julilili42/papers huggingface dataset:
Associations between peri‐implant crevicular fluid volume, concentrations of crevicular inflammatory mediators, and composite IL‐1A –889 and IL‐1B +3954 genotype: A cross‐sectional study on implant recall patients with and without clinical signs of peri‐implantitis
2007-01-11

Abstract Objectives: To assess possible relationships between peri‐implant crevicular fluid (PICF) volumes, biochemical markers of the peri‐implant immune response, and periodontitis‐associated genotype. Material and methods: PICF samples from 29 implant maintenance patients, 24 wearing overdentures, five having single crowns and bridgework (11 patients with peri‐implantitis and 18 individuals with healthy peri‐implant conditions), were analyzed for per site and per crevicular‐fluid‐volume concentrations of interleukin‐1β, plasminogen activator inhibitor type 2, and prostaglandin E2 by ELISA. Associations between the three substance concentrations and to crevicular fluid flow rate were analyzed by linear regression analysis. The possible differentiating influence of the composite interleukin‐1A and ‐1B genotype on the patients' peri‐implant health and biochemical inflammatory status was checked formally with t ‐test statistics and the Wilcoxon' test. One implant per patient was chosen for analysis. Results: In patients with healthy peri‐implant conditions, genotype‐positive individuals showed elevated crevicular fluid flow rates and at the same time reduced mediator concentrations. In patients with an implant affected from peri‐implantitis, no statistically significant influence of the periodontitis‐associated genotype around the fixture can be stated. There was no statistical difference between per site and per crevicular‐fluid‐volume concentration analyses. All three mediator concentrations were positively related to each other, while there was a strong negative correlation between crevicular fluid volume and plasminogen activator inhibitor 2 or prostaglandin E2. Conclusions: The Interleukin‐1 polymorphism investigated exerted only little influence on the peri‐implant crevicular immune response, and this influence appeared to be of limited impact in sites with established peri‐implantitis lesions.
Abnormal Hippocampal Neurochemistry in Smokers
2007-01-11

The results are consistent with prior observations of hippocampal neuronal damage in rodents receiving nicotine and working memory deficits in human tobacco smokers. The positive relationship between tCho and lifetime tobacco exposure suggests that a component of tobacco smoke, presumably nicotine, may increase cortical membrane turnover or modify cell density. Together, these results add to growing evidence that nicotine exerts neurotoxic effects in human brain, although an a priori nature of the findings cannot be ruled out.
Computer literacy and inquiry learning: when geeks learn less
2007-01-11

Abstract A low level of computer literacy has often been hypothesized as constituting a disadvantage in knowledge acquisition. However, within the field of computer‐supported inquiry learning systematic investigations of these purported relations have not been conducted. This classroom study investigates the role of computer literacy (procedural computer‐related knowledge, self‐confidence in using the computer, and familiarity with computers) as a learning prerequisite for knowledge acquisition, and analyses the learners' patterns of media use as processes that might explain this role. Thirty‐seven students from two final classes of a secondary school worked in pairs on the project ‘How far does light go?’ in the Web‐based Inquiry Science Environment. Findings did indicate significant relations of neither procedural computer‐related knowledge nor self‐confidence in using the computer to knowledge acquisition. However, students with greater familiarity with computers acquired significantly less knowledge. In the light of the patterns of media use, these findings might be explained by different navigation styles adopted by students with high and low familiarity with computers: students with high familiarity with computers exhibit more shallow processing strategies (‘browsing’) which are less functional for learning.
Non-malignant migration of B16 mouse melanoma cells in the neural crest and invasive growth in the eye cup of the chick embryo
2007-01-11

Melanocytes originate from the neural crest. In a previous study, we observed that human SK-Mel 28 human melanoma cells resumed neural crest cell migration after transplantation into the chick embryo neural tube. Here, we used transgenic mouse B16-F1 melanoma cells transfected with green fluorescent protein-vasodilator-stimulated phosphoprotein construct to extend these observations. After the injection of a cell suspension into the trunk neural tube of E2 chick embryos, the migration of melanoma cells was followed by live fluorescence microscopy. Within 12 h, the melanoma cells formed clusters in the neural tube at the levels of the intersegmental clefts between somites. After 24 h, a segmental pattern of emigration was visible. Emigrated melanoma cells were identified in serial paraffin sections by immunohistochemistry with ab732 as a marker for melanoma cells and by in-situ hybridization of mouse-specific repetitive genomic sequence mL1. After 24 h, melanoma cells were found along the medial neural crest pathway and in the sympathetic trunk ganglia and, after 48 h, also in the lateral melanocytic pathway. During migration along the neural crest pathways, mouse melanoma cells underwent apoptosis, which was assessed by anti-caspase 3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining. To prove the ablation of malignant behavior after back-transplantation into the original embryonic neural crest environment, we injected the same cell suspension into the eye cup of the E3 embryo. In this location, invasive melanomas formed.
MaltParser: A language-independent system for data-driven dependency parsing
2007-01-12

Parsing unrestricted text is useful for many language technology applications but requires parsing methods that are both robust and efficient. MaltParser is a language-independent system for data-driven dependency parsing that can be used to induce a parser for a new language from a treebank sample in a simple yet flexible manner. Experimental evaluation confirms that MaltParser can achieve robust, efficient and accurate parsing for a wide range of languages without language-specific enhancements and with rather limited amounts of training data.
Sequencing and Analysis of the Biosynthetic Gene Cluster of the Lipopeptide Antibiotic Friulimicin in Actinoplanes friuliensis
2007-01-13

ABSTRACT Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from A. friuliensis was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in Escherichia coli , we provide biochemical evidence for the stereoselective synthesis of l -pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene pip . Furthermore, we show the involvement of the dabA and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.
TOPP—the OpenMS proteomics pipeline
2007-01-15

Abstract Motivation: Experimental techniques in proteomics have seen rapid development over the last few years. Volume and complexity of the data have both been growing at a similar rate. Accordingly, data management and analysis are one of the major challenges in proteomics. Flexible algorithms are required to handle changing experimental setups and to assist in developing and validating new methods. In order to facilitate these studies, it would be desirable to have a flexible ‘toolbox’ of versatile and user-friendly applications allowing for rapid construction of computational workflows in proteomics. Results: We describe a set of tools for proteomics data analysis—TOPP, The OpenMS Proteomics Pipeline. TOPP provides a set of computational tools which can be easily combined into analysis pipelines even by non-experts and can be used in proteomics workflows. These applications range from useful utilities (file format conversion, peak picking) over wrapper applications for known applications (e.g. Mascot) to completely new algorithmic techniques for data reduction and data analysis. We anticipate that TOPP will greatly facilitate rapid prototyping of proteomics data evaluation pipelines. As such, we describe the basic concepts and the current abilities of TOPP and illustrate these concepts in the context of two example applications: the identification of peptides from a raw dataset through database search and the complex analysis of a standard addition experiment for the absolute quantitation of biomarkers. The latter example demonstrates TOPP's ability to construct flexible analysis pipelines in support of complex experimental setups. Availability: The TOPP components are available as open-source software under the lesser GNU public license (LGPL). Source code is available from the project website at Contact: oliver.kohlbacher@uni-tuebingen.de
Electrostatic potentials of proteins in water: a structured continuum approach
2007-01-15

Abstract Electrostatic interactions play a crucial role in many biomolecular processes, including molecular recognition and binding. Biomolecular electrostatics is modulated to a large extent by the water surrounding the molecules. Here, we present a novel approach to the computation of electrostatic potentials which allows the inclusion of water structure into the classical theory of continuum electrostatics. Based on our recent purely differential formulation of nonlocal electrostatics [Hildebrandt, et al. (2004)Phys. Rev. Lett., 93, 108104] we have developed a new algorithm for its efficient numerical solution. The key component of this algorithm is a boundary element solver, having the same computational complexity as established boundary element methods for local continuum electrostatics. This allows, for the first time, the computation of electrostatic potentials and interactions of large biomolecular systems immersed in water including effects of the solvent's structure in a continuum description. We illustrate the applicability of our approach with two examples, the enzymes trypsin and acetylcholinesterase. The approach is applicable to all problems requiring precise prediction of electrostatic interactions in water, such as protein–ligand and protein–protein docking, folding and chromatin regulation. Initial results indicate that this approach may shed new light on biomolecular electrostatics and on aspects of molecular recognition that classical local electrostatics cannot reveal. Contact: anhi@bioinf.uni-sb.de
Onchocerca volvulus-specific antibody and cytokine responses in onchocerciasis patients after 16 years of repeated ivermectin therapy
2007-01-15

Summary The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 μg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-γ at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity.
Searching for the best model: ambiguity of inverse solutions and application to fetal magnetoencephalography
2007-01-16

Fetal brain signals produce weak magnetic fields at the maternal abdominal surface. In the presence of much stronger interference these weak fetal fields are often nearly indistinguishable from noise. Our initial objective was to validate these weak fetal brain fields by demonstrating that they agree with the electromagnetic model of the fetal brain. The fetal brain model is often not known and we have attempted to fit the data to not only the brain source position, orientation and magnitude, but also to the brain model position. Simulation tests of this extended model search on fetal MEG recordings using dipole fit and beamformers revealed a region of ambiguity. The region of ambiguity consists of a family of models which are not distinguishable in the presence of noise, and which exhibit large and comparable SNR when beamformers are used. Unlike the uncertainty of a dipole fit with known model plus noise, this extended ambiguity region yields nearly identical forward solutions, and is only weakly dependent on noise. The ambiguity region is located in a plane defined by the source position, orientation, and the true model centre, and will have a diameter approximately 0.67 of the modelled fetal head diameter. Existence of the ambiguity region allows us to only state that the fetal brain fields do not contradict the electromagnetic model; we can associate them with a family of models belonging to the ambiguity region, but not with any specific model. In addition to providing a level of confidence in the fetal brain signals, the ambiguity region knowledge in combination with beamformers allows detection of undistorted temporal waveforms with improved signal-to-noise ratio, even though the source position cannot be uniquely determined.
Simultaneous blockade of VEGFR‐1 and VEGFR‐2 activation is necessary to efficiently inhibit experimental melanoma growth and metastasis formation
2007-01-17

Abstract Metastasis continues to be the major cause of morbidity and mortality in malignant melanoma. In our study, we explored whether inhibition of VEGFR‐1 or VEGFR‐2 signaling conveys distinct suppressive effects on B16 melanoma subcutaneous growth and metastasis formation. The inhibition of VEGFR‐1 or ‐2 alone had no significant influence on both melanoma growth and metastasis formation. In contrast, simultaneous blockade of VEGFR‐1 and ‐2 signaling strongly suppressed progression in both B16 tumor models. There was no expression of VEGFR‐1 or ‐2 detectable on the B16 cells used, excluding the melanoma cells as direct therapeutic targets. Analyzing the contribution of progenitor‐like cells during melanoma metastasis formation, we observed an enhanced proliferation and mobilization of VEGFR‐1+ myeloid and VEGFR‐2+ endothelial cells with progenitor potential by the induction of melanoma lung metastasis, which was not influenced by interference with VEGFR signaling. These results indicate that the antimetastatic effects exerted by combined inhibition of VEGFR‐1 and ‐2 signaling were mediated via targeting cell populations other than progenitors only. Sole inhibition of VEGFR‐1 signaling led to a strong reduction of the CD45‐positive inflammatory infiltrate in the tumor tissue. However, the formation of lung metastasis was not affected, indicating that inhibition of the inflammatory response was not sufficient to efficiently block B16 melanoma metastasis development. Taken together, our data suggest that in the utilized B16 tumor models the blockade of both the inflammatory and the VEGFR‐2‐dependent angiogenic response are necessary to effectively inhibit solid tumor growth and formation of lung metastasis by B16 melanoma cells. © 2007 Wiley‐Liss, Inc.
Fluvial environmental contexts for archaeological sites in the Upper Khabur basin (northeastern Syria)
2007-01-17

Abstract Today the eastern tributaries of the Upper Khabur run dry during the summer and the landscape is devoid of trees. This picture is misleading when we try to understand archaeological sites within their former environmental context. Interdisciplinary geomorphological, archaeobotanical and ostracod research on a sequence from the Wadi Jaghjagh indicates that relatively stable, perennial flow velocities occurred during the mid 4th to mid-3rd millennium BC. Evidence was found for a gallery forest and swamp belt along the Jaghjagh during the mid-4th millennium BC. Oak park woodland was present within the region in the 3rd millennium BC and probably up to at least the 3rd century AD. Shortly after 2500 BC, Jaghjagh stream velocities probably decreased or the stream bed had changed its location. Later deposits, possibly dating to the 5th century BC, indicate similar, rather stable flow of the Jaghjagh. More recently however, about ca. AD 900 or afterwards, a flashflood-like regime occurred, which may relate to deforestation. The Wadi Khanzir sediment archives reflect the flashy intermittent regime of this stream, like it still is today, with flashflood evidence dating to the first half of the Holocene and probably dating to approximately AD 400 or later. Along the Jarrah, topsoil was eroded and redeposited by the wadi sometime between 1300 and 600 BC. This may have been caused by the intensive resettlement program of this region around 800 BC. Between about 600 and 300 BC 1.5 m of clay was deposited on the plain.
Data protection in biomaterial banks for Parkinson's disease research: The model of GEPARD (Gene bank Parkinson's Disease Germany)
2007-01-17

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease. Although 10 gene loci have been identified to cause a Parkinsonian syndrome, these loci account only for a minority of PD patients. Large, systematic research programs are required to collect, store, and analyze DNA samples and clinical information to support further discovery of additional genetic components of PD or other movement disorders. Such programs facilitate research into the relationship between genotype and phenotype. The German Competence Network on Parkinson's disease (CNP) initiated the Ge ne Bank Par kinson's D isease Germany (GEPARD), providing an administrative and scientific infrastructure for the storage of DNA and clinical data that are electronically accessible and protective of patient rights. In this article, we offer guidance on how to establish a framework for a clinical genetic data and DNA bank, and describe GEPARD as a model that may be useful to other local, national, and international research groups developing similar programs. © 2006 Movement Disorder Society
Water Solubility in Aluminous Orthopyroxene and the Origin of Earth's Asthenosphere
2007-01-18

Plate tectonics is based on the concept of rigid lithosphere plates sliding on a mechanically weak asthenosphere. Many models assume that the weakness of the asthenosphere is related to the presence of small amounts of hydrous melts. However, the mechanism that may cause melting in the asthenosphere is not well understood. We show that the asthenosphere coincides with a zone where the water solubility in mantle minerals has a pronounced minimum. The minimum is due to a sharp decrease of water solubility in aluminous orthopyroxene with depth, whereas the water solubility in olivine continuously increases with pressure. Melting in the asthenosphere may therefore be related not to volatile enrichment but to a minimum in water solubility, which causes excess water to form a hydrous silicate melt.
Predictive Value of Known and Novel Alleles of CYP2B6 for Efavirenz Plasma Concentrations in HIV-infected Individuals
2007-01-18

To assess the association of CYP2B6 allelic diversity with efavirenz (EFV) pharmacokinetics, we performed extensive genotyping of 15 relevant single nucleotide polymorphism in 169 study participants, and full resequencing of CYP2B6 in individuals with abnormal EFV plasma levels. Seventy-seven (45.5%) individuals carried a known (CYP2B6*6, *11, *15, or *18) or new loss/diminished-function alleles. Resequencing defined two new loss-of-function alleles: allele *27 (marked by 593T>C [M198T]), that results in 85% decrease in enzyme activity and allele *28 (marked by 1132C>T), that results in protein truncation at arginine 378. Median AUC levels were 188.5 microg h/ml for individuals homozygous for a loss/diminished-function allele, 58.6 microg h/ml for carriers, and 43.7 microg h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer genotype had a likelihood ratio of 35 (95% CI, 11-110) of presenting very high EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.
Interface Fermi Level Pinning at Contacts Between PEDOT: PSS and Molecular Organic Semiconductors
2007-01-18

Abstract Photoemission studies of interfaces between molecular organic semiconductors and the conducting polymer PEDOT: PSS [mixture of PEDOT (poly‐3,4‐ethylenedioxy‐thiophene) and PSS (polystyrenesulfonate)] demonstrate that it is impossible to control the charge injection barriers at such contacts by either a systematic change of the work function of the conducting polymer or that of the organic semiconductor. Instead, these interfaces are, in all cases, characterized by a charge transfer across the interface and a resulting Fermi level pinning. Thus interfacial charge barriers do not explain observed changes in device parameters as a function of the work function of the polymer electrode.