bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitation of Azoles and Echinocandins in Compartments of Peripheral Blood by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Farowski Fedja , Cornely Oliver A. , Vehreschild Jörg J. , Hartmann Pia , Bauer Tim , Steinbach Angela , Rüping Maria J. G. T. , Müller Carsten 
Published: February 2010

ABSTRACT
A rapid turnaround is a prerequisite of therapeutic drug monitoring (TDM). For antifungals, this need is still unmet, since hardly any method has been established to simultaneously quantitate concentrations of different antifungal classes. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed allowing quantitation of anidulafungin (ANF), caspofungin (CSF), isavuconazole (ISC), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). Quantitation was successful with diluted plasma samples, peripheral blood mononuclear cells (PBMC), polymorphonuclear leukocytes (PMN), and erythrocytes (RBC). A triple quadrupole mass spectrometer in selected reaction monitoring mode was used with positive electrospray ionization. Cells and calibration standards were extracted with acetonitrile containing internal standard. Internal standards were a CSF derivate for echinocandins and itraconazole for triazoles. Chromatographic separation of the supernatant was achieved by a gradient method facilitating a BetaBasic C4 column. Analytes were quantified in a single 8-min run. Calibration curves were linear and fitted using least squares with a weighting factor of the reciprocal concentration. Limits of detection (ng/ml) were ANF, 8.3; CSF, 31.5; ISC, 1.5; MCF, 97.7; PSC, 3.3; and VRC, 1.4. The lower limits of quantitation (ng/ml) were ANF, 64; CSF, 108; ISC, 4.5; MCF, 160; PSC, 10; and VRC, 4.2. Intraday precisions ranged from 6.3% to 8.8% for azoles and 8.8% to 15.4% for echinocandins. Intraday and interday accuracies (percent bias) of all analytes were within 13.8%. The method was established as standard practice for the quantitation of intracellular antifungal concentrations and optimizes TDM by applying a rapid single method for 6 antifungals.
Involvement of the Beta Subunit of RNA Polymerase in Resistance to Streptolydigin and Streptovaricin in the Producer OrganismsStreptomyces lydicusandStreptomyces spectabilis
Authors: Sánchez-Hidalgo Marina , Núñez Luz Elena , Méndez Carmen , Salas José A. 
Published: February 2010

ABSTRACTStreptomyces lydicusNRRL2433 andS. spectabilisNRRL2494 produce two inhibitors of bacterial RNA polymerase: the 3-acyltetramic acid streptolydigin and the naphthalenic ansamycin streptovaricin, respectively. Both strains are highly resistant to their own antibiotics. Independent expression of theS. lydicusandS. spectabilis rpoBandrpoCgenes, encoding the β- and β′-subunits of RNA polymerase, respectively, inS. albusshowed that resistance is mediated byrpoB, with no effect ofrpoC. Within the β-subunit, resistance was confined to an amino acid region harboring the “rif region.” Comparison of the β-subunit amino acid sequences of this region from the producer strains and those of other streptomycetes and site-directed mutagenesis of specific differential residues located in it (L485 and D486 inS. lydicusand N474 and S475 inS. spectabilis) showed their involvement in streptolydigin and streptovaricin resistance. Other amino acids located close to the “Stl pocket” in theS. lydicusβ-subunit (L555, F593, and M594) were also found to exert influence on streptolydigin resistance.
The MACODO middleware for context-driven dynamic agent organizations
Authors: Weyns Danny , Haesevoets Robrecht , Helleboogh Alexander , Holvoet Tom , Joosen Wouter 
Published: February 2010

One of the major challenges in engineering distributed multiagent systems is the coordination necessary to align the behavior of different agents. Decentralization of control implies a style of coordination in which the agents cooperate as peers with respect to each other and no agent has global control over the system, or global knowledge about the system. The dynamic interactions and collaborations among agents are usually structured and managed by means of roles and organizations. In existing approaches agents typically have a dual responsibility: on the one hand playing roles within the organization, on the other hand managing the life-cycle of the organization itself, for example, setting up the organization and managing organization dynamics. Engineering realistic multiagent systems in which agents encapsulate this dual responsibility is a complex task.
In this article, we present a middleware for context-driven dynamic agent organizations. The middleware is part of an integrated approach, called MACODO: Middleware Architecture for COntext-driven Dynamic agent Organizations. The complementary part of the MACODO approach is an organization model that defines abstractions to support application developers in describing dynamic organizations, as described in Weyns et al. [2010].
The MACODO middleware offers the life-cycle management of dynamic organizations as a reusable service separated from the agents, which makes it easier to understand, design, and manage dynamic organizations in multiagent systems. We give a detailed description of the software architecture of the MADOCO middleware. The software architecture describes the essential building blocks of a distributed middleware platform that supports the MACODO organization model. We used the middleware architecture to develop a prototype middleware platform for a traffic monitoring application. We evaluate the MACODO middeware architecture by assessing the adaptability, scalability, and robustness of the prototype platform.
Cooperation through self-similar social networks
Authors: Allen Stuart M. , Colombo Gualtiero , Whitaker Roger M. 
Published: February 2010

We address the problem of cooperation in decentralized systems, specifically looking at interactions between independent pairs of peers where mutual exchange of resources (e.g., updating or sharing content) is required. In the absence of any enforcement mechanism or protocol, there is no incentive for one party to directly reciprocate during a transaction with another. Consequently, for such decentralized systems to function, protocols for self-organization need to explicitly promote cooperation in a manner where adherence to the protocol is incentivized.
In this article we introduce a new generic model to achieve this. The model is based on peers repeatedly interacting to build up and maintain a dynamic social network of others that they can trust based on similarity of cooperation. This mechanism effectively incentivizes unselfish behavior, where peers with higher levels of cooperation gain higher payoff. We examine the model's behavior and robustness in detail. This includes the effect of peers self-adapting their cooperation level in response to maximizing their payoff, representing a Nash-equilibrium of the system. The study shows that the formation of a social network based on reflexive cooperation levels can be a highly effective and robust incentive mechanism for autonomous decentralized systems.
Measurement Precision in the Optimization of Cardiac Resynchronization Therapy
Authors: Turcott Robert G. , Witteles Ronald M. , Wang Paul J. , Vagelos Randall H. , Fowler Michael B. , Ashley Euan A. 
Published: February 2010

Background—
Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.

Methods and Results—
An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%–82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.

Conclusions—
Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.
Teratogen-induced alterations in microRNA-34, microRNA-125b and microRNA-155 expression: correlation with embryonic p53 genotype and limb phenotype
Authors: Gueta Keren , Molotski Natali , Gerchikov Natalie , Mor Eyal , Savion Shoshana , Fein Amos , Toder Vladimir , Shomron Noam , Torchinsky Arkady 
Published: February 2010

Abstract

Background
In a large number of studies, members of the microRNA (miRNA)-34 family such as miRNA-34a, miRNA-34b, miRNA-34c, as well as miRNA-125b and miRNA-155, have been shown to be regulators of apoptosis. The ability of these miRNAs to perform this function is mainly attributed to their ability to interact with the p53 tumor suppressor, which is a powerful regulator of the teratologic susceptibility of embryos. We chose to explore whether miRNA-34a/b/c, miRNA-125b and miRNA-155 may play a role in teratogenesis by using p53+/- pregnant mice treated with cyclophosphamide (CP) as a model. We evaluated how CP-induced alterations in the expression of these miRNAs in the embryonic limbs correlate with embryonic p53 genotype and CP-induced limb phenotypes.

Results
The limbs of p53 positive embryos were more sensitive to CP-induced teratogenic insult than the limbs of p53 negative embryos. The hindlimbs were more severely affected than the forelimbs. Robust miRNA-34a expression was observed in the fore- and hindlimbs of p53+/+ embryos exposed to 12.5 mg/kg CP. The dose of 20 mg/kg CP induced almost a two-fold increase in the level of miRNA-34a expression as compared to that exhibited by p53+/+ embryos exposed to a lower dose. Increased miRNA-34b and miRNA-34c expression was also observed. Of note, this dose activated miRNA-34a and miRNA-34c in the forelimbs of p53-/- embryos. When embryos were exposed to 40 mg/kg CP, the expression pattern of the miRNA-34a/b/c was identical to that registered in the limbs of embryos exposed to 20 mg/kg CP. However, this dose suppressed miRNA-125b and miRNA-155 expression in the fore- and hindlimbs of p53+/+ embryos.

Conclusion
This study demonstrates that teratogen-induced limb dysmorphogenesis may be associated with alterations in miRNA-34, miRNA-125b and miRNA-155 expression. It also suggests for the first time that p53-independent mechanisms exist contributing to teratogen-induced activation of miRNA-34a and miRNA-34c. At the same time, teratogen-induced suppression of miRNA-125b and miRNA-155 expression may be p53 dependent. The analysis of correlations between the expression pattern of the tested miRNAs and CP induced limb phenotypes implies that miRNAs regulating apoptosis may differ from each other with respect to their functional role in teratogenesis: some miRNAs act to protect embryos, whereas other miRNAs boost a teratogen-induced process of maldevelopment to induce embryonic death.
Making the diagnosis of Chronic Fatigue Syndrome/Myalgic Encephalitis in primary care: a qualitative study
Authors: Chew-Graham Carolyn , Dowrick Christopher , Wearden Alison , Richardson Victoria , Peters Sarah 
Published: February 2010

Abstract

Background
NICE guidelines emphasise the role of the primary care team in the management of patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME). A key stage in effective management is making an accurate early diagnosis, supported by appropriate referral.

Methods
A nested qualitative study within a multi-centre randomised controlled trial which aimed to explore GPs' views on their role in making the diagnosis of CFS/ME and subsequent management of patients in primary care. Semi-structured interviews with 22 GPs. Interviews were transcribed verbatim and an iterative approach used to develop themes from the dataset.

Results
GPs described difficulties in defining CFS/ME and suggested that their role in making a diagnosis was to exclude physical causes for the patient's symptoms, but they reported little confidence in positively attributing the label of CFS/ME to a patient and their symptoms. GPs suggested that the label of CFS/ME could be potentially harmful for the patient. The role of referral to secondary care was debated and GPs struggled defining their own role in management of this group of patients.

Conclusions
Until GPs feel comfortable making the diagnosis of CFS/ME and facilitating initial management, and have appropriate services to refer patients to, there will continue to be delays in confirming the diagnosis and patients presenting in primary care with fatigue may not receive appropriate care.

Trial Registration
ISRCTN 74156610
Study of the serotonin transporter (SLC6A4) and BDNF genes in French patients with non syndromic mental deficiency
Authors: Tabagh Refaat , Andres Christian R , Védrine Sylviane , Cherpi-Antar Catherine , Thepault Rose-Anne , Mignon Laurence , Dufour-Rainfray Diane , Moraine Claude , Vourc'h Patrick 
Published: February 2010

Abstract

Background
Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF) pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4) and the brain-derived neurotrophic factor gene (BDNF), are associated with mental deficiency (MD).

Methods
We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034) of the SLC6A4 gene and one functional polymorphism (Val66 Met) of the BDNF gene in 98 patients with non-syndromic mental deficiency (NS-MD) and in an ethnically matched control population of 251 individuals.

Results
We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the SLC6A4 and BDNF genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D') in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed.

Conclusion
Altogether, results from the present study do not support a role for any of the five functional polymorphisms of SLC6A4 and BDNF genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in BDNF and SLC6A4. However, we suggest that further studies on these two pathways in NS-MD remain necessary.
Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling
Authors: Yoo Byong Chul , Kong Sun-Young , Jang Sang-Geun , Kim Kyung-Hee , Ahn Sun-A , Park Weon-Seo , Park Sohee , Yun Tak , Eom Hyeon-Seok 
Published: February 2010

Abstract

Background
Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.

Methods
To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.

Results
The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.

Conclusions
The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.
Cyclooxygenase-2 enhances α2β1 integrin expression and cell migration via EP1 dependent signaling pathway in human chondrosarcoma cells
Authors: Liu Ju-Fang , Fong Yi-Chin , Chang Chih-Shiang , Huang Chun-Yin , Chen Hsien-Te , Yang Wei-Hung , Hsu Chin-Jung , Jeng Long-Bin , Chen Chih-Yi , Tang Chih-Hsin 
Published: February 2010

Abstract

Background
Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. Interaction of COX-2 with its specific EP receptors on the surface of cancer cells has been reported to induce cancer invasion. However, the effects of COX-2 on migration activity in human chondrosarcoma cells are mostly unknown. In this study, we examined whether COX-2 and EP interaction are involved in metastasis of human chondrosarcoma.

Results
We found that over-expression of COX-2 or exogenous PGE2 increased the migration of human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the COX-2 which was higher than that in normal cartilage. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptors, we discovered that the EP1 receptor but not other PGE receptors is involved in PGE2-mediated cell migration and α2β1 integrin expression. Furthermore, we found that human chondrosarcoma tissues expressed a higher level of EP1 receptor than normal cartilage. PGE2-mediated migration and integrin up-regulation were attenuated by phospholipase C (PLC), protein kinase C (PKC) and c-Src inhibitor. Activation of the PLCβ, PKCα, c-Src and NF-κB signaling pathway after PGE2 treatment was demonstrated, and PGE2-induced expression of integrin and migration activity were inhibited by the specific inhibitor, siRNA and mutants of PLC, PKC, c-Src and NF-κB cascades.

Conclusions
Our results indicated that PGE2 enhances the migration of chondrosarcoma cells by increasing α2β1 integrin expression through the EP1/PLC/PKCα/c-Src/NF-κB signal transduction pathway.
Associations between attributes of live poultry trade and HPAI H5N1 outbreaks: a descriptive and network analysis study in northern Vietnam
Authors: Soares Magalhães Ricardo J , Ortiz-Pelaez Angel , Thi Kim Lan Lai , Dinh Quoc Hoang , Otte Joachim , Pfeiffer Dirk U 
Published: February 2010

Abstract

Background
The structure of contact between individuals plays an important role in the incursion and spread of contagious diseases in both human and animal populations. In the case of avian influenza, the movement of live birds is a well known risk factor for the geographic dissemination of the virus among poultry flocks. Live bird markets (LBM's) contribute to the epidemiology of avian influenza due to their demographic characteristics and the presence of HPAI H5N1 virus lineages. The relationship between poultry producers and live poultry traders (LPT's) that operate in LBM's has not been adequately documented in HPAI H5N1-affected SE Asian countries. The aims of this study were to document and study the flow of live poultry in a poultry trade network in northern Vietnam, and explore its potential role in the risk for HPAI H5N1 during 2003 to 2006.

Results
Our results indicate that LPT's trading for less than a year and operating at retail markets are more likely to source poultry from flocks located in communes with a past history of HPAI H5N1 outbreaks during 2003 to 2006 than LPT's trading longer than a year and operating at wholesale markets. The results of the network analysis indicate that LPT's tend to link communes of similar infection status.

Conclusions
Our study provides evidence which can be used for informing policies aimed at encouraging more biosecure practices of LPT's operating at authorised LBM's. The results suggest that LPT's play a role in HPAI H5N1 transmission and may contribute to perpetuating HPAI H5N1 virus circulation amongst certain groups of communes. The impact of current disease prevention and control interventions could be enhanced by disseminating information about outbreak risk and the implementation of a formal data recording scheme at LBM's for all incoming and outgoing LPT's.
Liquefaction behavior of Western red cedar and Japanese beech in the ionic liquid 1-ethyl-3-methylimidazolium chloride
Authors: Nakamura Atsushi , Miyafuji Hisashi , Saka Shiro 
Published: February 2010

Abstract
Western red cedar and Japanese beech are studied concerning their liquefaction behavior with an ionic liquid, 1-ethyl-3-methylimidazolium chloride ([C2mim][Cl]). Significant differences in liquefaction behavior were observed in terms of solubility and the lignin content of the insoluble residues. Thioacidolysis analysis of the residues confirmed that β-O-4 bonds in lignin were cleaved preferentially by the treatment with [C2mim][Cl]. The differences in liquefaction behavior can be explained by structural differences between softwood and hardwood lignins. Furthermore, gel permeation chromatography and GC-MS analyses revealed that cellulose and hemicelluloses were decomposed partly to monomeric sugars such as glucose, mannose, galactose, xylose, and arabinose.