Increased Prothrombin, Apolipoprotein A-IV, and Haptoglobin in the Cerebrospinal Fluid of Patients with Huntington's Disease

Huntington's disease (HD) is a progressive neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion. The need for biomarkers of onset and progression in HD is imperative, since currently reliable outcome measures are lacking. We used two-dimensional electrophoresis and mass spectrometry to analyze the proteome profiles in cerebrospinal fluid (CSF) of 6 pairs of HD patients and controls. Prothrombin, apolipoprotein A-IV (Apo A-IV) and haptoglobin were elevated in CSF of the HD patients in comparison with the controls. We used western blot as a semi-quantified measurement for prothrombin and Apo A-IV, as well as enzyme linked immunosorbent assay (ELISA) for measurement of haptoglobin, in 9 HD patients and 9 controls. The albumin quotient (Qalb), a marker of blood-brain barrier (BBB) function, was not different between the HD patients and the controls. The ratios of CSF prothrombin/albumin (prothrombin/Alb) and Apo A-IV/albumin (Apo A-IV/Alb), and haptoglobin level were significantly elevated in HD. The ratio of CSF prothrombin/Alb significantly correlated with the disease severity assessed by Unified Huntington's Disease Rating Scale (UHDRS). The results implicate that increased CSF prothrombin, Apo A-IV, and haptoglobin may be involved in pathogenesis of HD and may serve as potential biomarkers for HD

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Degradation aspects of water formation and transport in Proton Exchange Membrane Fuel Cell: A review

This review paper summarises the key aspects of Proton Exchange Membrane Fuel Cell (PEMFC) degradation that are associated with water formation, retention, accumulation, and transport mechanisms within the cell. Issues related to loss of active surface area of the catalyst, ionomer dissolution, membrane swelling, ice formation, corrosion, and contamination are also addressed and discussed. The impact of each of these water mechanisms on cell performance and durability was found to be different and to vary according to the design of the cell and its operating conditions. For example, the presence of liquid water within Membrane Electrode Assembly (MEA), as a result of water accumulation, can be detrimental if the operating temperature of the cell drops to sub-freezing. The volume expansion of liquid water due to ice formation can damage the morphology of different parts of the cell and may shorten its life-time. This can be more serious, for example, during the water transport mechanism where migration of Pt particles from the catalyst may take place after detachment from the carbon support. Furthermore, the effect of transport mechanism could be augmented if humid reactant gases containing impurities poison the membrane, leading to the same outcome as water retention or accumulation. Overall, the impact of water mechanisms can be classified as aging or catastrophic. Aging has a long-term impact over the duration of the PEMFC life-time whereas in the catastrophic mechanism the impact is immediate. The conversion of cell residual water into ice at sub-freezing temperatures by the water retention/ accumulation mechanism and the access of poisoning contaminants through the water transport mechanism are considered to fall into the catastrophic category. The effect of water mechanisms on PEMFC degradation can be reduced or even eliminated by (a) using advanced materials for improving the electrical, chemical and mechanical stability of the cell components against deterioration, and (b) implementing effective strategies for water management in the cell

Aligning the CMS Muon Chambers with the Muon Alignment System during an Extended Cosmic Ray Run

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Differentially-expressed protein molecules in CSF of Huntington's disease (HD) patients.

a)<p>Spots numbered as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015809#pone-0015809-g001" target="_blank">Figure 1</a>.</p>b)<p>The accession numbers on SWISS-PROT database.</p>c)<p>The MASCOT search score of identified proteins.</p>d)<p>The percentage of sequence coverage of matched peptides in the identified protein.</p>e)<p>The mean protein expression level in the HD patients over that in the controls in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015809#pone-0015809-g001" target="_blank">Figure 1C</a>.</p>f)<p>The frequency of the target protein, for which the expression ratio of HD/C was >1.5. <i>P</i><0.05 indicates a significant difference in expression levels between HD patients and controls analyzed by paired student's <i>t</i>-test.</p

Clinical characteristics of the Huntington's disease (HD) patients and the controls.

<p>Values are expressed as means ± SE (range; minimum–maximum).</p><p>UHDRS: The Unified Huntington's Disease Rating Scale. Scale ranges (normal to most severe) include motor score (0 to 124), independence score (100 to 10), and functional capacity (13 to 0).</p><p>#Three different groups from controls (9 in each group) were compared with 9 HD patients for prothrombin/Alb, Apo A-IV/Alb, and haptoglobin, respectively (The ages of the 3 groups were 41.7±4.3, 45.7±4.7, and 41.1±4.1).</p><p>*<i>P</i> = 0.09.</p

Representative Western blots of Apo A-IV (46 kD) and albumin (64 kD) in CSF and serum, respectively, of HD patients and their corresponding controls (C).

<p>The Apo A-IV/Alb ratios in CSF and serum in comparison with their corresponding control groups are illustrated in scatter plots with median and interquartile rang, respectively. The Apo A-IV/Alb ratio in CSF of HD patients (n = 9) is significantly higher when compared with the controls (n = 9). *<i>p</i><0.01, Mann-Whitney U test.</p

Linear regression of prothrombin/Alb to motor score, independence scale, and function capacity of UHDRS, respectively.

<p>The ratio of prothrombin/Alb was significantly correlated to subscales of UHDRS, with a positive correlation to motor score (A, <i>r</i> = 0.810, <i>p</i> = 0.008) and a negative correlation to independence scale (B, <i>r</i> = −0.908, <i>p</i><0.001) and functional capacity (C, <i>r</i> = −0.891, <i>p</i> = 0.001).</p

Representative Western blots of prothrombin (72 kD) and albumin (64 kD) in CSF and serum of HD patients and their corresponding controls (C).

<p>The resulting data are illustrated in scatter plots with median and interquartile range. The prothrombin/Alb ratio in CSF of HD patients (n = 9) is higher than that in controls (n = 9). *<i>p</i><0.05, Mann-Whitney U test.</p

Qalb, CSF haptoglobin, and serum haptoglobin concentration in HD patients.

<p>Data are illustrated in scatter plots with median and interquartile rang. Either the Qalb or serum haptoglobin concentration was not different between HD (n = 9) and the controls (n = 9), whereas the CSF haptoglobin was significantly increased in HD. *<i>p</i><0.05, Mann-Whitney U test.</p