bluuebunny/crossref_metadata_2025 huggingface dataset:
Manipulation effects of prior exercise intensity feedback by the Borg scale during open-loop cycling
Authors: Pires Flávio Oliveira , Hammond John
Published: January 2011

Objective

To verify the effects of exercise intensity deception by the Borg scale on the ratings of perceived exertion (RPE), heart rate (HR) and performance responses during a constant power output open-loop exercise.

Methods

Eight healthy men underwent a maximal incremental test on a cycle ergometer to identify the peak power output (PPO) and heart rate deflection point (HRDP). Subsequently, they performed a constant power output trial to exhaustion set at the HRDP intensity, in deception (DEC) and informed (INF) conditions: DEC—subjects were told that they would be cycling at an intensity corresponding to two categories below the RPE quantified at the HRDP; INF—subjects were told that they would cycle at the exact intensity corresponding to the RPE quantified at the HRDP.

Results

The PPO and power output at the HRDP obtained in maximal incremental tests were 247.5±32.1 W and 208.1±27.1 W, respectively. No significant difference in the time to exhaustion was found between DEC (525±244 s) or INF (499±224 s) trials. The slope and the first and second measurements of the RPE and HR parameters showed no significant difference between trials.

Conclusions

Psychophysiological variables such as RPE and HR as well as performance were not affected when exercise intensity was deceptively manipulated via RPE scores. This may suggest that unaltered RPE during exercise is a regulator of performance in this open-loop exercise.
Effect of ethnicity, gender and drug use history on achieving high rates of affirmative informed consent for genetics research: impact of sharing with a national repository
Authors: Ray Brenda , Jackson Colin , Ducat Elizabeth , Ho Ann , Hamon Sara , Kreek Mary Jeanne
Published: January 2011

Aim

Genetic research representative of the population is crucial to understanding the underlying causes of many diseases. In a prospective evaluation of informed consent we assessed the willingness of individuals of different ethnicities, gender and drug dependence history to participate in genetic studies in which their genetic sample could be shared with a repository at the National Institutes of Health.

Methods

Potential subjects were recruited from the general population through the use of flyers and referrals from previous participants and clinicians with knowledge of our study. They could consent to 11 separate choices so that they could specify how and with whom their genetic sample could be shared. Rates of affirmative consent were then analysed by gender, ethnicity and drug dependence history.

Results

Of 1416 volunteers enrolled, 99.7% gave affirmative informed consent for studies of addiction conducted in our laboratory. No significant difference was found for participation in genetic studies conducted in our laboratory by gender, ethnicity or drug dependence history. Over all 11 questions, individuals with a history of drug use were more likely to agree to consent to participate in our study than were healthy volunteers.

Conclusion

A high percentage of each category of gender, ethnicity and drug history, gave affirmative consent at all levels. The level of detail in and the amount of time spent reviewing the informed consent, and a relationship of trust with the clinical investigator may contribute to this outcome.
Veterinary surgeons' attitudes towards physician-assisted suicide: an empirical study of Swedish experts on euthanasia
Authors: Lerner Henrik , Lindblad Anna , Algers Bo , Lynöe Niels
Published: January 2011

Aim

To examine the hypothesis that knowledge about physician-assisted suicide (PAS) and euthanasia is associated with a more restrictive attitude towards PAS.

Design

A questionnaire about attitudes towards PAS, including prioritisation of arguments pro and contra, was sent to Swedish veterinary surgeons. The results were compared with those from similar surveys of attitudes among the general public and physicians.

Participants

All veterinary surgeons who were members of the Swedish Veterinary Association and had provided an email address (n=2421).

Main outcome measures

Similarities or differences in response pattern between veterinary surgeons, physicians and the general public.

Results

The response pattern among veterinary surgeons and the general public was almost similar in all relevant aspects. Of the veterinarians 75% (95% CI 72% to 78%) were in favour of PAS, compared with 73% (95% CI 69% to 77%) among the general public. Only 10% (95% CI 5% to 15%) of the veterinary surgeons were against PAS, compared with 12% (95% CI 5% to 19%) among the general public. Finally, 15% (95% CI 10% to 21%) of veterinarians were undecided, compared with 15% (95% CI 8% to 22%) among the general public. Physicians had a more restrictive attitude to PAS than the general public.

Conclusions

Since veterinary surgeons have frequent practical experience of euthanasia in animals, they do have knowledge about what euthanasia really is. Veterinary surgeons and the general public had an almost similar response pattern. Accordingly it seems difficult to maintain that knowledge about euthanasia is unambiguously associated with a restrictive attitude towards PAS.
Cerebral revascularization for the treatment of complex intracranial aneurysms of the posterior circulation: microsurgical anatomy, techniques and outcomes
Authors: Pisapia Jared M , Walcott Brian P , Nahed Brian V , Kahle Kristopher T , Ogilvy Christopher S
Published: January 2011

While the trend for endovascular therapy of posterior circulation aneurysms is permeating, cerebrovascular bypass remains essential in the armamentarium for complex lesions not amendable to these techniques. This review discusses the microsurgical anatomy of the posterior fossa intracranial circulation, as well as the techniques and outcomes related to cerebrovascular bypass.
Neonatal outcomes of preterm infants in breech presentation according to mode of birth in Canadian NICUs
Authors: Lodha Abhay , Zhu Qiaohao , Lee Shoo K , Shah Prakesh S ,   the Canadian Neonatal Network
Published: January 2011

Background

Many medical practitioners have adopted the practice of caesarean section for preterm infants in breech presentation based on term infant data. Some studies have highlighted deleterious effects on survival, such as intraventricular haemorrhage and periventricular leucomalacia, while others have reported no difference from the outcomes after vaginal delivery.

Objective

To compare outcomes of preterm infants of ≤32 weeks' gestational age who were in breech position at the time of birth according to mode of birth in Canadian neonatal intensive care units (NICUs).

Settings

29 Canadian NICUs.

Design

Neonates admitted to participating NICUs in the Canadian Neonatal Network between 2003 and 2007 were included in this retrospective study. Infants who were in breech position at the time of birth were divided into two groups: vaginal birth (VB) and caesarean section (CS). Data on common neonatal outcomes were compared using univariate and multivariate logistic regression.

Main outcome measures

Neonatal mortality and other neonatal morbidities.

Results

Of 3552 preterm infants in breech position at birth, 2937 (83%) were delivered by CS and 615 (17%) by VB. Multivariate regression analysis with adjustment for perinatal risk factors indicated that VB was associated with an increased risk of death (OR 1.7; 95% CI 1.3 to 2.3), chronic lung disease (OR 1.5; 95% CI 1.1 to 1.9) and severe retinopathy of prematurity (OR 1.6; 95% CI 1.1 to 2.3).

Conclusion

Vaginal birth for preterm infants in breech presentation is possibly associated with a higher risk of adverse neonatal outcomes compared with caesarean birth in Canadian NICUs. It is not clear whether adverse outcomes are due to the mode of delivery or whether breech birth is associated with other risk factors, an issue that can only be resolved by a randomised controlled trial.
Personal Knowledge Abilities and Knowledge Management Success
Authors: Hussain Iftikhar , Ahmed Shakeel , Si Steven
Published: January 2011

Knowledge management success is a hot issue in SMEs. It is obvious that several important factors must be considered for successful implementation, but most small and medium firms have no idea what factors should be considered most heavily. Therefore, the purpose of this study is to expand the base of knowledge in that area, and empirically test the relationship between personal capabilities within SMEs and knowledge management system success. Six factors related to personal capabilities were measured: ambition, skills, behaviour, tools and techniques, time management and personal knowledge. The results of the study indicate that there is a significant relationship between these factors and knowledge management system success.
Knowledge Management in Small- and Medium-Sized Enterprises
Authors: DiPasquale Joanna , McInerney Claire R.
Published: January 2011

KM principles often apply to large companies (more than 200 employees), where issues of general management and skill sets, as well as resources, often require comprehensive and multi-department solutions. However, many small businesses experience the same issues of knowledge sharing and management, but may find boundaries in the development and implementation of programs. How can small- to medium-sized enterprises (SMEs) benefit from KM principles? What areas in the traditional literature immediately apply, and what boundaries arise? Often encompassing multiple roles, managerial practices, and efforts in microcosm, how can these smaller companies provide the structure and impact needed to make KM principles work for them? This work analyses the problems that small businesses face in the collection, dissemination, and storage of company knowledge, including issues of technology, communities of practice, and "stickiness" for best-practice goals. The definitions of small business, as outlined by the European Commission and U.S. Small Business Administration (SBA), will serve as a useful tool for scope and discussion. This research will explore three key classifications of traits — structural or systemic, communication, and qualitative — through a review of the areas in which the challenges of small businesses, because of their size, imply somewhat different approaches to KM.
Staff Motivation at Kuwait University Libraries
Authors: Alqudsi-ghabra Taghreed , Mansouri Huda H.
Published: January 2011

Motivation is a force that leads people to act or perform. Motivating staff is a key element in making workers productive. It has the potential to increase incentive, put staff members at ease, and derive some satisfaction from their jobs. Factors that motivate staff vary across the professional, para-professional, and non-professional levels. The research here is a study of motivation techniques used by managers of Kuwait University libraries to improve employees' job satisfaction levels. In the process, it examines techniques and issues that motivate library staff and how these differ among professionals and non-professionals. It appears that high productivity depends on the level of library workers.
FEASIBILITY AND PROBLEMS OF EARTHQUAKE DISASTER REDUCTION MEASURES BASED ON ACTIVE FAULT DATA
Authors: KIYOMINE TERUMOTO , ITSUKI NAKABAYASHI
Published: January 2011

Active fault data have been more widely and closely investigated and extensive data have also been collected. However, there are only a few examples related to land use planning for disaster reduction measures based on active fault data. The purpose of this study is (1) to categorize the disaster reduction measures, and (2) to examine problems and important factors for promoting disaster reduction measures based on a questionnaire survey. The cases of the measures that are able to be distinguished included building restriction, nonconstruction restriction, and risk communication. The questionnaire survey was conducted with the residents of Yokosuka city. The results of analyses showed that disaster reduction measures based on active fault data tended to be approximately accepted. Other results indicated that as the public's understanding related to earthquake risk and risk mitigation measures increases, the awareness of risk reduction measures based on active fault data is promoted, and the objectives of disaster reduction measures would be realized.
Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome
Authors: Montecucco Fabrizio , Bertolotto Maria , Vuilleumier Nicolas , Franciosi Ulisse , Puddu Alessandra , Minetti Silvia , Delrio Andrea , Quercioli Alessandra , Bergamini Ettore , Ottonello Luciano , Pende Aldo , Lenglet Sébastien , Pelli Graziano , Mach François , Dallegri Franco , Viviani Giorgio Luciano
Published: January 2011

Metabolic syndrome is a proatherosclerotic condition clustering cardiovascular risk factors, including glucose and lipid profile alterations. The pathophysiological mechanisms favoring atherosclerotic inflammation in the metabolic syndrome remain elusive. Here, we investigated the potential role of the antilipolytic drug acipimox on neutrophil- and monocyte-mediated inflammation in the metabolic syndrome. Acipimox (500 mg) was orally administered to metabolic syndrome patients ( n = 11) or healthy controls ( n = 8). Serum and plasma was collected before acipimox administration ( time 0) as well as 2–5 h afterward to assess metabolic and hematologic parameters. In vitro, the effects of the incubation with metabolic syndrome serum were assessed on human neutrophil and monocyte migration toward the proatherosclerotic chemokine CCL3. Two to five hours after acipimox administration, a significant reduction in circulating levels of insulin and nonesterified fatty acid (NEFA) was shown in metabolic syndrome patients. At time 0 and 2 h after acipimox administration, metabolic syndrome serum increased neutrophil migration to CCL3 compared with healthy controls. No effect was shown in human monocytes. At these time points, serum-induced neutrophil migration positively correlated with serum levels of insulin and NEFA. Metabolic syndrome serum or recombinant insulin did not upregulate CCR5 expression on neutrophil surface membrane, but it increased intracellular JNK1/2 phosphorylation. Insulin immunodepletion blocked serum-induced neutrophil migration and associated JNK1/2 phosphorylation. Although mRNA expression of acipimox receptor (GPR109) was shown in human neutrophils, 5–500 μM acipimox did not affect insulin-induced neutrophil migration. In conclusion, results suggest that acipimox inhibited neutrophil proatherosclerotic functions in the metabolic syndrome through the reduction in circulating levels of insulin.
Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6
Authors: Green Christopher D. , Olson L. Karl
Published: January 2011

Induction of endoplasmic reticulum (ER) stress and apoptosis by elevated exogenous saturated fatty acids (FAs) plays a role in the pathogenesis of β-cell dysfunction and loss of islet mass in type 2 diabetes. Regulation of monounsaturated FA (MUFA) synthesis through FA desaturases and elongases may alter the susceptibility of β-cells to saturated FA-induced ER stress and apoptosis. Herein, stearoyl-CoA desaturase (SCD)1 and SCD2 mRNA expression were shown to be induced in islets from prediabetic hyperinsulinemic Zucker diabetic fatty (ZDF) rats, whereas SCD1, SCD2, and fatty acid elongase 6 (Elovl6) mRNA levels were markedly reduced in diabetic ZDF rat islets. Knockdown of SCD in INS-1 β-cells decreased desaturation of palmitate to MUFA, lowered FA partitioning into complex neutral lipids, and increased palmitate-induced ER stress and apoptosis. Overexpression of SCD2 increased desaturation of palmitate to MUFA and attenuated palmitate-induced ER stress and apoptosis. Knockdown of Elovl6 limited palmitate elongation to stearate, increasing palmitoleate production and attenuating palmitate-induced ER stress and apoptosis, whereas overexpression of Elovl6 increased palmitate elongation to stearate and palmitate-induced ER stress and apoptosis. Overall, these data support the hypothesis that enhanced MUFA synthesis via upregulation of SCD2 activity can protect β-cells from elevated saturated FAs, as occurs in prediabetic states. Overt type 2 diabetes is associated with diminished islet expression of SCD and Elovl6, and this can disrupt desaturation of saturated FAs to MUFAs, rendering β-cells more susceptible to saturated FA-induced ER stress and apoptosis.
Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats
Authors: Koeners Maarten P. , Wesseling Sebastiaan , Ulu Arzu , Sepúlveda Rocío López , Morisseau Christophe , Braam Branko , Hammock Bruce D. , Joles Jaap A.
Published: January 2011

We hypothesized that perinatal inhibition of soluble epoxide hydrolase (SEH), which metabolizes epoxyeicosatrienoic acids in the arachidonic acid (AA) cascade, with an orally active SEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), would persistently reduce blood pressure (BP) in adult SHR despite discontinuation of AUDA at 4 wk of age. Renal cytoplasmic epoxide hydrolase-2 (Ephx2) gene expression was enhanced in SHR vs. WKY from 2 days to 24 wk. Effects of perinatal treatment with AUDA, supplied to SHR dams until 4 wk after birth, on BP in female and male offspring and renal oxylipin metabolome in female offspring were observed and contrasted to female SHR for direct effects of AUDA (8–12 wk). Briefly, inhibition of SEH was effective in persistently reducing BP in female SHR when applied during the perinatal phase. This was accompanied by marked increases in major renal AA epoxides and decreases in renal lipoxygenase products of AA. Early inhibition of SEH induced a delayed increase in renal 5-HETE at 24 wk, in contrast to a decrease at 2 wk. Inhibition of SEH in female SHR from 8 to 12 wk did not reduce BP but caused profound decreases in renal 15( S)-HETrE, LTB4, TBX2, 5-HETE, and 20-HETE and increases in TriHOMEs. In male SHR, BP reduction after perinatal AUDA was transient. Thus, Ephx2 transcription and SEH activity in early life may initiate mechanisms that eventually contribute to high BP in adult female SHR. However, programmed BP-lowering effects of perinatal SEH inhibition in female SHR cannot be simply explained by persistent reduction in renal SEH activity but rather by more complex and temporally dynamic interactions between the renal SEH, lipoxygenase, and cyclooxygenase pathways.
Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats
Authors: Mizuno Masaki , Kawada Toru , Kamiya Atsunori , Miyamoto Tadayoshi , Shimizu Shuji , Shishido Toshiaki , Smith Scott A. , Sugimachi Masaru
Published: January 2011

We examined the transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained (16 wk, treadmill for 1 h, 5 times/wk at 15 m/min and 15-degree grade) rats for comparison to HR variability assessed in the conscious resting state. The transfer function from sympathetic stimulation to HR response was similar between groups (gain, 4.2 ± 1.5 vs. 4.5 ± 1.5 beats·min−1·Hz−1; natural frequency, 0.07 ± 0.01 vs. 0.08 ± 0.01 Hz; damping coefficient, 1.96 ± 0.55 vs. 1.69 ± 0.15; and lag time, 0.7 ± 0.1 vs. 0.6 ± 0.1 s; sedentary vs. exercise trained, respectively, means ± SD). The transfer gain from vagal stimulation to HR response was 6.1 ± 3.0 in the sedentary and 9.7 ± 5.1 beats·min−1·Hz−1 in the exercise-trained group ( P = 0.06). The corner frequency (0.11 ± 0.05 vs. 0.17 ± 0.09 Hz) and lag time (0.1 ± 0.1 vs. 0.2 ± 0.1 s) did not differ between groups. When the sympathetic transfer gain was averaged for very-low-frequency and low-frequency bands, no significant group effect was observed. In contrast, when the vagal transfer gain was averaged for very-low-frequency, low-frequency, and high-frequency bands, exercise training produced a significant group effect ( P < 0.05 by two-way, repeated-measures ANOVA). These findings suggest that, in the frequency domain, exercise training augments the dynamic HR response to vagal stimulation but not sympathetic stimulation, regardless of the frequency bands.
Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis in response to anti-TNF-α treatments
Authors: Meugnier E. , Coury F. , Tebib J. , Ferraro-Peyret C. , Rome S. , Bienvenu J. , Vidal H. , Sibilia J. , Fabien N.
Published: January 2011

The efficacy of anti-TNF-α therapies highlights the role of TNF-α in the pathogenesis of rheumatoid arthritis (RA). However, the mechanism of action of these agents is poorly understood at the molecular level. The aim of this study was to characterize the effects of anti-TNF-α treatment on the global gene expression profile in peripheral blood mononuclear cells (PBMCs) of responder RA patients. Changes in gene expression were determined using oligonucleotide microarrays (25,341 genes) in PBMCs obtained before and after 12 wk of treatment with either etanercept or adalimumab from responder RA patients. Two hundred fifty-one genes displayed significant changes (false discovery rate < 0.1%) in expression level (178 upregulations with mean fold change = 1.5 and 73 downregulations with mean fold change = −1.50) after 12 wk of treatment. Importantly, the expression of several genes, including those coding for the calcium binding proteins S100A12 and A8, CD14 antigen, Selectin P, or ribosomal protein L39, reported to be upregulated in RA patients, were found to be decreased after anti-TNF-α treatment. Globally, inflammation, immune response, apoptosis, protein synthesis, and mitochondrial oxido-reduction were the most affected pathways in response to anti-TNF-α treatment. The obtained gene expression signature in PBMCs provides new information to better understand the mechanisms of action of anti-TNF-α treatment in RA patients.
Blood gene expression signatures associate with heart failure outcomes
Authors: VanBuren Peter , Ma Jun , Chao Samuel , Mueller Enkhtuyaa , Schneider David J. , Liew Choong-Chin
Published: January 2011

Gene expression signatures in blood correlate with specific diseases. Such signatures may serve as valuable diagnostic and prognostic tools in disease management. Blood gene expression signatures associated with heart failure may be applied to predict prognosis, monitor disease progression, and optimize treatment. Blood gene expression profiles were generated for 71 subjects with heart failure and 15 controls without heart failure, using the Affymetrix GeneChip U133Plus2.0. Survival analysis identified 197 “mortality genes” that were significantly associated with patient outcome. Functional categorization showed that genes associated with T cell receptor signaling were most significantly overpresented. Cluster analysis of these T cell receptor signaling genes significantly categorized heart failure patients into three risk groups ( P = 0.031) that were distinct from the three risk groups categorized by New York Heart Association (NYHA) Classification ( P = 0.0002). By combining the analysis of clinical assessment (NYHA class) with T cell receptor signaling gene expression, we proposed a model that demonstrated an even greater differentiation of patients at risk ( P = 0.0001). In this discovery study, we identified blood expression signatures associated with heart failure patient outcomes. Characterization of these mortality genes helped identify a set of T cell receptor signaling genes that may be of utility in predicting survival of heart failure patients. These data raise the possibility of prospectively risk stratifying patients with heart failure by integrating blood gene expression signatures with current clinical assessment.
Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis identifies multiple sites of molecular regulation
Authors: Xie Ting , Liang Jiurong , Guo Rishu , Liu Ningshan , Noble Paul W. , Jiang Dianhua
Published: January 2011

The molecular mechanisms of lung injury and fibrosis are incompletely understood. MicroRNAs (miRNAs) are crucial biological regulators that act by suppressing their target genes and are involved in a variety of pathophysiological processes. To gain insight into miRNAs in the regulation of lung fibrosis, total RNA was isolated from mouse lungs harvested at different days after bleomycin treatment, and miRNA array with 1,810 miRNA probes was performed thereafter. MiRNAs expressed in lungs with bleomycin treatment at different time points were compared with miRNAs expressed in lungs without bleomycin treatment, resulting in 161 miRNAs differentially expressed. Furthermore, miRNA expression patterns regulated in initial and late periods after bleomycin were identified. Target genes were predicted in silico for differentially expressed miRNAs, including let-7f, let-7g, miR-196b, miR-16, miR-195, miR-25, miR-144, miR-351, miR-153, miR-468, miR-449b, miR-361, miR-700, miR-704, miR-717, miR-10a, miR-211, miR-34a, miR-367, and miR-21. Target genes were then cross-referenced to the molecular pathways, suggesting that the differentially expressed miRNAs regulate apoptosis, Wnt, Toll-like receptor, and TGF-β signaling. Our study demonstrated a relative abundance of miRNA levels in bleomycin-induced lung fibrosis. The miRNAs and their potential target genes identified may contribute to the understanding of the complex transcriptional program of lung fibrosis.
Intuitionistic Fuzzy Stability of a Quadratic Functional Equation
Authors: Wang Liguang
Published: January 2011

We consider the intuitionistic fuzzy stability of the quadratic functional equation "Equation missing" by using the fixed point alternative, where "Equation missing" is a positive integer.
Relationships between Obesity, Cardiorespiratory Fitness, and Cardiovascular Function
Authors: Davison Kade , Bircher Stefan , Hill Alison , Coates Alison M. , Howe Peter R. C. , Buckley Jonathan D.
Published: January 2011

Background. Obesity and low cardiorespiratory fitness (CRF) have been shown to independently increase the risk of CVD mortality. The aim of this study was to investigate the relationship between CRF, body fatness and markers of arterial function.Method and Results. Obese (9 male, 18 female; BMI 35.3 ± 0.9 kg·m-2) and lean (8 male, 18 female; BMI 22.5 ± 0.3 kg·m-2) volunteers were assessed for body composition (DXA), cardiorespiratory fitness (predicted max), blood pressure (BP), endothelial vasodilatator function (FMD), and arterial compliance (AC) (via radial artery tonometry). The obese group had more whole body fat and abdominal fat (43.5 ± 1.2% versus 27.2 ± 1.6%; and 48.6 ± 0.9% versus 28.9 ± 1.8%; resp.), and lower FMD (3.2 ± 0.4% versus 5.7 ± 0.7%; ) than the lean subjects, but there was no difference in AC. AC in large arteries was positively associated with CRF (; ) but not with fatness.Conclusion. These results indicate distinct influences of obesity and CRF on blood vessel health. FMD was impaired with obesity, which may contribute to arterial and metabolic dysfunction. Low CRF was associated with reduced elasticity in large arteries, which could result in augmentation of aortic afterload.
Effect of Glucose or Fat Challenge on Aspirin Resistance in Diabetes
Authors: Yassine Hussein N. , Davis-Gorman Grace , Stump Craig S. , Thomson Stephen S. , Peterson Justin , McDonagh Paul F.
Published: January 2011

Aspirin has lower antiplatelet activity in diabetic patients. Our aim is to study the roles of acute hyperglycemia and hyperlipidemia on aspirin function in diabetic subjects with and without cardiovascular disease. Using urine thromboxane (pg/mg creatinine) and VerifyNow (Aspirin Resistance Measures-ARU), we investigated diabetic subjects during a 2-hour glucose challenge (n=49) or a 4-hour fat challenge (n=11). All subjects were currently taking aspirin (81 or 325 mg). After fat ingestion, urine thromboxane increased in all subjects (Mean ± SE before: after) (1209±336:1552±371,P=.01), while we noted a trend increase in VerifyNow measures (408±8:431±18,P=.1). The response to glucose ingestion was variable. Diabetic subjects with cardiac disease and dyslipidemia increased thromboxane (1693±364:2799±513,P<.05) and VerifyNow (457.6±22.3:527.1±25.8,P<.05) measures after glucose. We conclude that saturated fat ingestion increasesin vivothromboxane production despite aspirin therapy.
Trajectory Planning for Nonholonomic Mobile Robot Using Extended Kalman Filter
Authors: de Melo Leonimer Flavio , Junior Jose Fernando Mangili
Published: January 2011

In the mobile robotic systems, a precise estimate of the robot pose with the intention of the optimization in the path planning is essential for the correct performance, on the part of the robots, for tasks that are destined to it. This paper describes the use of RF digital signal interacting with beacons for computational triangulation in the way to provide a pose estimative at bidimensional indoor environment, where GPS system is out of range. This methodology takes advantage of high‐performance multicore DSP processors to calculate ToF of the order about ns. Sensors data like odometry, compass, and the result of triangulation Cartesian estimative, are fused for better position estimative. It uses a mathematical and computational tool for nonlinear systems with time‐discrete sampling for pose estimative calculation of mobile robots, with the utilization of extended Kalman filter (EKF). A mobile robot platform with differential drive and nonholonomic constraints is used as a base for state space, plants and measurements models that are used in the simulations and validation of the experiments.
On Approximation of Entropy Solutions for One System of Nonlinear Hyperbolic Conservation Laws with Impulse Source Terms
Authors: D'Apice Ciro , Kogut Peter I. , Manzo Rosanna
Published: January 2011

We study one class of nonlinear fluid dynamic models with impulse source terms. The model consists of a system of two hyperbolic conservation laws: a nonlinear conservation law for the goods density and a linear evolution equation for the processing rate. We consider the case when influx-rates in the second equation take the form of impulse functions. Using the vanishing viscosity method and the so-called principle of fictitious controls, we show that entropy solutions to the original Cauchy problem can be approximated by optimal solutions of special optimization problems.
Hepatoprotective Activity of Dried‐ and Fermented‐Processed Virgin Coconut Oil
Authors: Zakaria Z. A. , Rofiee M. S. , Somchit M. N. , Zuraini A. , Sulaiman M. R. , Teh L. K. , Salleh M. Z. , Long K.
Published: January 2011

The present study aims to determine the hepatoprotective effect of MARDI‐produced virgin coconut oils, prepared by dried‐ or fermented‐processed methods, using the paracetamol‐induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in‐depth study.
Existence and Multiplicity of Solutions for Discrete Nonlinear Two‐Point Boundary Value Problems
Authors: Guo Jianmin , Guo Caixia
Published: January 2011

By using Morse theory, the critical point theory, and the character
of K1/2, we consider the existence and multiplicity results of solutions to the following discrete
nonlinear two‐point boundary value problem −Δ2x(k − 1) = f(k, x(k)), k ∈ ℤ(1, T) subject to x(0) = 0 = Δx(T), where T is a positive integer, ℤ(1, T) = {1, 2, …, T}, Δ is the forward difference operator defined by Δx(k) = x(k + 1) − x(k), and f : ℤ(1, T) × ℝ → ℝ is continuous. In argument, Morse inequalities play an important role.
Mycobacterial PE/PPE Proteins at the Host-Pathogen Interface
Authors: Sampson Samantha L.
Published: January 2011

The mycobacterial PE/PPE proteins have attracted much interest since their formal identification just over a decade ago. It has been widely speculated that these proteins may play a role in evasion of host immune responses, possibly via antigenic variation. Although a cohesive understanding of their function(s) has yet to be established, emerging data increasingly supports a role for the PE/PPE proteins at multiple levels of the infectious process. This paper will delineate salient features of the families revealed by comparative genomics, bioinformatic analyses and genome-wide screening approaches and will summarise existing knowledge of subcellular localization, secretion pathways, and protein structure. These characteristics will be considered in light of findings on innate and adaptive host responses to PE/PPE proteins, and we will review the increasing body of data on B and T cell recognition of these proteins. Finally, we will consider how current knowledge and future explorations may contribute to a more comprehensive understanding of these intriguing proteins and their involvement in host pathogen interactions. Ultimately this information could underpin future intervention strategies, for example, in the area of new and improved diagnostic tools and vaccine candidates.
Rectourinary Fistula after Radical Prostatectomy: Review of the Literature for Incidence, Etiology, and Management
Authors: Kitamura Hiroshi , Tsukamoto Taiji
Published: January 2011

Although rectourinary fistula (RUF) after radical prostatectomy (RP) is rare, it is an important issue impairing the quality of life of patients. If the RUF does not spontaneously close after colostomy, surgical closure should be considered. However, there is no standard approach and no consensus in the literature. A National Center for Biotechnology Information (NVBI) PubMed search for relevant articles published between 1995 and December 2010 was performed using the medical subject headings “radical prostatectomy” and “fistula.” Articles relevant to the treatment of RUF were retained. RUF developed in 0.6% to 9% of patients after RP. Most cases required colostomy, but more than 50% of them needed surgical fistula closure thereafter. The York-Mason technique is the most common approach, and closure using a broad-based flap of rectal mucosa is recommended after excision of the RUF. New techniques using a sealant or glue are developing, but further successful reports are needed.
Feedback Control in a Periodic Delay Single‐Species Difference System
Authors: Yang Yi , Liu Zhijun
Published: January 2011

A periodic delay single‐species difference system with
feedback control is established. With the help of analysis method and Lyapunov
function, a good understanding of the permanence and global attractivity of the
system is gained. Numerical simulations are presented to verify the validity of the
proposed criteria. Our results show that feedback control has no influence on the
permanence while it has influence on the global attractivity of the system.
Phosphorylation Regulates c-Myc's Oncogenic Activity in the Mammary Gland
Authors: Wang Xiaoyan , Cunningham Melissa , Zhang Xiaoli , Tokarz Sara , Laraway Bryan , Troxell Megan , Sears Rosalie C.
Published: January 2011

Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c-myc knock-in mice that conditionally express either c-MycWT or the c-MycT58A or c-MycS62A phosphorylation mutant from the constitutively active ROSA26 locus in response to Cre recombinase to study the role of these phosphorylation sites in vivo. Using a mammary-specific Cre model, we found that expression of c-MycWT resulted in increased mammary gland density, but normal morphology and no tumors at the level expressed from the ROSA promoter. In contrast, c-MycT58A expression yielded enhanced mammary gland density, hyperplastic foci, cellular dysplasia, and mammary carcinoma, associated with increased genomic instability and suppressed apoptosis relative to c-MycWT. Alternatively, c-MycS62A expression reduced mammary gland density relative to control glands, and this was associated with increased genomic instability and normal apoptotic function. Our results indicate that specific activities of c-Myc are differentially affected by T58 and S62 phosphorylation. This model provides a robust platform to interrogate the role that these phosphorylation sites play in c-Myc function during development and tumorigenesis. Cancer Res; 71(3); 925–36. ©2011 AACR.
Multiple Mutations and Bypass Mechanisms Can Contribute to Development of Acquired Resistance to MET Inhibitors
Authors: Qi Jie , McTigue Michele A. , Rogers Andrew , Lifshits Eugene , Christensen James G. , Jänne Pasi A. , Engelman Jeffrey A.
Published: January 2011

Therapies targeting receptor tyrosine kinases have shown efficacy in molecularly defined subsets of cancers. Unfortunately, cancers invariably develop resistance, and overcoming or preventing resistance will ultimately be key to unleashing their full therapeutic potential. In this study, we examined how cancers become resistant to MET inhibitors, a class of drugs currently under clinical development. We utilized the highly sensitive gastric carcinoma cell line, SNU638, and two related MET inhibitors PHA-665752 and PF-2341066. To our surprise, we observed at least two mechanisms of resistance that arose simultaneously. Both resulted in maintenance of downstream PI3K (phosphoinositide 3-kinase)-AKT and MEK (MAP/ERK kinase)-ERK signaling in the presence of inhibitor. One mechanism, observed by modeling resistance both in vitro and in vivo, involved the acquisition of a mutation in the MET activation loop (Y1230). Structural analysis indicates that this mutation destabilizes the autoinhibitory conformation of MET and abrogates an important aromatic stacking interaction with the inhibitor. The other cause of resistance was activation of the epidermal growth factor receptor (EGFR) pathway due to increased expression of transforming growth factor α. Activation of EGFR bypassed the need for MET signaling to activate downstream signaling in these cells. This resistance could be overcome by combined EGFR and MET inhibition. Thus, therapeutic strategies that combine MET inhibitors capable of inhibiting Y1230 mutant MET in combination with anti-EGFR–based therapies may enhance clinical benefit for patients with MET-addicted cancers. Importantly, these results also underscore the notion that a single cancer can simultaneously develop resistance induced by several mechanisms and highlight the daunting challenges associated with preventing or overcoming resistance. Cancer Res; 71(3); 1081–91. ©2011 AACR.
Agonist Anti-CD137 mAb Act on Tumor Endothelial Cells to Enhance Recruitment of Activated T Lymphocytes
Authors: Palazón Asís , Teijeira Alvaro , Martínez-Forero Iván , Hervás-Stubbs Sandra , Roncal Carmen , Peñuelas Iván , Dubrot Juan , Morales-Kastresana Aizea , Pérez-Gracia José Luis , Ochoa M. Carmen , Ochoa-Callejero Laura , Martínez Alfredo , Luque Alfonso , Dinchuk Joseph , Rouzaut Ana , Jure-Kunkel Maria , Melero Ignacio
Published: January 2011

Agonist monoclonal antibodies (mAb) to the immune costimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment on the basis of their costimulatory effects on primed T cells and perhaps other cells of the immune system. Here we provide evidence that CD137 is selectively expressed on the surface of tumor endothelial cells. Hypoxia upregulated CD137 on murine endothelial cells. Treatment of tumor-bearing immunocompromised Rag−/− mice with agonist CD137 mAb did not elicit any measurable antiangiogenic effects. In contrast, agonist mAb stimulated tumor endothelial cells, increasing cell surface expression of the adhesion molecules intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin. When adoptively transferred into mice, activated T lymphocytes derived from CD137-deficient animals entered more avidly into tumor tissue after treatment with agonist mAb. This effect could be neutralized with anti–ICAM-1 and anti–VCAM-1 blocking antibodies. Thus, stimulation of CD137 not only enhanced T-cell activation but also augmented their trafficking into malignant tissue, through direct actions on the blood vessels that irrigate the tumor. Our findings identify an additional mechanism of action that can explain the immunotherapeutic effects of agonist CD137 antibodies. Cancer Res; 71(3); 801–11. ©2011 AACR.
Hydrophilic Agarose Macrobead Cultures Select for Outgrowth of Carcinoma Cell Populations That Can Restrict Tumor Growth
Authors: Smith Barry H. , Gazda Lawrence S. , Conn Bryan L. , Jain Kanti , Asina Shirin , Levine Daniel M. , Parker Thomas S. , Laramore Melissa A. , Martis Prithy C. , Vinerean Horatiu V. , David Eric M. , Qiu Suizhen , North Alison J. , Couto C. Guillermo , Post Gerald S. , Waters David J. , Cordon-Cardo Carlos , Hall Richard D. , Gordon Bruce R. , Diehl Carolyn H. , Stenzel Kurt H. , Rubin Albert L.
Published: January 2011

Cancer cells and their associated tumors have long been considered to exhibit unregulated proliferation or growth. However, a substantial body of evidence indicates that tumor growth is subject to both positive and negative regulatory controls. Here, we describe a novel property of tumor growth regulation that is neither species nor tumor-type specific. This property, functionally a type of feedback control, is triggered by the encapsulation of neoplastic cells in a growth-restricting hydrogel composed of an agarose matrix with a second coating of agarose to form 6- to 8-mm diameter macrobeads. In a mouse cell model of renal adenocarcinoma (RENCA cells), this process resulted in selection for a stem cell–like subpopulation which together with at least one other cell subpopulation drove colony formation in the macrobeads. Cells in these colonies produced diffusible substances that markedly inhibited in vitro and in vivo proliferation of epithelial-derived tumor cells outside the macrobeads. RENCA cells in monolayer culture that were exposed to RENCA macrobead-conditioned media exhibited cell-cycle accumulation in S phase due to activation of a G2/M checkpoint. At least 10 proteins with known tumor suppression functions were identified by analysis of RENCA macrobead-conditioned media, the properties of which offer opportunities to further dissect the molecular basis for tumor growth control. More generally, macrobead culture may permit the isolation of cancer stem cells and other cells of the stem cell niche, perhaps providing strategies to define more effective biologically based clinical approaches to treat neoplastic disease. Cancer Res; 71(3); 725–35. ©2011 AACR.
EGFR Nuclear Translocation Modulates DNA Repair following Cisplatin and Ionizing Radiation Treatment
Authors: Liccardi Gianmaria , Hartley John A. , Hochhauser Daniel
Published: January 2011

Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. It modulates DNA repair after radiation-induced damage through association with the catalytic subunit of DNA protein kinase (DNA-PKcs). We investigated the role of EGFR nuclear import and its association with DNA-PKcs on DNA repair after exposure to cisplatin or ionizing radiation (IR). The model system was based on EGFR-null murine NIH3T3 fibroblasts in which EGFR expression was restored with isoforms that were wild-type (wt), derived from human cancers (L858R, EGFRvIII), or mutated in the nuclear localization signal (NLS) sequence. In cells expressing wtEGFR or EGFRvIII, there was complete unhooking of cisplatin-induced interstrand cross-links and repair of IR-induced strand breaks. In contrast, cells expressing L858R or NLS mutations showed reduced unhooking of interstrand cross-links and repair of strand breaks. Immunoprecipitation showed wtEGFR and EGFRvIII binding to DNA-PKcs, increasing 2-fold 18 hours after cisplatin therapy. Confocal microscopy and proximity ligation assay showed that this interaction in the cytoplasm and nucleus was associated with increased DNA protein kinase complex (DNA-PK) activity. Cells expressing the EGFR L858R mutation, which has constitutive kinase activity, exhibited reduced DNA repair without nuclear localization. EGFR-NLS mutants showed impaired nuclear localization and DNA-PKcs association with reduced DNA repair and DNA-PK kinase activity. In summary, EGFR nuclear localization was required for modulation of cisplatin and IR-induced repair of DNA damage. EGFR–DNA-PKcs binding was induced by cisplatin or IR but not by EGFR nuclear translocation per se. Our findings show that EGFR subcellular distribution can modulate DNA repair kinetics, with implications for design of EGFR-targeted combinational therapies. Cancer Res; 71(3); 1103–14. ©2011 AACR.
HSulf-1 Modulates FGF2- and Hypoxia-Mediated Migration and Invasion of Breast Cancer Cells
Authors: Khurana Ashwani , Liu Peng , Mellone Pasquale , Lorenzon Laura , Vincenzi Bruno , Datta Kaustubh , Yang Bo , Linhardt Robert J. , Lingle Wilma , Chien Jeremy , Baldi Alfonso , Shridhar Viji
Published: January 2011

HSulf-1 modulates the sulfation states of heparan sulfate proteoglycans critical for heparin binding growth factor signaling. In the present study, we show that HSulf-1 is transcriptionally deregulated under hypoxia in breast cancer cell lines. Knockdown of HIF-1α rescued HSulf-1 downregulation imposed by hypoxia, both at the RNA and protein levels. Chromatin immunoprecipitation with HIF-1α and HIF-2α antibodies confirmed recruitment of HIF-α proteins to the two functional hypoxia-responsive elements on the native HSulf-1 promoter. HSulf-1 depletion in breast cancer cells resulted in an increased and sustained bFGF2 (basic fibroblast growth factor) signaling and promoted cell migration and invasion under hypoxic conditions. In addition, FGFR2 (fibroblast growth factor receptor 2) depletion in HSulf-1–silenced breast cancer cells attenuated hypoxia-mediated cell invasion. Immunohistochemical analysis of 53 invasive ductal carcinomas and their autologous metastatic lesions revealed an inverse correlation for the expression of HSulf-1 to CAIX in both the primary tumors (P ≥ 0.0198) and metastatic lesions (P ≥ 0.0067), respectively, by χ2 test. Finally, HSulf-1 expression levels in breast tumors by RNA in situ hybridization showed that high HSulf-1 expression is associated with increased disease-free and overall survival (P ≥ 0.03 and P ≥ 0.0001, respectively). Collectively, these results reveal an important link between loss of HSulf-1 under hypoxic microenvironment and increased growth factor signaling, cell migration, and invasion. Cancer Res; 71(6); 2152–61. ©2011 AACR.