bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of kinin B2receptors by bradykinin in human lung cells
Authors: Bengtson Sara H. , Eddleston Jane , Mörgelin Matthias , Zuraw Bruce L. , Herwald Heiko 
Published: September 2008

AbstractBradykinin is a potent mediator of inflammation that has been shown to participate in allergic airway inflammation. The biologic effects of bradykinin are mediated by binding and activation of its cognate receptor, the B2receptor (B2R). In the lung fibroblast cell line IMR-90, binding of bradykinin to B2R triggers down-regulation of receptor surface expression, suggesting that bradykinin-induced inflammation is transient and self-limited. Notably, subjects with chronic airway inflammation continue to respond to BK following a first challenge. B2Rs are expressed on many different lung cell types, including airway epithelial cells. We therefore compared IMR-90 cells with the human lung epithelial cell line BEAS2B and found that B2R expression in the two cell types is differently regulated by BK. Whereas BK induces down-regulation of B2R in IMR-90 cells, the same treatment leads to up-regulation of the receptor in BEAS2B cells. These results provide a possible explanation for the potency of bradykinin in inducing ongoing airway inflammation.
Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner
Authors: Hofmann Lotte P. , Ren Shuyu , Schwalm Stephanie , Pfeilschifter Josef , Huwiler Andrea 
Published: September 2008

Abstract
Sphingosine kinases (SKs) are key enzymes regulating the production of sphingosine-1-phosphate (S1P), which determines important cell responses including cell growth and death. Here we show that renal mesangial cells isolated from wild-type, SK-1-/-, and SK-2-/- mice show a differential response to apoptotic stimuli. Wild-type mesangial cells responded to staurosporine with increased DNA fragmentation and caspase-3 processing, which was enhanced in SK-1-/- cells. In contrast, SK-2-/- cells were highly resistant to staurosporine-induced apoptosis. Furthermore, the basal phosphorylation and activity of the anti-apoptotic protein kinase B (PKB) and of its substrate Bad were decreased in SK-1-/- but not in SK-2-/- cells. Upon staurosporine treatment, phosphorylation of PKB and Bad decreased in wild-type and SK-1-/- cells, but remained high in SK-2-/- cells. In addition, the anti-apoptotic Bcl-XL was significantly upregulated in SK-2-/- cells, which may further contribute to the protective state of these cells. In summary, our data show that SK-1 and SK-2 have opposite effects on the capacity of mesangial cells to resist apoptotic stimuli. This is due to differential modulation of the PKB/Bad pathway and of Bcl-XL expression. Thus, subtype-selective targeting of SKs will be critical when considering these enzymes as therapeutic targets for the treatment of inflammation or cancer.
Molecular profile of breast versus ovarian cancer cells in response to treatment with the anticancer drugs cisplatin, carboplatin, doxorubicin, etoposide and taxol
Authors: Thomadaki Hellinida , Scorilas Andreas 
Published: September 2008

Abstract
We assessed changes in the apoptosis-related genes BCL2, BAX, BCL2L12, FAS and CASPASE-3 in OVCAR-3 human ovarian cancer cells and BT-20 human breast cancer cells to provide an insight into the molecular mechanisms involved in the response of these cells to treatment with anticancer drugs and to assess their value as potential biomarkers of chemotherapy response in breast and ovarian cancer. Cells were treated with different chemotherapeutic drugs (cisplatin, carboplatin, doxorubicin, etoposide and taxol) and assessed for changes in the expression of apoptosis-related genes at the mRNA level. Total RNA was extracted, reverse-transcribed into cDNA and amplified by PCR using gene-specific primers. GAPDH was used as a housekeeping gene. Cytotoxicity was assessed by MTT assay. Both cancer cell lines responded differentially at the molecular level to the drug treatments. OVCAR-3 cells showed more pronounced sensitivity and changes compared to BT-20 cells at the mRNA level for different apoptosis-related genes, leading to cell and cancer type dependence in conjunction with drug dependence.
Acid β-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy
Authors: Kacher Yaacov , Brumshtein Boris , Boldin-Adamsky Swetlana , Toker Lilly , Shainskaya Alla , Silman Israel , Sussman Joel L. , Futerman Anthony H. 
Published: September 2008

Abstract
In mammalian cells, glucosylceramide (GlcCer), the simplest glycosphingolipid, is hydrolyzed by the lysosomal enzyme acid β-glucosidase (GlcCerase). In the human metabolic disorder Gaucher disease, GlcCerase activity is significantly decreased owing to one of approximately 200 mutations in the GlcCerase gene. The most common therapy for Gaucher disease is enzyme replacement therapy (ERT), in which patients are given intravenous injections of recombinant human GlcCerase; the Genzyme product Cerezyme® has been used clinically for more than 15 years and is administered to approximately 4000 patients worldwide. Here we review the crystal structure of Cerezyme® and other recombinant forms of GlcCerase, as well as of their complexes with covalent and non-covalent inhibitors. We also discuss the stability of Cerezyme®, which can be altered by modification of its N-glycan chains with possible implications for improved ERT in Gaucher disease.
Anaphoric pronominal reference in Russian and German narratives: bilingual and monolingual settings
Authors: Gagarina Natalia 
Published: September 2008

Abstract
The study compares the rate and type of the anaphoric pronominalisation in narratives produced by adults, by monolingual and by consecutive and simultaneous bilingual five-year-old children. In particular, it addresses the question which types of pronouns children use to refer to previously introduced antecedents and which syntactic role these antecedent NPs exhibit. Results show that consecutive bilinguals show a lower pronominalisation rate as compared to the narratives of monolingual German-speaking children and to their own Russian narratives. These findings are discussed within the construction-based model of language acquisition (Tomasello 2003). Language-specific organisation of the pronominal systems as well as the language-specific structural features are argued to have an impact on the pronominalisation rate in discourse.
Peptidase activities in Crotalus durissus terrificus semen
Authors: Marinho Camila Eduardo , Almeida-Santos Selma Maria , Carneiro Sylvia Mendes , Yamasaki Simone Cristina , Silveira Paulo Flavio 
Published: September 2008

AbstractTo understand the role of peptidases in seminal physiology of Crotalus durissus terrificus, activity levels of representative enzymes in semen and their sensitivities to inhibitors, cofactors, and peptide hormones were evaluated. The existence of seminal fractions and the association of peptidases with these fractions were also characterized for the first time in snakes. The prominent inhibitors of aminopeptidases (APs) were amastatin for acid, basic, and neutral; bestatin for basic; and diprotin A for dipeptidyl-IV. Cystyl and prolyl-imino APs were similarly susceptible to the majority of these inhibitors. The basic and neutral were characterized as metallo-peptidases, acid AP was activated by MnCl2, and cystyl, prolyl-imino, and type I pyroglutamyl were characterized as sulphydryl-dependent APs. Angiotensin II, vasotocin, bradykinin, fertilization-promoting peptide, and TRH altered the majority of these peptidase activities; these peptides are possible substrates and/or modulators of these peptidases. Peptidase activities were found in all seminal fractions: seminal plasma (SP), prostasome-like (PR) structures, and soluble (S-) and membrane-bound fractions (MFs) of spermatozoa. The levels of activity of each peptidase varied among different seminal fractions. In SP, the higher activities were puromycin-insensitive neutral and basic APs. In PR, the higher activity was puromycin-insensitive neutral AP. In spermatozoa, the higher activity in subcellular SF was puromycin-sensitive neutral, while in MF both puromycin-sensitive and -insensitive neutral APs were equally higher than the other examined peptidases. Data suggested that these peptidases, mainly basic and neutral, have a high relevance in regulating seminal functions of C. d. terrificus.
Chromosomal Regions Underlying Noncoagulation of Milk in Finnish Ayrshire Cows
Authors: Tyrisevä Anna-Maria , Elo Kari , Kuusipuro Arja , Vilva Veijo , Jänönen Isto , Karjalainen Heidi , Ikonen Tiina , Ojala Matti 
Published: September 2008

Abstract
About 10% of Finnish Ayrshire cows produce noncoagulating milk, i.e., milk that does not form a curd in a standard 30-min testing time and is thus a poor raw material for cheese dairies. This phenomenon is associated with peak and midlactation, but some cows produce noncoagulating milk persistently. A genomewide scan under a selective DNA pooling method was carried out to locate genomic regions associated with the noncoagulation of milk. On the basis of the hypothesis of the same historical mutation, we pooled the data across sires. Before testing pools for homogeneity, allele intensities were corrected for PCR artifacts, i.e., shadow bands and differential amplification. Results indicating association were verified using daughter design and selective genotyping within families. Data consisted of 18 sire families with 477 genotyped daughters in total, i.e., 12% of each tail of the milk coagulation ability. Data were analyzed using interval mapping under maximum-likelihood and nonparametric methods. BMS1126 on chromosome 2 and BMS1355 on chromosome 18 were associated with noncoagulation of milk across families on an experimentwise 0.1% significance level. By scanning gene databases, we found two potential candidate genes: LOC538897, a nonspecific serine/threonine kinase on chromosome 2, and SIAT4B, a sialyltransferase catalyzing the last step of glycosylation of κ-casein on chromosome 18. Further studies to determine the role of the candidates in the noncoagulation of milk are clearly needed.
On the Detection of Imprinted Quantitative Trait Loci in Line Crosses: Effect of Linkage Disequilibrium
Authors: Sandor Cynthia , Georges Michel 
Published: September 2008

Abstract
Imprinted quantitative trait loci (QTL) are commonly reported in studies using line-cross designs, especially in livestock species. It was previously shown that such parent-of-origin effects might result from the nonfixation of QTL alleles in one or both parental lines, rather than from genuine molecular parental imprinting. We herein demonstrate that if linkage disequilibrium exists between marker loci and nonfixed QTL, spurious detection of pseudo-imprinting is increased by an additional 40–80% in scenarios mimicking typical livestock situations. This is due to the fact that imprinting can be tested only in F2 offspring whose sire and dam have distinct marker genotypes. In the case of linkage disequilibrium between markers and QTL, such parents have a higher chance to have distinct QTL genotypes as well, thus resulting in distinct padumnal and madumnal allele substitution effects, i.e., QTL pseudo-imprinting.
A Fundamental Relationship Between Genotype Frequencies and Fitnesses
Authors: Lachance Joseph 
Published: September 2008

Abstract
The set of possible postselection genotype frequencies in an infinite, randomly mating population is found. Geometric mean heterozygote frequency divided by geometric mean homozygote frequency equals two times the geometric mean heterozygote fitness divided by geometric mean homozygote fitness. The ratio of genotype frequencies provides a measure of genetic variation that is independent of allele frequencies. When this ratio does not equal two, either selection or population structure is present. Within-population HapMap data show population-specific patterns, while pooled data show an excess of homozygotes.
FDA Report: Eculizumab (Soliris®) for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Dmytrijuk Andrew , Robie-Suh Kathy , Cohen Martin H. , Rieves Dwaine , Weiss Karen , Pazdur Richard 
Published: September 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the mechanism of action of eculizumab in PNH.Discuss the efficacy findings upon which the approval of eculizumab was based.Manage the safety concerns surrounding the use of eculizumab for the treatment of patients with PNH.Discuss the efficacy and side effect profile of eculizumab.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
On March 16, 2007, eculizumab (Soliris®; Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double-blind, placebo-controlled clinical trial in 87 RBC transfusion–dependent adult PNH patients and in a supportive single-arm study in 96 patients. The eculizumab dose was 600 mg as a 35-minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab-treated patients, compared with none of 44 placebo-treated patients. Eculizumab-treated patients required significantly fewer RBC transfusions than placebo-treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti-human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated.
Medical Accuracy in Sexuality Education: Ideology and the Scientific Process
Authors: Santelli John S. 
Published: September 2008

Recently, many states have implemented requirements for scientific or medical accuracy in sexuality education and HIV prevention programs. Although seemingly uncontroversial, these requirements respond to the increasing injection of ideology into sexuality education, as represented by abstinence-only programs. I describe the process by which health professionals and government advisory groups within the United States reach scientific consensus and review the legal requirements and definitions for medical accuracy. Key elements of this scientific process include the weight of scientific evidence, the importance of scientific theory, peer review, and recognition by mainstream scientific and health organizations. I propose a concise definition of medical accuracy that may be useful to policymakers, health educators, and other health practitioners.
Mechanistic Understanding of Rock/Phosphonate Interactions and the Effect of Metal Ions on Inhibitor Retention
Authors: Tomson Mason B. , Kan Amy T. , Fu Gongmin , Shen Dong , Nasr-El-Din Hisham A. , Al-Saiari Hamad , Al-Thubaiti Musaed 
Published: September 2008

Summary
This paper discusses the effects of Ca2+, Mg2+, and Fe2+ on inhibitor retention and release. Better understanding of phosphonate reactions during inhibitor squeeze treatments has direct implication on how to design and improve scale inhibitor squeeze treatments for optimum scale control. Putting various amounts of metal ions in the inhibitor pill adds another degree of freedom in squeeze design, especially in controlling return concentrations and squeeze life.
Phosphonate reactions during squeeze treatments involve a series of self-regulating reactions with calcite and other minerals. However, excess calcite does not improve the retention of phosphonate due to the surface poisoning effect of Ca2+. The squeeze can be designed so that maximum squeeze life is achieved by forming a low solubility phase in the formation. Addition of Ca2+, Mg2+, and Fe2+ in the pill solution at 0.1 to 1 molar ratios significantly improves the retention of phosphonate. Alternatively, these metal ions can be dissolved from the formation while an acidic inhibitor pill is in contact with the formation minerals. Both BHPMP and DTPMP returns were significantly extended by the addition of metal ions (e.g., Ca2+ and Fe2+). The addition of Mg2+ may increase the long-term return concentration, which is important for some wells where a higher inhibitor return concentration is needed.
The laboratory squeeze simulations were compared to return data obtained from squeeze treatments performed on two wells located in a sandstone reservoir in Saudi Arabia. The sandstone formation contains significant amounts of iron-bearing minerals.
Data Analysis of Barnett Shale Completions
Authors: Shelley Bob , Grieser Bill , Johnson Bill J. , Fielder Eugene O. , Heinze James R. , Werline J. R. 
Published: September 2008

Summary
The north Texas Barnett shale illustrates the successful commercialization of an unconventional reservoir. However, it took 17 years to evolve from pumping crosslinked gel (XLG) carrying more than 1 million lbm of proppant per job to sand waterfracs (SWFs) consisting of large volumes of water with friction reducer and small quantities of sand. This transition to SWF stimulation opened the door for widespread development that has advanced the Newark East (Barnett shale) to the largest producing gas field in Texas.
This paper investigates Barnett completion strategy from 1993 to 2002. The 393-well data set includes completion, reservoir, and production data. Unique data-evaluation tools and techniques were used to investigate various completion and reservoir parameters to determine their effects on production (Shelley and Stephenson 2000; Zangl and Hannerer 2003).
We found that production results show a broad scattering when crossplotted with various completion and reservoir inputs. This result is not uncommon when analyzing field data. However, general trends were identified through comparisons of large numbers of wells. These trends were confirmed through the use of more-advanced data-mining techniques, which included self-organizing mapping (SOM) of data. The results show that SWF-type stimulation of the Barnett outperformed to varying degrees XLG treatments for the five reservoir types used in this evaluation.
Experimental Investigation and Modeling of the Effects of Rising Gas Bubbles in a Closed Pipe
Authors: Al-Darmaki S. , Falcone G. , Hale C. P. , Hewitt G. F. 
Published: September 2008

Summary
Transient multiphase flow in the wellbore causes problems in well-test interpretation when the well is shut in at surface and the pressure is measured downhole. Pressure-buildup data recorded during a test can be dominated by transient wellbore effects (i.e., phase change, flow reversal, and re-entry of the denser phase into the producing zone), making it difficult to distinguish between true reservoir features and transient wellbore artifacts (Gringarten et al. 2000).
This paper is a follow-up to paper SPE 96587 (Ali et al. 2005), which presented experimental results of phase redistribution effects on pressure-buildup data. Though the results of the experiments were revealing, they are complex because they reflect the real well situation. To obtain results in which the phase redistribution in the well is studied independently of the interaction with the reservoir, a further set of experiments was carried out. In these experiments, the tube (simulating the well) was isolated at both the top and the bottom at the same time. The pressure distribution was measured during the transient following shut-in and for the steady-state final condition, in which there was a liquid-filled zone at the bottom of the test section and a gas-filled zone at the top. A substantial number of tests were conducted in the bubbly-flow region and could therefore be analyzed by a simple 1D model for bubbly flow. The results of the comparison between the model and the experimental data are presented in this paper.
Gelation Kinetics and Performance Evaluation of an Organically Crosslinked Gel at High Temperature and Pressure
Authors: Al-Muntasheri G. A. , Nasr-El-Din H. A. , Zitha P. L. J. 
Published: September 2008

Summary
Organically crosslinked gels have been used to control water production in high temperature applications. These chemical systems are based on the crosslinking of a polyacrylamide-based polymer/copolymer with an organic crosslinker. Polyethyleneimine (PEI) has been used as an organic crosslinker for polyacrylamide-based copolymers to provide thermally stable gels.
Literature reported that PEI can form aqueous gels with polyacrylamide (PAM) at room temperature. In this paper, we show for the first time the possibility of crosslinking polyacrylamide with PEI at temperatures up to 140°C (285°F) and pressures up to 30 bars (435 psi). This paper reports data both in bulk and in porous media.
The gelation time of the PAM crosslinked with PEI at high temperatures up to 140°C (285°F) and pressures up to 435 psi (30 bars) was measured. The effects of polymer concentration, crosslinker concentration, temperature, salinity, initial pH value, and the initial degree of hydrolysis of the polymer on the gelation time were examined in detail. All measurements were conducted in the steady shear mode. 13C Nuclear Magnetic Resonance Spectroscopy (13C NMR) was used to relate the gelation time to changes in the structure of the polymer and hence explain the variation in the gelation time in terms of the gelling system chemistry.
In bulk, thermally stable gels were obtained by crosslinking PAM with PEI at 130°C (266°F) for at least 8 weeks. The performance of the PAM/PEI system in sandstone cores at a temperature of 90°C (194°F) and pressure drops of 68.95 bars (1,000 psi) was examined. The system was found to be stable for 3 weeks, where the permeability was reduced by a factor of 100%.
Lobbying and Contract Delegation in Public Procurement
Authors: Theilen Bernd 
Published: September 2008

Abstract
Interest groups exert influence on legislators' decisions about how to organize the contracting process in public procurement. Traditionally, centralized contracting structures have been favored to avoid allocative inefficiency. However, legislators have recently started to allow more and more contract delegation in public procurement projects. Different interest groups argue in favor and against this tendency. The objective of this paper is to judge from a normative perspective what socially efficient contracting structures are and from a positive perspective what contracting structure we can expect to find as equilibria of an endogenous lobby formation game. From the normative perspective, it is shown that both contracting structures can be socially efficient. Furthermore, the conditions under which a certain contracting structure is socially superior are identified. From the positive perspective the main result shows that we can have equilibria of the lobby formation game with socially efficient contracting structures and with socially inefficient contracting structures. Again, the circumstances under which the different equilibria occur are identified.