bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study)
Authors: Schilcher Gernot , Ribitsch Werner , Otto Ronald , Portugaller Rupert H , Quehenberger Franz , Truschnig-Wilders Martini , Zweiker Robert , Stiegler Philipp , Brodmann Marianne , Weinhandl Klemens , Horina Joerg H 
Published: August 2011

Abstract

Background
Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration.

Methods/Design
The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.
We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the study.

Discussion
A volume expansion strategy showing a benefit from earlier intervention for patients with markedly elevated urinary NGAL values, indicating a CIN, might arise from data from this study.

Trial registration
ClinicalTrials.gov NCT01292317
Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin/mitomycin C resistance in other bacteria
Authors: Yu Shen , Vit Allegra , Devenish Sean , Mahanty H Khris , Itzen Aymelt , Goody Roger S , Blankenfeldt Wulf 
Published: August 2011

Abstract

Background
The phenazines are redox-active secondary metabolites that a large number of bacterial strains produce and excrete into the environment. They possess antibiotic activity owing to the fact that they can reduce molecular oxygen to toxic reactive oxygen species. In order to take advantage of this activity, phenazine producers need to protect themselves against phenazine toxicity. Whereas it is believed that phenazine-producing pseudomonads possess highly active superoxide dismutases and catalases, it has recently been found that the plant-colonizing bacterium Enterobacter agglomerans expresses a small gene ehpR to render itself resistant towards D-alanyl-griseoluteic acid, the phenazine antibiotic produced by this strain.

Results
To understand the resistance mechanism installed by EhpR we have determined its crystal structure in the apo form at 2.15 Å resolution and in complex with griseoluteic acid at 1.01 Å, respectively. While EhpR shares a common fold with glyoxalase-I/bleomycin resistance proteins, the ligand binding site does not contain residues that some related proteins employ to chemically alter their substrates. Binding of the antibiotic is mediated by π-stacking interactions of the aromatic moiety with the side chains of aromatic amino acids and by a few polar interactions. The dissociation constant KD between EhpR and griseoluteic acid was quantified as 244 ± 45 μM by microscale thermophoresis measurements.

Conclusions
The data accumulated here suggest that EhpR confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. It is tempting to speculate that EhpR acts in concert with EhpJ, a transport protein of the major facilitator superfamily that is also encoded in the phenazine biosynthesis operon of E. agglomerans. The low affinity of EhpR for griseoluteic acid may be required for its physiological function.
Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials
Authors: Carter Nick , Pamba Allan , Duparc Stephan , Waitumbi John N 
Published: August 2011

Abstract

Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme.

Methods
Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine.

Results
Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline parasitaemia (p = 0.365). There was no effect of G6PD genotype (p = 0.490) or phenotype (p = 0.391) on the rate of malaria recrudescence, or reinfection (p = 0.134 and p = 0.354, respectively).

Conclusions
G6PD deficiency is common in African patients with malaria and until a reliable and simple G6PD test is available, the use of 8-aminoquinolines will remain problematic. G6PD status did not impact baseline haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial therapy.

Trial registration
Clinicaltrials.gov: NCT00344006 and NCT00371735.
Layer-dependent nanoscale electrical properties of graphene studied by conductive scanning probe microscopy
Authors: Zhao Shihua , Lv Yi , Yang Xinju 
Published: August 2011

Abstract
The nanoscale electrical properties of single-layer graphene (SLG), bilayer graphene (BLG) and multilayer graphene (MLG) are studied by scanning capacitance microscopy (SCM) and electrostatic force microscopy (EFM). The quantum capacitance of graphene deduced from SCM results is found to increase with the layer number (n) at the sample bias of 0 V but decreases with n at -3 V. Furthermore, the quantum capacitance increases very rapidly with the gate voltage for SLG, but this increase is much slowed down when n becomes greater. On the other hand, the magnitude of the EFM phase shift with respect to the SiO2 substrate increases with n at the sample bias of +2 V but decreases with n at -2 V. The difference in both quantum capacitance and EFM phase shift is significant between SLG and BLG but becomes much weaker between MLGs with a different n. The layer-dependent quantum capacitance behaviors of graphene could be attributed to their layer-dependent electronic structure as well as the layer-varied dependence on gate voltage, while the layer-dependent EFM phase shift is caused by not only the layer-dependent surface potential but also the layer-dependent capacitance derivation.
Spatial and temporal point tracking in real hyperspectral images
Authors: Aminov Benjamin , Nichtern Ofir , Rotman Stanley R 
Published: August 2011

Abstract
In this article, we consider the problem of tracking a point target moving against a background of sky and clouds. The proposed solution consists of three stages: the first stage transforms the hyperspectral cubes into a two-dimensional (2D) temporal sequence using known point target detection acquisition methods; the second stage involves the temporal separation of the 2D sequence into sub-sequences and the usage of a variance filter (VF) to detect the presence of targets using the temporal profile of each pixel in its group, while suppressing clutter-specific influences. This stage creates a new sequence containing a target with a seemingly faster velocity; the third stage applies the Dynamic Programming Algorithm (DPA) that tracks moving targets with low SNR at around pixel velocity. The system is tested on both synthetic and real data.
Analysing GCN4 translational control in yeast by stochastic chemical kinetics modelling and simulation
Authors: You Tao , Stansfield Ian , Romano M Carmen , Brown Alistair JP , Coghill George M 
Published: August 2011

Abstract

Background
The yeast Saccharomyces cerevisiae responds to amino acid starvation by inducing the transcription factor Gcn4. This is mainly mediated via a translational control mechanism dependent upon the translation initiation eIF2·GTP·Met-tRNAi
Met ternary complex, and the four short upstream open reading frames (uORFs) in its 5' mRNA leader. These uORFs act to attenuate GCN4 mRNA translation under normal conditions. During amino acid starvation, levels of ternary complex are reduced. This overcomes the GCN4 translation attenuation effect via a scanning/reinitiation control mechanism dependent upon uORF spacing.

Results
Using published experimental data, we have developed and validated a probabilistic formulation of GCN4 translation using the Chemical Master Equation (Model 1). Model 1 explains GCN4 translation's nonlinear dependency upon uORF placements, and predicts that an as yet unidentified factor, which was proposed to regulate GCN4 translation under some conditions, only has pronounced effects upon GCN4 translation when intercistronic distances are unnaturally short. A simpler Model 2 that does not include this unidentified factor could well represent the regulation of a natural GCN4 mRNA. Using parameter values optimised for this algebraic Model 2, we performed stochastic simulations by Gillespie algorithm to investigate the distribution of ribosomes in different sections of GCN4 mRNA under distinct conditions. Our simulations demonstrated that ribosomal loading in the 5'-untranslated region is mainly determined by the ratio between the rates of 5'-initiation and ribosome scanning, but was not significantly affected by rate of ternary complex binding. Importantly, the translation rate for codons starved of cognate tRNAs is predicted to be the most significant contributor to the changes in ribosomal loading in the coding region under repressing and derepressing conditions.

Conclusions
Our integrated probabilistic Models 1 and 2 explained GCN4 translation and helped to elucidate the role of a yet unidentified factor. The ensuing stochastic simulations evaluated different factors that may impact on the translation of GCN4 mRNA, and integrated translation status with ribosomal density.
Utility of a simplified ultrasound assessment to assess interstitial pulmonary fibrosis in connective tissue disorders - preliminary results
Authors: Gutierrez Marwin , Salaffi Fausto , Carotti Marina , Tardella Marika , Pineda Carlos , Bertolazzi Chiara , Bichisecchi Elisabetta , Filippucci Emilio , Grassi Walter 
Published: August 2011

Abstract
Introduction
Interstitial pulmonary fibrosis (IPF) is a frequent manifestation in patients with connective tissue disorders (CTD). Recently the ultrasound (US) criterion validity for its assessment has been proposed; however, the US scoring systems adopted include the study of several lung intercostal spaces (LIS), which could be time-consuming in daily clinical practice. The aim of this study was to investigate the utility of a simplified US B-lines scoring system compared with both the US comprehensive assessment and the high-resolution computed tomography (HRCT) findings of IPF in CTD patients.

Methods
Thirty-six patients with a diagnosis of CTD were enrolled. Each patient underwent chest HRCT and lung US by an experienced radiologist and rheumatologist, respectively. Both comprehensive and simplified US B-lines assessments were scanned. The comprehensive US assessment was performed at 50 LIS level, whereas the simplified US assessment included bilaterally 14 LIS; for the anterior chest: the second LIS along the para-sternal lines, the fourth LIS along the mid-clavear, anterior axillary and mid-axillary lines; for the posterior chest: the eighth LIS along the paravertebral, sub-scapular and posterior axillary lines.
For criterion validity, HRCT was considered the gold standard. Feasibility, inter and intra-observer reliability was also investigated.

Results
A highly significant correlation between comprehensive and simplified US assessment was found (P = 0.0001). A significant correlation was also found between the simplified US assessment and HRCT findings (P = 0.0006). Kappa values for the inter-observer simplified US assessment were in a range from 0.769 to 0.885, whereas the concordance correlation coefficient values for the intra-observer were from 0.856 to 0.955. There was a relevant difference in time spent on comprehensive (mean 23.3 ± SD 4.5 minutes) with respect to the simplified US assessment (mean 8.6 ± SD 1.4) (P < 0.00001).

Conclusions
Our results provide a new working hypothesis in favor of the utility of a simplified US B-lines assessment as an adjunct method to assess IPF in patients with CTD.
Conformational changes of the chaperone SecB upon binding to a model substrate – bovine pancreatic trypsin inhibitor (BPTI)
Authors: Haimann Michaela M. , Akdogan Yasar , Philipp Reinhard , Varadarajan Raghavan , Hinderberger Dariush , Trommer Wolfgang E. 
Published: August 2011

Abstract
SecB is a homotetrameric cytosolic chaperone that forms part of the protein translocation machinery in E. coli. Due to SecB, nascent polypeptides are maintained in an unfolded translocation-competent state devoid of tertiary structure and thus are guided to the translocon. In vitro SecB rapidly binds to a variety of ligands in a non-native state. We have previously investigated the bound state conformation of the model substrate bovine pancreatic trypsin inhibitor (BPTI) as well as the conformation of SecB itself by using proximity relationships based on site-directed spin labeling and pyrene fluorescence methods. It was shown that SecB undergoes a conformational change during the process of substrate binding. Here, we generated SecB mutants containing but a single cysteine per subunit or an exposed highly reactive new cysteine after removal of the nearby intrinsic cysteines. Quantitative spin labeling was achieved with the methanethiosulfonate spin label (MTS) at positions C97 or E90C, respectively. Highfield (W-band) electron paramagnetic resonance (EPR) measurements revealed that with BPTI present the spin labels are exposed to a more polar/hydrophilic environment. Nanoscale distance measurements with double electron-electron resonance (DEER) were in excellent agreement with distances obtained by molecular modeling. Binding of BPTI also led to a slight change in distances between labels at C97 but not at E90C. While the shorter distance in the tetramer increased, the larger diagonal distance decreased. These findings can be explained by a widening of the tetrameric structure upon substrate binding much like the opening of two pairs of scissors.
mRNA expression levels of the biological factors uPAR, uPAR-del4/5, and rab31, displaying prognostic value in breast cancer, are not clinically relevant in advanced ovarian cancer
Authors: Kotzsch Matthias , Dorn Julia , Doetzer Kristina , Schmalfeldt Barbara , Krol Janna , Baretton Gustavo , Kiechle Marion , Schmitt Manfred , Magdolen Viktor 
Published: August 2011

Abstract
High tumor tissue mRNA expression of the tumor biological factors uPAR, uPAR-del4/5, or rab31 is associated with shorter distant metastasis-free and overall survival in breast cancer patients. To evaluate whether these factors are also clinically relevant in ovarian cancer, we quantified the respective mRNA levels in primary tumor tissue of advanced ovarian cancer patients (n=103) and evaluated their association with clinicopathological parameters and patients’ prognosis. mRNA expression levels of all three markers did not show any significant association with overall or progression-free survival, demonstrating that these factors have no prognostic value in advanced ovarian cancer.
Iron-catalyzed oxidation of Trp residues in low-density lipoprotein
Authors: Chen Hsin-Hung , Chen Ching-Yi , Chow Lu-Ping , Chen Chu-Huang , Lee Yuan-Teh , Smith Charles V. , Yang Chao-Yuh 
Published: August 2011

Abstract
The mechanisms of oxidation of low-density lipoproteins (LDLs) are not well defined, but epidemiological and experimental studies suggest that iron-catalyzed processes may contribute to atherogenesis. The aim of this study was to test the hypothesis that iron-catalyzed oxidations of LDLs in vitro produce diagnostic biomarkers of oxidation of the apolipoprotein that could be applied to studies in vivo. LDLs were oxidized in the presence of Fe2+, EDTA, and ascorbic acid for up to 40 h. Following delipidation and trypsin digestion, the peptides were separated by HPLC, with four peaks detected at 365 nm, whereas none were observed in peptides from unoxidized LDLs. The peptides were identified by MALDI-QTOF mass spectrometry as IVQILP(W+4) EQNEQVK, IYSL(W+4)EHSTK, FEGLQE(W+4)EGK, and YH(W+4)EHTGLTLR, with (W+4) rather than the W residues of the unoxidized protein. The mass gains (+4 increase in m/z in tryptophan, W) and absorbance at 365 nm indicate kynurenines, which were trypsin-releasable peptides that are on the surface of LDL particles. All four peptides thus characterized share the sequence of WE. The preferential oxidation of W residues in WE sequences suggest contributions from the C-proximate glutamate residues in chelation of the iron species, thereby influencing site selectivities of oxidation. These kynurenine-containing peptides might serve as biomarkers of iron-mediated oxidations in vivo.
Evolvability, epigenetics and transposable elements
Authors: Fablet Marie , Vieira Cristina 
Published: August 2011

AbstractEvolvability can be defined as the capacity of an individual to evolve and thus to capture adaptive mutations. Transposable elements (TE) are an important source of mutations in organisms. Their capacity to transpose within a genome, sometimes at a high rate, and their copy number regulation are environment-sensitive, as are the epigenetic pathways that mediate TE regulation in a genome. In this review we revisit the way we see evolvability with regard to transposable elements and epigenetics.
Zur Problematik der virusdiagnostischen Qualitätskontrolle/Laboratory diagnosis of viral principles and problems
Authors: Doerr Hans W. 
Published: August 2011

Zusammenfassung
Die Labordiagnose einer Infektionskrankheit beruht auf dem Nachweis des Infektionserregers oder der spezifischen Immunreaktion unter Berücksichtigung der klinischen Plausibilität. Biologische Testverfahren wie der Zellkulturversuch erbringen nur näherungsweise ein quantitatives Ergebnis und sind mit einer relativ großen Streuung behaftet. Das gilt auch für Antikörperassays, soweit sie über ein biologisches Testsignal abgelesen werden (CPE, Agglutination, Komplementverbrauch). Moderne serologische und molekularbiologische Untersuchungsmethoden der Virologie werden i. d. R. über ein physikochemisches Testssignal abgelesen und quantitativ ausgewertet. Dadurch gelingt die nationale und internationale Standardisierung, die sich in Ringversuchen gut überprüfen lässt. Aus biologischen Gründen ist meist eine log. Ergebnisberechnung angezeigt, was für „signifikante“ Unterschiede in Verlaufsuntersuchungen zu berücksichtigen ist: Da sowohl Infektion als auch Immunreaktion dynamische Prozesse darstellen, können Normalwerte in der virologischen Labordiagnostik nur restriktiv definiert werden. Ihre Ergebnisse sind mehr oder minder individuell interpretationsbedürftig.
DART: Deutsche Antibiotika-Resistenzstrategie. Bericht zu Vorgeschichte und Sachstand/DART: the German strategy to fight antimicrobial resistance. Report on history and current state
Authors: Wiegel Bernhard 
Published: August 2011

Zusammenfassung
Der vorliegende Bericht zeigt die aus zehn Zielen – Stärkung der Surveillance-Systeme zur Antibiotika-Resistenz und zum Antibiotika-Verbrauch, Systematische Rückkopplung von Daten zur Antibiotika-Resistenz und zum Antibiotika-Verbrauch, Förderung der Anwendung von Leitlinien, Sicherstellung der Diagnostik, Förderung der Aus-, Weiter- und Fortbildung von medizinischen Berufsgruppen, Apothekerinnen und Apothekern sowie Naturwissenschaftlerinnen und Naturwissenschaftlern, Nationale Zusammenarbeit, Internationale Zusammenarbeit, Förderung von Evaluierungsmaßnahmen in der Humanmedizin, Förderung des Wissenstransfers im Bereich Antibiotika-Resistenz sowie Vernetzung und Stärkung der Wissenschaft im Bereich Antibiotika-Resistenz – bestehende Deutsche Antibiotika-Resistenzstrategie auf. Die beabsichtigten gesetzlichen Vorhaben und offene Fragen zur nachhaltigen Sicherung guter Laborpraxis werden angesprochen.
Approach to develop a screw configuration for compounding solid fillers on a twin screw extruder using the example of polyethylene-layered silicate masterbatches
Authors: Michaeli Walter , Elas Athanassios , Puch Florian 
Published: August 2011

Abstract
The high potential of layered silicate improving material properties of plastics has been discussed in a significant number of publications. However, homogeneously dispersing it with twin screw extruders is demanding. Available information on optimum screw configuration is contradictory. In this investigation, we develop a practical method for individually designing and optimising extruder sections. This method is applied for designing extruder sections for compounding masterbatches of high-density polyethylene and layered silicate. We found out that for best dispersion, dispersing sections should only be partially filled with melt. Thus, only right-handed kneading elements should be applied.