bluuebunny/crossref_metadata_2025 huggingface dataset:
Prorenin Contributes to Angiotensin Peptide Formation in Transgenic Rats With Rat Prorenin Expression Targeted to the Liver
Authors: Campbell Duncan J. , Karam Habib , Ménard Joël , Bruneval Patrick , Mullins John J.
Published: October 2009

We reported previously that targeted expression of rat prorenin to the liver under the control of the human α1-antitrypsin promoter increased plasma prorenin levels by several-hundred–fold in male transgenic rats and caused cardiac hypertrophy, severe renal lesions, and myocardial fibrosis by 20 weeks of age, despite normal blood pressure. We examined the evolution of the phenotype of male transgenic rats over 12 months and the effects of binephrectomy on the renin-angiotensin (Ang) system. Plasma prorenin levels were >1000-fold higher than in wild type littermates, whereas plasma and renal Ang II levels were no different from wild-type (WT) levels, and kidney renin levels were suppressed in transgenic rats. In contrast to our earlier report, transgenic rats had increased systolic blood pressure at 3 to 12 months of age, and only modest renal lesions and myocardial fibrosis were evident after 6 months of age. Binephrectomy reduced plasma renin activity and concentration and prorenin levels by 50% to 80% and Ang II levels by 90% in WT rats. By contrast, binephrectomy increased plasma renin activity and concentration and prorenin levels by 52.0-, 13.0-, and 5.8-fold, respectively, without change in Ang II levels in transgenic rats. We conclude that, in the animals studied in this report, elevated prorenin levels did not cause renal lesions or myocardial fibrosis during the first 6 months of age. Ang peptide formation consequent to the increased prorenin levels prevented reduction of Ang II levels after binephrectomy and was likely to have contributed to hypertension, cardiac hypertrophy, and suppression of kidney renin levels in these transgenic rats.
Cross-Correlations in High-Conductance States of a Model Cortical Network
Authors: Hertz John
Published: October 2009

Neuronal firing correlations are studied using simulations of a simple network model for a cortical column in a high-conductance state with dynamically balanced excitation and inhibition. Although correlations between individual pairs of neurons exhibit considerable heterogeneity, population averages show systematic behavior. When the network is in a stationary state, the average correlations are generically small: correlation coefficients are of order 1/N, where N is the number of neurons in the network. However, when the input to the network varies strongly in time, much larger values are found. In this situation, the network is out of balance, and the synaptic conductance is low, at times when the strongest firing occurs. However, examination of the correlation functions of synaptic currents reveals that after these bursts, balance is restored within a few milliseconds by a rapid increase in inhibitory synaptic conductance. These findings suggest an extension of the notion of the balanced state to include balanced fluctuations of synaptic currents, with a characteristic timescale of a few milliseconds.
Supervised Learning in Spiking Neural Networks with ReSuMe: Sequence Learning, Classification, and Spike Shifting
Authors: Ponulak Filip , Kasiński Andrzej
Published: October 2009

Learning from instructions or demonstrations is a fundamental property of our brain necessary to acquire new knowledge and develop novel skills or behavioral patterns. This type of learning is thought to be involved in most of our daily routines. Although the concept of instruction-based learning has been studied for several decades, the exact neural mechanisms implementing this process remain unrevealed. One of the central questions in this regard is, How do neurons learn to reproduce template signals (instructions) encoded in precisely timed sequences of spikes?

Here we present a model of supervised learning for biologically plausible neurons that addresses this question. In a set of experiments, we demonstrate that our approach enables us to train spiking neurons to reproduce arbitrary template spike patterns in response to given synaptic stimuli even in the presence of various sources of noise.

We show that the learning rule can also be used for decision-making tasks. Neurons can be trained to classify categories of input signals based on only a temporal configuration of spikes. The decision is communicated by emitting precisely timed spike trains associated with given input categories. Trained neurons can perform the classification task correctly even if stimuli and corresponding decision times are temporally separated and the relevant information is consequently highly overlapped by the ongoing neural activity.

Finally, we demonstrate that neurons can be trained to reproduce sequences of spikes with a controllable time shift with respect to target templates. A reproduced signal can follow or even precede the targets. This surprising result points out that spiking neurons can potentially be applied to forecast the behavior (firing times) of other reference neurons or networks.
Dispute Settlement under the UN Convention on the Law of the Sea: Survey for 2008
Authors: Churchill Robin
Published: October 2009

This is the fifth of a series of annual surveys reviewing dispute settlement under the UN Convention on the Law of the Sea. The main developments during 2008 were the fourth triennial elections to the International Tribunal for the Law of the Sea; an order made by the Tribunal further continuing the suspension of proceedings in the Swordfish case; and the referral of a maritime boundary dispute between Peru and Chile to the International Court of Justice.
Climate Change and Renewable Energy from the Ocean and Tides: Calming the Sea of Regulatory Uncertainty
Authors: Leary David , Esteban Miguel
Published: October 2009

We examine the state of ocean energy in 2009 and consider its potential as a source of renewable energy. We provide a background on the current state of technology and commercial development, and examine the implications for law and policy of the re-emergence of ocean energy as a source of renewable energy in 2009. In the 1970s much of the academic and policy literature highlighted jurisdictional uncertainty surrounding ocean energy under international law. This is not the case today. Although some questions remain with respect to navigation rights, most questions surrounding the nature and extent of coastal State jurisdiction in relation to ocean energy have been resolved by the 1982 United Nations Convention on the Law of the Sea. Instead we argue that one of the biggest challenges faced by ocean energy today is the uncertain state of regulation under domestic legal systems. We highlight issues requiring attention by policy-makers and legislators, including managing hazards to navigation, providing further financial incentives for wide-scale commercialisation of this technology (such as increased research and development funding and feed-in tariffs) and managing ocean energy's relatively benign environmental impacts.
The Homogeneity of International Criminal Court with Islamic Jurisprudence
Authors: Malekian Farhad
Published: October 2009

When implemented, the systems of the International Criminal Court (ICC) and Islamic criminal jurisdiction have to ensure equality, justice and peace for humanity. Consequently, implementation of international or Islamic justice does not necessarily emphasise applying the power of law but rather, as well as possible, the power to achieve appropriate human rights principles, which can reach the heart of the international community as a whole. Giving priority to any concept of law, thus recognizing one concept over another, diminishes the value of international criminal justice and creates contradictions in the application of an impartial equal jurisdiction and basic philosophy of cultural attitudes. Therefore, when the ICC Statute was being drafted, there was a strong tendency to overlook the cultural context of law within the social structures of various nations. The chief purpose of this article is to look into the basic principles of the Statute and examine whether similar principles can also be found within Islamic criminal jurisprudence. The article indicates the ability of both systems to function together and increase the practical intensification of international criminal justice. The study also offers, in a homogenous manner, to expand the juridical relationship, seeking cooperation and accommodation between the two systems in order to modify, adapt, adjust or alter laws for the better understanding of justice and equality between nations around the world. Prevention of international crimes will not be achieved through Islamic or ICC jurisprudence, or through any other system of law, but solely by cultivating equal justice together with the spirit of love and mutual admiration. This is the only seed for the promulgation of the ethic of reciprocity or the celebration of the golden rule of humanity.
Using Real-Time Output Gaps to Examine Past and Future Policy Choices
Authors: Adam Christopher , Cobham David
Published: October 2009

Alternative measures of the UK output gap are considered for 1984–2007. The real-time series is strongly affected by the rolling-time estimation of the trend, and produces a picture of the business cycle which is not consistent with contemporary perceptions of the large fluctuations of the late 1980s and early 1990s. A new, ‘nearly-real’, measure developed here may be better for estimating historical reaction functions. In the context of the current recession, none of these mechanically derived measures of the output gap are useful. Policymakers should make careful estimates of the likely fall in potential output on the basis of other information.
Nowcasting is not Just Contemporaneous Forecasting
Authors: Castle Jennifer L. , Fawcett Nicholas W.P. , Hendry David F.
Published: October 2009

We consider the reasons for nowcasting, the timing of information and sources thereof, especially contemporaneous data, which introduce different aspects compared to forecasting. We allow for the impact of location shifts inducing nowcast failure and nowcasting during breaks, probably with measurement errors. We also apply a variant of the nowcasting strategy proposed in Castle and Hendry (2009) to nowcast Euro Area GDP growth. Models of disaggregate monthly indicators are built by automatic methods, forecasting all variables that are released with a publication lag each period, then testing for shifts in available measures including survey data, switching to robust forecasts of missing series when breaks are detected.
Nowcasting Euro Area Economic Activity in Real Time: The Role of Confidence Indicators
Authors: Giannone Domenico , Reichlin Lucrezia , Simonelli Saverio
Published: October 2009

This paper assesses the role of qualitative surveys for the early estimation of GDP in the Euro Area in a model-based automated procedure which exploits the timeliness of their release. The analysis is conducted using both an historical evaluation and a real-time case study on the current conjuncture.
Specific and Pronounced Impacts of Lisinopril and Lisinopril Plus Simvastatin on Erythrocyte Antioxidant Enzymes
Authors: Kaminsky Yury , Suslikov Alexander , Kosenko Elena
Published: October 2009

Angiotensin‐converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis. It is hypothesized that these medications may improve blood pressure and serum cholesterol by modifying the antioxidative status and energy metabolism of erythrocytes. In this study, the effects of 2 treatments are compared: lisinopril alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy metabolic enzymes. Patients with atherosclerosis and moderate hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower glutathione peroxidase activity are observed in 94% to 100% patients from both groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is increased significantly only after 24 weeks. No changes of glutathione reductase, lactate dehydrogenase, and phosphofructokinase activities are found under any conditions indicated. Both treatments decrease systolic and diastolic blood pressure equally. Only lisinopril + simvastatin treatment decreases plasma total cholesterol and low‐density lipoprotein cholesterol. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit specific and pronounced effects on antioxidant and energy metabolic enzyme activities in erythrocytes of hypertensive patients.
Exposure‐Response Analysis in Patients With Schizophrenia to Assess the Effect of Asenapine on QTc Prolongation
Authors: Chapel Sunny , Hutmacher Matt M. , Haig George , Bockbrader Howard , de Greef Rik , Preskorn Sheldon H. , Lalonde Richard L.
Published: October 2009

An exposure‐response (E‐R) analysis using linear mixed effects modeling was conducted on data from a thorough QTc trial for asenapine in 148 patients with schizophrenia. In a parallel design, patients received asenapine 5 mg twice daily (BID) for 10 days (10d) followed by 10 mg BID (6d), asenapine 15 mg BID (10d) followed by 20 mg BID (6d), quetiapine 375 mg BID (for assay sensitivity; 16d) or placebo (16d). Triplicate 12‐lead electrocardiograms and concentration measurements were obtained on day −1 (baseline), 1, 10, and 16 at 8 scheduled times on each day. At mean Cmax for all asenapine doses, the E‐R model predicted that the mean QTcF increase was less than 5 milliseconds, the International Conference on Harmonisation—established threshold for clinical concern. The model predicted a mean increase of 7 to 8 milliseconds for quetiapine. The corresponding upper bounds of the 95% confidence intervals were 7.5 milliseconds and 11.2 milliseconds for asenapine and quetiapine, respectively.
No Pharmacokinetic Interaction Between Lacosamide and Carbamazepine in Healthy Volunteers
Authors: Cawello Willi , Nickel Brunhild , Eggert‐Formella Andrea
Published: October 2009

Lacosamide is a new antiepileptic drug for adjunctive treatment of adult partial‐onset seizures. Two open‐label, multiple‐dose clinical trials were conducted to evaluate the potential for pharmacokinetic interaction between lacosamide and carbamazepine. The influence of carbamazepine on lacosamide pharmacokinetics (trial A) and lacosamide on carbamazepine pharmacokinetics (trial B) was investigated in 19 (trial A) and 18 (trial B) healthy male participants. Trial A participants received lacosamide 200 mg bid alone and with carbamazepine 200 mg bid. Trial B participants received carbamazepine 200 mg bid alone and with lacosamide 200 mg bid. Pharmacokinetic parameters, area under the concentration‐time curve during a dosage interval at steady state (AUCτ,ss), and maximum steady‐state plasma drug concentration during a dosage interval (Cmax,ss) of lacosamide, carbamazepine, and carbamazepine‐10,11‐epoxide were measured and compared for each drug alone and together. The AUCτ,ss and Cmax,ss point estimates (combined vs sole treatment) showed relative bioavailability of approximately 100% for both drugs. All 90% confidence intervals of AUCτ,ss and Cmax,ss were within the generally accepted bioequivalence ranges of 80% to 125%. No changes in rate or extent of absorption or terminal half‐life were observed. These results suggest that lacosamide and carbamazepine have a low potential for pharmacokinetic drug‐drug interaction in clinical use.
Exploring the Origins of Organizational Paths: Empirical Evidence From Newly Founded Firms
Authors: Gruber Marc
Published: October 2009

The notion of path dependence in organizational processes has intrigued scholars for several decades. Yet, while extant studies provide rich insights on the factors that cause persistence in organizational paths, research that explores the origins of organizational paths remains scant. Analyzing data collected from 446 firm founders, the author investigates the creation of product—market paths in new firms. The analysis reveals systematic relationships between key pre-entry human capital endowments of founders and the consideration of alternative solutions in path creation, thereby helping us to better explain, and predict, organizational path creation. Implications for the organizational and entrepreneurship literatures are discussed.
Prison to Society: A Mixed Methods Analysis of Coping With Reentry
Authors: Phillips Lindsay A. , Lindsay Mary
Published: October 2009

This research investigates how individuals who reenter society from prison use coping strategies. Participants are incarcerated individuals who recidivated following a previous release from prison ( n = 20). Participants examine their most recent reentry experience via an interview. The research question under investigation is, “What themes describe how individuals cope with reentry from prison to society?” Data and results combine qualitative and quantitative analysis methods. The predominant coping strategy for dealing with reentry barriers is avoidance. There is a defined process experienced by participants, which is initial optimism about release, followed by craving substances, facing practical barriers, and/or feeling overwhelmed. This eventually results in avoidance of managing problems and emotions and substance abuse relapse, which culminates in recidivism.
Use of a Type I/III Bilayer Collagen Membrane Decreases Reoperation Rates for Symptomatic Hypertrophy after Autologous Chondrocyte Implantation
Authors: Gomoll Andreas H. , Probst Christian , Farr Jack , Cole Brian J. , Minas Tom
Published: October 2009

Background

Autologous chondrocyte implantation is associated with a high rate of reoperation, mostly due to hypertrophy of the periosteal patch. European studies investigating the use of collagen membranes as a periosteal substitute report significant decreases in reoperation rates to less than 5%. This multicenter study investigates the off-label use of 1 collagen membrane as a periosteal substitute for autologous chondrocyte implantation.

Hypothesis

The use of a collagen membrane for autologous chondrocyte implantation will decrease reoperation rates for hypertrophy with comparable rates of failure.

Study Design

Cohort study; Level of evidence, 3.

Methods

A multicenter cohort of 300 patients treated with periosteal-covered autologous chondrocyte implantation was compared with a consecutive series of 101 patients who underwent collagen membrane–covered autologous chondrocyte implantation with the Bio-Gide membrane by the same group of surgeons. The 1-year hypertrophy-related reoperation rates and overall failure rates of autologous chondrocyte implantation were evaluated in both groups.

Results

Both groups were comparable for age (periosteal autologous chondrocyte implantation, 31.9 years; collagen autologous chondrocyte implantation, 32.4 years; P 5 .8) and average defect size (4.6 cm2 and 4.7 cm2, respectively; P 5 .7). The average number of defects (1.5 and 1.8; P 5 .001) and total defect area per knee (6.7 cm2 and 8.6 cm2; P 5 .003) were larger in the collagen membrane group. Within 1 year of surgery, 25.7% of patients treated with periosteal-covered autologous chondrocyte implantation required reoperation for hypertrophy and 2.3% were considered to have failed their treatment with autologous chon-drocyte implantation. In comparison, only 5% of patients required reoperation for hypertrophy after collagen membrane–covered autologous chondrocyte implantation, and 4% were considered treatment failures.

Conclusion

The use of a collagen membrane for autologous chondrocyte implantation decreased the reoperation rate for hypertrophy after autologous chondrocyte implantation from 25.7% to 5% (P < .0001). Overall 1-year failure rates were comparable between the groups (P 5 .2). Even though the use of a collagen membrane for autologous chondrocyte implantation constitutes an off-label indication, its application appears justified by the lower morbidity to patients and decreased cost to the health care system. A detailed discussion with the patient is required regarding the use of an off-label device.
RETRACTED: The Effect of Kevlar Pulp Content on Mechanical and Tribological Properties of Thermoplastic Polyimide Composites
Authors: Li J.
Published: October 2009

Retracted
“It Actually Made Me Think”: Problem-Based Learning in the Business Communications Classroom
Authors: Pennell Michael , Miles Libby
Published: October 2009

We advocate for problem-based learning (PBL) as a rhetorical pedagogy for business communication. Briefly put, classic PBL inverts the typical instructional sequence; rather than presenting concepts first and then asking students to apply them, PBL creates situations in which students must learn the concepts in order to solve a “problem” constructed for that purpose. Thus, students learn in an iterative process as they cycle through the three key questions: “What do we know?” “What do we need to know?” and “How will we learn it?” We advocate emphasizing three key elements inherent in classic PBL: rhetoricity, locality, and change.
The Status of the Business Communication Course at U.S. Colleges and Universities
Authors: Russ Travis L.
Published: October 2009

This study examines the current status of the introductory business communication course at colleges and universities across the United States. Using data collected during the spring of 2008 from a national sample of 505 instructors, this study reveals a number of pedagogical and programmatic insights about (1) major course sponsors; (2) academic levels at which the course is taught; (3) instructors’ ideal and actual class sizes; (4) use of distance learning; (5) content coverage; and (6) required learning assignments. Findings from this study are compared with results from previous audits. Future research ideas as well as implications for business communication education are presented.
Amputations in PAD patients: Data from the German Federal Statistical Office
Authors: Gutacker Nils , Neumann Anja , Santosa Frans , Moysidis Theodorus , Kröger Knut
Published: October 2009

Much effort has been spent to reduce the number of amputees within the last two decades, but it remains unclear how effective the different strategies have been. We analyzed the prevalence of amputations in inpatient cases in the federal statistics. Detailed lists of all amputations coded as major amputations (OPS 5-864) and minor amputations (OPS 5-865) performed in 2005 and 2006, divided into the 4th and 5th number of the OPS-code, were provided by the Federal Statistical Office. In 2006, a total of 62,880 amputations affecting the lower extremities (2005: 63,005) were performed in Germany. Because of multiple amputations within a single case the corresponding cases amounted to 55,705 in 2006 and 55,689 in 2005. Based on these data age-adjusted incidence rates of major amputations per 100,000 inhabitants increased from 2 at the age of < 50 years to 201 at the age of > 80 years. For minor amputations the prevalence rates increased from 4 at the age of < 50 years to 209 at the age of > 80 years. It can be assumed that peripheral arterial disease or neurovascular disease as the underlying disease necessitating the amputation were present in 74.9% of all inpatient cases who finally underwent amputation. There were 12.9% with non-vascular or non-diabetic reasons for amputations. In patients presenting with gangrene, the rate of minor amputations decreased with age, whereas the rate of major amputations increased, especially within the 8th to 10th decades of life. In conclusion, amputations affecting the lower limbs are still a relevant problem in Germany. At the time of an aging German population it has to be an important goal to lower or at least to stabilize the rate of amputations. The DRG statistics enable the Federal Ministry of Health and health politics to monitor amputation rates easily.
Synthesis of porous silicon carbide from cellulose fibre templates infiltrated with polycarbosilane
Authors: Harris A. T. , Maddocks A. R.
Published: October 2009

Amorphous silicon carbide (SiC) with a stable porous structure was synthesised using a cellulose fibre preform (ash less filter paper) infiltrated with poly(methyl-carbosilane) and heated to 1000°C, first under N2 and then air. Scanning electron microscopy and Hg porosimetry confirmed the structure and porosity of the preform was largely reproduced in the final material; the porosity of the untreated template (72·4%) decreased following pyrolysis (58·1%) and then increased after treatment in air (80·0%). The SiC yield, inferred from thermogravimetric analysis of the infiltrated template, was linearly correlated with the number of infiltration steps and ranged between 3 and 21 wt-% for one and five infiltrations respectively.
Influence of nanodispersions on strength–ductility properties of semisolid cast A356 Al alloy
Authors: El-Mahallawi I. S. , Shash Y. , Eigenfeld K. , Mahmoud T. S. , Ragaie R. M. , Shash A. Y. , El Saeed M. A.
Published: October 2009

The present investigation studies the prospects of using nanoparticles as reinforcement agents to gain improved performance of A356 Al cast alloy by adding up to 5% Al2O3 and TiO2 particles. The particles size was intentionally reduced from 10 μm to 500 nm to 40 nm. To evaluate the results, the alloys were further characterised by various metallurgical and mechanical characterisation methods. The results showed that introducing nanoparticles into semisolid slurries has a beneficial effect on optimising strength–ductility relationship in Al–Si cast alloys. The new material showed higher strength values with improved ductility compared to the monolithic alloy under the same casting conditions. Those particles were incorporated and entrapped within the interdendritic and/or grain boundary interface, as well as within the grains, developed during solidification.
Relation between corset use and lung function postural variation in spinal cord injury
Authors: Prigent H. , Roche N. , Laffont I. , Lejaille M. , Falaize L. , Barbot F. , Lofaso F.
Published: October 2009

Corsets are widely used to improve trunk stability in patients with spinal cord injury (SCI) and can improve respiratory function. The aim of the present study was to identify predictors of respiratory benefits from wearing a corset in SCI patients.

In a prospective observational study, respiratory function was tested in the supine and upright seated position with and without a corset in 36 SCI patients who regularly used a corset. SCI patients who no longer used a corset were matched to users on sex, injury level and severity.

Vital capacity (VC) did not differ between users and nonusers in the supine position. In users, contrary to nonusers, VC increased significantly in the supine position compared to the seated position (increase of 0.43±0.39versus-0.05±0.32 L in nonusers; p<0.0001). Corset use was associated with a significant VC increase in the upright position (2.13±0.71 L withoutversus2.41±0.69 L with the corset; p<0.001). The VC increase with the corset in the upright position correlated significantly with the VC increase induced by being supine, compared to sitting without the corset.

The VC increase induced in SCI patients by lying supine may predict the effects of wearing a corset. The long-term effects of corset use should be evaluated.
A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia
Authors: Papon J. F. , Coste A. , Roudot-Thoraval F. , Boucherat M. , Roger G. , Tamalet A. , Vojtek A. M. , Amselem S. , Escudier E.
Published: October 2009

Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for the diagnosis of primary ciliary dyskinesia (PCD). We report our extensive experience of TEM analysis in a large series of patients in order to evaluate its feasibility and results.

TEM analysis performed in 1,149 patients with suspected PCD was retrospectively reviewed. Biopsies (1,450) were obtained from nasal (44%) or bronchial (56%) mucosa in children (66.5%) and adults (33.5%).

TEM analysis was feasible in 71.4% of patients and showed a main defect suggestive of PCD in 29.9%. TEM was more feasible in adults than in children, regardless of the biopsy site. Main defects suggestive of PCD were found in 76.9% of patients with sinopulmonary symptoms and in only 0.4% of patients with isolated upper and 0.4% with isolated lower respiratory tract infections. The defect pattern was similar in children and adults, involving dynein arms (81.2%) or central complex (CC) (18.8%). Situs inversus was never observed in PCD patients with CC defect. Kartagener syndrome with normal ciliary ultrastructure was not an exceptional condition (10.2% of PCD).

In conclusion, TEM analysis is feasible in most patients and is particularly useful for PCD diagnosis in cases of sinopulmonary syndrome of unknown origin.
Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation
Authors: McKeon D. J. , Cadwallader K. A. , Idris S. , Cowburn A. S. , Pasteur M. C. , Barker H. , Haworth C. S. , Bilton D. , Chilvers E. R. , Condliffe A. M.
Published: October 2009

Previous studies have identified abnormalities in the oxidative responses of the neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or to the inflammatory environment present in this disease. The aim of the present study was to determine whether neutrophils from CF patients demonstrate an intrinsic abnormality of the respiratory burst.

The respiratory burst activity of neutrophils isolated from stable ΔF508 homozygote CF patients and matched healthy controls was quantified by both chemiluminscence and cytochrome C reduction. Expression of NADPH oxidase components and CFTR was determined by Western blotting and RT-PCR.

The oxidative output from neutrophils from CF in response to receptor-linked and particulate stimuli did not differ from that of controls. Expression of NADPH oxidase components was identical in CF and non-CF neutrophils. While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates.

CFTR has no role in controlling neutrophil oxidative activity; previously reported differences in neutrophil function between CF and non-CF subjects most likely relate to the inflammatory milieu from which the cells were isolated.
No evidence for interstitial lung oedema by extensive pulmonary function testing at 4,559 m
Authors: Dehnert C. , Luks A. M. , Schendler G. , Menold E. , Berger M. M. , Mairbäurl H. , Faoro V. , Bailey D. M. , Castell C. , Hahn G. , Vock P. , Swenson E. R. , Bärtsch P.
Published: October 2009

The aim of the present study was to better understand previously reported changes in lung function at high altitude.

Comprehensive pulmonary function testing utilising body plethysmography and assessment of changes in closing volume were carried out at sea level and repeatedly over 2 days at high altitude (4,559 m) in 34 mountaineers.

In subjects without high-altitude pulmonary oedema (HAPE), there was no significant difference in total lung capacity, forced vital capacity, closing volume and lung compliance between low and high altitude, whereas lung diffusing capacity for carbon monoxide increased at high altitude. Bronchoconstriction at high altitude could be excluded as the cause of changes in closing volume because there was no difference in airway resistance and bronchodilator responsiveness to salbutamol. There were no significant differences in these parameters between mountaineers with and without acute mountain sickness. Mild alveolar oedema on radiographs in HAPE was associated only with minor decreases in forced vital capacity, diffusing capacity and lung compliance and minor increases in closing volume.

Comprehensive lung function testing provided no evidence of interstitial pulmonary oedema in mountaineers without HAPE during the first 2 days at 4,559 m. Data obtained in mountaineers with early mild HAPE suggest that these methods may not be sensitive enough for the detection of interstitial pulmonary fluid accumulation.
Transcriptomic and proteomic analyses of seasonal photoperiodism in the pea aphid
Authors: Le Trionnaire G , Francis F , Jaubert-Possamai S , Bonhomme J , De Pauw E , Gauthier J-P , Haubruge E , Legeai F , Prunier-Leterme N , Simon J-C , Tanguy S , Tagu D
Published: October 2009

Background

Aphid adaptation to harsh winter conditions is illustrated by an alternation of their reproductive mode. Aphids detect photoperiod shortening by sensing the length of the night and switch from viviparous parthenogenesis in spring and summer, to oviparous sexual reproduction in autumn. The photoperiodic signal is transduced from the head to the reproductive tract to change the fate of the future oocytes from mitotic diploid embryogenesis to haploid formation of gametes. This process takes place in three consecutive generations due to viviparous parthenogenesis. To understand the molecular basis of the switch in the reproductive mode, transcriptomic and proteomic approaches were used to detect significantly regulated transcripts and polypeptides in the heads of the pea aphidAcyrthosiphon pisum.

Results

The transcriptomic profiles of the heads of the first generation were slightly affected by photoperiod shortening. This suggests that trans-generation signalling between the grand-mothers and the viviparous embryos they contain is not essential. By analogy, many of the genes and some of the proteins regulated in the heads of the second generation are implicated in visual functions, photoreception and cuticle structure. The modification of the cuticle could be accompanied by a down-regulation of theN-β-alanyldopamine pathway and desclerotization. InDrosophila, modification of the insulin pathway could cause a decrease of juvenile hormones in short-day reared aphids.

Conclusion

This work led to the construction of hypotheses for photoperiodic regulation of the switch of the reproductive mode in aphids.
Glycogenome expression dynamics during mouse C2C12 myoblast differentiation suggests a sequential reorganization of membrane glycoconjugates
Authors: Janot Mathilde , Audfray Aymeric , Loriol Céline , Germot Agnès , Maftah Abderrahman , Dupuy Fabrice
Published: October 2009

Background

Several global transcriptomic and proteomic approaches have been applied in order to obtain new molecular insights on skeletal myogenesis, but none has generated any specific data on glycogenome expression, and thus on the role of glycan structures in this process, despite the involvement of glycoconjugates in various biological events including differentiation and development. In the present study, a quantitative real-time RT-PCR technology was used to profile the dynamic expression of 375 glycogenes during the differentiation of C2C12 myoblasts into myotubes.

Results

Of the 276 genes expressed, 95 exhibited altered mRNA expression when C2C12 cells differentiated and 37 displayed more than 4-fold up- or down-regulations. Principal Component Analysis and Hierarchical Component Analysis of the expression dynamics identified three groups of coordinately and sequentially regulated genes. The first group included 12 down-regulated genes, the second group four genes with an expression peak at 24 h of differentiation, and the last 21 up-regulated genes. These genes mainly encode cell adhesion molecules and key enzymes involved in the biosynthesis of glycosaminoglycans and glycolipids (neolactoseries, lactoseries and ganglioseries), providing a clearer indication of how the plasma membrane and extracellular matrix may be modified prior to cell fusion. In particular, an increase in the quantity of ganglioside GM3 at the cell surface of myoblasts is suggestive of its potential role during the initial steps of myogenic differentiation.

Conclusion

For the first time, these results provide a broad description of the expression dynamics of glycogenes during C2C12 differentiation. Among the 37 highly deregulated glycogenes, 29 had never been associated with myogenesis. Their biological functions suggest new roles for glycans in skeletal myogenesis.
Newly formed cystic lesions for the development of pneumomediastinum in Pneumocystis jirovecii pneumonia
Authors: Cho Ju-Yeon , Kim Dong-Min , Kwon Yong Eun , Yoon Sung Ho , Lee Seung Il
Published: October 2009

Background

Pneumocystis jirovecii, formerly named Pneumocystis carinii, is one of the most common opportunistic infections in human immunodeficiency virus (HIV)-infected patients.

Case presentations

We encountered two cases of spontaneous pneumomediastinum with subcutaneous emphysema in HIV-infected patients being treated for Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole.

Conclusion

Clinicians should be aware that cystic lesions and bronchiectasis can develop in spite of trimethoprim/sulfamethoxazole treatment for P. jirovecii pneumonia. The newly formed bronchiectasis and cyst formation that were noted in follow up high resolution computed tomography (HRCT) but were not visible on HRCT at admission could be risk factors for the development of pneumothorax or pneumomediastinum with subcutaneous emphysema in HIV-patients.
Motorcyclists' reactions to safety helmet law: a qualitative study
Authors: Zamani-Alavijeh Fereshteh , Niknami Shamsaddin , Mohammadi Eesa , Montazeri Ali , Ghofranipour Fazlollah , Ahmadi Fazlollah , Bazargan Shahrzad Hejazi
Published: October 2009

Background

Extensive body of the literature reveals that proper use of helmets is an effective way to reduce the severity of injuries and fatalities among motorcyclists. However, many motorcyclists do not use safety helmet properly. This study aimed to empirically explore reactions of motorcyclists to the safety helmet laws, in Iran.

Methods

Qualitative data were collected via four focus groups and 11 in-depth interviews. Participants were 28 male motorcyclists who never used a safety helmet during rides, and 4 male police officers. All transcripts, codes and categories were read for several times to exhaust identifiable major themes. During this process data were reduced from text to codes and themes.

Results

Five major themes emerged from the data analyses, including themes related to the following: (1) circumventing or dodging police officers; (2) simulating a helmet wearing behavior; (3) accepting the probability of receiving a ticket; (4) taking advantage of the police neglect and carelessness; and (5) using a cheap or convenient helmet.

Conclusion

Our findings suggest certain levels of reckless driving among the participating motorcyclists in this study. They also point to a system of law enforcement that operates haphazardly and fails to consistently penalize those who deviate from it. Further studies are needed to investigate how "risks" are perceived and relate to "reactions", and how a 'culture of masculinity' may encourage risk tolerance and a disposition toward lawlessness and carelessness among male motorcyclists. Also, there is a need for the development and implementation of multidimensional interventions that would offer socio-culturally sensitive educational and motivational messages to the motorcyclists and the in-service traffic-enforcement officers in Iran.
Machine learning integration for predicting the effect of single amino acid substitutions on protein stability
Authors: Özen Ayşegül , Gönen Mehmet , Alpaydın Ethem , Haliloğlu Türkan
Published: October 2009

Background

Computational prediction of protein stability change due to single-site amino acid substitutions is of interest in protein design and analysis. We consider the following four ways to improve the performance of the currently available predictors: (1) We include additional sequence- and structure-based features, namely, the amino acid substitution likelihoods, the equilibrium fluctuations of the alpha- and beta-carbon atoms, and the packing density. (2) By implementing different machine learning integration approaches, we combine information from different features or representations. (3) We compare classification vs. regression methods to predict the sign vs. the output of stability change. (4) We allow a reject option for doubtful cases where the risk of misclassification is high.

Results

We investigate three different approaches: early, intermediate and late integration, which respectively combine features, kernels over feature subsets, and decisions. We perform simulations on two data sets: (1) S1615 is used in previous studies, (2) S2783 is the updated version (as of July 2, 2009) extracted also from ProTherm. For S1615 data set, our highest accuracy using both sequence and structure information is 0.842 on cross-validation and 0.904 on testing using early integration. Newly added features, namely, local compositional packing and the mobility extent of the mutated residues, improve accuracy significantly with intermediate integration. For S2783 data set, we also train regression methods to estimate not only the sign but also the amount of stability change and apply risk-based classification to reject when the learner has low confidence and the loss of misclassification is high. The highest accuracy is 0.835 on cross-validation and 0.832 on testing using only sequence information. The percentage of false positives can be decreased to less than 0.005 by rejecting 10 per cent using late integration.

Conclusion

We find that in both early and late integration, combining inputs or decisions is useful in increasing accuracy. Intermediate integration allows assessing the contributions of individual features by looking at the assigned weights. Overall accuracy of regression is not better than that of classification but it has less false positives, especially when combined with the reject option. The server for stability prediction for three integration approaches and the data sets are available athttp://www.prc.boun.edu.tr/appserv/prc/mlsta.
Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria
Authors: Naka Izumi , Nishida Nao , Patarapotikul Jintana , Nuchnoi Pornlada , Tokunaga Katsushi , Hananantachai Hathairad , Tsuchiya Naoyuki , Ohashi Jun
Published: October 2009

Background

It has been previously demonstrated that a single nucleotide polymorphism (SNP) in the IL13 promoter region, IL13 -1055T>C (rs1800925), was associated with susceptibility to severe malaria in Thais. In the present study, fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13 on chromosome 5q31 was conducted using the same malaria subjects to refine the region containing a primary variant or a haplotype susceptible to severe malaria.

Methods

A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in 368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe malaria patients).

Results

Only rs1881457 located in the promoter region of IL13, which is in linkage disequilibrium with rs1800925 (r2 = 0.73), showed a significant association with severe malaria after adjusting for multiple testing (P = 0.046 by permutation test). This SNP was in a haplotype block spanning 97 kb (from rs2069812 to rs2240032). The detected haplotype block contained the RAD50 gene and the promoter of IL13, but not the other genes.

Conclusion

A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.
The infective cycle of Cabbage leaf curl virus (CaLCuV) is affected by CRUMPLED LEAF (CRL) gene in Arabidopsis thaliana
Authors: Trejo-Saavedra Diana L , Vielle-Calzada Jean P , Rivera-Bustamante Rafael F
Published: October 2009

Background

Geminiviruses are single-stranded DNA viruses that cause serious crop losses worldwide. Successful infection by these pathogens depends extensively on virus-host intermolecular interactions that allow them to express their gene products, to replicate their genomes and to move to adjacent cells and throughout the plant.

Results

To identify host genes that show an altered regulation in response to Cabbage leaf curl virus (CaLCuV) infection, a screening of transposant Arabidopsis thaliana lines was carried out. Several genes were identified to be virus responsive and one, Crumpled leaf (CRL) gene, was selected for further characterization. CRL was previously reported by Asano et al., (2004) to affect the morphogenesis of all plant organs and the division of plastids. We report here that CRL expression, during CaLCuV infection, shows a short but strong induction at an early stage (3-5 days post inoculation, dpi). To study the role of CRL in CaLCuV infection, CRL over-expressing and silenced transgenic plants were generated. We compared the replication, movement and infectivity of CaLCuV in transgenic and wild type plants.

Conclusion

Our results showed that CRL over-expressing plants showed an increased susceptibility to CaLCuV infection (as compared to wt plants) whereas CRL-silenced plants, on the contrary, presented a reduced susceptibility to viral infection. The possible role of CRL in the CaLCuV infection cycle is discussed.
Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis
Authors: Zhu Mingzhe , Ji Guozhen , Jin Gang , Yuan Zuobiao
Published: October 2009

Background

To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6) and DBA/2J (D2) inbred mice.

Methods

B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data.

Results

After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis.

Conclusion

Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.