bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased frequency and activated phenotype of blood CD27 IgD IgM B lymphocytes is a permanent abnormality in systemic lupus erythematosus patients
Authors: Rodríguez-Bayona Beatriz , Ramos-Amaya Ana , Pérez-Venegas José J , Rodríguez Carmen , Brieva José A 
Published: June 2010

Abstract
Introduction
Systemic lupus erythematosus (SLE) is characterized by B cell hyper-activation and auto-reactivity resulting in pathogenic auto-antibody generation. The phenotypic analysis of blood B cell subsets can be used to understand these alterations.

Methods
The combined detection of CD19, CD27 and IgD (or IgM) by flow cytometry (FC) analysis delineates five well-defined blood B cell-subsets: naive, switched (S) memory, double negative (DN) memory and CD27 IgD IgM (non-switched memory) B lymphocytes, and plasma cells (PCs). This phenotypic study was performed in 69 consecutive SLE patients and 31 healthy controls.

Results
SLE patients exhibited several abnormalities in the distribution of these B cell subsets, including elevated levels of DN memory B cells and PCs, and decreased CD27 IgD IgM B cells. Active SLE patients also showed decreased presence of S memory B cells and increased proportions of naive B lymphocytes. Nevertheless, when the patients in remission who did not require treatment were studied separately, the only remaining abnormality was a reduction of the CD27 IgD IgM B cell-subset detectable in most of these patients. The level of reduction of CD27 IgD IgM B cells was associated with elevated values of serum SLE auto-antibodies. Further analysis of this latter B cell-subset specifically showed increased expression of CD80, CD86, CD95, 9G4 idiotype and functional CXCR3 and CXCR4.

Conclusions
The presence of a reduced blood CD27 IgD IgM B cell-subset, exhibiting an activated state and enriched for auto-reactivity, is a consistent B cell abnormality in SLE. These findings suggest that CD27 IgD IgM B lymphocytes play a role in the pathogenesis of this disease.
Phenotype and functional changes of Vγ9/Vδ2 T lymphocytes in Behçet's disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity
Authors: Accardo-Palumbo Antonina , Giardina Anna Rita , Ciccia Francesco , Ferrante Angelo , Principato Alfonso , Impastato Rosalia , Giardina Ennio , Triolo Giovanni 
Published: June 2010

Abstract
Introduction
Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vγ9/Vδ2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity.

Methods
We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vγ9/Vδ2 T lymphocytes by means of fluorescence-activated cell sorter analysis of lymphocyte cultures from patients with active and inactive BD and healthy subjects.

Results
Cell expansion, expression of TNFRII, perforin and gamma IFN content and release of granzyme A were significantly higher in active patients. In vitro and ex vivo treatment with infliximab resulted in a significant reduction of all parameters together with changes in the phenotype of Vγ9/Vδ2 T cells.

Conclusions
All together these data indicate that infliximab is capable of interfering with Vγ9/Vδ2 T cell function in BD and although cell culture models cannot reliably predict all potential effects of the drug in vivo, our results present the possibility that this drug may find use in a range of immunological disorders, characterized by dysregulated cell-mediated immunity.
Meeting Report: Nuclear Receptors: Transcription Factors and Drug Targets Connecting Basic Research with Translational Medicine
Authors: Tuckermann Jan , Bourguet William , Mandrup Susanne 
Published: June 2010

Abstract
The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25–29, 2009. The meeting brought together researchers from all over the world covering a wide spectrum from fundamental mechanistic studies to metabolism, clinical studies, and drug development. In this report, we summarize the recent and exciting findings presented by the speakers at the meeting.
A Comparison of Automated Infusion Device Technology to Prevent Medication Errors in Pediatric and Adult Intensive Care Unit Patients
Authors: Hennings Steven , Romero Andrew , Erstad Brian L. , Franke Hillary , Theodorou Andreas A. 
Published: June 2010

Objective To compare possible differences in the proportion of medication errors associated with high-risk medications that were avoided by the use of automated infusion device (AID) technology in pediatric and adult intensive care unit (ICU) patients. A secondary purpose was to investigate the number of serious adverse drug events (ADEs) identified by root-cause analyses (RCA). Method The study included pediatric and adult patients receiving high-risk medications by continuous infusion in an academic medical center with mixed medical-surgical ICUs. A retrospective evaluation of 1 year's data collected prospectively in an AID database was used to compare the proportion of medication errors avoided based on reprogramming events (2.5 times limit as a low threshold) and overrides (10 times limit as high). Information obtained from RCAs was used to compare the proportion of serious ADEs that occurred during the 5-year periods before and after AID implementation. Results The pediatric population was 1.68 times (95% confidence interval [CI], 1.18 to 2.38) more likely to require a reprogramming event than the adult acute care population for all high-risk medications combined. Significantly more reprogramming events occurred in the pediatric patients with potassium (relative risk [RR], 2.77; 95% CI, 1.15 to 6.68) and insulin (RR, 2.73; 95% CI, 1.15 to 6.45) infusions. Additionally, there were more overrides in the pediatric compared to the adult population for the high-risk medications (RR, 1.82; 95% CI, 1.32 to 2.53). The number of serious adverse or sentinel events as identified in RCAs decreased from six before (four deemed preventable by AID technology) to three (zero preventable) after AID implementation. Conclusions This study demonstrates that AID technology when properly used leads to reductions in medication errors and possibly serious ADEs in critically ill patients receiving high-risk medications. The technology appears to be particularly beneficial in pediatric patients with weight-based dosing strategies. However, the potential for clinicians to override the alerts remains a concern.
Potential Cost Savings for a Health System–Based Employee Outpatient Pharmacy
Authors: Phillippe Haley M. , Andrus Miranda R. , Sims Matthew , McDaniel Michael R. 
Published: June 2010

Abstract Hospitals everywhere are faced with the same dilemma as other companies, struggling to manage rising health care expenses while providing optimal care for their employees. One of the often overlooked drug expense is the drugs consumed by the facility's employees. Although the average pharmacy department manager has a considerable amount of experience and expertise in dealing with drug expense issues for inpatients or even classic outpatients, the path to optimizing the drug expense investment strategies for their fellow employees can be difficult and elusive to discern. This article should provide a pharmacy manager with a few examples of how to contain costs for employee outpatient pharmacies.
Interaction between Warfarin and Transdermal Selegiline: First Case Report and Literature Review
Authors: Ensor Christopher R. , Dean Stacey R. 
Published: June 2010

AbstractA procoagulant effect may occur when enzymatic inhibitors of CYP2C9, 1A2, or 3A4 are therapeutically coadministered with warfarin. To our knowledge, there have been no case reports of such an interaction between warfarin and selegiline. We describe a case of a 49-year-old female who was taking warfarin for prevention of a venous thromboembolism after orthopedic surgery. During routine follow-up, the patient's international normalized ratio (INR) suddenly elevated to 9.0. Her INR had been subtherapeutic for 2 months prior despite escalating doses of warfarin. The only identifiable change to the patient's lifestyle or medications was the initiation of transdermal selegiline 5 days prior to this supratherapeutic INR. Recent laboratory tests revealed no significant abnormalities, with the exception of slightly depressed serum albumin. Her warfarin was held for 2 days, oral phytonadione 2.5 mg was given, and selegiline was held. The Drug Interaction Probability Scale revealed a probable drug-drug interaction between warfarin and selegiline. The likely mechanism of this interaction is selegiline-mediated moderate inhibition of CYP1A2 and weak or competitive inhibition of 2C9 and 3A4. Clinicians should be hypervigilant to this probable drug-drug interaction when initiating either therapy in a patient maintained on the opposing drug.
An Experimental Technique for Determining the Hydraulic Properties of Unsaturated Pyroclastic Soils
Authors: Nicotera Marco Valerio , Papa Raffaele , Urciuoli Gianfranco 
Published: June 2010

Abstract
The experimental technique proposed in the paper was designed to rapidly and reliably determine both the water retention curve and the permeability function of undisturbed natural pyroclastic soil samples. The technique was developed in the framework of an experimental research project on mudflows in pyroclastic soils in the southern Italian region of Campania (Italy). Grain-size distribution and void ratio of the particular pyroclastic soils suggested investigation of the hydraulic behavior for matric suction values in the range between 0 and 100 kPa. Our experimental technique consisted of a sequence of testing phases to be conducted on a single undisturbed soil sample: A constant head permeation test, a forced evaporation test, and finally a drying test in a pressure plate apparatus. Interpretation of the experimental data was based on inverse modelling and allowed both water retention curves and permeability functions to be determined. The six parameters of the Mualem–van Genuchten model were adopted to describe the hydraulic behavior of the tested soils. Each testing phase supplied experimental data to be used in the interpretation procedure: The permeation phase provided a matching data point for the permeability function near saturation; the forced evaporation test was related to the hydraulic behavior for matric suction values ranging from a few kPa to less than 80–90 kPa (i.e., mini-tensiometer functioning range); and the drying steps in the pressure plate apparatus provided information about the retention properties for matric suction values up to 1 MPa. The results shown in the paper clearly confirm the goodness of the experimental design and the interpretation procedure.
Fractography of ASTM D2512 Tested Polymeric Isotropic Material Residuals Generated External to the Impacting Indenter
Authors: Gerzeski Roger 
Published: June 2010

Abstract
An examination of the fracture surfaces found on residuals originating external to the specimen contacting indenter of a ASTM D2512 tested isotropic polymeric material has been conducted for the first time. The repeated appearance and interrelationship of a select series of distinct features was identified. Cracks which plunge from the surface into the bulk of the tested specimen were routinely observed. They are developed by the independent mechanism of sliding Hertzian fracture. Radial cracks, propagating through the entire thickness of the tested specimen, from the most central portion of the original specimen through to its back edge were always observed. They were developed by the independent mechanism of tensile hoop failure. This tensile hoop mechanism also caused the point loaded backside impact damage feature occasionally observed. Shield shaped cracks and indications of secondary point loaded impacts were also routinely observed. Extrinsically generated, finely crushed granular and/or flake powder was commonly found tenaciously adhering to the fractured and top edges of many of these residuals. This powder feature always exhibited indications of having flowed onto the residual and frequently indications of having experienced intense heating. The forced flow of the powder caused the powder’s surface to be heated by the mechanism of kinetic friction heating. While kinetic friction heating did generate features indicative of exposure to intense heat, there were effectively no lasting indications that ignition had originated on these external residuals.
Design and Use of Expansion Joints in New and Existing Clay Masonry Wall Systems
Authors: Farmer Matthew C. , Gerns Edward A. 
Published: June 2010

Abstract
In modern masonry wall construction, integration of expansion joints (both vertical and horizontal) has become commonplace, but the rationale behind their width, placement, detailing, and maintenance is often misunderstood. With restoration projects and older wall systems it is often not clear whether expansion joints are needed and should be added as part of a restoration. Older structures in particular offer unique challenges. Damage of masonry wall systems can occur as a result of volume changes in the masonry materials despite the presence of expansion joints; this is frequently because joints are placed or installed inappropriately for the construction of the wall system, the particular wall geometry, or other factors related to the placement of joints designed to accommodate movement. This paper attempts to clarify and expand on the reasoning behind many of the standard guidelines commonly used for joint placement, size, and spacing. In addition, suggestions are provided for joint placement and detailing in several atypical situations, such as existing buildings, parapets, solid masonry wall systems, and window lintels. Factors leading to the need for expansion joints are reviewed, along with several lesser known concepts regarding expansion joint implementation. Also addressed are common problems with installation and maintenance of existing expansion joints.
Loading Mixity on the Interfacial Failure Mode in Lead-Free Solder Joint
Authors: Gao Feng , Jing Jianping , Liang Frank Z. , Williams Richard L. , Qu Jianmin 
Published: June 2010

Abstract
In this paper, single solder joints (SSJs) were subjected to moderate speed loading (5 mm/s) in different directions, from pure tensile mixity mode to pure shear. Fracture surfaces from different loading directions were examined both experimentally and numerically. The intermetallic compound (IMC) is formed between the solder alloy and the Cu pad, and the failure typically occurs at or near the solder/IMC/Cu interfaces of the board side. Pure tensile loading typically leads to interfacial fracture along the IMC/Cu interface. Mixity mode loading usually results in a mixture of interfacial and cohesive failure with damage propagating in a zigzag fashion between the solder/IMC interface and the solder alloy. Loading with higher shear component tends to result in more cohesive failure of the solder alloy near the solder/IMC interface. Under pure shear loading, failure is almost always cohesive within the solder alloy near the solder/IMC interface.
Using Environmental Correlations to Identify Loci Underlying Local Adaptation
Authors: Coop Graham , Witonsky David , Di Rienzo Anna , Pritchard Jonathan K 
Published: June 2010

Abstract
Loci involved in local adaptation can potentially be identified by an unusual correlation between allele frequencies and important ecological variables or by extreme allele frequency differences between geographic regions. However, such comparisons are complicated by differences in sample sizes and the neutral correlation of allele frequencies across populations due to shared history and gene flow. To overcome these difficulties, we have developed a Bayesian method that estimates the empirical pattern of covariance in allele frequencies between populations from a set of markers and then uses this as a null model for a test at individual SNPs. In our model the sample frequencies of an allele across populations are drawn from a set of underlying population frequencies; a transform of these population frequencies is assumed to follow a multivariate normal distribution. We first estimate the covariance matrix of this multivariate normal across loci using a Monte Carlo Markov chain. At each SNP, we then provide a measure of the support, a Bayes factor, for a model where an environmental variable has a linear effect on the transformed allele frequencies compared to a model given by the covariance matrix alone. This test is shown through power simulations to outperform existing correlation tests. We also demonstrate that our method can be used to identify SNPs with unusually large allele frequency differentiation and offers a powerful alternative to tests based on pairwise or global FST. Software is available at http://www.eve.ucdavis.edu/gmcoop/.
The Consequences of Regulation of desat1 Expression for Pheromone Emission and Detection inDrosophila melanogaster
Authors: Houot Benjamin , Bousquet François , Ferveur Jean-François 
Published: June 2010

AbstractSensory communication depends on the precise matching between the emission and the perception of sex- and species-specific signals; understanding both the coevolutionary process and the genes involved in both production and detection is a major challenge. desat1 determines both aspects of communication—a mutation in desat1 simultaneously alters both sex pheromone emission and perception in Drosophila melanogaster flies. We investigated whether the alteration of pheromonal perception is a consequence of the altered production of pheromones or if the two phenotypes are independently controlled by the same locus. Using several genetic tools, we were able to separately manipulate the two pheromonal phenotypes, implying that desat1 is the sole gene responsible, exerting a pleiotropic effect on both transmission and detection. The levels of the five desat1 trancripts, measured in the head and body of manipulated flies, were related to variation in pheromone production. This suggests that the pleiotropic action of desat1 on pheromonal communication depends on the fine regulation of its transcriptional activity.
Detecting Selection in Population Trees: The Lewontin and Krakauer Test Extended
Authors: Bonhomme Maxime , Chevalet Claude , Servin Bertrand , Boitard Simon , Abdallah Jihad , Blott Sarah , SanCristobal Magali 
Published: June 2010

AbstractDetecting genetic signatures of selection is of great interest for many research issues. Common approaches to separate selective from neutral processes focus on the variance of FST across loci, as does the original Lewontin and Krakauer (LK) test. Modern developments aim to minimize the false positive rate and to increase the power, by accounting for complex demographic structures. Another stimulating goal is to develop straightforward parametric and computationally tractable tests to deal with massive SNP data sets. Here, we propose an extension of the original LK statistic (TLK), named TF–LK, that uses a phylogenetic estimation of the population's kinship ($\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{\mathcal{F}}\) \end{document}$) matrix, thus accounting for historical branching and heterogeneity of genetic drift. Using forward simulations of single-nucleotide polymorphisms (SNPs) data under neutrality and selection, we confirm the relative robustness of the LK statistic (TLK) to complex demographic history but we show that TF–LK is more powerful in most cases. This new statistic outperforms also a multinomial-Dirichlet-based model [estimation with Markov chain Monte Carlo (MCMC)], when historical branching occurs. Overall, TF–LK detects 15–35% more selected SNPs than TLK for low type I errors (P &lt; 0.001). Also, simulations show that TLK and TF–LK follow a chi-square distribution provided the ancestral allele frequencies are not too extreme, suggesting the possible use of the chi-square distribution for evaluating significance. The empirical distribution of TF–LK can be derived using simulations conditioned on the estimated $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{\mathcal{F}}\) \end{document}$ matrix. We apply this new test to pig breeds SNP data and pinpoint outliers using TF–LK, otherwise undetected using the less powerful TLK statistic. This new test represents one solution for compromise between advanced SNP genetic data acquisition and outlier analyses.
The gypsy Insulator of Drosophila melanogaster, Together With Its Binding Protein Suppressor of Hairy-Wing, Facilitate High and Precise Expression of Transgenes in Arabidopsis thaliana
Authors: She Wenjing , Lin Weiqiang , Zhu Yubin , Chen Yong , Jin Weiyuan , Yang Yanjun , Han Ning , Bian Hongwu , Zhu Muyuan , Wang Junhui 
Published: June 2010

Abstract
The variation of expression pattern exhibited by a transgene as a result of random integration, known as position effect, is, among other mechanisms, a particular challenge to reverse genetics. We present a strategy to counteract position effect in Arabidopsis thaliana by flanking the transgenes with the gypsy insulator from Drosophila melanogaster. In addition, Suppressor of Hairy-wing [Su(Hw)], the binding protein of the gypsy insulator, was coexpressed. Results indicated that the gypsy insulators could efficiently improve the expression levels of reporter genes driven by various kinds of promoters by 8- to 13-fold. Coexpression of the Su(Hw) protein led to a more uniform expression level of transgenes, as the coefficient of variation of expression levels was reduced further. The gypsy-Su(Hw) system enhanced expression levels, but did not alter the specificity of promoter activities, as experimentally evidenced by the promoters of the PIN and the AFB gene families. Interestingly, the gypsy insulator was also able to improve the expression of a selectable marker gene outside the insulated region, which facilitated the screen of transformants. Our system will likely decrease the number of lines that experimenters need to create and examine for a given transgene by contributing to relatively high and precise expression of transgenes in plants. Certain features of the gypsy insulator in Arabidopsis also provide new perspectives on the insulator field.
A High Frequency of Beneficial Mutations Across Multiple Fitness Components inSaccharomyces cerevisiae
Authors: Hall David W , Joseph Sarah B 
Published: June 2010

AbstractMutation-accumulation experiments are widely used to estimate parameters of spontaneous mutations affecting fitness. In many experiments only one component of fitness is measured. In a previous study involving the diploid yeast Saccharomyces cerevisiae, we measured the growth rate of 151 mutation-accumulation lines to estimate parameters of mutation. We found that an unexpectedly high frequency of fitness-altering mutations was beneficial. Here, we build upon our previous work by examining sporulation efficiency, spore viability, and haploid growth rate and find that these components of fitness also show a high frequency of beneficial mutations. We also examine whether mutation-acycumulation (MA) lines show any evidence of pleiotropy among accumulated mutations and find that, for most, there is none. However, MA lines that have zero fitness (i.e., lethality) for any one fitness component do show evidence for pleiotropy among accumulated mutations. We also report estimates of other parameters of mutation based on each component of fitness.