bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated control of internet services
Authors: Arnaud Jean
Published: August 2010

Finding an efficient configuration for cluster-based multi-tier Internet services is often a difficult task. Moreover, even a good configuration could become obsolete, depending on workload evolution. In this paper, we address both problems by dynamically calculating an optimal configuration for multi-tier Internet services and applying this configuration to the managed application. Our approach is based on two main components. A model of the underlying application, and a controller using this model to find the optimal configuration according current environment and performance objectives. We evaluate the model accuracy and the controller efficiency. Experiments show that our solution improves resource consumption, and may lead to significant energy savings, besides matching the performance objectives even with a dynamic workload.
Control strategies for H.264 video decoding under resources constraints
Authors: Alt Anne-Marie , Simon Daniel
Published: August 2010

Automatic control appears to be an enabling technology to handle both the performance dispersion in highly integrated chips and computing power adaptability under varying loads and energy storage constraints. This work in progress paper presents a case study, where a video decoder is controlled via quality loops and frequency scaling, to meet end-users requirements mixing quality and energy consumption related constraints.
Accurate offline synchronization of distributed traces using kernel-level events
Authors: Poirier Benjamin , Roy Robert , Dagenais Michel
Published: August 2010

Tracing has proven to be a valuable tool for identifying functional and performance problems. In order to use it on distributed nodes, the timestamps in the traces need to be precisely synchronized. The objective of this work is to improve synchronization of traces recorded on distributed nodes. We aim for high precision and low intrusiveness. In this paper, we present an offline trace synchronization algorithm that is directly applicable to pairs of nodes and that can report approximate bounds on accuracy over short tracing durations. We also present an efficient implementation of this algorithm and an experimental study of parameters that affect synchronization accuracy.
Why the grass may not be greener on the other side
Authors: McKenney Paul E. , Michael Maged M. , Triplett Josh , Walpole Jonathan
Published: August 2010

The advent of multi-core and multi-threaded processor architectures highlights the need to address the well-known shortcomings of the ubiquitous lock-based synchronization mechanisms. To this end, transactional memory has been viewed by many as a promising alternative to locking. This paper therefore presents a constructive critique of locking and transactional memory: their strengths, weaknesses, and opportunities for improvement.
Blog track research at TREC
Authors: Macdonald Craig , Santos Rodrygo L.T. , Ounis Iadh , Soboroff Ian
Published: August 2010

The TREC Blog track aims to explore information seeking behaviour in the blogosphere, by building reusable test collections for blog-related search tasks. Since, its advent in TREC 2006, the Blog track has led to much research in this growing field, and encapsulated cross-pollination from natural language processing research. This paper recaps on the tasks addressed at the TREC Blog track thus far, covering the period 2006 - 2009. In particular, we describe the used corpora, the tasks addressed within the track, and the resulting published research.
Predicting the effectiveness of queries and retrieval systems
Authors: Hauff Claudia
Published: August 2010

We consider users' attempts to express their information needs through queries, or search requests and try to predict whether those requests will be of high or low quality. The second type of methods under investigation are those which attempt to estimate the quality of search systems themselves. Given a number of search systems to consider, these methods estimate how well or how poorly the systems will perform in comparison to each other.

First, pre-retrieval predictors are investigated, which predict a query's effectiveness before the retrieval step and are thus independent of the ranked list of results. Such predictors base their predictions solely on query terms, collection statistics and possibly external sources. Twenty-two prediction algorithms are categorized and their quality is assessed on three different TREC test collections. A number of newly applied methods for combining various predictors are examined to obtain a better prediction of a query's effectiveness.

Building on the analysis of pre-retrieval predictors, post-retrieval approaches are then investigated, which estimate a query's effectiveness on the basis of the retrieved results. The thesis focuses in particular on the Clarity Score approach and provides an analysis of its sensitivity towards different variables such as the collection, the query set and the retrieval approach. Adaptations to Clarity Score are introduced which improve the estimation accuracy of the original algorithm.

The utility of query effectiveness prediction methods is commonly evaluated by reporting correlation coefficients, such as Kendall's Tau. Largely unexplored though is the question of the relationship between the current evaluation methodology for query effectiveness prediction and the change in effectiveness of retrieval systems that employ a predictor. We investigate this question by examining how the observed quality of predictors (with respect to Kendall's Tau) affects the retrieval effectiveness in two adaptive system settings: selective query expansion and meta-search.

The last part of the thesis is concerned with the task of estimating the ranking of retrieval systems according to their retrieval effectiveness without relying on costly relevance judgments. Five different system ranking estimation approaches are evaluated on a wide range of data sets which cover a variety of retrieval tasks and test collections. It is shown that under certain conditions, automatic methods yield a highly accurate ranking of systems.

Available online at http://www.cs.utwente.nl/~hauffc/phd/thesis.pdf.
The construction of mental models of information-rich web spaces
Authors: Zhang Yan
Published: August 2010

This study investigated the dynamic process of people constructing mental models of an information-rich web space during their interactions with the system and the impact of task complexity on model construction. In the study, subjects' mental models of MedlinePlus were measured at three time points: after subjects freely explored the system for 5 minutes, after the first search session, and after the second search session. During the first search session, the 39 subjects were randomly divided into two groups; one group completed 12 simple search tasks and the other group completed 3 complex search tasks. During the second search session, all subjects completed a set of 4 simple tasks and 2 complex tasks. Measures of the subjects' mental models included a concept listing protocol, a semi-structured interview, and a drawing task.

The analysis revealed that subjects' mental models were a rich representation of the cognitive and emotional processes involved in their interaction with information systems. The mental models consisted of three dimensions (structure, evaluation and emotion, and (expected) behaviors); the structure and evaluation/emotion dimensions consisted of four components each: system, content, information organization, and interface. The construction of mental models was a process coordinated by people's internal cognitive structure and the external sources (the system, system feedback, and tasks) and a process distributed through time, in the sense that earlier mental models impacted later ones. Task complexity also impacted the construction of mental models by influencing what objects in the system were perceived and represented by the user, the specificity of the representations, and the user's feelings about the objects.

Based on the study results, recommendations for employing mental models as a tool to assist designers in constructing user models, eliciting user requirements, and performing usability evaluations are put forward.
Ionic currents in intimal cultured synoviocytes from the rabbit
Authors: Large R. J. , Hollywood M. A. , Sergeant G. P. , Thornbury K. D. , Bourke S. , Levick J. R. , McHale N. G.
Published: August 2010

Hyaluronan, a joint lubricant and regulator of synovial fluid content, is secreted by fibroblast-like synoviocytes lining the joint cavity, and secretion is greatly stimulated by Ca2+-dependent protein kinase C. This study aimed to define synoviocyte membrane currents and channels that may influence synoviocyte Ca2+ dynamics. Resting membrane potential ranged from −30 mV to −66 mV (mean −45 ± 8.60 mV, n = 40). Input resistance ranged from 0.54 GΩ to 2.6 GΩ (mean 1.28 ± 0.57 GΩ; ν = 33). Cell capacitance averaged 97.97 ± 5.93 pF. Voltage clamp using Cs+ pipette solution yielded a transient inward current that disappeared in Ca2+-free solutions and was blocked by 1 μM nifedipine, indicating an L-type calcium current. The current was increased fourfold by the calcium channel activator FPL 64176 (300 nM). Using K+ pipette solution, depolarizing steps positive to −40 mV evoked an outward current that showed kinetics and voltage dependence of activation and inactivation typical of the delayed rectifier potassium current. This was blocked by the nonspecific delayed rectifier blocker 4-aminopyridine. The synoviocytes expressed mRNA for four Kv1 subtypes (Kv1.1, Kv1.4, Kv1.5, and Kv1.6). Correolide (1 μM), margatoxin (100 nM), and α-dendrotoxin block these Kv1 subtypes, and all of these drugs significantly reduced synoviocyte outward current. The current was blocked most effectively by 50 nM κ-dendrotoxin, which is specific for channels containing a Kv1.1 subunit, indicating that Kv1.1 is critical, either as a homomultimeric channel or as a component of a heteromultimeric Kv1 channel. When 50 nM κ-dendrotoxin was added to current-clamped synoviocytes, the cells depolarized by >20 mV and this was accompanied by an increase in intracellular calcium concentration. Similarly, depolarization of the cells with high external potassium solution caused an increase in intracellular calcium, and this effect was greatly reduced by 1 μM nifedipine. In conclusion, fibroblast-like synoviocytes cultured from the inner synovium of the rabbit exhibit voltage-dependent inward and outward currents, including Ca2+ currents. They thus express ion channels regulating membrane Ca2+ permeability and electrochemical gradient. Since Ca2+-dependent kinases are major regulators of synovial hyaluronan secretion, the synoviocyte ion channels are likely to be important in the regulation of hyaluronan secretion.
Effects of blebbistatin and Ca2+ concentration on force produced during stretch of skeletal muscle fibers
Authors: Minozzo Fabio C. , Rassier Dilson E.
Published: August 2010

When activated muscle fibers are stretched at low speeds [≤2 optimal length ( Lo)/s], force increases in two phases, marked by a change in slope [critical force (Pc)] that happens at a critical sarcomere length extension ( Lc). Some studies attribute Pc to the number of attached cross bridges before stretch, while others attribute it to cross bridges in a pre-power-stroke state. In this study, we reinvestigated the mechanisms of forces produced during stretch by altering either the number of cross bridges attached to actin or the cross-bridge state before stretch. Two sets of experiments were performed: 1) activated fibers were stretched by 3% Lo at speeds of 1.0, 2.0, and 3.0 Lo/s in different pCa2+ (4.5, 5.0, 5.5, 6.0), or 2) activated fibers were stretched by 3% Lo at 2 Lo/s in pCa2+ 4.5 containing either 5 μM blebbistatin(+/−) or its inactive isomer (+/+). All stretches started at a sarcomere length (SL) of 2.5 μm. When fibers were activated at a pCa2+ of 4.5, Pc was 2.47 ± 0.11 maximal force developed before stretch (Po) and decreased with lower concentrations of Ca2+. Lc was not Ca2+ dependent; the pooled experiments provided a Lc of 14.34 ± 0.34 nm/half-sarcomere (HS). Pc and Lc did not change with velocities of stretch. Fibers activated in blebbistatin(+/−) showed a higher Pc (2.94 ± 0.17 Po) and Lc (16.30 ± 0.38 nm/HS) than control fibers (Pc 2.31 ± 0.08 Po; Lc 14.05 ± 0.63 nm/HS). The results suggest that forces produced during stretch are caused by both the number of cross bridges attached to actin and the cross bridges in a pre-power-stroke state. Such cross bridges are stretched by large amplitudes before detaching from actin and contribute significantly to the force developed during stretch.
ESCRT-dependent targeting of plasma membrane localized KCa3.1 to the lysosomes
Authors: Balut Corina M. , Gao Yajuan , Murray Sandra A. , Thibodeau Patrick H. , Devor Daniel C.
Published: August 2010

The number of intermediate-conductance, Ca2+-activated K+channels (KCa3.1) present at the plasma membrane is deterministic in any physiological response. However, the mechanisms by which KCa3.1 channels are removed from the plasma membrane and targeted for degradation are poorly understood. Recently, we demonstrated that KCa3.1 is rapidly internalized from the plasma membrane, having a short half-life in both human embryonic kidney cells (HEK293) and human microvascular endothelial cells (HMEC-1). In this study, we investigate the molecular mechanisms controlling the degradation of KCa3.1 heterologously expressed in HEK and HMEC-1 cells. Using immunofluorescence and electron microscopy, as well as quantitative biochemical analysis, we demonstrate that membrane KCa3.1 is targeted to the lysosomes for degradation. Furthermore, we demonstrate that either overexpressing a dominant negative Rab7 or short interfering RNA-mediated knockdown of Rab7 results in a significant inhibition of channel degradation rate. Coimmunoprecipitation confirmed a close association between Rab7 and KCa3.1. On the basis of these findings, we assessed the role of the ESCRT machinery in the degradation of heterologously expressed KCa3.1, including TSG101 [endosomal sorting complex required for transport (ESCRT)-I] and CHMP4 (ESCRT-III) as well as VPS4, a protein involved in the disassembly of the ESCRT machinery. We demonstrate that TSG101 is closely associated with KCa3.1 via coimmunoprecipitation and that a dominant negative TSG101 inhibits KCa3.1 degradation. In addition, both dominant negative CHMP4 and VPS4 significantly decrease the rate of membrane KCa3.1 degradation, compared with wild-type controls. These results are the first to demonstrate that plasma membrane-associated KCa3.1 is targeted for lysosomal degradation via a Rab7 and ESCRT-dependent pathway.
Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels
Authors: Guo Kai , Wang Xianming , Gao Guofeng , Huang Congxin , Elmslie Keith S. , Peterson Blaise Z.
Published: August 2010

We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149–1159, 2010). The short 17 amino acid extracellular NH2-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate CaV1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with CaV1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on CaV1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca2+ dynamics in the heart.
High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats
Authors: Saeed Aso , DiBona Gerald F. , Marcussen Niels , Guron Gregor
Published: August 2010

The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg−1·min−1sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats ( n = 8–10 per group) were either on a normal (NNa; 0.4% NaCl)- or high (HNa; 8% NaCl)-NaCl diet. Separate groups were treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol; 1 M in drinking water). Transfer function analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR; 0.06–0.09 Hz) and the tubuloglomerular feedback mechanism (TGF; 0.03–0.06 Hz). MAP was elevated in ANG II-infused rats compared with sham groups ( P < 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 ± 0.3 vs. 7.9 ± 0.3 and 9.1 ± 0.3 ml·min−1·g kidney wt−1, P < 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 ± 0.50 dB, P < 0.05 vs. all other groups) and in the frequency range of the TGF (−0.02 ± 0.50 dB, P < 0.05 vs. sham NNa and sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by tempol in ANG II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in ANG II HNa, and these abnormalities were attenuated by tempol, suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response.
Hyperaldosteronism in Klotho-deficient mice
Authors: Fischer Stephanie S. , Kempe Daniela S. , Leibrock Christina B. , Rexhepaj Rexhep , Siraskar Balasaheb , Boini Krishna M. , Ackermann Teresa F. , Föller Michael , Hocher Berthold , Rosenblatt Kevin P. , Kuro-o Makoto , Lang Florian
Published: August 2010

Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D3 [1,25(OH)2D3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice ( klotho hm) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho hm mice and wild-type mice ( klotho+/+) were subjected to a normal (D+) or vitamin D-deficient (D−) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D−/+). At the age of 8 wk, body weight was significantly lower in klotho hmD+ mice than in klotho+/+D+ mice, klotho hmD− mice, and klotho hmD−/+ mice. Plasma concentrations of 1,25(OH)2D3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klotho hmD+ mice than in klotho+/+D+ mice. Plasma volume was significantly smaller in klotho hmD−/+ mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klotho hmD+ mice than in klotho+/+D+ mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klotho hmD+ mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)2D3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.
Constitutive endocytosis and recycling of NKCC2 in rat thick ascending limbs
Authors: Ares Gustavo R. , Ortiz Pablo A.
Published: August 2010

The Na-K-2Cl cotransporter (NKCC2) mediates NaCl absorption by the thick ascending limb of Henle's loop (THAL). Exocytosis and endocytosis regulates surface expression of most transporters. However, little is known about the mechanism of NKCC2 trafficking in the absence of stimulating hormones and whether this mechanism contributes to regulation of steady-state surface expression of apical NKCC2 in the THAL. We tested whether NKCC2 undergoes constitutive endocytosis that regulates steady-state surface NKCC2 and NaCl reabsorption in THALs. We measured steady-state surface NKCC2 levels and the rate of NKCC2 endocytosis by surface biotinylation and Western blot and confocal microscopy of isolated perfused rat THALs. We observed constitutive NKCC2 endocytosis over 30 min that averaged 21.5 ± 2.7% of the surface pool. We then tested whether methyl-β-cyclodextrin (MβCD), a compound that inhibits endocytosis by chelating membrane cholesterol, blocked NKCC2 endocytic retrieval. We found that 30-min treatment with MβCD (5 mM) blocked NKCC2 endocytosis by 81% ( P < 0.01). Blockade of endocytosis by MβCD induced accumulation of NKCC2 at the apical membrane as demonstrated by a 60 ± 16% ( P < 0.05) increase in steady-state surface expression and enhanced apical surface NKCC2 immunostaining in isolated, perfused THALs. Acute treatment with MβCD did not change the total pool of NKCC2. MβCD did not affect NKCC2 trafficking when it was complexed with cholesterol before treatment. Inhibition endocytosis with MβCD enhanced NKCC2-dependent NaCl entry by 57 ± 16% ( P < 0.05). Finally, we observed that a fraction of retrieved NKCC2 recycles back to the plasma membrane (36 ± 7%) over 30 min. We concluded that constitutive NKCC2 trafficking maintains steady-state surface NKCC2 and regulates NaCl reabsorption in THALs. These are the first data showing an increase in apical membrane NKCC2 in THALs by altering the rates of constitutive NKCC2 trafficking, rather than by stimulation of hormone-dependent signaling.
Direct demonstration of tubular fluid flow sensing by macula densa cells
Authors: Sipos Arnold , Vargas Sarah , Peti-Peterdi János
Published: August 2010

Macula densa (MD) cells in the cortical thick ascending limb (cTAL) detect variations in tubular fluid composition and transmit signals to the afferent arteriole (AA) that control glomerular filtration rate [tubuloglomerular feedback (TGF)]. Increases in tubular salt at the MD that normally parallel elevations in tubular fluid flow rate are well accepted as the trigger of TGF. The present study aimed to test whether MD cells can detect variations in tubular fluid flow rate per se. Calcium imaging of the in vitro microperfused isolated JGA-glomerulus complex dissected from mice was performed using fluo-4 and fluorescence microscopy. Increasing cTAL flow from 2 to 20 nl/min (80 mM [NaCl]) rapidly produced significant elevations in cytosolic Ca2+concentration ([Ca2+]i) in AA smooth muscle cells [evidenced by changes in fluo-4 intensity (F); F/F0= 1.45 ± 0.11] and AA vasoconstriction. Complete removal of the cTAL around the MD plaque and application of laminar flow through a perfusion pipette directly to the MD apical surface essentially produced the same results even when low (10 mM) or zero NaCl solutions were used. Acetylated α-tubulin immunohistochemistry identified the presence of primary cilia in mouse MD cells. Under no flow conditions, bending MD cilia directly with a micropipette rapidly caused significant [Ca2+]ielevations in AA smooth muscle cells (fluo-4 F/F0: 1.60 ± 0.12) and vasoconstriction. P2 receptor blockade with suramin significantly reduced the flow-induced TGF, whereas scavenging superoxide with tempol did not. In conclusion, MD cells are equipped with a tubular flow-sensing mechanism that may contribute to MD cell function and TGF.
Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise
Authors: La Gerche André , MacIsaac Andrew I. , Burns Andrew T. , Mooney Don J. , Inder Warrick J. , Voigt Jens-Uwe , Heidbüchel Hein , Prior David L.
Published: August 2010

Pulmonary transit of agitated contrast (PTAC) occurs to variable extents during exercise. We tested the hypothesis that the onset of PTAC signifies flow through larger-caliber vessels, resulting in improved pulmonary vascular reserve during exercise. Forty athletes and fifteen nonathletes performed maximal exercise with continuous echocardiographic Doppler measures [cardiac output (CO), pulmonary artery systolic pressure (PASP), and myocardial velocities] and invasive blood pressure (BP). Arterial gases and B-type natriuretic peptide (BNP) were measured at baseline and peak exercise. Pulmonary vascular resistance (PVR) was determined as the regression of PASP/CO and was compared according to athletic and PTAC status. At peak exercise, athletes had greater CO (16.0 ± 2.9 vs. 12.4 ± 3.2 l/min, P < 0.001) and higher PASP (60.8 ± 12.6 vs. 47.0 ± 6.5 mmHg, P < 0.001), but PVR was similar to nonathletes ( P = 0.71). High PTAC (defined by contrast filling of the left ventricle) occurred in a similar proportion of athletes and nonathletes (18/40 vs. 10/15, P = 0.35) and was associated with higher peak-exercise CO (16.1 ± 3.4 vs. 13.9 ± 2.9 l/min, P = 0.010), lower PASP (52.3 ± 9.8 vs. 62.6 ± 13.7 mmHg, P = 0.003), and 37% lower PVR ( P < 0.0001) relative to low PTAC. Right ventricular (RV) myocardial velocities increased more and BNP increased less in high vs. low PTAC subjects. On multivariate analysis, maximal oxygen consumption (V̇o2max) ( P = 0.009) and maximal exercise output ( P = 0.049) were greater in high PTAC subjects. An exercise-induced decrease in arterial oxygen saturation (98.0 ± 0.4 vs. 96.7 ± 1.4%, P < 0.0001) was not influenced by PTAC status ( P = 0.96). Increased PTAC during exercise is a marker of pulmonary vascular reserve reflected by greater flow, reduced PVR, and enhanced RV function.
Sympathetic nerve-dependent regulation of mucosal vascular tone modifies airway smooth muscle reactivity
Authors: Mazzone Stuart B. , Lim Lina H. K. , Wagner Elizabeth M. , Mori Nanako , Canning Brendan J.
Published: August 2010

The airways contain a dense subepithelial microvascular plexus that is involved in the supply and clearance of substances to and from the airway wall. We set out to test the hypothesis that airway smooth muscle reactivity to bronchoconstricting agents may be dependent on airway mucosal blood flow. Immunohistochemical staining identified vasoconstrictor and vasodilator nerve fibers associated with subepithelial blood vessels in the guinea pig airways. Intravital microscopy of the tracheal mucosal microvasculature in anesthetized guinea pigs revealed that blockade of α-adrenergic receptors increased baseline arteriole diameter by ∼40%, whereas the α-adrenergic receptor agonist phenylephrine produced a modest (5%) vasoconstriction in excess of the baseline tone. In subsequent in vivo experiments, tracheal contractions evoked by topically applied histamine were significantly reduced ( P < 0.05) and enhanced by α-adrenergic receptor blockade and activation, respectively. α-Adrenergic ligands produced similar significant ( P < 0.05) effects on airway smooth muscle contractions evoked by topically administered capsaicin, intravenously administered neurokinin A, inhaled histamine, and topically administered antigen in sensitized animals. These responses were independent of any direct effect of α-adrenergic ligands on the airway smooth muscle tone. The data suggest that changes in blood flow in the vessels supplying the airways regulate the reactivity of the underlying airway smooth muscle to locally released and exogenously administered agents by regulating their clearance. We speculate that changes in mucosal vascular function or changes in neuronal regulation of the airway vasculature may contribute to airways responsiveness in disease.
Molecular Layer Inhibitory Interneurons Provide Feedforward and Lateral Inhibition in the Dorsal Cochlear Nucleus
Authors: Roberts Michael T. , Trussell Laurence O.
Published: August 2010

In the outer layers of the dorsal cochlear nucleus, a cerebellum-like structure in the auditory brain stem, multimodal sensory inputs drive parallel fibers to excite both principal (fusiform) cells and inhibitory cartwheel cells. Cartwheel cells, in turn, inhibit fusiform cells and other cartwheel cells. At the microcircuit level, it is unknown how these circuit components interact to modulate the activity of fusiform cells and thereby shape the processing of auditory information. Using a variety of approaches in mouse brain stem slices, we investigated the synaptic connectivity and synaptic strength among parallel fibers, cartwheel cells, and fusiform cells. In paired recordings of spontaneous and evoked activity, we found little overlap in parallel fiber input to neighboring neurons, and activation of multiple parallel fibers was required to evoke or alter action potential firing in cartwheel and fusiform cells. Thus neighboring neurons likely respond best to distinct subsets of sensory inputs. In contrast, there was significant overlap in inhibitory input to neighboring neurons. In recordings from synaptically coupled pairs, cartwheel cells had a high probability of synapsing onto nearby fusiform cells or other nearby cartwheel cells. Moreover, single cartwheel cells strongly inhibited spontaneous firing in single fusiform cells. These synaptic relationships suggest that the set of parallel fibers activated by a particular sensory stimulus determines whether cartwheel cells provide feedforward or lateral inhibition to their postsynaptic targets.
Phosphorylation-State-Dependent Regulation of NMDA Receptor Short-Term Plasticity Modifies Hippocampal Dendritic Ca2+ Transients
Authors: Chatterjea Debika , Hamid Edaeni , Leonard John P. , Alford Simon
Published: August 2010

N-methyl-d-aspartate (NMDA) receptor-mediated currents are enhanced by phosphorylation. We have investigated effects of phosphorylation-dependent short-term plasticity of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) on the induction of long-term depression (LTD). We confirmed in whole cell clamped CA1 pyramidal neurons that LTD is induced by pairing stimulus protocols. However, after serine-threonine phosphorylation was modified by postsynaptic introduction of a protein phosphatase-1 (PP1) inhibitor, the same pairing protocol evoked long-term potentiation (LTP). We determined effects of modification of phosphatase activity on evoked NMDA EPSCs during LTD induction protocols. During LTD induction, using a protocol pairing depolarization to –40 mV and 0.5 Hz stimulation, NMDA receptor-mediated EPSCs undergo a short-term enhancement at the start of the protocol. In neurons in which PP1 activity was inhibited, this short-term enhancement was markedly amplified. We then investigated the effect of this enhancement on Ca2+ entry during the start of the LTD induction protocol. Enhancement of NMDA receptor-mediated responses was accompanied by an amplification of induction protocol-evoked Ca2+ transients. Furthermore, this amplification required synaptic activation during the protocol, consistent with an enhancement of Ca2+ entry mediated by NMDA receptor activation. The sign of NMDA receptor-mediated long-term plasticity, whether potentiation or depression depends on the amplitude of the synaptic Ca2+ transient during induction. We conclude that short-term phosphorylation-dependent plasticity of the NMDA receptor-mediated EPSCs contributes significantly to the effect of phosphatase inhibition on the subsequent induction of LTD or LTP.
A New Iterative Method for Solving Equilibrium Problems and Fixed Point Problems for Infinite Family of Nonexpansive Mappings
Authors: Wang Shenghua , Cho YeolJe , Qin Xiaolong
Published: August 2010

We introduce a new iterative scheme for finding a common element of the solutions sets of a finite family of equilibrium problems and fixed points sets of an infinite family of nonexpansive mappings in a Hilbert space. As an application, we solve a multiobjective optimization problem using the result of this paper.
Comparison of Tracheal Diameter Measured by Chest X-Ray and by Computed Tomography
Authors: Sakuraba Shigeki , Serita Ryohei , Kuribayashi Junya , Kosugi Shizuko , Arisaka Hirofumi , Yoshida Kazuichi , Takeda Junzo
Published: August 2010

Assessments of tracheal diameter (TD) are important to select proper endotracheal tubes. Previous studies have used X-ray and physical indices to estimate tracheal diameter but these may not reflect the actual TD. We compared TD measured by X-ray (TD-XP) and by computer tomography (TD-CT) in 200 patients. Also, we analyzed correlation of TD-CT with physical indices such as age, height, weight, and BMI. TD-XP and TD-CT were significantly correlated (male:n=55,P=.0146; female:n=91,P=.001). TD-XP was 0.4 mm wider in male and 1.0 mm wider in female than TD-CT. However, correlation coefficients of TD-XP and TD-CT are very weak (male:r=0.36; female:r=0.653). TD-CT did not correlate with age, height, weight, or BMI. Our findings suggest that correlations of TD-XP and TD are statistically significant but not clinically significant. Physical indices are not useful to estimate TD.
Self‐Assembled TiO2 Nanotube Arrays with U‐Shaped Profile by Controlling Anodization Temperature
Authors: Chen Jingfei , Lin Jia , Chen Xianfeng
Published: August 2010

TiO2 nanotube arrays with uniform diameter from top to bottom were fabricated. The synthesizing approach is based on the investigation of the influence of electrolyte temperature on the tube diameter. We found that the inner diameter of the tubes increased with the electrolyte temperature. Accordingly, we improved the tube profile from the general V shape to U shape by raising the electrolyte temperature gradually. This is a simple and fast approach to fabricate uniform TiO2 nanotubes in diameter. The improved TiO2 nanotube arrays may show better properties and have broad potential applications.
Elliptically Bent X-Ray Mirrors with Active Temperature Stabilization
Authors: Yuan Sheng , Church Matthew , Yashchuk Valeriy V. , Goldberg Kenneth A. , Celestre Richard S. , McKinney Wayne R. , Kirschman Jonathan , Morrison Gregory , Noll Tino , Warwick Tony , Padmore Howard A.
Published: August 2010

We present details of design of elliptically bent Kirkpatrick-Baez mirrors developed and successfully used at the advanced light source for submicron focusing. A distinctive feature of the mirror design is an active temperature stabilization based on a Peltier element attached directly to the mirror body. The design and materials have been carefully optimized to provide high heat conductance between the mirror body and substrate. We describe the experimental procedures used when assembling and precisely shaping the mirrors, with special attention paid to laboratory testing of the mirror-temperature stabilization. For this purpose, the temperature dependence of the surface slope profile of a specially fabricated test mirror placed inside a temperature-controlled container was measured. We demonstrate that with active mirror-temperature stabilization, a change of the surrounding temperature by more than 3 K does not noticeably affect the mirror figure. Without temperature stabilization, the rms slope error is changed by approximately 1.5 μrad (primarily defocus) under the same conditions.
Hyperphosphorylated FAK Delocalizes from Focal Adhesions to Membrane Ruffles
Authors: Hamadi Abdelkader , Deramaudt Therese B. , Takeda Kenneth , Rondé Philippe
Published: August 2010

Cell adhesion and migration are key determinants in tumor metastasis. Adherence of tumor cell to the extracellular matrix is mediated via integrin containing focal adhesions (FAs). Binding of integrins to ECM triggers phosphorylation of two major components of FAs, focal adhesion kinase (FAK) and Src, activating downstream signaling pathway which leads to FA disassembly and cell migration. In this paper, we analyze how phosphorylation of FAK regulates its trafficking at FAs in living human astrocytoma cells. Upon pervanadate-induced FAK phosphorylation, phosphorylated FAK appeared highly expressed at newly formed membrane ruffles. This effect was abolished in presence of the specific Src inhibitor PP2. Our findings demonstrate that upon phosphorylation, FAK delocalizes from FAs to membrane ruffles.
Applying Small-Scale DNA Signatures as an Aid in Assembling Soybean Chromosome Sequences
Authors: Peto Myron , Grant David M. , Shoemaker Randy C. , Cannon Steven B.
Published: August 2010

Previous work has established a genomic signature based on relative counts of the 16 possible dinucleotides. Until now, it has been generally accepted that the dinucleotide signature is characteristic of a genome and is relatively homogeneous across a genome. However, we found some local regions of the soybean genome with a signature differing widely from that of the rest of the genome. Those regions were mostly centromeric and pericentromeric, and enriched for repetitive sequences. We found that DNA binding energy also presented large-scale patterns across soybean chromosomes. These two patterns were helpful during assembly and quality control of soybean whole genome shotgun scaffold sequences into chromosome pseudomolecules.
Inhibition of Carboplatin-Induced DNA Interstrand Cross-link Repair by Gemcitabine in Patients Receiving these Drugs for Platinum-Resistant Ovarian Cancer
Authors: Ledermann Jonathan A. , Gabra Hani , Jayson Gordon C. , Spanswick Victoria J. , Rustin Gordon J.S. , Jitlal Mark , James Lindsay E. , Hartley John A.
Published: August 2010

Background: The potential of gemcitabine to interact with carboplatin was explored in a phase II trial in platinum-resistant ovarian cancer. Peripheral blood lymphocytes were sampled after drug administration to measure DNA interstrand cross-link formation and repair.

Patients and Methods: Forty patients received carboplatin target area under concentration-time curve (AUC 4) followed by gemcitabine 1,000 mg/m2 with a second dose of gemcitabine on day 8. Peripheral blood lymphocytes were obtained in 12 patients before and at intervals during the first cycle of chemotherapy. DNA cross-link formation and repair (unhooking) were measured by the single-cell gel electrophoresis (comet) assay following ex vivo incubation.

Results: The global response rate was 47% (Response Evaluation Criteria in Solid Tumors rate, 29%; CA125 rate, 63%). Delays in treatment were seen in 24% of cycles largely due to myelosuppression; 15% of day 8 administration was omitted. Peak carboplatin-induced DNA cross-linking was seen by 24 hours. Significant reduction was seen in the repair of in vivo carboplatin-induced DNA cross-links following administration of gemcitabine.

Conclusion: An enhanced activity of carboplatin in platinum-resistant ovarian cancer may be due to synergy with gemcitabine through inhibition of repair of DNA cross-links. Future studies should explore coadministration of these drugs, as this may be a more effective schedule. Clin Cancer Res; 16(19); 4899–905. ©2010 AACR.
Evaluation of the Role of Vascular Endothelial Growth Factor in Diabetic Retinopathy
Authors: Mahdy Reda A. , Nada Waled M.
Published: August 2010

Purpose: The study is aiming at investigating the correlation between vascular endothelial growth factor (VEGF) as an angiogenic factor and diabetic retinopathy in type 2 diabetic patients and the effect of panretinal coagulation and glycemic control on VEGF. Methods: The study included 30 patients of type 2 diabetes, 10 of them did not suffer from any of the vascular complications of type 2 diabetes mellitus (group 1), 10 patients had nonproliferative diabetic retinopathy (group 2), 10 patients had proliferative diabetic retinopathy (PDR) (group 3) and (group 4), as well as 10 healthy subjects that served as control group. All participants were subjected to complete clinical examination including ophthalmic and medical examination, laboratory investigations comprising complete blood count, liver function test, serum creatinine, 24-hour urinary albumin excretion, lipid profile, fasting and 2-hour postprandial blood glucose, HbA1C and serum VEGF. Results: The study reported a highly significant increase in the serum VEGF in the diabetic patients compared to the control group (p < 0.001), and there was also a highly significant increase in the serum VEGF in the patients with PDR versus nonproliferative diabetic retinopathy (40.55 ± 8.28 vs. 20.3 ± 2.45, p < 0.001). There was a reduction in the serum VEGF in a group of diabetic patients with poor glycemic control when their diabetic state corrected through 4 months of follow-up was highly significant (17.29 ± 1.61 before vs. 9.39 ± 0.82 after control p < 0.001) as well as the reduction in the serum VEGF which was observed in a group of patients with PDR when proper panretinal photocoagulation (PRP) was applied to their retinae with 4 months of follow-up (40.55 ± 8.28 before vs. 21.15 ± 1.76 after PRP, p < 0.001). Conclusion: Serum VEGF is significantly increased in diabetic patients, especially those with PDR, and this elevation of VEGF was reduced in uncontrolled diabetic patients with proper gycemic control, and in patients with PDR with proper PRP, indicating that VEGF is an angiogenic factor that reflects the degree of neovascularization in diabetic complications.
Functional Outcome after Stroke in Patients with Aphasia and Neglect: Assessment by the Motor and Cognitive Functional Independence Measure Instrument
Authors: Gialanella Bernardo , Ferlucci Cristina
Published: August 2010

Background: The role of neuropsychological deficits in predicting functional outcome in patients with aphasia and neglect at the end of rehabilitation after stroke has been poorly investigated. This was the aim of this prospective study evaluated using a Functional Independence Measure (FIM) instrument. Methods: Patients with a primary diagnosis of cerebrovascular accident [125 patients with aphasia, 45 with neglect and 131 without either aphasia or neglect (WAN)] were enrolled. Backward multiple linear regression analysis was used to predict motor and cognitive FIM, discharge destination, and length of stay. The independent variables were age, gender, aphasia, stroke type, stroke lesion size, comorbidity, bladder catheter, stroke severity, trunk control test, initial motor FIM, and committed caregiver identified on admission to rehabilitation. Results: At the end of rehabilitation, patients with neglect had significantly lower final motor FIM scores and lower daily efficiency improvement in motor FIM scores compared with those with aphasia (both p < 0.001) and WAN (both p < 0.001). Patients with aphasia showed lower final cognitive FIM scores compared with those with neglect (p < 0.001) and those without deficits (p < 0.001). Neglect was a predictor of final motor FIM (β = –0.24) and efficiency in motor FIM (β = –0.29), while aphasia was a predictor of final cognitive FIM (β = –0.54). Neglect and aphasia did not differ and were not predictors of discharge destination and length of stay. Conclusions: Patients with neglect have lower motor FIM scores if compared with those with aphasia, while patients with aphasia have lower cognitive FIM scores. Neglect is a predictor of motor FIM, while aphasia is a predictor of cognitive FIM scores.
Estimating the Rate of Non-Participation and Its Influence on the Study Results: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study Report 32
Authors: Raman Rajiv , Rachapalli Sudhir R. , Kulothungan Vaitheeswaran , Saumya Pal Swakshyar , Verma Aditya , Sharma Tarun
Published: August 2010

Purpose: To report the non-participation rates in a cross-sectional study, compare participants with non-participants, elucidate barriers for non-response and evaluate the influence of non-responders on the outcome measure. Methods: The Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study had 2 steps in which non- participation was possible. Step 1 was an estimation of fasting blood sugar at the participants’ homes, and step 2 a base hospital examination. The sociodemographic information was collected at the time of enumeration. The barriers against participation were noted at refusal. The data of the participants were compared with the urban Tamil Nadu population data from the 2001 census. Results: The non-participation rate was 3.6% in the field (step 1), and 13.9% at the base hospital (step 2). At step 1, older men and unemployed women had a lesser odds ratio for non-participation than younger age groups. At step 2, employment was significant for non-participation in men, and age between 50 and 59 years, illiteracy and unemployment in women. Conclusion: The barriers against participation differed between steps 1 and 2. The study participants were similar to the population of urban Tamil Nadu. Hence, the results of the study can be generalized to the urban Indian population.
Blockade of Osteopontin Inhibits Glomerular Fibrosis in a Model of Anti-Glomerular Basement Membrane Glomerulonephritis
Authors: Zhou Cindy , Wu Jean , Torres Lisa , Hicks John M. , Bartkowiak Todd , Parker Kiana , Lou Ya-Huan
Published: August 2010

Background: In our rat model for anti-GBM GN, severe fibrosis follows glomerular inflammation. A potential role of extracellular matrix protein osteopontin (OPN) in glomerular fibrosis was investigated. Methods: Neutralizing OPN antiserum or control normal serum was injected into the experimental rats at late inflammatory/early fibrotic stage. Glomerular inflammation and fibrosis were determined. Results: OPN antiserum treatment had little effect on glomerular inflammation. However, the antiserum treatment resulted in a significant reduction in number of fibrotic glomeruli (50% of the controls). Histology observation showed that fibrotic tissue in glomeruli of the antiserum treated rats was mild and poorly developed. OPN antiserum treatment resulted in downregulated glomerular expression of collagen 1α1; collagen deposition in the antiserum treated rats reduced to <30% of that for normal serum controls. Conclusion: Neutralization of OPN inhibited progression of fibrosis in vivo when given at early fibrotic stage. Thus, OPN may be a therapeutic target for glomerular fibrosis.