bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regular Paper: Interactive N-Body Simulations On the Grid: HLA Versus MPI
Authors: Rycerz Katarzyna , Tirado-Ramos Alfredo , Gualandris Alessia , Portegies Zwart Simon F. , Bubak Marian , Sloot Peter M. A. 
Published: April 2007

The grid paradigm for distributed computation provides an interesting framework for the simulation of dense stellar systems, which remains a great challenge for astrophysicists. In this work we apply a distributed simulation model to the astrophysical N-body problem: the High Level Architecture (HLA), using distributed federations on top of grid infrastructures for the communication between simulation and visualization components. To achieve this goal, we use a grid HLA Management system (G-HLAM) for HLA-based simulations running on the grid. We compare this setup with a direct parallelization of the N-body code using MPI on the grid. Our aim is to provide scientists with an interactive environment where, in contrast to traditional MPI-based parallel processing, seamless simulation process migration and rollbacks can be invoked on the fly to improve the overall computational performance. We found that MPI and HLA are complementary rather than competing technologies, as they can be used simultaneously to improve the performance of complex simulations on different fronts. On one hand, if the communication to computation ratio is small enough, the MPI parallelization proves to be a relatively easy and efficient method for taking advantage of grid technology. On the other hand, HLA provides advanced mechanisms to synchronize simulation and visualization components located on different grid nodes and can be used to add steering mechanisms to improve interaction. Finally, we found that HLA allows migration of running simulations to be easily managed, reducing overall communication times between simulation and the user, effectively improving the overall system performance.
Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor κB target genes and induction of apoptosis in chronic lymphocytic leukemia B cells
Authors: Ougolkov Andrei V. , Bone Nancy D. , Fernandez-Zapico Martin E. , Kay Neil E. , Billadeau Daniel D. 
Published: April 2007

Abstract
Chronic lymphocytic leukemia (CLL) is commonly defined as a disease of failed apoptosis of B cells and remains an incurable disease. The mechanism of resistance to apoptosis in CLL is complex and influenced by numerous factors, including nuclear factor κB (NFκB)-mediated expression of antiapoptotic molecules. Recent evidence indicates that glycogen synthase kinase-3β (GSK-3β) positively regulates NFκB-mediated gene transcription and cell survival. Using malignant B cells collected from patients with CLL, we find that both GSK-3β and NFκB accumulate in the nucleus of CLL B cells, and pharmacologic inhibition of GSK-3 results in decreased expression of two NFκB target genes Bcl-2 and XIAP and a subsequent increase in CLL B-cell apoptosis ex vivo. Furthermore, we observed that inhibition of GSK-3 leads to a decrease in NFκB-mediated gene transcription but does not affect the nuclear accumulation of NFκB in CLL B cells. Last, using chromatin immunoprecipitation, we show that GSK-3 inhibition abrogates NFκB binding to its target gene promoters (XIAP, Bcl-2), in part through epigenetic modification of histones. Our results establish that inhibition of GSK-3 abrogates NFκB binding to its target gene promoters through an epigenetic mechanism, enhances apoptosis in CLL B cells ex vivo and identifies GSK-3 as a potential therapeutic target in the treatment of CLL.
The role of atypical respiratory pathogens in exacerbations of chronic obstructive pulmonary disease
Authors: Diederen B. M. W. , van der Valk P. D. L. P. M. , Kluytmans J. A. W. J. , Peeters M. F. , Hendrix R. 
Published: April 2007

The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Serological studies have suggested thatMycoplasma pneumoniae, Chlamydia pneumoniaeandLegionella pneumophilamay play a role in acute exacerbations of COPD.The presence of these atypical pathogens in sputum samples was investigated in patients with stable COPD and with acute exacerbations of COPD using real-time PCR. The present study was part of a randomised, double-blind, single-centre study and a total of 248 sputum samples from 104 COPD patients were included. In total, 122 samples obtained during stable disease (stable-state sputa) and 126 samples obtained during acute exacerbations of COPD (exacerbation sputa) were tested.Of the 122 stable-state sputa, all samples were negative forM. pneumoniaeandC. pneumoniaeDNA, whereas one sample was positive for Legionella non-pneumophila DNA. Of the 126 exacerbation sputa, all samples were negative forM. pneumoniaeandC. pneumoniaeDNA, whereas one sample was positive for Legionella non-pneumophila DNA.The possible relationship between the presence of atypical pathogens and the aetiology of acute exacerbations in chronic obstructive pulmonary disease was investigated in patients with stable disease and in those with acute exacerbations using real-time PCR. No indication was found of a role for Legionella spp.,Chlamydia pneumoniaeorMycoplasma pneumoniaein stable, moderately severe chronic obstructive pulmonary disease and in its exacerbations.
PulmonaryMycobacterium aviumcomplex infection: association withNRAMP1polymorphisms
Authors: Tanaka G. , Shojima J. , Matsushita I. , Nagai H. , Kurashima A. , Nakata K. , Toyota E. , Kobayashi N. , Kudo K. , Keicho N. 
Published: April 2007

The present study aimed to elucidate risk factors for nonimmunocompromised pulmonaryMycobacterium aviumcomplex (MAC) infection.Epidemiological data and variations of candidate genes for mycobacterial diseases were analysed in 111 patients with pulmonary MAC infection. Four polymorphisms of the human natural resistance-associated macrophage protein (NRAMP)1gene, the 5′(GT)n, 469+14 G/C, D543N and the 3′untranslated region (3'TGTG) insertion/deletion, were genotyped using PCR-based methods.FokI andTaqI polymorphisms of the vitamin D receptor gene and -221 X/Y and codon 54 A/B polymorphisms of the mannose binding lectin gene were also evaluated.Females were more susceptible to MAC infection mainly affecting the right middle lobe or lingular segment of the lung. Patients' residence at the onset of the disease was distributed evenly irrespective of a waterfront or city water supply system. As compared with homozygotes for major alleles of the D543N and TGTG insertion/deletion polymorphism of theNRAMP1gene, heterozygotes containing minor alleles were less often observed in MAC cases than in controls. This genetic effect was more significant in patients without comorbidity but not in patients with comorbidity. Other polymorphisms did not show any association with the MAC infection.The human natural resistance-associated macrophage protein 1 gene might be involved in susceptibility to pulmonaryMycobacterium aviumcomplex infection.
Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families
Authors: Bouzigon E. , Siroux V. , Dizier M-H. , Lemainque A. , Pison C. , Lathrop M. , Kauffmann F. , Demenais F. , Pin I. 
Published: April 2007

There is ongoing debate as to how asthma should be defined in order to forward understanding of the underlying mechanisms. The aim of the present study was to build quantitative scores of asthma and asthma severity and to assess whether refinement of disease phenotypes can facilitate the identification of chromosomal regions harbouring susceptibility genes.A genome-wide linkage scan was conducted in 110 families with at least two asthmatic siblings (n = 508) from the French Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma severity score (assessed among asthmatics by combining clinical data and treatment), forced expiratory volume in one second (FEV1) and an asthma score (including both asthmatics and nonasthmatics and representing the whole disease spectrum).This analysis showed genome-wide suggestive evidence of linkage of the asthma score to 18p11, a novel region undetected in a previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score and of three regions (1p36, 2q36 and 6q14) to FEV1. Moreover, FEV1appeared to have no genetic determinant in common with asthma severity and asthma scores.Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provide support for considering these phenotypes in future genetic studies.
CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system
Authors: Schaer Christian A , Vallelian Florence , Imhof Alexander , Schoedon Gabriele , Schaer Dominik J 
Published: April 2007

AbstractHemoglobin (Hb) is released into the circulation during intravascular hemolysis and exerts toxic effects through oxidative damage and NO scavenging. According to the traditional concept of Hb clearance, free Hb is bound to the plasma protein haptoglobin (Hp), and the Hb-Hp complexes are cleared by liver and spleen macrophages via the Hb scavenger receptor CD163. Using a novel whole blood assay, we demonstrate that clearance of Hb-Hp is also mediated by CD14high/CD64high peripheral blood monocytes, which express CD163. Hb-Hp uptake by these cells is Ca2+-dependent and is abrogated by the addition of CD163-blocking antibodies. Accordingly, LPS treatment reduces monocyte surface CD163 and impairs Hb-Hp uptake. Monocytes likely mediate Hp-Hb uptake in vivo, as a high expression of the heme breakdown enzyme heme oxygenase-1 was observed in CD163+ monocytes but not in other leukocyte populations obtained from healthy blood donors. We propose that CD163-mediated Hb-Hp uptake by peripheral blood monocytes constitutes an Hb-Hp clearance pathway, which acts at the site of intravascular hemolysis to reduce Hb-Hp circulation time and toxicity. Disruption of monocyte Hb-Hp clearance may increase Hb-Hp toxicity and contribute to the pathogenesis of systemic inflammatory diseases associated with reduced monocyte CD163 expression.
Continuous intravenous infusion in athymic (nude) rats: an animal model for evaluating the efficacy of anti-cancer agents
Authors: van Wijk H. , Dick A. , Greenough R. J. , Oshodi R. O. , Robb D. 
Published: April 2007

The athymic (nude) rat (rnu/rnu) has been used for a number of years in research into various human tumours involving xenotransplantation. We now report the validation of a continuous intravenous infusion method in nude rats using a tail cuff tether, which enables the study of the efficacy of novel anti-cancer materials in this mutant strain, using intravenous infusion and with no restriction of the animals or of the tumour implantation sites by jackets. Ten animals each had a cannula surgically implanted into the vena cava via the femoral vein and exteriorized via a tail cuff. Animals were housed singly in conventional cages following surgery. Following a recovery period of 5 days all animals were continuously infused with physiological saline at an infusion rate of 0.5 ml/h for a further 37 days. Body weights and food consumption were recorded weekly. Blood samples were taken approximately 14 days post-surgery and analysed for haematology and clinical chemistry parameters. All animals were successfully cannulated, and no unexpected adverse clinical signs were noted during the recovery period and the 37 days of infusion. The results demonstrate that it is possible to surgically cannulate the femoral vein of athymic (nude) rats and infuse them in conventional cages for a period of up to 37 days with minimal adverse effects. The minimal restraint required provides benefits both to the animal and to the conduct of studies such as assessment of tumour growth in the absence of a jacket. Recent work has demonstrated that the same techniques can be successfully applied to the nude mouse.
Midazolam-fentanyl-isoflurane anaesthesia is suitable for haemodynamic and fluid balance studies in pigs
Authors: Husby P. , Heltne J. K. , Koller M.-E. , Birkeland S. , Westby J. , Fosse R. , Lund T. 
Published: April 2007

The domestic pig is a useful model in certain areas of biomedical research. Effective use of this species is often encumbered by lack of reference values in conscious as well as anaesthetized animals. Anaesthesia itself influences physiological and biological variables; the anaesthetic technique often affects experimental results. The relationship between anaesthesia and haemodynamics is well characterized in man, but less established in pigs. We studied the effect of midazolam-fentanyl-isoflurane anaesthesia in six immature, male, domestic pigs (Norwegian landrace). Haemodynamic variables (heart rate, arterial systolic, mean, diastolic pressures, pulmonary systolic, mean, diastolic pressures, pulmonary capillary wedge pressure), tissue perfusion, lymph flow (thoracic duct) were recorded for 3 h in animals with open chest through midline sternotomy. Variables relevant to fluid balance, e.g. interstitial hydrostatic pressure (Pi), serum-colloid osmotic pressure (s-COP) and serum-albumin (s-albumin) and -protein (s-protein) concentrations were measured. With the chosen anaesthetic technique haemodynamic variables, including lymph flow, and laboratory variables remained constant during the study period. Most variables were similar to conditions in humans. In contrast to adult humans exposed to the same anaesthetic technique, these pigs had lower haemoglobin-, s-albumin- and s-protein concentrations. A finding which may reflect immaturity. Liver and lung perfusion decreased significantly during the study period whereas perfusion of the other organs studied remained constant. Lack of responses to defined noxious stimuli during the study period suggest adequate analgesia. We conclude that midazolam, fentanyl and isoflurane provide cardiovascular stability including normal microvascular fluid exchange, which are essential elements for securing the quality of results obtained during cardiovascular research in anaesthetized pigs.
Monitoring of piglets' open field activity and choice behaviour during the replay of maternal vocalization: a comparison between Observer and PID technique
Authors: Puppe B. , Schön P. C. , Wendland K. 
Published: April 2007

The paper presents a new system for the automatic monitoring of open field activity and choice behaviour of medium-sized animals. Passive infrared motion detectors (PID) were linked on-line via a digital I/O interface to a personal computer provided with self-developed analysis software based on LabVIEW (PID technique). The set up was used for testing 18 one-week-old piglets ( Sus scrofa) for their approach to their mother's nursing vocalization replayed through loudspeakers. The results were validated by comparison with a conventional Observer technique, a computer-aided direct observation. In most of the cases, no differences were seen between the Observer and PID technique regarding the percentage of stay in previously defined open field segments, the locomotor open field activity, and the choice behaviour. The results revealed that piglets are clearly attracted by their mother's nursing vocalization. The monitoring system presented in this study is thus suitable for detailed behavioural investigations of individual acoustic recognition. In general, the PID technique is a useful tool for research into the behaviour of individual animals in a restricted open field which does not rely on subjective analysis by a human observer.
A new porcine model of reperfusion injury after lung transplantation
Authors: Clark S. C. , Sudarshan C. D. , Khanna R. , Roughan J. V. , Flecknell P. A , Dark J. H. 
Published: April 2007

Rodent models have been described to investigate lung preservation and reperfusion injury but have significant disadvantages. In large animals single lung transplant studies are probably optimal but problems remain over the ability to rigorously separate the lungs for assessment while promoting medium to long-term animal survival for meaningful investigation. Our aim was to develop a novel and refined large animal model to assess reperfusion injury in the transplanted lung, overcoming the difficulties associated with existing models. Specifically, small animal models of lung transplantation usually have short perfusion times (often one hour) and include extracorporeal circuits while larger animal models often require the contralateral lung to be excluded after transplantation-an unphysiological situation under which to evaluate the graft. A porcine model of left lung allotransplantation was developed in which native and donor lungs are individually ventilated. Sampling catheters placed within the graft lung allowed specimen withdrawal without mixing of blood from the contralateral lung after reimplantation. The model permits a variety of clinical scenarios to be simulated with the native lung supporting the animal irrespective of function in the graft. This model has been used in over 60 transplant procedures with a postoperative survival time of 12 h being readily achieved. The mean operating time was 2.6 h. The mortality rate is 4% in our series. We have found the model to be reliable, reproducible and flexible. We propose this model as an adaptable investigation for evaluating lung reperfusion injury and preservation.
The VX2 carcinoma in the rabbit auricle as an experimental model for intra-arterial embolization of head and neck squamous cell carcinoma with dextran microspheres
Authors: van Es R. J. J. , Franssen O. , Dullens H. F. J. , Bernsen M. R. , Bosman F. , Hennink W. E. , Slootweg P. J. 
Published: April 2007

A head and neck cancer model is developed using the VX2 carcinoma cell line injected s.c. in both ears of New Zealand White (NZW) rabbits. The study is focused on the effects of intra-arterial embolization of the carcinomas with a new type of dextran hydrogel microspheres. During the phase of exponential growth the tumour-surface doubling-time was 7.1 ± 2.0 days. Standard deviation in growth of the tumours was significantly larger between separate animals than between tumours growing in the left and right auricle of each individual animal (2.0 versus 0.65 days). A fresh cell suspension containing at least 10.106 vital tumour cells was necessary to yield a tumour-take of 85%. The caudal auricular artery perfuses the caudal half of the external ear and is very suitable for macroscopic cannulation. Histological evaluation shows, that the use of dextran hydrogel micro spheres of at least 25 μm in combination with ligation of non-tumour perfusing branches of the central auricular artery yields diffuse embolization of the VX2 carcinoma. This tumour model can be of use in further studies to optimize particle size and dosage for embolization as well as to evaluate the effect of different anti-neoplastic drugs, slowly released by controlled degradation of dextran microspheres.
Short-term immobilization of mice by methohexitone
Authors: Dörr W. , Weber-Frisch M. 
Published: April 2007

The feasibility of short-term immobilization for <5 min of female mice by methohexitone sodium was studied. In C3H/Neu mice, methohexitone at a dose <40 mg/kg did not result in chemical restraint, doses >50 mg/kg caused considerable lethality. A dose of 44 mg/kg, applied intraperitoneally at a concentration of 6.46 mg/ml, is suitable for immobilization without complications. This concentration was chosen in order to achieve an injection volume of about 0.15 ml for a mouse with an average body weight of 22 g, corresponding to about 1 mg/mouse. Complete immobilization, defined as absence of the righting reflex, was observed within 3.3±0.8 min (mean±SD, n = 10) after the injection and lasted for 1.5±0.7 min. Recovery of the animals was complete after a total period of 10 to 15 min post-injection. No gross pathomorphological changes were induced when intraperitoneal injections of methohexitone were repeated 10 times within 10 days. In the present study, complete immobilization of the mice was safely achieved after 87 out of 90 injections. In conclusion, immobilization by intraperitoneal injection of methohexitone is a feasible and reliable method in the experimental studies of female mice.
Chromium and cobalt ion release following the Durom high carbon content, forged metal-on-metal surface replacement of the hip
Authors: Vendittoli P.-A. , Mottard S. , Roy A. G. , Dupont C. , Lavigne M. 
Published: April 2007

We evaluated the concentrations of chromium and cobalt ions in blood after metal-on-metal surface replacement arthroplasty using a wrought-forged, high carbon content chromium-cobalt alloy implant in 64 patients. At one year, mean whole blood ion levels were 1.61 μg/L (0.4 to 5.5) for chromium and 0.67 μg/L (0.23 to 2.09) for cobalt. The pre-operative ion levels, component size, female gender and the inclination of the acetabular component were inversely proportional to the values of chromium and/or cobalt ions at one year postoperatively. Other factors, such as age and level of activity, did not correlate with the levels of metal ions. We found that the levels of the ions in the serum were 1.39 and 1.37 times higher for chromium and cobalt respectively than those in the whole blood. The levels of metal ions obtained may be specific to the hip resurfacing implant and reflect its manufacturing process.
Early results of the Acclaim elbow replacement
Authors: Bassi R. S. , Simmons D. , Ali F. , Nuttall D. , Birch A. , Trail I. A. , Stanley J. K. 
Published: April 2007

The Acclaim total elbow replacement is a modular system which allows implantation in both unlinked and linked modes. The results of the use of this implant in primary total elbow replacement in 36 patients, operated on between July 2000 and August 2002, are presented at a mean follow-up of 36 months (24 to 49). Only one patient did not have good relief of pain, but all had improved movement and function. No implant showed clinical or radiological loosening, although one had a lucent area in three of seven humeral zones. The short-term results of the Acclaim total elbow replacement are encouraging. However, 11 patients (30.5%) suffered an intra-operative fracture of the humeral condyle. This did not affect the outcome, or the requirement for further surgery, except in one case where the fracture failed to unite. This problem has hopefully been addressed by redesigning the humeral resection guide. Other complications included three cases of ulnar neuropathy (8.3%) and one of deep infection (2.8%).
Two-level reconstruction of comminuted posterior-wall fractures of the acetabulum
Authors: Giannoudis P. V. , Tzioupis C. , Moed B. R. 
Published: April 2007

Our aim was to evaluate the efficacy of a two-level reconstruction technique using subchondral miniscrews for the stabilisation of comminuted posterior-wall marginal acetabular fragments before applying lag screws and a buttress plate to the main overlying posterior fragment. Between 1995 and 2003, 29 consecutive patients with acute comminuted displaced posterior-wall fractures of the acetabulum were treated operatively using this technique. The quality of reduction measured from three standard plain radiographs was graded as anatomical in all 29 hips. The clinical outcome at a mean follow-up of 35 months (24 to 90) was considered to be excellent in five patients (17%), very good in 16 (55%), good in six (21%) and poor in two (7%). The use of the two-level reconstruction technique appears to provide stable fixation and is associated with favourable results in terms of the incidence of post-traumatic osteoarthritis and the clinical outcome. However, poor results may occur in patients over the age of 55 years.