bluuebunny/crossref_metadata_2025 huggingface dataset:
Target animal safety study of meloxicam administered via transmucosal oral spray (Promist® technology) for 6 months in dogs
Authors: Hare J. E. , Niemuller C. A. , Petrick D. M.
Published: September 2012

This study evaluated the safety of meloxicam administered via transmucosal oral spray (TMOS) at 1, 2, 3 and 5 times the maximum proposed dose for 6 months in dogs. After baseline assessments, 40 Beagles (20 M, 20 F) were randomized to gender‐balanced groups administered either water or meloxicam TMOS at 1, 2, 3 and 5 times the maximum proposed dose once daily for 26 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose site observations. Periodic evaluations were made of body weight, physical examination, clinical pathology, urinalysis, buccal mucosal bleeding time (BMBT) and gastroduodenal endoscopy. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on tissues from dogs in groups 0X and 5X and from selected tissues in other dose groups. Clinical signs of previously reported NSAID‐associated gastrointestinal upset were noted with higher frequency in meloxicam‐dosed animals than in controls. Despite the presence of statistically significant effects on some clinicopathological variables, no toxicologically relevant dose‐associated effects were determined on these or on food consumption, dose site observations, body weight, physical examination, urinalysis, BMBT, endoscopic examination or gross and histopathological examination of necropsy tissues.
AXING WICKSELL'S DURABILITY RESULT
Authors: Steedman Ian
Published: September 2012

In the course of discussing Åkerman's problem, Wicksell maintained that, when capitalists can choose the length of life of a fixed capital good, the chosen lifetime will be positively related to the real wage. It is shown that this conclusion collapses once we drop Wicksell's extreme assumption that the capital good is made by unassisted labour.
Antigenic differences between the EG95‐related proteins from Echinococcus granulosus G1 and G6 genotypes: implications for vaccination
Authors: Alvarez Rojas C. A. , Gauci C. G. , Lightowlers M. W.
Published: September 2012

Cystic echinococcosis caused by Echinococcus granulosus remains an important and neglected issue in public health. The study of the likely efficacy of the currently available EG95 vaccine against other genotypes of the parasite is important to improve the vaccine as a potential tool to be used in control programmes. The recombinant vaccine EG95‐1G1 was developed based on the G1 genotype of E. granulosus. Characterization of the eg95 gene family in the G6 genotype by genomic DNA cloning previously produced the first unequivocal information about the composition of the gene family in a different genotype. The information was used in this study to predict and express two EG95‐related proteins from the G6 genotype as recombinants, for assessment of their capacity to bind antibodies raised in sheep vaccinated with the EG95‐1G1 vaccine. The proteins (EG95‐1G6 and EG95‐5G6) from the G6 genotype of E. granulosus were unable to bind all the antibodies raised by sheep vaccinated with EG95‐1G1. Differences in the amino acid sequence of EG95‐related proteins from G6 and likely the differences in the encoded FnIII domain may be responsible for changes in the conformation of these epitopes.
The AAA ATPase VPS4/SKD1 Regulates Endosomal Cholesterol Trafficking Independently of ESCRT‐III
Authors: Du Ximing , Kazim Abdulla S. , Dawes Ian W. , Brown Andrew J. , Yang Hongyuan
Published: September 2012

The exit of low‐density lipoprotein derived cholesterol (LDL‐C) from late endosomes (LE)/lysosomes (Ly) is mediated by Niemann–Pick C1 (NPC1), a multipass integral membrane protein on the limiting membranes of LE/Ly, and by NPC2, a cholesterol‐binding protein in the lumen of LE/Ly. NPC2 delivers cholesterol to the N‐terminal domain of NPC1, which is believed to insert cholesterol into the limiting membrane for subsequent transport to other subcellular organelles. Few cytoplasmic factors have been identified to govern cholesterol efflux from LE/Ly, and much less is known about the underlying molecular mechanisms. Here we establish VPS4, an AAA ATPase that has a well‐established role in disassembling the ESCRT (endosomal sorting complex required for transport)‐III polymer, as an important regulator of endosomal cholesterol transport. Knocking down VPS4 in HeLa cells resulted in prominent accumulation of LDL‐C in LE/Ly, and disrupted cholesterol homeostatic responses at the endoplasmic reticulum. The level and localization of NPC1 and NPC2 appeared to be normal in VPS4 knockdown cells. Importantly, depleting any of the ESCRT‐III components did not exert a significant effect on endosomal cholesterol transport. Our results thus identify an important cytoplasmic regulator of endosomal cholesterol trafficking and represent the first functional separation of VPS4 from ESCRT‐III.
Validation of an Improved Method to Calculate the Orientation and Magnitude of Pedicle Screw Bending Moments
Authors: Freeman Andrew L. , Fahim Mina S. , Bechtold Joan E.
Published: September 2012

Previous methods of pedicle screw strain measurement have utilized complex, time consuming methods of strain gauge application, experience high failure rates, do not effectively measure resultant bending moments, and cannot predict moment orientation. The purpose of this biomechanical study was to validate an improved method of quantifying pedicle screw bending moment orientation and magnitude. Pedicle screws were instrumented to measure biplanar screw bending moments by positioning four strain gauges on flat, machined surfaces below the screw head. Screws were calibrated to measure bending moments by hanging certified weights a known distance from the strain gauges. Loads were applied in 30 deg increments at 12 different angles while recording data from two independent strain channels. The data were then analyzed to calculate the predicted orientation and magnitude of the resultant bending moment. Finally, flexibility tests were performed on a cadaveric motion segment implanted with the instrumented screws to demonstrate the implementation of this technique. The difference between the applied and calculated orientation of the bending moments averaged (±standard error of the mean (SEM)) 0.3 ± 0.1 deg across the four screws for all rotations and loading conditions. The calculated resultant bending moments deviated from the actual magnitudes by an average of 0.00 ± 0.00 Nm for all loading conditions. During cadaveric testing, the bending moment orientations were medial/lateral in flexion–extension, variable in lateral bending, and diagonal in axial torsion. The technique developed in this study provides an accurate method of calculating the orientation and magnitude of screw bending moments and can be utilized with any pedicle screw fixation system.
Modeling Degenerative Disk Disease in the Lumbar Spine: A Combined Experimental, Constitutive, and Computational Approach
Authors: Ayturk Ugur M. , Gadomski Benjamin , Schuldt Dieter , Patel Vikas , Puttlitz Christian M.
Published: September 2012

Using a continuum approach for modeling the constitutive mechanical behavior of the intervertebral disk’s annulus fibrosus holds the potential for facilitating the correlation of morphology and biomechanics of this clinically important tissue. Implementation of a continuum representation of the disk’s tissues into computational models would yield a particularly valuable tool for investigating the effects of degenerative disease. However, to date, relevant efforts in the literature towards this goal have been limited due to the lack of a computationally tractable and implementable constitutive function. In order to address this, annular specimens harvested from a total of 15 healthy and degenerated intervertebral disks were tested under planar biaxial tension. Predictions of a strain energy function, which was previously shown to be unconditionally convex, were fit to the experimental data, and the optimized coefficients were used to modify a previously validated finite element model of the L4/L5 functional spinal unit. Optimization of material coefficients based on experimental results indicated increases in the micro-level orientation dispersion of the collagen fibers and the mechanical nonlinearity of these fibers due to degeneration. On the other hand, the finite element model predicted a progressive increase in the stress generation in annulus fibrosus due to stepwise degeneration of initially the nucleus and then the entire disk. Range of motion was predicted to initially increase with the degeneration of the nucleus and then decrease with the degeneration of the annulus in all rotational loading directions, except for axial rotation. Overall, degeneration was observed to specifically impact the functional effectiveness of the collagen fiber network of the annulus, leading to changes in the biomechanical behavior at both the tissue level and the motion-segment level.
A Quasi-Nonlinear Analysis of the Anisotropic Behaviour of Human Gallbladder Wall
Authors: Li W. G. , Luo X. Y. , Hill N. A. , Ogden R. W. , Smythe A. , Majeed A. W. , Bird N.
Published: September 2012

Estimation of biomechanical parameters of soft tissues from noninvasive measurements has clinical significance in patient-specific modeling and disease diagnosis. In this work, we present a quasi-nonlinear method that is used to estimate the elastic moduli of the human gallbladder wall. A forward approach based on a transversely isotropic membrane material model is used, and an inverse iteration is carried out to determine the elastic moduli in the circumferential and longitudinal directions between two successive ultrasound images of gallbladder. The results demonstrate that the human gallbladder behaves in an anisotropic manner, and constitutive models need to incorporate this. The estimated moduli are also nonlinear and patient dependent. Importantly, the peak stress predicted here differs from the earlier estimate from linear membrane theory. As the peak stress inside the gallbladder wall has been found to strongly correlate with acalculous gallbladder pain, reliable mechanical modeling for gallbladder tissue is crucial if this information is to be used in clinical diagnosis.
A Novel Device to Quantify the Mechanical Properties of Electrospun Nanofibers
Authors: Fee Timothy J. , Dean Derrick R. , Eberhardt Alan W. , Berry Joel L.
Published: September 2012

Mechanical deformation of cell-seeded electrospun matrices plays an important role in cell signaling. However, electrospun biomaterials have inherently complex geometries due to the random deposition of fibers during the electrospinning process. This confounds attempts at quantifying strains exerted on adherent cells during electrospun matrix deformation. We have developed a novel mechanical test platform that allows deposition and tensile testing of electrospun fibers in a highly parallel arrangement to simplify mechanical analysis of the fibers alone and with adherent cells. The device is capable of optically recording fiber strain in a cell culture environment. Here we report on the mechanical and viscoelastic properties of highly parallel electrospun poly(ε-caprolactone) fibers. Force-strain data derived from this device will drive the development of cellular mechanotransduction studies as well as the customization of electrospun matrices for specific engineered tissue applications.
Superbinder SH2 Domains Act as Antagonists of Cell Signaling
Authors: Kaneko Tomonori , Huang Haiming , Cao Xuan , Li Xing , Li Chengjun , Voss Courtney , Sidhu Sachdev S. , Li Shawn S. C.
Published: September 2012

Engineered SH2 domains with high affinity for phosphorylated tyrosine inhibit cell signaling downstream of receptor tyrosine kinases.
Where EGF Receptors Transmit Their Signals
Authors: Lill Nancy L. , Sever Nurettin Ilter
Published: September 2012

Trafficking of activated epidermal growth factor receptors controls the transcriptional response to this oncogenic pathway.
Peptide-Binding Domains: Are Limp Handshakes Safest?
Authors: Haslam Niall J. , Shields Denis C.
Published: September 2012

Engineered high-affinity SH2 domains inhibit signaling and may be evolutionarily unfavorable.
Cell Responses to Growth Factors: The Role of Receptor Tyrosine Kinase Intracellular Domain Fragments
Authors: Carpenter Graham , Pozzi Ambra
Published: September 2012

Proteolysis of receptor tyrosine kinases produces intracellular fragments with distinct roles in growth factor signaling.
Draft Genome Sequence of Halomonas smyrnensis AAD6
T
Authors: Sogutcu Elif , Emrence Zeliha , Arikan Muzzaffer , Cakiris Aris , Abaci Neslihan , Öner Ebru Toksoy , Üstek Duran , Arga Kazim Yalcin
Published: September 2012

Halomonas smyrnensis
AAD6
T
is a Gram-negative, aerobic, exopolysaccharide-producing, and moderately halophilic bacterium that produces levan, a fructose homopolymer with many potential uses in various industries. We report the draft genome sequence of
H. smyrnensis
AAD6
T
, which will accelerate research on the rational design and optimization of microbial levan production.
Complete Genome Sequence of Desulfurococcus fermentans, a Hyperthermophilic Cellulolytic Crenarchaeon Isolated from a Freshwater Hot Spring in Kamchatka, Russia
Authors: Susanti Dwi , Johnson Eric F. , Rodriguez Jason R. , Anderson Iain , Perevalova Anna A. , Kyrpides Nikos , Lucas Susan , Han James , Lapidus Alla , Cheng Jan-Fang , Goodwin Lynne , Pitluck Sam , Mavrommatis Konstantinos , Peters Lin , Land Miriam L. , Hauser Loren , Gopalan Venkat , Chan Patricia P. , Lowe Todd M. , Atomi Haruyuki , Bonch-Osmolovskaya Elizaveta A. , Woyke Tanja , Mukhopadhyay Biswarup
Published: September 2012

Desulfurococcus fermentans
is the first known cellulolytic archaeon. This hyperthermophilic and strictly anaerobic crenarchaeon produces hydrogen from fermentation of various carbohydrates and peptides without inhibition by accumulating hydrogen. The complete genome sequence reported here suggested that
D. fermentans
employs membrane-bound hydrogenases and novel glycohydrolases for hydrogen production from cellulose.
Whole-Genome Sequence of Corynebacterium pseudotuberculosis Strain Cp162, Isolated from Camel
Authors: Hassan Syed Shah , Schneider Maria Paula C. , Ramos Rommel Thiago Jucá , Carneiro Adriana R. , Ranieri Alex , Guimarães Luis Carlos , Ali Amjad , Bakhtiar Syeda Marriam , Pereira Ulisses de Pádua , dos Santos Anderson Rodrigues , Soares Siomar de Castro , Dorella Fernanda , Pinto Anne Cybelle , Ribeiro Dayana , Barbosa Maria Silvanira , Almeida Síntia , Abreu Vinícius , Aburjaile Flávia , Fiaux Karina , Barbosa Eudes , Diniz Carlos , Rocha Flavia S. , Saxena Rashmi , Tiwari Sandeep , Zambare Vasudeo , Ghosh Preetam , Pacheco Luis G. C. , Dowson Christopher G. , Kumar Anil , Barh Debmalya , Miyoshi Anderson , Azevedo Vasco , Silva Artur
Published: September 2012

Corynebacterium pseudotuberculosis
is a pathogen of great veterinary and economic importance, since it affects livestock, mainly sheep and goats, worldwide, together with reports of its presence in camels in several Arabic, Asiatic, and East and West African countries, as well as Australia. In this article, we report the genome sequence of
Corynebacterium pseudotuberculosis
strain Cp162, collected from the external neck abscess of a camel in the United Kingdom.
Analysis of the Genome of Mycobacterium abscessus Strain M94 Reveals an Uncommon Cluster of tRNAs
Authors: Choo Siew Woh , Wong Yan Ling , Leong Mee Lian , Heydari Hamed , Ong Chia Sui , Ng Kee Peng , Ngeow Yun Fong
Published: September 2012

Mycobacterium abscessus
is a species of rapidly growing nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. Here, we report the annotated genome sequence of
M. abscessus
strain M94, which showed an unusual cluster of tRNAs.
Increased Nasopharyngeal Bacterial Titers and Local Inflammation Facilitate Transmission of Streptococcus pneumoniae
Authors: Short Kirsty R. , Reading Patrick C. , Wang Nancy , Diavatopoulos Dimitri A. , Wijburg Odilia L.
Published: September 2012

The transmission of the bacteriumStreptococcus pneumoniae(the pneumococcus) marks the first step toward disease development. To date, our ability to prevent pneumococcal transmission has been limited by our lack of understanding regarding the factors which influence the spread of this pathogen. We have previously developed an infant mouse model of pneumococcal transmission which was strictly dependent on influenza A virus (IAV) coinfection of both the experimentally colonized “index mice” and the naive cohoused “contact mice.” Here, we sought to use this model to further elucidate the factors which facilitateS. pneumoniaetransmission. In the present report, we demonstrate that increasing the nasopharyngeal load ofS. pneumoniaein the colonized index mice (via the depletion of neutrophils) and inducing a proinflammatory response in the naive cohoused contact mice (as demonstrated by cytokine production) facilitatesS. pneumoniaetransmission. Thus, these data provide the first insights into the factors that help mediate the spread ofS. pneumoniaethroughout the community.

IMPORTANCEStreptococcus pneumoniae(the pneumococcus) is a major cause of worldwide morbidity and mortality and is a leading cause of death among children under the age of five years. Transmission ofS. pneumoniaemarks the first step toward disease development. Therefore, understanding the factors that influence the spread of pneumococci throughout the community plays an essential role in preventing pneumococcal disease. We previously developed the first reproducible infant mouse model for pneumococcal transmission and showed that coinfection with influenza virus facilitates the spread ofS. pneumoniae. Here, we show that increasing the bacterial load in the nasal cavity of colonized individuals as well as inducing an inflammatory response in naive “contact cases” facilitates the spread of pneumococci. Therefore, this study helps to identify the factors which must be inhibited in order to successfully prevent pneumococcal disease.
Propionibacterium acnes Bacteriophages Display Limited Genetic Diversity and Broad Killing Activity against Bacterial Skin Isolates
Authors: Marinelli Laura J. , Fitz-Gibbon Sorel , Hayes Clarmyra , Bowman Charles , Inkeles Megan , Loncaric Anya , Russell Daniel A. , Jacobs-Sera Deborah , Cokus Shawn , Pellegrini Matteo , Kim Jenny , Miller Jeff F. , Hatfull Graham F. , Modlin Robert L.
Published: September 2012

Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant,
Propionibacterium acnes
, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect
P. acnes
, 11
P. acnes
phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the
P. acnes
phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the
P. acnes
phages display a broad host range against clinical isolates of
P. acnes
, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the
P. acnes
bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.

IMPORTANCE
Propionibacterium acnes
is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11
P. acnes
phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages,
P. acnes
phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of
P. acnes
; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.
Positive associations between consumerism and tobacco and alcohol use in early adolescence: cross-sectional study
Authors: Sweeting Helen N , Bhaskar Abita , Hunt Kate
Published: September 2012

Background

There is concern about the negative impact of modern consumer culture on young people's mental health, but very few studies have investigated associations with substance use. In those which have, positive associations have been attributed to attempts to satisfy the unmet needs of more materialistic individuals.

Objectives

This study examines associations between different dimensions of consumerism and tobacco and alcohol use among Scottish early adolescents.

Design

Cross-sectional study.

Setting and participants

2937 (92% of those eligible) secondary school pupils (ages 12–14) completed questionnaires in examination conditions. Analyses were restricted to those with complete data on all relevant variables (N=2736 smoking; N=2737 drinking).

Measures

Dependent variables comprised ever smoking and current drinking. Measures of consumerism comprised number of ‘premium’ (range 0–7) and ‘standard’ (range 0–5) material possessions and three Consumer Involvement subscales, ‘dissatisfaction’, ‘consumer orientation’ and ‘brand awareness’ (each range 3–12). Analyses also included school-year group and family affluence.

Results

Ever smoking and current drinking were both more prevalent among adolescents with more ‘premium’ and ‘standard’ material possessions, greater consumer ‘dissatisfaction’ and ‘brand awareness’ (mutually adjusted analyses including school-year group and family affluence). The strongest relationships occurred for ‘brand awareness’: for each unit increase in ‘brand awareness’ the ORs (95% CI) of ever smoking were 1.17 (1.08 to 1.26) and 1.23 (1.14 to 1.33) in males and females, respectively; and those for drinking were 1.15 (1.08 to 1.23) and 1.21 (1.13 to 1.30). ‘Brand awareness’ had an equal or stronger relationship with both smoking and drinking than did family affluence.

Conclusions

These results suggest aassociations between consumerism and both smoking and drinking might arise because adolescent identities incorporate both consumerism and substance use, or be the result of promotion (indirectly in the case of tobacco) linking consumerist or aspirational lifestyles with these behaviours.
Oral health as a risk factor for mortality in middle-aged men: the role of socioeconomic position and health behaviours
Authors: Sabbah Wael , Mortensen Laust Hvas , Sheiham Aubrey , Batty David
Published: September 2012

Background

There is evidence of an association between poor oral health and mortality. This association is usually attributed to inflammatory and nutrition pathways. However, the role of health behaviours and socioeconomic position has not been adequately examined. The aims of this study were to examine the association between oral health and premature death among middle-aged men and to test whether it was explained by socioeconomic position and behaviours.

Methods

Data were from the Vietnam Experience Study, a prospective cohort study of Vietnam War-era (1965–1971), American male army personnel. The authors examined risk of cause-specific and all-cause mortality in relation to poor oral health in middle age, adjusting for age, ethnicity, socioeconomic position, IQ, behavioural factors and systemic conditions.

Results

Men with poor oral health experienced a higher risk of cause-specific and all-cause mortality. HRs for all-cause mortality were 2.94 (95% CI 2.11 to 4.08) among individuals with poor oral health and 3.98 (95% CI 2.43 to 6.49) among edentates compared with those with good oral health after adjusting for ethnicity and age. The association attenuated but remained significant after further adjustment for systemic conditions, socioeconomic position and behaviours. Socioeconomic and behavioural factors explained 52% and 44% of mortality risks attributed to poor oral health and being edentate, respectively.

Conclusion

The findings suggest that oral health–mortality relation is partly due to measured covariates in the present study. Oral health appears to be a marker of socioeconomic and behavioural risk factors related to all-cause mortality.
Modelling and application of an uncovered freezing bed technology for septage treatment
Authors: Kinsley C. , Kennedy K. , Crolla A.
Published: September 2012

A series of pilot scale freezing bed experiments were conducted to evaluate and model the freeze–thaw treatment of septic tank sludge (septage). Filtrate quality is similar to a low strength domestic wastewater and the sludge cake has a dry matter content of 25% with E. coli numbers below 2.0 × 106 CFU/g dry solids. Experimental results showed no impact of snow cover on bed performance in a region with moderate snowfall (1.3–1.6 m) as new layers of sludge effectively melted any accumulated snow; suggesting that it is not necessary to cover the bed or remove the snow in areas where sludge dosing exceeds snowfall. Both freezing and thawing processes were successfully modelled with readily available climatic data. Model output for North American climatic conditions indicates that the freezing bed technology can be widely applied throughout the northern United States and Alaska and most of Canada with the exception of coastal areas and southern Ontario.
PROTEIN MOTOR F1 AS A MODEL SYSTEM FOR FLUCTUATION THEORIES OF NON-EQUILIBRIUM STATISTICAL MECHANICS
Authors: HAYASHI KUMIKO , HAYASHI RYUNOSUKE
Published: September 2012

F1-ATPase (F1) is a rotary motor protein in which the rotor γ subunit rotates in the α3β3 ring hydrolyzing adenosine-5′-triphosphate (ATP). Several fluctuation theories of nonequilibrium statistical mechanics have been applied recently to the single-molecule experiments on F1. For example, the fluctuation theorem, a recent achievement in the field of nonequilibrium statistical mechanics, has been suggested to be useful for measuring the rotary torque of F1. In this paper, we introduce F1 as a good biological model for experimentally testing the theories of nonequilibrium statistical mechanics.
DIFFUSION AND HIGH-FREQUENCY NOISE OF ELECTRONS IN AMORPHOUS SEMICONDUCTORS AT LOW ELECTRIC FIELDS
Authors: BUSCEMI FABRIZIO , PICCININI ENRICO , RUDAN MASSIMO , BRUNETTI ROSSELLA , JACOBONI CARLO
Published: September 2012

The Ohmic conduction, diffusion, and high-frequency noise in amorphous semiconductors are here investigated by means of a Monte Carlo implementation of a full three-dimensional variable-range hopping transport model between localized states. Quantities like the carrier-velocity autocorrelation function, the noise power spectrum, the diffusion coefficient and the ohmic conductivity are obtained from numerical simulations at room and lower temperatures. Some interesting features of the linear-response regime typical of hopping transport are observed and discussed.
GUMBEL DISTRIBUTION AND CURRENT FLUCTUATIONS IN CRITICAL SYSTEMS
Authors: ALFINITO ELEONORA , MILLITHALER JEAN FRANÇOIS , REGGIANI LINO
Published: September 2012

We investigate a particular phase transition between two different tunneling regimes, direct and injection (Fowler–Nordheim), experimentally observed in the current–voltage characteristics of the light receptor bacteriorhodopsin (bR). Here, the sharp increase of the current above about 3 V is theoretically interpreted as the cross-over between the direct and injection sequential-tunneling regimes. Theory also predicts a very special behavior for the associated current fluctuations around steady state. We find the remarkable result that in a large range of bias around the transition between the two tunneling regimes, the probability density functions can be traced back to the generalization of the Gumbel distribution. This non-Gaussian distribution is the universal standard to describe fluctuations under extreme conditions.
Portal glucose delivery stimulates muscle but not liver protein metabolism
Authors: Kraft Guillaume , Coate Katie C. , Dardevet Dominique , Farmer Ben , Donahue E. Patrick , Williams Phillip E. , Cherrington Alan D. , Moore Mary Courtney
Published: September 2012

Portal vein glucose delivery (the portal glucose signal) stimulates glucose uptake and glycogen storage by the liver, whereas portal amino acid (AA) delivery (the portal AA signal) induces an increase in protein synthesis by the liver. During a meal, both signals coexist and may interact. In this study, we compared the protein synthesis rates in the liver and muscle in response to portal or peripheral glucose infusion during intraportal infusion of a complete AA mixture. Dogs were surgically prepared with hepatic sampling catheters and flow probes. After a 42-h fast, they underwent a 3-h hyperinsulinemic (4× basal) hyperglucagonemic (3× basal) hyperglycemic (≈160 mg/dl) hyperaminoacidemic (hepatic load 1.5× basal; delivered intraportally) clamp (postprandial conditions). Glucose was infused either via a peripheral (PeG; n = 7) or the portal vein (PoG; n = 8). Protein synthesis was assessed with a primed, continuous [14C]leucine infusion. Net hepatic glucose uptake was stimulated by portal glucose infusion (+1 mg·kg−1·min−1, P < 0.05) as expected, but hepatic fractional AA extraction and hepatic protein synthesis did not differ between groups. There was a lower arterial AA concentration in the PoG group (−19%, P < 0.05) and a significant stimulation (+30%) of muscle protein synthesis associated with increased expression of LAT1 and ASCT2 AA transporters and p70S6 phosphorylation. Concomitant portal glucose and AA delivery enhances skeletal muscle protein synthesis compared with peripheral glucose and portal AA delivery. These data suggest that enteral nutrition support may have an advantage over parenteral nutrition in stimulating muscle protein synthesis.
Arginine de novo and nitric oxide production in disease states
Authors: Luiking Yvette C. , Ten Have Gabriella A. M. , Wolfe Robert R. , Deutz Nicolaas E. P.
Published: September 2012

Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production. The latter may be linked to the availability of citrulline, which is the immediate precursor of arginine and limiting factor for de novo arginine production. Arginine metabolism is highly compartmentalized due to the expression of the enzymes involved in arginine metabolism in various organs. A small fraction of arginine enters the NO synthase (NOS) pathway. Tetrahydrobiopterin (BH4) is an essential and rate-limiting cofactor for the production of NO. Depletion of BH4 in oxidative-stressed endothelial cells can result in so-called NOS3 “uncoupling,” resulting in production of superoxide instead of NO. Moreover, distribution of arginine between intracellular transporters and arginine-converting enzymes, as well as between the arginine-converting and arginine-synthesizing enzymes, determines the metabolic fate of arginine. Alternatively, NO can be derived from conversion of nitrite. Reduced arginine availability stemming from reduced de novo production and elevated arginase activity have been reported in various conditions of acute and chronic stress, which are often characterized by increased NOS2 and reduced NOS3 activity. Cardiovascular and pulmonary disorders such as atherosclerosis, diabetes, hypercholesterolemia, ischemic heart disease, and hypertension are characterized by NOS3 uncoupling. Therapeutic applications to influence (de novo) arginine and NO metabolism aim at increasing substrate availability or at influencing the metabolic fate of specific pathways related to NO bioavailability and prevention of NOS3 uncoupling. These include supplementation of arginine or citrulline, provision of NO donors including inhaled NO and nitrite (sources), NOS3 modulating agents, or the targeting of endogenous NOS inhibitors like asymmetric dimethylarginine.
Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk
Authors: Cornford Andrea S. , Barkan Ariel L. , Hinko Alexander , Horowitz Jeffrey F.
Published: September 2012

Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass−1·day−1; 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance ( P < 0.05) and increased fasting lipidemia (all P < 0.05 vs. control). In addition, preventing the suppression in GH with overeating also blunted the increase in systemic proteolysis ( P < 0.05 GHT vs. control). However, GHT did not alter lipolysis or FSR in response to overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating.
Expression of genes involved in fatty acid transport and insulin signaling is altered by physical inactivity and exercise training in human skeletal muscle
Authors: Lammers Gerwen , Poelkens Fleur , van Duijnhoven Noortje T. L. , Pardoel Elisabeth M. , Hoenderop Joost G. , Thijssen Dick H. J. , Hopman Maria T. E.
Published: September 2012

Physical deconditioning is associated with the development of chronic diseases, including type 2 diabetes and cardiovascular disease. Exercise training effectively counteracts these developments, but the underlying mechanisms are largely unknown. To gain more insight into these mechanisms, muscular gene expression levels were assessed after physical deconditioning and after exercise training of the lower limbs in humans by use of gene expression microarrays. To exclude systemic effects, we used human models for local physical inactivity (3 wk of unilateral limb suspension) and for local exercise training (6 wk of functional electrical stimulation exercise of the extremely deconditioned legs of individuals with a spinal cord injury). The most interesting subset of genes, those downregulated after deconditioning as well as upregulated after exercise training, contained 18 genes related to both the “insulin action” and “adipocytokine signaling” pathway. Of these genes, the three with strongest up/downregulation were the muscular fatty acid-binding protein-3 (FABP3), the fatty acid oxidizing enzyme hydroxyacyl-CoA dehydrogenase (HADH), and the mitochondrial fatty acid transporter solute carrier 25 family member A20 (SLC25A20). The expression levels of these genes were confirmed using RT-qPCR. The results of the present study indicate an important role for a decreased transport and metabolism of fatty acids, which provides a link between physical activity levels and insulin signaling.
Curcumin Protects against Ovariectomy-Induced Bone Changes in Rat Model
Authors: Hussan Farida , Ibraheem Nawwar Ghassan , Kamarudin Taty Anna , Shuid Ahmad Nazrun , Soelaiman Ima Nirwana , Othman Faizah
Published: September 2012

Osteoporosis is a metabolic disease affecting both men and women especially in postmenopausal women. Curcumin possesses many medicinal properties. In this study, thirty two female Sprague-Dawley rats were used to determine the potential effect of curcumin in prevention of bone loss following ovariectomy. The animals were divided into Sham group, ovariectomised control, ovariectomised treated with curcumin 110 mg/kg and ovariectomised treated with Premarin 100 μg/kg. The treatments were given via daily oral gavages for 60 days. The structural parameters such as bone volume, trabecular number, trabecular thickness and trabecular separation were found to be deteriorated in ovariectomised rats compared to Sham group. Moreover, the reduced osteoblast count, the increased osteoclast count and increased eroded surface were found in ovariectomised groups. Treatment with curcumin was able to reverse all these ovariectomy-induced deteriorations. Curcumin treatment was as effective as Premarin in most parameters except the bone volume and eroded surface, which were better than Premarin. The high dose of curcumin treatment was not only able to reduce the osteoclast number but also increase the osteoblast count. Therefore, the potential effect of curcumin can be applied as an alternative to oestrogen for prevention of postmenopausal osteoporosis.
Eisenstein Series Identities Involving the Borweins′ Cubic Theta Functions
Authors: Xia Ernest X. W. , Yao Olivia X. M.
Published: September 2012

Based on the theories of Ramanujan′s elliptic functions and the (p, k)‐parametrization of theta functions due to Alaca et al. (2006, 2007, 2006) we derive certain Eisenstein series identities involving the Borweins′ cubic theta functions with the help of the computer. Some of these identities were proved by Liu based on the fundamental theory of elliptic functions and some of them may be new. One side of each identity involves Eisenstein series, the other products of the Borweins′ cubic theta functions. As applications, we evaluate some convolution sums. These evaluations are different from the formulas given by Alaca et al.
The Role ofHelicobacter pyloriand NSAIDs in the Pathogenesis of Uncomplicated Duodenal Ulcer
Authors: Cekin Ayhan Hilmi , Taskoparan Muharrem , Duman Adil , Sezer Cem , Cekin Yesim , Yolcular Basak Oguz , Can Hasan , Pehlivan Fatma Seher , Cayirci Mine
Published: September 2012

Background/Aim. To identify the etiological role ofHelicobacter pylori(Hp) and nonsteroidal anti-inflammatory drugs (NSAIDs) in endoscopically diagnosed duodenal ulcers (DUs).Methods. Patients undergoing esophagogastroduodenoscopy in two major hospitals in Antalya and Adiyaman were included in this study and assigned as duodenal ulcer (n=152; median age: 41.0 (16–71) years; 58.6% males) or control group (n=70; median age: 41.0 (18–68) years; 57.1% males). Patient demographics, risk factors, and NSAID/acetylsalicylic acid (ASA) use were recorded.Results.HPwas more commonly located in the corpus (75.0 versus 50.0%; odds ratio [OR] = 3.00; 95% confidence interval [CI]: 1.66–5.44;P<0.001), incisura (75.7 versus 60.0%;OR=2.07; 95% CI: 1.13–3.79;P=0.017), and antrum (80.3 versus 60.0%;OR=2.71; 95% CI: 1.45–5.05;P=0.001) among DU patients than controls.Hppositivity was 84.9% whileHpwas negative in 15.1% of patients including those accompanied with NSAID and/or ASA use (9.2%), and those were negative for all three etiological factors (5.9%).Conclusion. Our findings indicate the substantial role ofHpin the pathogenesis of DU disease as identified in 84.9% of DU patients compatible with the background prevalence of 61.4% among age-matched control subjects.Hpwas the single causative factor in 44.1% of our patients, while NSAID/ASA exposure was in 9.2%.
Aurones: A Promising Heterocyclic Scaffold for the Development of Potent Antileishmanial Agents
Authors: Roussaki Marina , Costa Lima Sofia , Kypreou Anna-Maria , Kefalas Panagiotis , Cordeiro da Silva Anabela , Detsi Anastasia
Published: September 2012

A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a–4f) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g–4l). Among the latter, two aurones possessing a 2′-methoxy or a 2′-methyl group (compounds 4i and 4j) exhibit potent antileishmanial activity (IC50=1.3±0.1 μM and IC50=1.6±0.2 μM, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index.
Validation and Application of the Thermal Hydraulic System Code TRACE for Analysis of BWR Transients
Authors: Sánchez V. H. , Thieme M. , Tietsch W.
Published: September 2012

The Karlsruhe Institute of Technology (KIT) is participating on (Code Applications and Maintenance Program) CAMP of the US Nuclear Regulatory Commission (NRC) to validate TRACE code for LWR transient analysis. The application of TRACE for the safety assessment of BWR requires a throughout verification and validation using experimental data from separate effect and integral tests but also using plant data. The validation process is normally focused on safety-relevant phenomena for example, pressure drop, void fraction, heat transfer, and critical power models. The purpose of this paper is to validate selected BWR-relevant TRACE-models using both data of bundle tests such as the (Boiling Water Reactor Full-Size Fine-Mesh Bundle Test) BFBT and plant data recorded during a turbine trip event (TUSA) occurred in a Type-72 German BWR plant. For the validation, TRACE models of the BFBT bundle and of the BWR plant were developed. The performed investigations have shown that the TRACE code is appropriate to describe main BWR-safety-relevant phenomena (pressure drop, void fraction, and critical power) with acceptable accuracy. The comparison of the predicted global BWR plant parameters for the TUSA event with the measured plant data indicates that the code predictions are following the main trends of the measured parameters such as dome pressure and reactor power.
Successive‐Stage Speed Limit on Exit Ramp Upstream of Direct‐Type Freeway in China
Authors: Li Hongwei , Lu Jian , Ma Yongfeng , Liu Yuanlin
Published: September 2012

The first objective of this study is to analyze a successive‐stage speed limit model developed for vehicles along the exit upstream ramp of direct‐type freeway in China. This paper (1) explains the necessity to implement speed limit to the exit ramp upstream, (2) analyzes whether speed limit is related to the length of the deceleration lane, vehicle type, saturation, and turning ratio and (3) proposes a speed prediction model and calibrates speed‐limit sign validity model and establishes successive‐stage speed limit model. The results. Δν85 ≥ 10 illustrates the necessity of the using speed limit on the exit ramp. Speed‐deceleration lane length curve presents two trends bounded by 200 m, so the speed limit should be in accordance with the deceleration length. Speed‐small vehicle curve closing to speed‐large vehicle curve presents that the vehicle type is not the factor of the speed limit. After curve fitting and polynomial regression, saturation is considered to be the most influential factor of speed. Speed‐saturation prediction model and calibrated speed‐limit sign validity model are built through linearization. According to the above results, successive‐stage speed limit model is established. An exit ramp was implemented to verify the feasibility and validity of the model.
Accurate GLONASS Time Transfer for the Generation of the Coordinated Universal Time
Authors: Jiang Z. , Lewandowski W.
Published: September 2012

The spatial techniques currently used in accurate time transfer are based on GPS, TWSTFT, and GLONASS. The International Bureau of Weights and Measures (BIPM) is mandated for the generation of Coordinated Universal Time (UTC) which is published monthly in the BIPM Circular T. In 2009, the international Consultative Committee for Time and Frequency (CCTF) recommended the use of multitechniques in time transfer to ensure precision, accuracy, and robustness in UTC. To complement the existing GPS and TWSTFT time links, in November 2009 the first two GLONASS time links were introduced into the UTC worldwide time link network. By November 2011, 6 GLONASS time links are used in the UTC computation. In the frame of the application in the UTC computation, we establish the technical features of GLONASS time transfer: the short- and long-term stabilities, the calibration process, and in particular the impact of the multiple GLONASS frequency biases. We then outline various considerations for future developments, including the uses of P-codes and carrier-phase information.
Modeling Spike-Train Processing in the Cerebellum Granular Layer and Changes in Plasticity Reveal Single Neuron Effects in Neural Ensembles
Authors: Medini Chaitanya , Nair Bipin , D'Angelo Egidio , Naldi Giovanni , Diwakar Shyam
Published: September 2012

The cerebellum input stage has been known to perform combinatorial operations on input signals. In this paper, two types of mathematical models were used to reproduce the role of feed-forward inhibition and computation in the granular layer microcircuitry to investigate spike train processing. A simple spiking model and a biophysically-detailed model of the network were used to study signal recoding in the granular layer and to test observations like center-surround organization and time-window hypothesis in addition to effects of induced plasticity. Simulations suggest that simple neuron models may be used to abstract timing phenomenon in large networks, however detailed models were needed to reconstruct population coding via evoked local field potentials (LFP) and for simulating changes in synaptic plasticity. Our results also indicated that spatio-temporal code of the granular network is mainly controlled by the feed-forward inhibition from the Golgi cell synapses. Spike amplitude and total number of spikes were modulated by LTP and LTD. Reconstructing granular layer evoked-LFP suggests that granular layer propagates the nonlinearities of individual neurons. Simulations indicate that granular layer network operates a robust population code for a wide range of intervals, controlled by the Golgi cell inhibition and is regulated by the post-synaptic excitability.