file; accepted on 1999 Feb 20 for publication in The Astrophysical Journa