bluuebunny/crossref_metadata_2025 huggingface dataset:
SUPERHEAVY RESEARCH AT RIKEN
Authors: MORITA KOSUKE
Published: December 2009

At RIKEN (The Institute of Physical and Chemical Research) in Japan, we have performed experiments to study the productions and decays of the heaviest elements produced by one neutron emission channels of 208 Pb and 209 Bi based heavy-ion induced fusion reactions. A gas-filled type recoil separator has been used for collecting evaporation residues of the reactions separating them from high intensity beam particles. The reactions studied were 208 Pb (58 Fe , n )265 Hs , 208 Pb (64 Ni , n ) 271 Ds , 209 Bi (64 Ni , n ) 272 Rg , 208 Pb (70 Zn , n ) 277112, and 209 Bi (70 Zn , n ) 278113. In studies of the first four reactions we have provided the independent confirmations of the productions and their decays of the isotopes, 265 Hs , 271 Ds , 272 Rg , and 277112, as well as the decay properties of their decay daughters, previously studied by Hofmann et al., a group of Gesellschaft für Schwerionenforschung (GSI), Germany. In the last reaction, we observed two decay chains originated from the isotope 278113, assigned firstly by generic correlation of the alpha decay chains connected into the previously known decay of 266 Bh and 262 Db via previously unknown alpha decays of 278113, 274 Rg and 270 Mt .
Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria
Authors: Feng Jianhua , Lucchinetti Eliana , Enkavi Giray , Wang Yi , Gehrig Peter , Roschitzki Bernd , Schaub Marcus C. , Tajkhorshid Emad , Zaugg Kathrin , Zaugg Michael
Published: December 2009

Phosphorylation of adenine nucleotide translocator 1 (ANT1) at residue Y194, which is part of the aromatic ladder located within the lumen of the carrier, critically regulates mitochondrial metabolism. Recent data support the concept that members of the Src family of nonreceptor tyrosine kinases are constitutively present in mitochondria and key to regulation of mitochondrial function. Herein, we demonstrate that site mutations of ANT1 (Y190→F190, Y194→F194) mimicking dephosphorylation of the aromatic ladder resulted in loss of oxidative growth and ADP/ATP exchange activity in respiration-incompetent yeast expressing mutant chimeric yN-hANT1. ANT1 is phosphorylated at Y194 by the Src family kinase members Src and Lck, and increased phosphorylation is tightly linked to reduced cell injury in preconditioned protected vs. unprotected cardiac mitochondria. Molecular dynamics simulations find the overall structure of the phosphorylated ANT1 stable, but with an increased steric flexibility in the region of the aromatic ladder, matrix loop m2, and four helix-linking regions. Combined with an analysis of the putative cytosolic salt bridge network, we reason that the effect of phosphorylation on transport is likely due to an accelerated transition between the main two conformational states (c↔m) of the carrier during the transport cycle. Since “aromatic signatures” are typical for other mitochondrial carrier proteins with important biological functions, our results may be more general and applicable to these carriers.
High concentrations of HGF inhibit skeletal muscle satellite cell proliferation in vitro by inducing expression of myostatin: a possible mechanism for reestablishing satellite cell quiescence in vivo
Authors: Yamada Michiko , Tatsumi Ryuichi , Yamanouchi Keitaro , Hosoyama Tohru , Shiratsuchi Sei-ichi , Sato Akiko , Mizunoya Wataru , Ikeuchi Yoshihide , Furuse Mitsuhiro , Allen Ronald E.
Published: December 2009

Skeletal muscle regeneration and work-induced hypertrophy rely on molecular events responsible for activation and quiescence of resident myogenic stem cells, satellite cells. Recent studies demonstrated that hepatocyte growth factor (HGF) triggers activation and entry into the cell cycle in response to mechanical perturbation, and that subsequent expression of myostatin may signal a return to cell quiescence. However, mechanisms responsible for coordinating expression of myostatin after an appropriate time lag following activation and proliferation are not clear. Here we address the possible role of HGF in quiescence through its concentration-dependent negative-feedback mechanism following satellite cell activation and proliferation. When activated/proliferating satellite cell cultures were treated for 24 h beginning 48-h postplating with 10–500 ng/ml HGF, the percentage of bromodeoxyuridine-incorporating cells decreased down to a baseline level comparable to 24-h control cultures in a HGF dose-dependent manner. The high level HGF treatment did not impair the cell viability and differentiation levels, and cells could be reactivated by lowering HGF concentrations to 2.5 ng/ml, a concentration that has been shown to optimally stimulate activation of satellite cells in culture. Coaddition of antimyostatin neutralizing antibody could prevent deactivation and abolish upregulation of cyclin-dependent kinase (Cdk) inhibitor p21. Myostatin mRNA expression was upregulated with high concentrations of HGF, as demonstrated by RT-PCR, and enhanced myostatin protein expression and secretion were revealed by Western blots of the cell lysates and conditioned media. These results indicate that HGF could induce satellite cell quiescence by stimulating myostatin expression. The HGF concentration required (over 10–50 ng/ml), however, is much higher than that for activation, which is initiated by rapid release of HGF from its extracellular association. Considering that HGF is produced by satellite cells and spleen and liver cells in response to muscle damage, local concentrations of HGF bathing satellite cells may reach a threshold sufficient to induce myostatin expression. This time lag may delay action of the quiescence signaling program in proliferating satellite cells during initial phases of muscle regeneration followed by induction of quiescence in a subset of cells during later phases.
Effects of insulin-like growth factor-I, insulin, and leucine on protein turnover and ubiquitin ligase expression in rainbow trout primary myocytes
Authors: Cleveland Beth M. , Weber Gregory M.
Published: December 2009

The effects of insulin-like growth factor-I (IGF-I), insulin, and leucine on protein turnover and pathways that regulate proteolytic gene expression and protein polyubiquitination were investigated in primary cultures of 4-day-old rainbow trout myocytes. Supplementing media with 100 nM IGF-I increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 14% ( P < 0.05). Treatment with 1 μM insulin increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 17% ( P < 0.05). Supplementing media containing 0.6 mM leucine with an additional 2.5 mM leucine did not increase protein synthesis rates but reduced rates of protein degradation by 8% ( P < 0.05). IGF-I (1 nM–100 nM) and insulin (1 nM-1 μM) independently reduced the abundance of ubiquitin ligase mRNA in a dose-dependent manner, with maximal reductions of ∼70% for muscle atrophy F-box (Fbx) 32, 40% for Fbx25, and 25% for muscle RING finger-1 (MuRF1, P < 0.05). IGF-I and insulin stimulated phosphorylation of FOXO1 and FOXO4 ( P < 0.05), which was inhibited by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, and decreased the abundance of polyubiquitinated proteins by 10–20% ( P < 0.05). Supplementing media with leucine reduced Fbx32 expression by 25% ( P < 0.05) but did not affect Fbx25 nor MuRF1 transcript abundance. Serum deprivation decreased rates of protein synthesis by 60% ( P < 0.05), increased protein degradation by 40% ( P < 0.05), and increased expression of all ubiquitin ligases. These data suggest that, similar to mammals, the inhibitory effects of IGF-I and insulin on proteolysis occur via P I3-kinase/protein kinase B signaling and are partially responsible for the ability of these compounds to promote protein accretion.
Nitric oxide synthase inhibition during treadmill exercise reveals fiber-type specific vascular control in the rat hindlimb
Authors: Copp Steven W. , Hirai Daniel M. , Hageman K. Sue , Poole David C. , Musch Timothy I.
Published: December 2009

The control of vascular tone during exercise is highly complex and integrated. Specifically, in regards to the contribution of nitric oxide (NO), the observed magnitude and muscle fiber-type dependency of the NO contribution to exercise hyperemia may differ depending on the timing of NO synthase (NOS) inhibition with respect to the exercise bout (i.e., administration prior to vs. during exercise). We tested the hypothesis that, in the presence of prior cyclooxygenase inhibition (indomethacin, 5 mg/kg-1), NOS inhibition ( NG-nitro-l-arginine methyl ester, l-NAME; 10 mg/kg) administered during submaximal treadmill exercise would blunt blood flow and vascular conductance (VC) in the hindlimb muscle(s) of the rat with the greatest reductions in blood flow and VC occurring in the predominantly oxidative muscles. Adult female Wistar rats ( n = 10, age: 3–4 mo) ran on a motor-driven treadmill (20 m/min, 10% grade). Total and regional hindlimb muscle blood flow and VC were determined via radiolabeled microspheres before (control) and after l-NAME administration during exercise. l-NAME reduced ( P < 0.05) total hindlimb muscle blood flow (control: 123 ± 10, l-NAME: 103 ± 7 ml·min−1·100g−1) and VC (control: 0.95 ± 0.09, l-NAME: 0.63 ± 0.05 ml·min−1·100g−1·mmHg−1). There was a significant correlation ( r = 0.51, P < 0.05) between the absolute reductions in VC after l-NAME and the percent sum of type I and IIa fibers in the individual muscles and muscle parts; however, there was no correlation ( P = 0.62) when expressed as blood flow. Surprisingly, the highly oxidative muscles demonstrated a marked ability to maintain oxygen delivery, which differs substantially from previous reports of l-NAME infusion prior to exercise in these muscles. The demonstration that NO is an important regulator of blood flow and VC in the rat hindlimb during treadmill exercise, but that the fiber-type dependency of NO is altered markedly when NOS inhibition is performed during, vs. prior to, exercise, lends important insights into the integrated nature of vascular control during exercise.
Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat
Authors: Ochodnický Peter , Henning Robert H. , Buikema Hendrik J. , de Zeeuw Dick , Provoost Abraham P. , van Dokkum Richard P. E.
Published: December 2009

It is unknown whether generalized vascular dysfunction precedes the development of kidney disease. Therefore, we studied myogenic constriction and endothelium-mediated dilatory responses in two inbred Fawn-Hooded (FH) rat strains, one of which spontaneously develops hypertension, proteinuria, and glomerulosclerosis (FHH), whereas the other (FHL) does not. Small renal, mesenteric resistance arteries and thoracic aorta isolated from FH rats before (7 wk old) and after the development of mild proteinuria (12 wks old) were mounted in perfused and isometric set-ups, respectively. Myogenic response, endothelium-dependent relaxation, and the contribution of endothelium-mediated dilatory compounds were studied using their respective inhibitors. Myogenic reactivity was assessed constructing pressure-diameter curves in the presence and absence of calcium. At the age of 7 wk, renal arteries isolated from kidneys of FHH rats developed significantly lower myogenic tone compared with FHL, most likely because of excessive cyclo-oxygenase 1-mediated production of constrictive prostaglandins. Consequently, young FHH demonstrated reduced maximal myogenic tone (22 ± 4.8 vs. 10.8 ± 2.0%, P = 0.03) and the peak myogenic index (−6.9 ± 4.8 vs. 0.6 ± 0.8%/mmHg, P = 0.07 for FHL vs. FHH, respectively). Active myogenic curves obtained in mesenteric arteries isolated from 7-wk-old rats did not differ between either strain, demonstrating a similar level of systemic myogenic tone in FHL and FHH rats. Therefore, before any renal end-organ damage is present, myogenic response seems selectively impaired in renal vasculature of FHH rats. Aortic reactivity did not differ between FHL and FHH at the time points studied. The present study shows that vascular dysfunction in both small renal and systemic arteries precedes renal end-organ damage in a spontaneous model of hypertension-associated renal damage. These early vascular changes might be potentially involved in the increased susceptibility of FHH rats to renal injury.
8-pCPT-cGMP stimulates αβγ-ENaC activity in oocytes as an external ligand requiring specific nucleotide moieties
Authors: Nie Hong-Guang , Zhang Wei , Han Dong-Yun , Li Qing-Nan , Li Jun , Zhao Run-Zhen , Su Xue-Feng , Peng Ji-Bin , Ji Hong-Long
Published: December 2009

Epithelial sodium channels (ENaC) are regulated by protein kinase A, in addition to a broad spectrum of other protein kinases. It is not clear whether cGMP/PKG signaling might regulate ENaC activity. We examined the responses of αβγ-ENaC channels expressed in Xenopus oocytes to 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP), a cell-permeable cGMP analog. This compound stimulated human αβγ-ENaC activity in a dose-dependent fashion, but cell-impermeable cGMP had no effect. Similar stimulatory effects of cGMP were observed in oocytes expressing either mouse or rat αβγ-ENaC channels. The identical ion selectivity and amiloride sensitivity of the 8-pCPT-cGMP-activated currents to those of αβγ-ENaC channels suggest that the cGMP-activated currents are associated with expressed ENaC. The PKGI activator Sp isomer of β-phenyl-1, N2-etheno-8-bromo-cGMP did not elicit a rise in ENaC current and that the 8-pCPT-cGMP-induced activation of ENaC channels was blocked by incubating oocytes with a PKG inhibitor, but not with other cGMP-sensitive kinase inactivators for PKA, MEK, MAP, and PKC. Surprisingly, both site-directed mutation of putative consensus PKG phosphorylation sites and truncation of entire cytosolic NH2- and COOH-terminal tails did not alter the response to 8-pCPT-cGMP. The ENaC activity was activated to the same extent by 8-pCPT-cGMP in cells in which PKGII expression was knocked down using small interfering RNA. Analog to 8-CPT-cAMP, 8-pCPT-cGMP was capable of activating ENaC in the identical manner in cell-free outside-out patches. We conclude that the rapid upregulation of human αβγ-ENaC activity in oocytes by external 8-pCPT-cGMP and 4-chlorothiolphenol-cAMP depends on the para-chlorophenylthiol and the hydroxy groups, and 8-pCPT-cGMP may serve as a novel ENaC ligand in addition to activating PKG signal.
Potential involvement of P2Y2receptor in diuresis of postobstructive uropathy in rats
Authors: Zhang Yue , Kohan Donald E. , Nelson Raoul D. , Carlson Noel G. , Kishore Bellamkonda K.
Published: December 2009

AVP resistance of the medullary collecting duct (mCD) in postobstructive uropathy (POU) has been attributed to increased production of PGE2. P2Y2receptor activation causes production of PGE2by the mCD. We hypothesize that increased P2Y2receptor expression and/or activity may contribute to the diuresis of POU. Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 h followed by release (BUO/R, n = 17) or sham operation (SHM/O, n = 15) and euthanized after 1 wk or 12 days. BUO/R rats developed significant polydipsia, polyuria, urinary concentration defect, and increased urinary PGE2and decreased aquaporin-2 protein abundance in the inner medulla compared with SHM/O rats. After BUO/R, the relative mRNA expression of P2Y2and P2Y6receptors was increased by 2.7- and 4.9-fold, respectively, without significant changes in mRNA expression of P2Y1or P2Y4receptor. This was associated with a significant 3.5-fold higher protein abundance of the P2Y2receptor in BUO/R than SHM/O rats. When freshly isolated mCD fractions were challenged with different types of nucleotides (ATPγS, ADP, UTP, or UDP), BUO/R and SHM/O rats responded to only ATPγS and UTP and released PGE2, consistent with involvement of the P2Y2, but not P2Y6, receptor. ATPγS- or UTP-stimulated increases in PGE2were much higher in BUO/R (3.20- and 2.28-fold, respectively, vs. vehicle controls) than SHM/O (1.68- and 1.30-fold, respectively, vs. vehicle controls) rats. In addition, there were significant 2.4- and 2.1-fold increases in relative mRNA expression of prostanoid EP1and EP3receptors, respectively, in the inner medulla of BUO/R vs. SHM/O rats. Taken together, these data suggest that increased production of PGE2by the mCD in POU may be due to increased expression and activity of the P2Y2receptor. Increased mRNA expression of EP1and EP3receptors in POU may also help accentuate PGE2-induced signaling in the mCD.
Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure
Authors: Kim Hyun Ju , Vaziri Nosratola D.
Published: December 2009

Oxidative stress and inflammation are constant features and major mediators of progression of chronic kidney disease (CKD). Nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against tissue injury by orchestrating antioxidant and detoxification responses to oxidative and electrophilic stress. While sources of oxidative stress and inflammation in the remnant kidney have been extensively characterized, the effect of CKD on Nrf2 activation and expression of its downstream gene products is unknown and was investigated. Subgroups of male Sprague-Dawley rats were subjected to 5/6 nephrectomy or sham operation and observed for 6 or 12 wk. Kidneys were then harvested, and Nrf2 activity and its downstream target gene products (antioxidant and phase II enzymes) were assessed. In addition, key factors involved in promoting inflammation and oxidative stress were studied. In confirmation of earlier studies, rats with chronic renal failure exhibited increased lipid peroxidation, glutathione depletion, NF-κB activation, mononuclear cell infiltration, and upregulation of monocyte chemoattractant protein-1, NAD(P)H oxidase, cyclooxygenase-2, and 12-lipoxygenase in the remnant kidney pointing to oxidative stress and inflammation. Despite severe oxidative stress and inflammation, remnant kidney tissue Nrf2 activity (nuclear translocation) was mildly reduced at 6 wk and markedly reduced at 12 wk, whereas the Nrf2 repressor Keap1 was upregulated and the products of Nrf2 target genes [catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase] were reduced or unchanged at 6 wk and significantly diminished at 12 wk. Thus oxidative stress and inflammation in the remnant kidney are compounded by conspicuous impairment of Nrf2 activation and consequent downregulation of the antioxidant enzymes.
Quantitative analysis of exercise-induced enhancement of early- and late-systolic retrograde coronary blood flow
Authors: Bender Shawn B. , van Houwelingen Marc J. , Merkus Daphne , Duncker Dirk J. , Laughlin M. Harold
Published: December 2009

Coronary blood flow (CBF) is reduced and transiently reversed during systole via cardiac contraction. Cardiac contractility, coronary tone, and arterial pressure each influence systolic CBF (CBFSYS), particularly by modulating the retrograde component of CBFSYS. The effect of concurrent changes in these factors on CBFSYS during dynamic exercise has not been examined. Using chronically instrumented swine, we hypothesized that dynamic exercise enhances retrograde CBFSYS. Phasic CBF was examined at rest and during treadmill exercise [2–5 miles/h (mph)]. Absolute values of mean CBF over the cardiac cycle (CBFCYCLE) as well as mean CBF in diastole (CBFDIAS) and mean CBFSYS were increased by exercise, while relative CBFDIAS and CBFSYS expressed as percentage of mean CBFCYCLE were principally unchanged. Early retrograde CBFSYS was present at rest and increased in magnitude (−33 ± 4 ml/min) and as a percent of CBFCYCLE (−0.6 ± 0.1%) at 5 mph. This reversal was transient, comprising 3.7 ± 0.3% of cardiac cycle duration at 5 mph. Our results also reveal that moderately intense exercise (>3 mph) induced a second CBF reversal in late systole before aortic valve closure. At 5 mph, late retrograde CBFSYS amounted to −53 ± 11 ml/min (−3.1 ± 0.7% of CBFCYCLE) while occupying 11.1 ± 0.3% of cardiac cycle duration. Wave-intensity analysis revealed that the second flow reversal coincided with an enhanced aortic forward-going decompression wave (vs. rest). Therefore, our data demonstrate a predictable increase in early-systolic CBF reversal during exercise and additionally that exercise induces a late-systolic CBF reversal related to the hemodynamic effects of left ventricular relaxation that is not predictable using current models of phasic CBF.
Theta Oscillations in Primate Prefrontal and Anterior Cingulate Cortices in Forewarned Reaction Time Tasks
Authors: Tsujimoto Toru , Shimazu Hideki , Isomura Yoshikazu , Sasaki Kazuo
Published: December 2009

Previously, we introduced a monkey model for human frontal midline theta oscillations as a possible neural correlate of attention. It was based on homologous theta oscillations found in the monkey's prefrontal and anterior cingulate cortices (areas 9 and 32) in a self-initiated hand-movement task. However, it has not been confirmed whether theta activity in the monkey model consistently appears in other situations demanding attention. Here, we examined the detailed properties of theta oscillations in four variations of forewarned reaction time tasks with warning (S1) and imperative (S2) stimuli. We characterized the theta oscillations generated exclusively in areas 9 and 32, as follows: 1) in the S1-S2 interval where movement preparation and reward expectation were presumably involved, the theta power was higher than in the pre-S1 period; 2) in the no-go trials of go/no-go tasks instructed by S1, the theta power in the S1-S2 interval was lower than in the pre-S1 period in an asymmetrical reward condition, whereas it was moderately higher in a symmetrical condition; 3) the theta power after reward delivery was higher than in the unrewarded trials; 4) the theta power in the pre-S1 period was higher than in the resting condition; and 5) when the monkey had to guess the S1-S2 duration internally without seeing S2, the theta power in the pre-S1 period was higher than in the original S1-S2 experiment. These findings suggest that attentional loads associated with different causes can induce the same theta activity, thereby supporting the consistency of attention-dependent theta oscillations in our model.
Common Fixed Point Theorem of Two Mappings Satisfying a Generalized Weak Contractive Condition
Authors: Abbas M. , Khan M. Ali
Published: December 2009

Existence of common fixed point for two mappings which satisfy a generalized weak contractive condition is established. As a consequence, a common fixed point result for mappings satisfying a contractive
condition of integral type is obtained. Our results generalize, extend, and unify several well‐known comparable results in literature.
A Novel Platelet Activating Factor Receptor Antagonist Reduces Cell Infiltration and Expression of Inflammatory Mediators in Mice Exposed to Desiccating Conditions after PRK
Authors: Esquenazi Salomon , He Jiucheng , Li Na , Bazan Nicolas G. , Esquenazi Isi , Bazan Haydee E. P.
Published: December 2009

Purpose. To study the contribution of a novel PAF receptor antagonist LAU-0901 in the modulation of the increased inflammatory response in mice exposed to dessicating conditions (DE) after PRK.Methods. Eighty 13-14 week old female Balb/C mice were used. They were divided into two groups: One group was treated with LAU-0901 topical drops. The other group was treated with vehicle. In each group ten mice served as controls and ten were placed in DE. The other twenty mice underwent bilateral PRK and were divided in two additional groups: ten mice remained under normal conditions (NC) and the other ten were exposed to DE. After 1 week all animals underwent in vivo confocal microscopy, immunostaining and western blotting analysis.Results. Confocal microscopy showed an increased number of reflective structures in the corneal epithelium after PRK and exposure to DE in eyes treated with vehicle as compared to eyes treated with LAU-0901. Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA cells was observed after PRK and exposure to DE in eyes treated with LAU-0901. Discussion: Exposure of mice to a DE after PRK increases the epithelial turnover rate. PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE.
Weak and Strong Forms of ω‐Continuous Functions
Authors: Al-Omari Ahmad , Noiri Takashi , Noorani Mohd. Salmi Md.
Published: December 2009

We introduce weak and strong forms of ω‐continuous
functions, namely, θ‐ω‐continuous and strongly θ‐ω‐continuous functions, and investigate their fundamental properties.
Magnetic Properties of Co6On (n = 0–9, 12)
Authors: Tamulienė Jelena , Vaišnoras Rimantas , Badenes Goncal , Balevičius Leonas-Mindaugas
Published: December 2009

We present quantum chemical investigations on magnetic properties of several Co6On (n = 0–9, 12) nanoparticles. The results of calculations show, that only Co6, and Co6O8 particles display paramagnetic properties while other nanoparticles investigated reveal diamagnetic ones. The reason of the derivative paramagnetizability is discussed here. Calculations reveal that the stability of these compounds increases with the increase of the number of O atoms. The limit when the future increase of oxygen atoms does not change binding energy per atoms remarkably is found. The reason why the O atoms could stabilize the Co nanoparticles and change magnetic properties of them is discussed.
Further Results Concerning Delay‐Dependent H∞ Control for Uncertain Discrete‐Time Systems with Time‐Varying Delay
Authors: Zong Guangdeng , Hou Linlin , Yang Hongyong
Published: December 2009

This paper addresses the problem of H∞ control for uncertain discrete‐time systems with time‐varying delays. The system under consideration is subject to time‐varying norm‐bounded parameter uncertainties in both the state and controlled output. Attention is focused on the design of a memoryless state feedback controller, which guarantees that the resulting closed‐loop system is asymptotically stable and reduces the effect of the disturbance input on the controlled output to a prescribed level irrespective of all the admissible uncertainties. By introducing some slack matrix variables, new delay‐dependent conditions are presented in terms of linear matrix inequalities (LMIs). Numerical examples are provided to show the reduced conservatism and lower computational burden than the previous results.
A Novel Flow‐Perfusion Bioreactor Supports 3D Dynamic Cell Culture
Authors: Sailon Alexander M. , Allori Alexander C. , Davidson Edward H. , Reformat Derek D. , Allen Robert J. , Warren Stephen M.
Published: December 2009

Background. Bone engineering requires thicker three‐dimensional constructs than the maximum thickness supported by standard cell‐culture techniques (2 mm). A flow‐perfusion bioreactor was developed to provide chemotransportation to thick (6 mm) scaffolds.
Methods. Polyurethane scaffolds, seeded with murine preosteoblasts, were loaded into a novel bioreactor. Control scaffolds remained in static culture. Samples were harvested at days 2, 4, 6, and 8 and analyzed for cellular distribution, viability, metabolic activity, and density at the periphery and core. Results. By day 8, static scaffolds had a periphery cell density of 67% ± 5.0%, while in the core it was 0.3% ± 0.3%. Flow‐perfused scaffolds demonstrated peripheral cell density of 94% ± 8.3% and core density of 76% ± 3.1% at day 8. Conclusions. Flow perfusion provides chemotransportation to thick scaffolds. This system may permit high throughput study of 3D tissues in vitro and enable prefabrication of biological constructs large enough to solve clinical problems.
Schauder Fixed Point Theorem in Spaces with Global Nonpositive Curvature
Authors: Niculescu Constantin P. , Rovenţa Ionel
Published: December 2009

The Schauder fixed point theorem is extended to the context of metric spaces with global nonpositive curvature. Some applications are included.
Thermodynamic Properties of Hydrogen + Tetra-n-Butyl Ammonium Bromide Semi-Clathrate Hydrate
Authors: Hashimoto Shunsuke , Tsuda Takaaki , Ogata Kyohei , Sugahara Takeshi , Inoue Yoshiro , Ohgaki Kazunari
Published: December 2009

Thermodynamic stability and hydrogen occupancy on the hydrogen + tetra-n-butyl ammonium bromide semi-clathrate hydrate were investigated by means of Raman spectroscopic and phase equilibrium measurements under the three-phase equilibrium condition. The structure of mixed gas hydrates changes from tetragonal to another structure around 95 MPa and 292 K depending on surrounding hydrogen fugacity. The occupied amount of hydrogen in the semi-clathrate hydrate increases significantly associated with the structural transition. Tetra-n-butyl ammonium bromide semi-clathrate hydrates can absorb hydrogen molecules by a pressure-swing without destroying the hydrogen bonds of hydrate cages at 15 MPa or over.
Factors Associated with Hepatitis A Vaccination Receipt in One-Year-Olds in the State of Michigan
Authors: Weston Andrea L. , Enger Kyle S.
Published: December 2009

The objectives of this study were to determine factors associated with hepatitis A vaccination and to assess overall hepatitis A vaccination coverage levels among one-year-olds in Michigan. The study population was the first hepatitis A vaccination-eligible birth cohort (n=134 226) enrolled in the Michigan Care Improvement Registry (MCIR) after 2006 recommendations were made to routinely vaccinate all one-year-olds. All children whose first birthday occurred on or between May 1, 2006 and April 31, 2007 were included in the study population. Racial/ethnic minorities had increased odds of receiving the hepatitis A vaccination in Michigan, and Medicaid and WIC status modified this relationship. Fully understanding these relationships will be useful in targeting vaccination outreach and education programs.
Kinematic Design of a Translational Parallel Manipulator with Fine Adjustment of Platform Orientation
Authors: Tanabe Masataka , Takeda Yukio
Published: December 2009

We present a kinematic design of a translational parallel manipulator with fine adjustment capability of platform orientation. In order to clarify possible kinematic structures for it, structural synthesis of fully decoupled mechanism and partially decoupled mechanism both with six degrees of freedom (dof) was carried out based on the synthesis results of translational and rotational parallel mechanisms with three dof. All possible kinematic structures were obtained. Of these, one partially decoupled mechanism was selected and a kinematic design of a prototype manipulator was done. Its characteristics in terms of workspace, singularity, orientation adjustment capability, and coupling characteristics between translational and rotational displacement were discussed with experimental results regarding fine adjustment capability of platform orientation.
Competition of Superconductivity and Charge Density Waves in Cuprates: Recent Evidence and Interpretation
Authors: Gabovich A. M. , Voitenko A. I. , Ekino T. , Li Mai Suan , Szymczak H. , Pękała M.
Published: December 2009

Explicit and implicit experimental evidence for charge density wave (CDW) presence in high-Tcsuperconducting oxides is analyzed. The theory of CDW superconductors is presented. It is shown that the observed pseudogaps and dip-hump structures in tunnel and photoemission spectra are manifestations of the same CDW gapping of the quasiparticle density of states. Huge pseudogaps are transformed into modest dip-hump structures at low temperatures,T, when the electron spectrum superconducting gapping dominates. Heat capacity jumps at the superconducting critical temperature and the paramagnetic limit are calculated for CDW superconductors. For a certain range of parameters, the CDW state in ad-wave superconductor becomes reentrant withT, the main control quantity being a portion of dielectrcally gapped Fermi surface. It is shown that in the weak-coupling approximation, the ratio between the superconducting gap at zero temperatureΔ(T=0)andTchas the Bardeen-Cooper-Schrieffer value fors-wave Cooper pairing and exceeds the corresponding value ford-wave pairing of CDW superconductors. Thus, large experimentally found values2Δ(T=0)/Tc≈5÷8are easily reproduced with reasonable input parameter values of the model. The conclusion is made that CDWs play a significant role in cuprate superconductivity.
Arginase in Parasitic Infections: Macrophage Activation, Immunosuppression, and Intracellular Signals
Authors: Stempin Cinthia C. , Dulgerian Laura R. , Garrido Vanina V. , Cerban Fabio M.
Published: December 2009

A type 1 cytokine-dependent proinflammatory response inducing classically activated macrophages (CaMϕs) is crucial for parasite control during protozoan infections but can also contribute to the development of immunopathological disease symptoms. Type 2 cytokines such as IL-4 and IL-13 antagonize CaMϕs inducing alternatively activated macrophages (AaMϕs) that upregulate arginase-1 expression. During several infections, induction of arginase-1-macrophages was showed to have a detrimental role by limiting CaMϕ-dependent parasite clearance and promoting parasite proliferation. Additionally, the role of arginase-1 in T cell suppression has been explored recently. Arginase-1 can also be induced by IL-10 and transforming growth factor-β(TGF-β) or even directly by parasites or parasite components. Therefore, generation of alternative activation states of macrophages could limit collateral tissue damage because of excessive type 1 inflammation. However, they affect disease outcome by promoting parasite survival and proliferation. Thus, modulation of macrophage activation may be instrumental in allowing parasite persistence and long-term host survival.
Quantitative Estimation of the Nonstationary Behavior of Neural Spontaneous Activity
Authors: Destro-Filho João-Batista , Estombelo-Montesco Carlos-Alberto , Murta-Junior Luiz-Otavio , Martinoia Sergio , Chiappalone Michela , Moreira-Marques Suelen , Neves Amanda F.
Published: December 2009

The “stationarity time” (ST) of neuronal spontaneous activity signals of rat embryonic cortical cells, measured by means of a planar Multielectrode Array (MEA), was estimated based on the “Detrended Fluctuation Analysis” (DFA). The ST is defined as the mean time interval during which the signal under analysis keeps its statistical characteristics constant. An upgrade on the DFA method is proposed, leading to a more accurate procedure. Strong statistical correlation between the ST, estimated from the Absolute Amplitude of Neural Spontaneous Activity (AANSA) signals and the Mean Interburst Interval (MIB), calculated by classical spike sorting methods applied to the interspike interval time series, was obtained. In consequence, the MIB may be estimated by means of the ST, which further includes relevant biological information arising from basal activity. The results point out that the average ST of MEA signals lies between 2-3 seconds. Furthermore, it was shown that a neural culture presents signals that lead to different statistical behaviors, depending on the relative geometric position of each electrode and the cells. Such behaviors may disclose physiological phenomena, which are possibly associated with different adaptation/facilitation mechanisms.
Contribution of Radiation Hybrids to Genome Mapping in Domestic Animals
Authors: Faraut T. , de Givry S. , Hitte C. , Lahbib-Mansais Y. , Morisson M. , Milan D. , Schiex T. , Servin B. , Vignal A. , Galibert F. , Yerle M.
Published: December 2009

Radiation hybrid mapping has emerged in the end of the 1990s as a successful and complementary approach to map genomes, essentially because of its ability to bridge the gaps between genetic and clone-based physical maps, but also using comparative mapping approaches, between ‘gene-rich’ and ‘gene-poor’ maps. Since its early development in human, radiation hybrid mapping played a pivotal role in the process of mapping animal genomes, especially mammalian ones. We review here all the different steps involved in radiation hybrid mapping from the constitution of panels to the construction of maps. A description of its contribution to whole genome maps with a special emphasis on domestic animals will also be presented. Finally, current applications of radiation hybrid mapping in the context of whole genome assemblies will be described.
Fluorescence in situ Hybridization Applied to Domestic Animal Cytogenetics
Authors: Rubes J. , Pinton A. , Bonnet-Garnier A. , Fillon V. , Musilova P. , Michalova K. , Kubickova S. , Ducos A. , Yerle M.
Published: December 2009

The aim of this article is not to present an exhaustive review of molecular cytogenetics applications in domestic animal species, but more to illustrate the considerable contribution of these approaches in diagnostics and research in economically important species. A short presentation of the main applications of molecular cytogenetics in humans points out the domains in which it has become an essential tool and underlines the specificities attached to this species in comparison to farm animals. This article is devoted to outlining the current resources available in domestic species and to some examples of fluorescence in situ hybridization applications in the cattle, pig, horse and avian species. From a clinical point of view, these examples illustrate the advantages of FISH for the study of chromosomal abnormalities (identification, characterization and estimation of their effects). Other applications of molecular cytogenetics are also illustrated, particularly ZOO-FISH, an approach which allows the determination of chromosome homologies between species. Finally, a specific emphasis was placed on the usefulness of molecular cytogenetics for the analysis of species such as poultry, which harbour a complex karyotype.
Chromosome Evolution in Domestic Bovids as Revealed by Chromosome Banding and FISH-Mapping Techniques
Authors: Iannuzzi L. , King W.A. , Di Berardino D.
Published: December 2009

The present review summarizes the basic cytogenetic information available pertaining to the most important Bovidae species, namely cattle, buffalo, sheep and goat, with the aim of tracing their evolutionary relationships and to provide – for the first time – the hypothetical ancestral karyotype of the Bovinae-Caprinae subfamilies, also in relation to the other nondomestic species which are included in this important taxonomic family. Evolution of the Bovinae-Caprinae autosomes and gonosomes is discussed on the basis of the most recent advances in chromosome banding, linkage studies, FISH-mapping and molecular information.
Molecular Cytogenetics and Gene Mapping in Sheep (Ovis aries, 2n = 54)
Authors: Goldammer T. , Di Meo G.P. , Lühken G. , Drögemüller C. , Wu C.H. , Kijas J. , Dalrymple B.P. , Nicholas F.W. , Maddox J.F. , Iannuzzi L. , Cockett N.E.
Published: December 2009

The development of a completely annotated sheep genome sequence is a key need for understanding the phylogenetic relationships and genetic diversity among the many different sheep breeds worldwide and for identifying genes controlling economically and physiologically important traits. The ovine genome sequence assembly will be crucial for developing optimized breeding programs based on highly productive, healthy sheep phenotypes that are adapted to modern breeding and production conditions. Scientists and breeders around the globe have been contributing to this goal by generating genomic and cDNA libraries, performing genome-wide and trait-associated analyses of polymorphism, expression analysis, genome sequencing, and by developing virtual and physical comparative maps. The International Sheep Genomics Consortium (ISGC), an informal network of sheep genomics researchers, is playing a major role in coordinating many of these activities. In addition to serving as an essential tool for monitoring chromosome abnormalities in specific sheep populations, ovine molecular cytogenetics provides physical anchors which link and order genome regions, such as sequence contigs, genes and polymorphic DNA markers to ovine chromosomes. Likewise, molecular cytogenetics can contribute to the process of defining evolutionary breakpoints between related species. The selective expansion of the sheep cytogenetic map, using loci to connect maps and identify chromosome bands, can substantially contribute to improving the quality of the annotated sheep genome sequence and will also accelerate its assembly. Furthermore, identifying major morphological chromosome anomalies and micro-rearrangements, such as gene duplications or deletions, that might occur between different sheep breeds and other Ovis species will also be important to understand the diversity of sheep chromosome structure and its implications for cross-breeding. To date, 566 loci have been assigned to specific chromosome regions in sheep and the new cytogenetic map is presented as part of this review. This review will also summarize the current cytogenomic status of the sheep genome, describe current activities in the sheep cytogenomics research sector, and will discuss the cytogenomics data in context with other major sheep genomics projects.
Molecular Cytogenetics and Comparative Mapping in Goats (Capra hircus, 2n = 60)
Authors: Schibler L. , Di Meo G.P. , Cribiu E.P. , Iannuzzi L.
Published: December 2009

Few goat genome analysis projects have been developed in the last 10 years. The aim of this review was to compile and update all available cytogenetic mapping data, according to the last goat chromosome nomenclature, as well as human and cattle whole genome sequences. In particular, human regions homologous to most of the FISH-mapped microsatellites were identified in silico. This new goat cytogenetic map made it possible to refine delineation of conserved segments relative to the human and cattle genomic sequence. These improvements did not lead to detection of major new rearrangements within ruminants but confirmed the good conservation of synteny and the numerous intrachromosomal rearrangements observed between goats and humans.
Fragile Sites in Domestic Animal Chromosomes: Molecular Insights and Challenges
Authors: Riggs P.K. , Rønne M.
Published: December 2009

Fragile sites are intriguing cytogenetic phenomena that have been extensively investigated in human and laboratory animal chromosomes over the past 40 years, but domestic animal species have been studied sporadically. Interest in the field has been recently renewed as increasing numbers of fragile site regions are cloned and characterized at the molecular level. Despite much effort, mechanisms by which specific DNA sequence confers fragility to a chromosome region remain unclear. Recent advancements in sequencing and mapping of domestic animal genomes provide tools for molecular characterization of fragile sites in animal chromosomes. Future comparative efforts may contribute insight into both the mechanisms that underlie chromosome fragility, and forces that drive rearrangements observed throughout evolution, and somatic changes that can result in disease or impair fertility.
Classical and Molecular Cytogenetics of Disorders of Sex Development in Domestic Animals
Authors: Villagómez D.A.F. , Parma P. , Radi O. , Di Meo G. , Pinton A. , Iannuzzi L. , King W.A.
Published: December 2009

The association of abnormal chromosome constitutions and disorders of sex development in domestic animals has been recorded since the beginnings of conventional cytogenetic analysis. Deviated karyotypes consisting of abnormal sex chromosome sets (e.g. aneuploidy) and/or the coexistence of cells with different sex chromosome constitutions (e.g. mosaicism or chimerism) in an individual seem to be the main causes of anomalies of sex determination and sex differentiation. Molecular cytogenetics and genetics have increased our understanding of these pathologies, where human and mouse models have provided a substantial amount of knowledge, leading to the discovery of a number of genes implicated in mammalian sex determination and differentiation. Additionally, other genes, which appeared to be involved in ovary differentiation, have been found by investigations in domestic species such as the goat. In this paper, we present an overview of the biology of mammalian sex development as a scientific background for better understanding the body of knowledge of the clinical cytogenetics of disorders of sex development in domestic animals. An attempt to summarize of what has been described in that particular subject of veterinary medicine for each of the main mammalian domestic species is presented here.
Characterization of the Bovine Pseudoautosomal Region and Comparison with Sheep, Goat, and Other Mammalian Pseudoautosomal Regions
Authors: Das P.J. , Chowdhary B.P. , Raudsepp T.
Published: December 2009

The pseudoautosomal region (PAR) is a small region of sequence homology between mammalian X and Y chromosomes and is needed for sex chromosome segregation in male meiosis. The region, though studied as yet in only a few species, shows considerable variation in size and gene content. We have constructed a medium-density gene map for the cattle PAR and the adjacent X-specific region by isolating and mapping 18 BAC clones which contain 20 PAR- and 5 X-specific genes. One BAC clone containing TBL1XY and GPR143 spanned the recently demarcated bovine pseudoautosomal boundary (PAB). Comparing the gene map of cattle PAR with the high-resolution maps of human, horse, and dog PAR allowed to estimate that the size of cattle PAR is approximately 5–9 Mb. BAC end sequence analysis showed that there is a gradient of decreasing GC content from PARter towards the PAB which is consistent with findings in human, mouse, and horse. The 20 PAR- and 5 X-specific cattle genes were mapped also in goat and sheep, showing that PAR in the 3 species is similar in size, gene content, and gene order. For the first time the PAB was determined in goat sex chromosomes. Comparison of cattle, goat, and sheep PAR with homologous regions on human and horse X chromosomes showed a high degree of linkage conservation between all species. However, the most terminal human, horse, and dog PAR gene, PLCXD1, is X-specific in ruminants. Since the human/horse linkage group containing PLCXD1 is of ancestral origin, the location of PLCXD1 can be considered as a de novo event in ruminant sex chromosome evolution. The gene map of the cattle PAR adds to our knowledge about the comparative organization and evolution of the eutherian PAR and aids the sequencing, sequence assembly, and annotation of the terminal region of BTAXq.
Polymorphic Heterochromatic Segments in Japanese Quail Microchromosomes
Authors: Krasikova A. , Daks A. , Zlotina A. , Gaginskaya E.
Published: December 2009

Using highly extended lampbrush chromosomes from diplotene oocytes, we have examined the distribution of heterochromatin protein 1 β (HP1β) and histone H3 modifications on chicken (Gallus gallus) and Japanese quail (Coturnix japonica) (2n = 78) microchromosomes. Acrocentric microchromosomes of chicken and submetacentric microchromosomes of quail differ in several morphological features. In addition to pericentromeric and subtelomeric blocks of constitutive heterochromatin, which are enriched in HP1β protein and repressive histone modifications, not completely condensed but heterochromatic segments were found to be an attribute of the short arms of submetacentric microchromosomes in Japanese quail. These heterochromatic regions are variable in length and do not form chiasmata in female germ cells. Dissimilarity in the centromere positions in chicken and Japanese quail microchromosomes is proposed to be due to the accumulation of repetitive sequences on the short arms of quail microchromosomes. Transcriptional activation of polymorphic heterochromatic segments of quail microchromosomes during the lampbrush stage is demonstrated.