Native and multimeric vitronectin exhibit similar affinity for heparin: Differences in heparin binding properties induced upon denaturation are due to self-association into a multivalent form

For many years, the concept that the heparin-binding sequence is sequestered within vitronectin and exposed upon denaturation of the protein has guided experimental design and interpretation of related structure- function studies on the protein. To evaluate binding of heparin to both native and denatured/renatured vitronectin, methods for monitoring binding in solution have been developed. A fluorescence method based on changes in an extrinsic probe attached to heparin has been used to evaluate heparin binding to native and denatured/renatured vitronectin. This approach indicates that there are not major differences in intrinsic heparin-binding affinities between native and renatured protein and invalidate the currently accepted model for a cryptic heparin-binding sequence in the protein. Denaturation and renaturation of vitronectin under near physiological solution conditions is accompanied invariably by self-association of the protein into a multimeric form (Zhuang, P., Blackburn, M. N., and Peterson, C. B. (1996) J. Biol. Chem. 271, 14323-14332), resulting in exposure of multiple heparin-binding sites on the surface of the oligomer. On the basis of the binding data from solution studies and interaction of the native monomer and the denatured multimeric form of vitronectin with a heparin column, along with evaluation of the ionic strength dependence of heparin binding to these vitronectin forms in solution, an alternative model is favored to account for the altered heparin binding properties of vitronectin associated with denaturation of the protein. This model proposes that multivalent interactions between heparin and multimeric vitronectin are responsible for differences in heparin affinity chromatography and ionic strength dependence compared with the native protein

Measurement of Position Acuity in Strabismus and Amblyopia: Specificity of the Vernier VEP Paradigm

PURPOSE. An objective measure of positional acuity is desirable in the nonverbal clinical population. This study was conducted to investigate the specificity of the vernier VEP as a measure of positional acuity, evaluating the potential confound of asymmetric motion responses that may be present in some groups of patients. These motion responses could masquerade as position-specific responses, since they occur at the same response frequency as the vernier-related response. METHODS. Twelve observers with early-onset esotropia (EOE), 30 children with untreated amblyopia, and 15 control children underwent swept vernier VEP acuity testing accompanied by a swept motion control stimulus. The control condition was used to detect the presence of artifactual responses not related to position sensitivity. The patients with EOE were selected for high levels of motion asymmetry as documented with oscillating gratings presented monocularly. As a measure of motion confound (penetration), the proportion of first-harmonic responses recorded in the control condition was determined. RESULTS. The penetration rate in the vernier condition in each study group (EOE: 0.93%; amblyopes: 4.26%; normal subjects: 2.40%) and the entire group (2.85%) was acceptably low. The level of penetration was not significantly influenced by the presence of amblyopia. CONCLUSIONS. The vernier VEP paradigm, when applied in the manner described, can be interpreted as a measure of position sensitivity. The presence of motion asymmetry or untreated amblyopia does not affect the validity of vernier measurements made. (Invest Ophthalmol Vis Sci. 2005;46:4563-4570) DOI: 10.1167/iovs.05-0792 I t is well-known, on the one hand, that grating acuity systematically underestimates optotype acuity losses in amblyopia. 1-7 On the other hand, losses on vernier acuity more closely match the loss of optotype acuity than do losses on grating acuity. Visual evoked potentials (VEPs) provide another means of assessing visual function in nonverbal subjects. VEPs specific to vernier offsets have been measured in several studies. The steady state vernier VEP 26 -29 involves the periodic introduction and withdrawal of vernier offsets in a high-contrast square-wave grating target 26 A difficulty in applying the steady state vernier VEP in clinical populations is the possible presence of motion responses that are not symmetric. A clear example of asymmetric motion VEP responses occurs in patients with early-onset esotropia (EOE) in which the monocular response to rapidly oscillating gratings is dominated by odd-harmonic components that reflect the asymmetry of motion processing. 30 -35 A similar asymmetry is found in the monocular response of normal infants. This evidence suggests that a horizontally oriented carrier grating with vertically introduced vernier offsets offers a better choice of stimulus design. In this study, we examine the levels of motion contamination and confound of the steady state vernier VEP by recordings of patients with early-onset esotropia who first had a high level of motion asymmetry docuFrom th

Status of the QCDSP project

We describe the completed 8,192-node, 0.4Tflops machine at Columbia as well as the 12,288-node, 0.6Tflops machine assembled at the RIKEN Brookhaven Research Center. Present performance as well as our experience in commissioning these large machines is presented. We outline our on-going physics program and explain how the configuration of the machine is varied to support a wide range of lattice QCD problems, requiring a variety of machine sizes. Finally a brief discussion is given of future prospects for large-scale lattice QCD machines.Comment: LATTICE98(machines), 3 pages, 1 picture, 1 figur

Research with real photons at the MAMI 1.6 GeV electron accelerator

The A2-CB Collaboration at Mainz is studying the structure of hadrons by meson photoproduction using unpolarised, linearly polarised and circularly polarised photons with energies up to 1.6 GeV. Photons are energy-tagged using the Glasgow-Mainz tagged photon spectrometer and a new high-energy end-point tagger which allows η’ reactions to be studied. Reaction products are detected in a ~4π detector consisting of the Crystal Ball detector and TAPS forward wall. Transverse or longitudinally polarised proton targets are available and new techniques have been developed to measure the polarisation of recoiling protons. These facilities have allowed an extensive programme of double-polarisation meson-photoproduction experiments to be carried out to search for so-called “missing baryon resonances” on proton and deuteron targets. Searches have also been carried out to investigate narrow resonances in the η-photoproduction channel at invariant masses around 1680 MeV. Coherent π0 production measurements have been used to estimate the neutron skin thickness in 208Pb. This paper presents selected highlights from the A2-CB collaboration research programme at MAMI

Ultrafast X-Ray Imaging of Laser-Metal Additive Manufacturing Processes

The high-speed synchrotron X-ray imaging technique was synchronized with a custom-built laser-melting setup to capture the dynamics of laser powder-bed fusion processes in situ. Various significant phenomena, including vapor-depression and melt-pool dynamics and powder-spatter ejection, were captured with high spatial and temporal resolution. Imaging frame rates of up to 10 MHz were used to capture the rapid changes in these highly dynamic phenomena. At the same time, relatively slow frame rates were employed to capture large-scale changes during the process. This experimental platform will be vital in the further understanding of laser additive manufacturing processes and will be particularly helpful in guiding efforts to reduce or eliminate microstructural defects in additively manufactured parts

Inhibition of Thrombin Receptor Signaling on alpha-Smooth Muscle Actin(+) CD34(+) Progenitors Leads to Repair After Murine Immune Vascular Injury

OBJECTIVE: The goal of this study was to use mice expressing human tissue factor pathway inhibitor (TFPI) on α-smooth muscle actin (α-SMA)(+) cells as recipients of allogeneic aortas to gain insights into the cellular mechanisms of intimal hyperplasia (IH). METHODS AND RESULTS: BALB/c aortas (H-2(d)) transplanted into α-TFPI-transgenic (Tg) mice (H-2(b)) regenerated a quiescent endothelium in contrast to progressive IH seen in C57BL/6 wild-type (WT) mice even though both developed aggressive anti-H-2(d) alloresponses, indicating similar vascular injuries. Adoptively transferred Tg CD34(+) (but not CD34(-)) cells inhibited IH in WT recipients, indicating the phenotype of α-TFPI-Tg mice was due to these cells. Compared with syngeneic controls, endogenous CD34(+) cells were mobilized in significant numbers after allogeneic transplantation, the majority showing sustained expression of tissue factor and protease-activated receptor-1 (PAR-1). In WT, most were CD45(+) myeloid progenitors coexpressing CD31, vascular endothelial growth factor receptor-2 and E-selectin; 10% of these cells coexpressed α-SMA and were recruited to the neointima. In contrast, the α-SMA(+) human TFPI(+) CD34(+) cells recruited in Tg recipients were from a CD45(-) lineage. WT CD34(+) cells incubated with a PAR-1 antagonist or taken from PAR-1-deficient mice inhibited IH as Tg cells did. CONCLUSIONS: Specific inhibition of thrombin generation or PAR-1 signaling on α-SMA(+) CD34(+) cells inhibits IH and promotes regenerative repair despite ongoing immune-mediated damage

Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease

Objective: Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods: We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory‐impaired PD (amnestic MCI; n = 9), PD with nonamnestic MCI (n = 10), PD without MCI (n = 11), and healthy controls (n = 14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results: Memory‐impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation: Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction

HopScotch - a low-power renewable energy base station network for rural broadband access

The provision of adequate broadband access to communities in sparsely populated rural areas has in the past been severely restricted. In this paper, we present a wireless broadband access test bed running in the Scottish Highlands and Islands which is based on a relay network of low-power base stations. Base stations are powered by a combination of renewable sources creating a low cost and scalable solution suitable for community ownership. The use of the 5~GHz bands allows the network to offer large data rates and the testing of ultra high frequency ``white space'' bands allow expansive coverage whilst reducing the number of base stations or required transmission power. We argue that the reliance on renewable power and the intelligent use of frequency bands makes this approach an economic green radio technology which can address the problem of rural broadband access

The history, geography, and sociology of slums and the health problems of people who live in slums

Massive slums have become major features of cities in many low-income and middle-income countries. Here, in the first in a Series of two papers, we discuss why slums are unhealthy places with especially high risks of infection and injury. We show that children are especially vulnerable, and that the combination of malnutrition and recurrent diarrhoea leads to stunted growth and longer-term effects on cognitive development. We find that the scientific literature on slum health is underdeveloped in comparison to urban health, and poverty and health. This shortcoming is important because health is affected by factors arising from the shared physical and social environment, which have effects beyond those of poverty alone. In the second paper we will consider what can be done to improve health and make recommendations for the development of slum health as a field of study