bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of angiotensin converting enzyme and bradykinin receptor B2 gene variants on voluntary fluid intake and fluid balance in healthy men during moderate-intensity exercise in the heat
Authors: Yau Adora M.W. , Moss Andrew D. , James Lewis John , Gilmore William , Ashworth Jason J. , Evans Gethin H.
Published: October 2014

Angiotensin converting enzyme (ACE) and bradykinin receptor B2 (B2R) genetic variation may affect thirst because of effects on angiotensin II production and bradykinin activity, respectively. To examine this, 45 healthy Caucasian men completed 60 min of cycle exercise at 62% ± 5% peak oxygen uptake in a room heated to 30.5 ± 0.3 °C with ad libitum fluid intake. Blood samples were collected pre-, mid-, and immediately post-cycle. Fluid intake, body mass loss (BML), sweat loss (determined via changes in body mass and fluid intake), and thirst sensation were recorded. All participants were genotyped for the ACE insert fragment (I) and the B2R insert sequence (P). Participants were homozygous for the wild-type allele (WW or MM), heterozygous (WI or MP) or homozygous for the insert (II or PP). No differences between genotype groups were found in mean (±SD) voluntary fluid intake (WW: 613 ± 388, WI: 753 ± 385, II: 862 ± 421 mL, p = 0.31; MM: 599 ± 322, MP: 745 ± 374, PP: 870 ± 459 mL, p = 0.20), percentage BML or any other fluid balance variables for both the ACE and B2R genes, respectively. Mean thirst perception in the B2R PP group, however, was higher (p < 0.05) than both MM and MP at 30, 45, and 60 min. In conclusion, the results of this study suggest that voluntary fluid intake and fluid balance in healthy men performing 60 min of moderate-intensity exercise in the heat are not predominantly influenced by ACE or B2R genetic variation.
Lime pile techniques for the improvement of clay soils
Authors: Abiodun Abiola Ayopo , Nalbantoglu Zalihe
Published: October 2014

Soil improvement is one of the basic requirements for preparing in situ soils for appropriate strengthening, stiffness, and stability in civil engineering designs and applications. The modification technique, which involves mechanical, thermal, and chemical components, requires monitoring techniques to determine its efficiency and suitability. This study examines the geotechnical improvement of clay soils using the lime pile technique on a laboratory-scale model. The clay–lime physicochemical reactions resulting from cation exchange were examined through basic experimental analyses. In addition, electrical conductivity measurements were performed on the selected treated soils to examine variations in their electrical properties. Remolded compacted clay soil blocks were carefully prepared in circular steel test tanks with lime piles installed in them. The treated soil block properties were then investigated as a function of radial lime pile distances and curing periods. It was observed that there are significant changes in the Atterberg limit, linear shrinkage, compaction characteristics, and strength of the treated soils due to the clay–lime reactions. The results indicate that these reactions have remarkable effects on the electrical properties of the lime pile–treated soil and produced strong interparticle bonds and unconfined compressive strength of the soil. This is attributed to the migration of Ca2+ and Mg2+ ions from the lime piles into the soil, flocculation of particles, and pozzolanic reactions. The significant changes in the electrical properties and shear strength values suggest that their correlative changes can be used as a monitoring technique to determine the improvement in geotechnical properties of chemically treated soils.
Incorporating economic weights into radiata pine breeding selection decisions
Authors: Evison David C. , Apiolaza Luis A.
Published: October 2014

This article introduces the concept of “robust selection”, which proposes tree selection based on the stochastic simulation of economic values to account for the inherent uncertainty of economic weights used in tree selection for breeding programs. The proposed method uses both median ranking and ranking variability as criteria for breeding selection. Using consensus genetic and economic parameters from the New Zealand Radiata Pine Breeding Company program, we compare three selection strategies: deterministic application of economic weights from a vertically integrated bioeconomic model, an equal-weight index often used in operations, and robust selection. All strategies aim to increase value for a breeding objective that includes four traits, i.e., volume, stem sweep, branch size, and wood stiffness (measured as modulus of elasticity), based on a selection index that considers five criteria, i.e., stem diameter at breast height (1.3 m), straightness, branching score, wood density, and modulus of elasticity. Two-thirds of the selected trees were unique for each of the selection strategies. Robust selection achieved the best realised gain for three of the four selection criteria and was the middle performer in the last selection criteria. Considering the high intrinsic uncertainty of economic weights, we suggest that the relevant criterion for the selection of individuals is the maximum median ranking, subject to an acceptable level of variation in that ranking, rather than their narrow performance under a single economic scenario. This will lead to tree selections that perform well under a wide range of economic circumstances.
Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar–Kyoto rats
Authors: Ahmad Ashfaq , Sattar Munavvar A. , Rathore Hassaan A. , Abdulla Mohammad H. , Khan Safia A. , Abdullah Nor A. , Kaur Gurjeet , Johns Edward J.
Published: October 2014

This study investigated the role of α1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar–Kyoto (WKY) rats with isoprenaline (5.0 mg·(kg body mass)–1, by subcutaneous injection every 72 h) and caffeine (62 mg·L–1 in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY 7378, a selective α1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P < 0.05). In the LVH group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P < 0.05), compared with the control group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY 7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the α1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state.
Plumage ornaments and reproductive investment in relation to oxidative status in the Iberian Pied Flycatcher (Ficedulahypoleuca iberiae)
Authors: López-Arrabé Jimena , Cantarero Alejandro , Pérez-Rodríguez Lorenzo , Palma Antonio , Moreno Juan
Published: October 2014

A key aspect in the study of plumage traits with a potential role in communication is the cost associated with trait production and maintenance, expressed in terms of oxidative stress. In the Iberian Pied Flycatcher (Ficedula hypoleuca iberiae (Witherby, 1928)), males and some females exhibit a white forehead patch and both sexes present conspicuous white patches on the wings. We examined associations between these plumage ornaments and their ability to cope with oxidative stress. Furthermore, we explored oxidative costs of reproductive investment. Total antioxidant status (TAS) in plasma and glutathione (tGSH) levels in red blood cells, as well as a marker of oxidative damage in plasma lipids (malondialdehyde (MDA)), were assessed simultaneously for the first time in studies of avian reproduction. We found negative associations between antioxidants and ornaments in incubating females, although this relationship was positive while feeding nestlings. For males, MDA levels were negatively associated with ornaments, while TAS showed a positive relation. Female MDA showed a positive correlation with intensity of incubation attendance, while this relation was negative for tGSH levels. These results indicate that multiple achromatic plumage ornaments signal the individual capacity to cope with costs related to oxidative stress. Moreover, this study highlights the critical role of incubation for avian life histories.
Haplotype-based analysis of selective sweeps in sheep
Authors: Kijas James W.
Published: October 2014

Domestic animals represent an extremely useful model for linking genotypic and phenotypic variation. One approach involves identifying allele frequency differences between populations, using FST, to detect selective sweeps. While simple to calculate, FST may generate false positives due to aspects of population history. This prompted the development of hapFLK, a metric that measures haplotype differentiation while accounting for the genetic relationship between populations. The focus of this paper was to apply hapFLK in sheep with available SNP50 genotypes. The hapFLK approach identified a known selective sweep on chromosome 10 with high precision. Further, five regions were identified centered on genes with strong evidence for positive selection (COL1A2, NCAPG, LCORL, and RXFP2). Estimation of global FST revealed many more genomic regions, providing empirical data in support of published simulation-based results concerning elevated type I error associated with FST when it is being used to characterize sweep regions. The findings, while conducted using sheep SNP data, are likely to be applicable across those domestic animal species that have undergone artificial selection for desirable phenotypic traits.
Genome-wide expression analysis of hereditary hyperplastic gingivitis in silver foxes (Vulpes vulpes) using canine microarrays
Authors: Clark Jo-Anna B.J. , Booman Marije , Hudson Robert C. , Marshall H. Dawn
Published: October 2014

Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive condition found predominantly in farmed silver foxes, first documented in Europe in the 1940s. Hereditary gingival fibromatosis (HGF) is an analogous condition occurring in humans. HGF has a heterogeneous aetiology with emphasis placed on the autosomal dominant forms of inheritance for which there are three known loci: HGF1, HGF2, and HGF3. Among these, only one causative mutation has been determined, in the Son of sevenless homolog 1 (SOS1) gene. The goal of this study was to explore potential molecular or cellular mechanisms underlying HHG by analysis of global gene expression patterns from Affymetrix Canine 2.0 microarrays cross-referenced against candidate genes within the human loci. We conclude that the SOS1 gene involved in HGF1 is not significantly up-regulated in HHG. However, the structurally and functionally similar SOS2 gene is up-regulated in affected foxes, and we propose this as a candidate gene for HHG. At HGF2 we identify RASA1 (rat sarcoma viral p21 protein activator 1) as a candidate gene for HHG, as it is up-regulated in affected foxes and is involved in MAPK signalling. From comparison to the genes within the HGF3 locus, we find evidence for a role of androgens in HHG phenotype severity by differential up-regulation of SRD5A2 in HHG-affected foxes. We hypothesize that the putative mutation occurs upstream of RAS in the extracellular signal-regulated kinase component of MAPK signalling.
Epoxyeicosatrienoic acids mediate insulin-mediated augmentation in skeletal muscle perfusion and blood volume
Authors: Shim Chi Young , Kim Sajeevani , Chadderdon Scott , Wu Melinda , Qi Yue , Xie Aris , Alkayed Nabil J. , Davidson Brian P. , Lindner Jonathan R.
Published: October 2014

Skeletal muscle microvascular blood flow (MBF) increases in response to physiological hyperinsulinemia. This vascular action of insulin may facilitate glucose uptake. We hypothesized that epoxyeicosatrienoic acids (EETs), a family of arachadonic, acid-derived, endothelium-derived hyperpolarizing factors, are mediators of insulin's microvascular effects. Contrast-enhanced ultrasound (CEU) was performed to quantify skeletal muscle capillary blood volume (CBV) and MBF in wild-type and obese insulin-resistant ( db/db) mice after administration of vehicle or trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid ( t-AUCB), an inhibitor of soluble epoxide hydrolase that converts EETs to less active dihydroxyeicosatrienoic acids. Similar studies were performed in rats pretreated with l-NAME. CEU was also performed in rats undergoing a euglycemic hyperinsulinemic clamp, half of which were pretreated with the epoxygenase inhibitor MS-PPOH to inhibit EET synthesis. In both wild-type and db/db mice, intravenous t-AUCB produced an increase in CBV (65–100% increase at 30 min, P < 0.05) and in MBF. In db/db mice, t-AUCB also reduced plasma glucose by ∼15%. In rats pretreated with l-NAME, t-AUCB after produced a significant ≈20% increase in CBV, indicating a component of vascular response independent of nitric oxide (NO) production. Hyperinsulinemic clamp produced a time-dependent increase in MBF (19 ± 36 and 76 ± 49% at 90 min, P = 0.026) that was mediated in part by an increase in CBV. Insulin-mediated changes in both CBV and MBF during the clamp were blocked entirely by MS-PPOH. We conclude that EETs are a mediator of insulin-mediated augmentation in skeletal muscle perfusion and are involved in regulating changes in CBV during hyperinsulinemia.
Wt1 dictates the fate of fetal and adult Leydig cells during development in the mouse testis
Authors: Wen Qing , Zheng Qiao-Song , Li Xi-Xia , Hu Zhao-Yuan , Gao Fei , Cheng C. Yan , Liu Yi-Xun
Published: October 2014

Wilms' tumor 1 ( Wt1) is a tumor suppressor gene encoding ∼24 zinc finger transcription factors. In the mammalian testis, Wt1 is expressed mostly by Sertoli cells (SCs) involved in testis development, spermatogenesis, and adult Leydig cell (ALC) steroidogenesis. Global knockout (KO) of Wt1 is lethal in mice due to defects in embryogenesis. Herein, we showed that Wt1 is involved in regulating fetal Leydig cell (FLC) degeneration and ALC differentiation during testicular development. Using Wt1−/flox; Amh-Cre mice that specifically deleted Wt1 in the SC vs. age-matched wild-type (WT) controls, FLC-like-clusters were found in Wt1-deficient testes that remained mitotically active from postnatal day 1 (P1) to P56, and no ALC was detected at these ages. Leydig cells in mutant adult testes displayed morphological features of FLC. Also, FLC-like cells in adult mutant testes had reduced expression in ALC-associated genes Ptgds, Sult1e1, Vcam1, Hsd11b1, Hsd3b6, and Hsd17b3 but high expression of FLC-associated genes Thbs2 and Hsd3b1. Whereas serum LH and testosterone level in mutant mice were not different from controls, intratesticular testosterone level was significantly reduced. Deletion of Wt1 gene also perturbed the expression of steroidogenic enzymes Star, P450c17, Hsd3b6, Hsd3b1, Hsd17b1, and Hsd17b3. FLCs in adult mutant testes failed to convert androstenedione to testosterone due to a lack of Hsd17b3, and this defect was rescued by coculturing with fetal SCs. In summary, FLC-like cells in mutant testes are putative FLCs that remain mitotically active in adult mice, illustrating that Wt1 dictates the fate of FLC and ALC during postnatal testis development.
Shp2 signaling in POMC neurons is important for leptin's actions on blood pressure, energy balance, and glucose regulation
Authors: do Carmo Jussara M. , da Silva Alexandre A. , Ebaady Sabira E. , Sessums Price O. , Abraham Ralph S. , Elmquist Joel K. , Lowell Bradford B. , Hall John E.
Published: October 2014

Previous studies showed that Src homology-2 tyrosine phosphatase (Shp2) is an important regulator of body weight. In this study, we examined the impact of Shp2 deficiency specifically in proopiomelanocortin (POMC) neurons on metabolic and cardiovascular function and on chronic blood pressure (BP) and metabolic responses to leptin. Mice with Shp2 deleted in POMC neurons (Shp2/Pomc-cre) and control mice ( Shp2 flox/flox) were implanted with telemetry probes and venous catheters for measurement of mean arterial pressure (MAP) and leptin infusion. After at least 5 days of stable control measurements, mice received leptin infusion (2 μg·kg−1·day−1 iv) for 7 days. Compared with Shp2 flox/flox controls, Shp2/Pomc-cre mice at 22 wk of age were slightly heavier (34 ± 1 vs. 31 ± 1 g) but consumed a similar amount of food (3.9 ± 0.3 vs. 3.8 ± 0.2 g/day). Leptin infusion reduced food intake in Shp2 flox/flox mice (2.6 ± 0.5 g) and Shp2/Pomc-cre mice (3.2 ± 0.3 g). Despite decreasing food intake, leptin infusion increased MAP in control mice, whereas no significant change in MAP was observed in Shp2/Pomc-cre mice. Leptin infusion also decreased plasma glucose and insulin levels in controls (12 ± 1 to 6 ± 1 μU/ml and 142 ± 12 to 81 ± 8 mg/100 ml) but not in Shp2/Pomc-cre mice. Leptin increased V̇o2 by 16 ± 2% in controls and 7 ± 1% in Shp2/Pomc-cre mice. These results indicate that Shp2 signaling in POMC neurons contributes to the long-term BP and antidiabetic actions of leptin and may play a modest role in normal regulation of body weight.
Selective inhibition of a multicomponent response can be achieved without cost
Authors: Xu Jing , Westrick Zachary , Ivry Richard B.
Published: October 2014

Behavioral flexibility frequently requires the ability to modify an on-going action. In some situations, optimal performance requires modifying some components of an on-going action without interrupting other components of that action. This form of control has been studied with the selective stop-signal task, in which participants are instructed to abort only one movement of a multicomponent response. Previous studies have shown a transient disruption of the nonaborted component, suggesting limitations in our ability to use selective inhibition. This cost has been attributed to a structural limitation associated with the recruitment of a cortico-basal ganglia pathway that allows for the rapid inhibition of action but operates in a relatively generic manner. Using a model-based approach, we demonstrate that, with a modest amount of training and highly compatible stimulus-response mappings, people can perform a selective-stop task without any cost on the nonaborted component. Prior reports of behavioral costs in selective-stop tasks reflect, at least in part, a sampling bias in the method commonly used to estimate such costs. These results suggest that inhibition can be selectively controlled and present a challenge for models of inhibitory control that posit the operation of generic processes.
Adaptation to visual feedback delay in a redundant motor task
Authors: Farshchiansadegh Ali , Ranganathan Rajiv , Casadio Maura , Mussa-Ivaldi Ferdinando A.
Published: October 2014

The goal of this study was to examine the reorganization of hand movements during adaptation to delayed visual feedback in a novel and redundant environment. In most natural behaviors, the brain must learn to invert a many-to-one map from high-dimensional joint movements and muscle forces to a low-dimensional goal. This spatial “inverse map” is learned by associating motor commands to their low-dimensional consequences. How is this map affected by the presence of temporal delays? A delay presents the brain with a new set of kinematic data, and, because of redundancy, the brain may use these data to form a new inverse map. We consider two possible responses to a novel visuomotor delay. In one case, the brain updates the previously learned spatial map, building a new association between motor commands and visual feedback of their effects. In the alternative case, the brain preserves the original map and learns to compensate the delay by a temporal shift of the motor commands. To test these alternative possibilities, we developed a virtual reality game in which subjects controlled the two-dimensional coordinates of a cursor by continuous hand gestures. Two groups of subjects tracked a target along predictable paths by wearing an instrumented data glove that recorded finger motions. The 19-dimensional glove signals controlled a cursor on a 2-dimensional computer display. The experiment was performed on 2 consecutive days. On the 1st day, subjects practiced tracking movements without delay. On the 2nd day, the test group performed the same task with a delay of 300 ms between the glove signals and the cursor display, whereas the control group continued practicing the nondelayed trials. We found evidence that to compensate for the delay, the test group relied on the coordination patterns established during the baseline, e.g., their hand-to-cursor inverse map was robust to the delay perturbation, which was counteracted by an anticipation of the motor command.
Posttonsillectomy Bacteremia and Comparison of Tonsillar Surface and Deep Culture
Authors: Shishegar Mahmood , Ashraf Mohammad Javad
Published: October 2014

Objective.This study aimed to identify the microorganisms of surface and depth of tonsils and whether these microorganisms bring the menace of bacteremia during tonsillectomy in the children under surgery.Materials and Methods.The culture specimens were taken from surface and depth of tonsil from the patients suffering from chronic tonsillitis at the time of operation. Also, 10 mL venous blood samples were taken 5 minutes before and after the operation for microbiological study.Results.According to the results, 112 (76.1%) and 117 (79.6%) cultures from surface and depth of tonsils represented multiple microorganisms, respectively. Besides, staphylococci coagulase positive was the most common organism in both surface and depth of tonsils. None of the preoperation blood cultures were positive, while 3 postoperation blood cultures (2.1%) were positive. Staphylococci coagulase negative and alpha hemolytic streptococcus were detected in 2 cases (1.4%) and 1 case (0.7%), respectively.Conclusion.In the present study, the two cultured sites were almost similar regarding the types of isolated microorganisms. Our results suggested that bacteremia might occur after tonsillectomy. Therefore, to avoid the possible dramatic outcomes after tonsillectomy, pre- and postoperation attendances are essential.
Eculizumab Therapy Leads to Rapid Resolution of Thrombocytopenia in Atypical Hemolytic Uremic Syndrome
Authors: Tsai Han-Mou , Kuo Elizabeth
Published: October 2014

Eculizumab is highly effective in controlling complement activation in patients with the atypical hemolytic uremic syndrome (aHUS). However, the course of responses to the treatment is not well understood. We reviewed the responses to eculizumab therapy for aHUS. The results show that, in patients with aHUS, eculizumab therapy, when not accompanied with concurrent plasma exchange therapy, led to steady increase in the platelet count and improvement in extra-renal complications within 3 days. By day 7, the platelet count was normal in 15 of 17 cases. The resolution of hemolytic anemia and improvement in renal function were less predictable and were not apparent for weeks to months in two patients. The swift response in the platelet counts was only observed in one of five cases who received concurrent plasma exchange therapy and was not observed in a case of TMA due to gemcitabine/carboplatin. In summary, eculizumab leads to rapid increase in the platelet counts and resolution of extrarenal symptoms in patients with aHUS. Concurrent plasma exchange greatly impedes the response of aHUS to eculizumab therapy. Eculizumab is ineffective for gemcitabine/carboplatin associated TMA.
Computer-Based Learning: The Use of SPSS Statistical Program for Improving Biostatistical Competence of Medical Students
Authors: Perry Zvi H. , Barak Aricha-Tamir , Neumann Lily , Levy Amalia
Published: October 2014

Background. We changed the biostatistics curriculum for our medical students and have created a course entitled “Multivariate analysis of statistical data, using the SPSS package.” Purposes. The aim of this course was to develop students’ skills in computerized data analysis, as well as enhancing their ability to read and interpret statistical data analysis in the literature. Methods. In the current study we have shown that a computer-based course for biostatistics and advanced data analysis is feasible and efficient, using course specific evaluation questionnaires. Results. Its efficacy is both subjective (our subjects felt better prepared to do their theses, as well as to read articles with advanced statistical data analysis) and objective (their knowledge of how and when to apply statistical procedures seemed to improve). Conclusions. We showed that a formal evaluative process for such a course is possible and that it enhances the learning experience both for the students and their teachers. In the current study we have shown that a computer-based course for biostatistics and advanced data analysis is feasible and efficient.
Predictors of Infections following Cranioplasty: A Retrospective Review of a Large Single Center Study
Authors: Zanaty Mario , Chalouhi Nohra , Starke Robert M. , Chitale Rohan , Hann Shannon , Bovenzi Cory D. , Saigh Mark P. , Schwartz Eric W. , Kunkel Emily S. I. , Efthimiadis-Budike Alexandra S. , Jabbour Pascal , Dalyai Richard , Rosenwasser Robert H. , Tjoumakaris Stavropoula I.
Published: October 2014

Introduction.The variables that predispose to postcranioplasty infections are poorly described in the literature. We formulated a multivariate model that predicts the risk of infection in patients undergoing cranioplasty.Method.Retrospective review of all patients who underwent cranioplasty following craniectomy from January, 2000, to December, 2011. Tested predictors were age, sex, diabetic status, hypertensive status, reason for craniectomy, urgency status of craniectomy, location of cranioplasty, reoperation for hematoma, hydrocephalus postcranioplasty, and material type. A multivariate logistic regression analysis was performed.Results.Three hundred forty-eight patients met the study criteria. Infection rate was 26.43% (92/348). Of these cases with infection, 56.52% (52/92) were superficial (supragaleal), 43.48% (40/92) were deep (subgaleal), and 31.52% (29/92) were present in both the supragaleal and subgaleal spaces. The predominant pathogen was coagulase-negative staphylococcus (30.43%) followed by methicillin-resistantStaphylococcus aureus(22.83%) and methicillin-sensitiveStaphylococcus aureus(15.22%). Approximately 15.22% of all cultures were polymicrobial. Multivariate analysis revealed convex craniectomy, hemorrhagic stroke, and hydrocephalus to be associated with an increased risk of infection (OR=14.41;P<0.05,OR=4.33;P<0.05,OR=1.90;P=0.054, resp.).Conclusion.Many of the risk factors for infection after cranioplasty are modifiable. Recognition and prevention of the risk factors would help decrease the infection’s rate.
Synthesis and Characterization of Electrodeposited C-PANI-Pd-Ni Composite Electrocatalyst for Methanol Oxidation
Authors: Mahapatra S. S. , Shekhar S. , Thakur B. K. , Priyadarshi H.
Published: October 2014

Electropolymerization of aniline at the graphite electrodes was achieved by potentiodynamic method. Electrodeposition of Pd (C-PANI-Pd) and Ni (C-PANI-Ni) and codeposition of Pd-Ni (C-PANI-Pd-Ni) microparticles into the polyaniline (PANI) film coated graphite (C-PANI) were carried out under galvanostatic control. The morphology and composition of the composite electrodes were obtained using scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) techniques. The electrochemical behavior and electrocatalytic activity of the electrode were characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and chronoamperometric (CA) methods in acidic medium. The C-PANI-Pd-Ni electrode showed an improved catalytic performance towards methanol oxidation in terms of lower onset potential, higher anodic oxidation current, greater stability, lower activation energy, and lower charge transfer resistance. The enhanced electrocatalytic activity might be due to the greater permeability of C-PANI films for methanol molecules, better dispersion of Pd-Ni microparticles into the polymer matrixes, and the synergistic effects between the dispersed metal particles and their matrixes.
Theoretical Foundations of Efficiently Organizing Production Processes: Using the Example of Combining Organizational Forms of Component Manufacture and Internal Transport
Authors: Schroeder Anne-Katrin , Nebl Theodor , Mainzinger Christian
Published: October 2014

This paper examines the problem of efficient production processes organization down to subprocesses levels. Subtasks of production within subprocesses necessitate a specific set of requirements for production organization. Through particular features and their respective characteristics, these requirements are further systemized and described as process types. The main manufacturing process “component manufacture” and its connected production support service “internal transport” have been chosen as examples to show relevant organizational principles and forms. From this baseline and together with a decision algorithm, selected organizational options and a combination thereof shall lead to theoretically optimized solutions which meet all predefined requirements. A multilevel organizational alignment model lays out interdependencies of combined process type-oriented organizational forms. Methods of comparative organizational profile analysis in support of reengineering approaches are systemized and further developed towards resulting organizational adaptations.
Can Preterm Labour Be Predicted in Low Risk Pregnancies? Role of Clinical, Sonographic, and Biochemical Markers
Authors: Tripathi Reva , Tyagi Shakun , Singh Nilanchali , Mala Yedla Manikya , Singh Chanchal , Bhalla Preena , Ramji Siddhartha
Published: October 2014

Background and Objectives.This is a prospective nested cohort study conducted over a period of 3 years. 2644 women were recruited, out of which final analysis was done for 1884 women.Methods. Cervicovaginal and blood samples were collected for all recruited women. Out of these, 137 women who delivered before 35 weeks were treated as cases and equal number of matched controls were chosen. Analysis of samples for serum G-CSF, AFP, ferritin, and cervicovaginal interleukin-6 and IGFBP-1 was done.Results. Poor orodental hygiene, which can be a social marker, was significantly more common in women who delivered preterm (P=0.008). Serum alkaline phosphatase and serum ferritin were found to be significantly associated with preterm deliveries. The 90th percentile value of these parameters was considered as cut-off as there is no specific cut-off.Conclusions. Our study did not prove usefulness of any predictive marker. Serum ferritin and alkaline phosphatase were found to have correlation but their values are affected in many conditions and need to be elucidated with caution. Larger studies are needed for predicting preterm labour in asymptomatic women.
Association of Interleukin-18 Gene Polymorphism with Susceptibility to Visceral Leishmaniasis in Endemic Area of Bihar, an Indian Population
Authors: Kumar Dinesh , Tiwary Puja , Chakravarty Jaya , Sundar Shyam
Published: October 2014

Interleukin-18 (IL-18) is a cytokine that mediates Th1 response by inducing interferon-gamma (IFN-γ) production in T cells and natural killer cells. Genetic polymorphisms in the IL-18 gene have been found to be associated with its expression in cancer, tuberculosis, HBV infection, and various other diseases. Lower plasma level of IL-18 in visceral leishmaniasis (VL) patients might be associated with polymorphisms in the regulating or coding region of the gene. Three single nucleotide polymorphisms (SNPs), rs1946519 (−656 G/T) and rs187238 (−137 G/C) in the promoter region and rs549908 (+105 A/C) in the codon region, were genotyped in 204 parasitological confirmed VL patients and 267 controls with no past history of VL. For each locus, polymerase chain reaction (PCR) followed by restriction digestion was performed. IL-18 expression in peripheral blood mononuclear cells (PBMC) collected from VL patients and controls was measured by quantitative real-time RT-PCR. Distribution of G allele at position −656(P<0.0001)and double haplotypes GGC/GGA(P=0.05)were found to be significantly associated with controls while genotypes TT(P<0.0001)and single haplotypes TGA(P=0.0002), with cases. The inheritance of G allele at the position −656 might be considered as a protective allele for VL.
Multiplicity of Solutions to a Potential Operator Equation and Its Applications
Authors: Huang Jincheng
Published: October 2014

We consider the multiplicity of solutions for operator equation involving homogeneous potential operators. With the help of Nehari manifold and fibering maps, we prove that such equation has at least two nontrivial solutions. Furthermore, we apply this result to prove the existence of two nonnegative solutions for three types of quasilinear elliptic systems involving (p, q)-Laplacian operator and concave-convex nonlinearities.
Development and Validation of Sleep Disturbance Questionnaire in Patients with Acute Coronary Syndrome
Authors: Sepahvand Elham , Jalali Rostam , Khaledi Paveh Behnam , Rezaei Mansour
Published: October 2014

Background and Objectives. Severe sleep disturbance is a common problem among patients in cardiac care units (CCUs). There are questionnaires to measure sleep disturbances. Therefore, the present study seeks to design a valid and reliable questionnaire to assess sleep disturbance in patients with acute coronary syndrome (ACS) hospitalized in CCUs. Materials and Methods. In the present methodological research, items of the questionnaire were extracted through a systematic review. The validity and reliability of the questionnaires was assessed by face validity, content validity, construct validity, Cronbach’s alpha coefficient, and test-retest methods. Results. Factor analysis provided a questionnaire of 23 items on 5 dimensions of sleep disturbance in coronary patients: “sleep onset and continuity disorder,” “disorder in daytime functioning,” “sleep disturbance caused by environmental factors,” “sleep disturbance as a result of cardiac diseases,” and “respiratory disorders during sleep.” Furthermore, test-retest analysis showed a reliability correlation coefficient of r=0.766 and α Cronbach’s reliability (α=0.855). Conclusion. Sleep disturbance questionnaire for patients with ACS hospitalized in coronary care unit (CCU) was identified in 5 dimensions and assessed for validity and reliability. To control and improve the sleep quality of CCU hospitalized patients, we need to identify and remove predisposing factors.
Relative Toxicity of Leaf Extracts of Eucalyptus globulus and Centella asiatica against Mosquito Vectors Aedes aegypti and Anopheles stephensi
Authors: Nair Savitha Sekhar , Shetty Vinaya , Shetty Nadikere Jaya
Published: October 2014

The larvicidal activity of different solvent leaf extracts (hexane, diethyl ether, dichloromethane, and methanol) of Eucalyptus globulus and Centella asiatica against two geographically different strains of Aedes aegypti and Anopheles stephensi was investigated. The extracts were tested against the late third instar larvae of Aedes aegypti and Anopheles stephensi, and larval mortality was observed after 24 hours of treatment. LC50 and LC90 were calculated. The LC50 values of hexane extract of Eucalyptus globulus against the late third instar larvae of the BSN and JPN strains of Aedes aegypti and the DLC and KNG strains of Anopheles stephensi were 225.2, 167.7, 118.8, and 192.8 ppm, while those of the hexane extract of Centella asiatica were 246.5, 268.7, 50.6, and 243.5 ppm, respectively. The LC50 values of diethyl ether extract of Centella asiatica were 339.6, 134.5, 241, and 14.7 ppm. The hexane extracts of both plants and the diethyl ether extract of C. asiatica presented the highest potential for the control of Aedes aegypti and Anopheles stephensi. The present findings also reveal the necessity of assaying multiple strains of a species to fully comprehend the larvicidal efficacy of a compound.
Myostatin Gene Inactivation Prevents Skeletal Muscle Wasting in Cancer
Authors: Gallot Yann S. , Durieux Anne-Cécile , Castells Josiane , Desgeorges Marine M. , Vernus Barbara , Plantureux Léa , Rémond Didier , Jahnke Vanessa E. , Lefai Etienne , Dardevet Dominique , Nemoz Georges , Schaeffer Laurent , Bonnieu Anne , Freyssenet Damien G.
Published: October 2014

Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice. Myostatin gene inactivation prevented the severe loss of skeletal muscle mass induced in mice engrafted with Lewis lung carcinoma (LLC) cells or in ApcMin/+ mice, an established model of colorectal cancer and cachexia. Mechanistically, myostatin loss attenuated the activation of muscle fiber proteolytic pathways by inhibiting the expression of atrophy-related genes, MuRF1 and MAFbx/Atrogin-1, along with autophagy-related genes. Notably, myostatin loss also impeded the growth of LLC tumors, the number and the size of intestinal polyps in ApcMin/+ mice, thus strongly increasing survival in both models. Gene expression analysis in the LLC model showed this phenotype to be associated with reduced expression of genes involved in tumor metabolism, activin signaling, and apoptosis. Taken together, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and link this condition to tumor growth, with implications for furthering understanding of cancer as a systemic disease. Cancer Res; 74(24); 7344–56. ©2014 AACR.
Cellular Factors Promoting Resistance to Effective Treatment of Glioma with Oncolytic Myxoma Virus
Authors: Zemp Franz J. , McKenzie Brienne A. , Lun Xueqing , Reilly Karlyne M. , McFadden Grant , Yong V. Wee , Forsyth Peter A.
Published: October 2014

Oncolytic virus therapy is being evaluated in clinical trials for human glioma. While it is widely assumed that the immune response of the patient to the virus infection limits the utility of the therapy, investigations into the specific cell type(s) involved in this response have been performed using nonspecific pharmacologic inhibitors or allogeneic models with compromised immunity. To identify the immune cells that participate in clearing an oncolytic infection in glioma, we used flow cytometry and immunohistochemistry to immunophenotype an orthotopic glioma model in immunocompetent mice after Myxoma virus (MYXV) administration. These studies revealed a large resident microglia and macrophage population in untreated tumors, and robust monocyte, T-, and NK cell infiltration 3 days after MYXV infection. To determine the role on the clinical utility of MYXV therapy for glioma, we used a combination of knockout mouse strains and specific immunocyte ablation techniques. Collectively, our experiments identify an important role for tumor-resident myeloid cells and overlapping roles for recruited NK and T cells in the clearance and efficacy of oncolytic MYXV from gliomas. Using a cyclophosphamide regimen to achieve lymphoablation prior and during MYXV treatment, we prevented treatment-induced peripheral immunocyte recruitment and, surprisingly, largely ablated the tumor-resident macrophage population. Virotherapy of cyclophosphamide-treated animals resulted in sustained viral infection within the glioma as well as a substantial survival advantage. This study demonstrates that resistance to MYXV virotherapy in syngeneic glioma models involves a multifaceted cellular immune response that can be overcome with cyclophosphamide-mediated lymphoablation. Cancer Res; 74(24); 7260–73. ©2014 AACR.
Molecular Pathways: Targeting the Kinase Effectors of RHO-Family GTPases
Authors: Prudnikova Tatiana Y. , Rawat Sonali J. , Chernoff Jonathan
Published: October 2014

RHO GTPases, members of the RAS superfamily of small GTPases, are adhesion and growth factor–activated molecular switches that play important roles in tumor development and progression. When activated, RHO-family GTPases such as RAC1, CDC42, and RHOA, transmit signals by recruiting a variety of effector proteins, including the protein kinases PAK, ACK, MLK, MRCK, and ROCK. Genetically induced loss of RHO function impedes transformation by a number of oncogenic stimuli, leading to an interest in developing small-molecule inhibitors that either target RHO GTPases directly, or that target their downstream protein kinase effectors. Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use, their potential value as cancer therapeutics continues to facilitate pharmaceutical research and development and is a promising therapeutic strategy. Clin Cancer Res; 21(1); 24–29. ©2014 AACR.
Molecular Characterization of Choroid Plexus Tumors Reveals Novel Clinically Relevant Subgroups
Authors: Merino Diana M. , Shlien Adam , Villani Anita , Pienkowska Malgorzata , Mack Stephen , Ramaswamy Vijay , Shih David , Tatevossian Ruth , Novokmet Ana , Choufani Sanaa , Dvir Rina , Ben-Arush Myran , Harris Brent T. , Hwang Eugene I. , Lulla Rishi , Pfister Stefan M. , Achatz Maria Isabel , Jabado Nada , Finlay Jonathan L. , Weksberg Rosanna , Bouffet Eric , Hawkins Cynthia , Taylor Michael D. , Tabori Uri , Ellison David W. , Gilbertson Richard J. , Malkin David
Published: October 2014

Purpose: To investigate molecular alterations in choroid plexus tumors (CPT) using a genome-wide high-throughput approach to identify diagnostic and prognostic signatures that will refine tumor stratification and guide therapeutic options.

Experimental Design: One hundred CPTs were obtained from a multi-institutional tissue and clinical database. Copy-number (CN), DNA methylation, and gene expression signatures were assessed for 74, 36, and 40 samples, respectively. Molecular subgroups were correlated with clinical parameters and outcomes.

Results: Unique molecular signatures distinguished choroid plexus carcinomas (CPC) from choroid plexus papillomas (CPP) and atypical choroid plexus papillomas (aCPP); however, no significantly distinct molecular alterations between CPPs and aCPPs were observed. Allele-specific CN analysis of CPCs revealed two novel subgroups according to DNA content: hypodiploid and hyperdiploid CPCs. Hyperdiploid CPCs exhibited recurrent acquired uniparental disomy events. Somatic mutations in TP53 were observed in 60% of CPCs. Investigating the number of mutated copies of p53 per sample revealed a high-risk group of patients with CPC carrying two copies of mutant p53, who exhibited poor 5-year event-free (EFS) and overall survival (OS) compared with patients with CPC carrying one copy of mutant p53 (OS: 14.3%, 95% confidence interval, 0.71%–46.5% vs. 66.7%, 28.2%–87.8%, respectively, P = 0.04; EFS: 0% vs. 44.4%, 13.6%–71.9%, respectively, P = 0.03). CPPs and aCPPs exhibited favorable survival.

Discussion: Our data demonstrate that differences in CN, gene expression, and DNA methylation signatures distinguish CPCs from CPPs and aCPPs; however, molecular similarities among the papillomas suggest that these two histologic subgroups are indeed a single molecular entity. A greater number of copies of mutated TP53 were significantly associated to increased tumor aggressiveness and a worse survival outcome in CPCs. Collectively, these findings will facilitate stratified approaches to the clinical management of CPTs. Clin Cancer Res; 21(1); 184–92. ©2014 AACR.
MUC1 Promoter–Driven DTA as a Targeted Therapeutic Strategy against Pancreatic Cancer
Authors: Tholey Renee M. , Lal Shruti , Jimbo Masaya , Burkhart Richard A. , Blanco Fernando F. , Cozzitorto Joseph A. , Eisenberg Josh D. , Jiang Wei , Iacobuzio-Donahue Christine A. , Witkiewicz Agnieszka K. , Glbert Melissa , Yeo Charles J. , Brody Jonathan R. , Sawicki Janet A. , Winter Jordan M.
Published: October 2014

Mucin1 (MUC1) is overexpressed in pancreatic ductal adenocarcinoma (PDA) and is associated with tumor aggressiveness, suggesting that MUC1 is a promising therapeutic target for promoter-driven diphtheria toxin A (DTA). Endogenous MUC1 transcript levels were analyzed by quantitative PCR (qPCR) in multiple PDA cells (Capan1, HPAFII, Su.86.86, Capan2, Hs766T, MiaPaCa2, and Panc1). Expression levels were correlated with luciferase activity and cell death after transfection with MUC1 promoter–driven luciferase and DTA constructs. MUC1-positive (+) cells had significantly elevated MUC1 mRNA expression compared with MUC1-negative (−) cells. Luciferase activity was significantly higher in MUC1+ cells when transfected with MUC1 promoter–driven luciferase and MUC1+ cells underwent enhanced cell death after transfection with a single dose of MUC1 promoter–driven DTA. IFNγ pretreatment enhanced MUC1 expression in MUC1− cells and induced sensitivity to MUC1–DTA therapy. Matched primary and metastatic tumor lesions from clinical specimens revealed similar MUC1 IHC labeling patterns, and a tissue microarray of human PDA biopsies revealed increased immunolabeling with a combination of MUC1 and mesothelin (MSLN) antibodies, compared with either antibody alone. Combining MUC1 with MSLN-targeted DTA enhanced drug efficacy in an in vitro model of heterogeneous PDA. These data demonstrate that MUC1 promoter–driven DTA preferentially kills MUC1-expressing PDA cells and drugs that enhance MUC1 expression sensitize PDA cells with low MUC1 expression.

Implications: MUC1 expression in primary and metastatic lesions provides a rationale for the development of a systemic MUC1 promoter–driven DTA therapy that may be further enhanced by combination with other promoter-driven DTA constructs. Mol Cancer Res; 13(3); 439–48. ©2014 AACR.
Proinflammation of Aging Central Arteries: A Mini-Review
Authors: Wang Mingyi , Monticone Robert E. , Lakatta Edward G.
Published: October 2014

Arterial aging is a cornerstone of organismal aging. The central arterial wall structurally and functionally remodels under chronic proinflammatory stress over a lifetime. The low-grade proinflammation that accompanies advancing age causes arterial wall thickening and stiffening. These structural and functional alterations are consequences of adverse molecular and cellular events, e.g. an increase in local angiotensin II signaling that induces an inflammatory phenotypic shift of endothelial and smooth muscle cells. Thus, interventions to restrict proinflammatory signaling are a rational approach to delay or prevent age-associated adverse arterial remodeling.