julilili42/papers huggingface dataset:
086 * A NEW STRATEGY IN THE TREATMENT OF CHEMORESISTANT LUNG ADENOCARCINOMA VIA siRNA SPECIFIC SILENCING OF SRF, E2F1, SURVIVIN, HIF AND STAT 3
2013-09-18

Objectives: According to the S3 guidelines for lung cancer, the current therapeutic regimen is an individualized, multidisciplinary concept. In addition, chemotherapy represents an important component of treatment for all stages of the disease. The development of chemoresistance (up to 60% for platinum derivates) represents the most important obstacle to an effective treatment. In our study, we proposed a new therapeutic strategy in the treatment of chemoresistant lung cancer via siRNA specific silencing of six crucial molecules implicated in lung carcinogenesis (SRF, E2F1, Survivin, HIF 1, HIF 2 and STAT 3). Methods: The chemoresistance against four different drugs used in the treatment of non-small-cell lung cancer (NSCLC), Gemcitabine, Vinflunine, Vinorelbin and Methotrexate, was induced artificially. The A549 adeonocarcinoma cell lines were cultured under standard conditions at 37°C and 5% CO2. The cells were transfected for two hours at 37°C with specific siRNA targeting SRF, E2F1, Survivin, HIF 1, HIF 2 and STAT 3 in a non-viral manner. The efficiency of siRNA silencing was evaluated via quantitative real time PCR and flow cytometry. The remaining tumour cells after siRNA transfection as an accurate predictor for tumour growth were analysed with a CASY cell counter system three days after transfection. Results: The response of the analysed chemotherapeutics after siRNA transfection was concentration dependent. At both 25 nM and at 100 nM, the suppression of tumour cells in all four groups was significantly more efficient than in the control group. The analysis of remaining chemoresistant tumour cells via CASY counter showed a moderate reduction of adenocarcinoma chemoresistant cell lines in the Gemcitabine and Vinflunine groups, as well a very accurate suppression of cell lines with consecutive reduction of tumours cells up to 81% in the Vinorelbin and Methotrexate groups. Conclusions: Our study proposed a new alternative in the treatment of chemoresistant NSCLC. Via siRNA specific silencing complex an accurate suppression of various chemoresistant cell lines can be achieved. Therefore, siRNA might represent an effective transient individualized regimen in the treatment of NSCLC as well an important platform for new chemotherapeutics.
156-I * MINIMALLY INVASIVE CATHETER-BASED MITRAL VALVE REPLACEMENT: HYBRID STRATEGY FOR HIGH-RISK PATIENTS
2013-09-18

Objectives: Mitral valve reconstruction shows excellent results and little perioperative risk. Nevertheless, perioperative morbidity and mortality of reoperations is high, especially in the elderly with concomitant pathologies. Several reports demonstrate the feasibility of transapical mitral valve replacement, although limitations exist. Alternative strategies are needed to meet the needs of the patients. Methods: We present a 78-year-old female patient with high-grade mitral valve stenosis after mitral valve reconstruction 16 years ago. Her operative risk was high due to age, reoperation, chronic obstructive pulmonary disease, pulmonary hypertension (systolic pulmonary artery pressure 60 mmHg), porcelain aorta and extracardiac arteriopathy (EuroSCORE 58.3%). The patient was highly symptomatic, suffering from recurrent decompensation. Transapical approaches did not apply since minor calcification and the flexible annuloplasty band repair were insufficient for proper anchoring. Therefore we chose a hybrid strategy via a right-sided thoracotomy and transatrial transcatheter implantation of a Sapien XT prosthesis. Results: Extracorporeal circulation was established via the femoral vessels. Surgical access was gained by right-sided anterolateral thoracotomy. To avoid aortic cross-clamping, ventricular fibrillation was induced before atriotomy. Sutures were placed at the commissures and the annular aspects of A2 and P2 segments respectively. Implantation of a 26 mm valve could be easily performed under direct vision. The balloon-expanded valve was additionally fixated with the previously placed sutures. Transoesophageal echocardiography showed regular valve function without paravalvular leakage. Postoperative course was uneventful with extubation on day 2. Conclusions: Hybrid transatrial transcatheter mitral valve replacement can be performed with good results in high-risk patients. The presented approach can form an alternative strategy for patients in whom other minimally invasive techniques do not apply.
The relative age effect in the German Football TID Programme: Biases in motor performance diagnostics and effects on single motor abilities and skills in groups of selected players
2013-09-19

Abstract This study examined the disturbing effects of relative age on the talent identification process in the talent development programme of the German Football Association. The bias in the selection rate was examined via the extent of relative age effects. The bias in motor performance diagnostics was analysed by comparing the motor performance of selected players with normal motor development. The mechanisms underlying the relative age biases in motor performance were examined by modelling the direct and indirect effects of relative age on single motor performance tests for sprint, running agility, dribbling and ball passing and control. Data from 10,130 selected football players from the U12 to U15 age groups were collected in autumn 2010. The birth distribution differed significantly from the reference population with approximately 61% of the players born in the first half of the year. The selection probability was approximately two times higher for players born in the first quarter of the year than for players born in the last quarter. Revised motor performance diagnostics showed better results on average for relatively younger players. Path analysis revealed significant direct and indirect relative age effects for physiologically demanding tests and almost no effects for technically demanding tests. Large sample sizes allowed high resolution in relative age with additional informational content and multivariate modelling of the complex relationships among relative age, physical development and motor performance. The results are discussed on how relative age affects the effectiveness and fairness of talent identification and development processes.
Isolation of Myeloid Dendritic Cells and Epithelial Cells from Human Thymus
2013-09-19

In this protocol we provide a method to isolate dendritic cells (DC) and epithelial cells (TEC) from the human thymus. DC and TEC are the major antigen presenting cell (APC) types found in a normal thymus and it is well established that they play distinct roles during thymic selection. These cells are localized in distinct microenvironments in the thymus and each APC type makes up only a minor population of cells. To further understand the biology of these cell types, characterization of these cell populations is highly desirable but due to their low frequency, isolation of any of these cell types requires an efficient and reproducible procedure. This protocol details a method to obtain cells suitable for characterization of diverse cellular properties. Thymic tissue is mechanically disrupted and after different steps of enzymatic digestion, the resulting cell suspension is enriched using a Percoll density centrifugation step. For isolation of myeloid DC (CD11c(+)), cells from the low-density fraction (LDF) are immunoselected by magnetic cell sorting. Enrichment of TEC populations (mTEC, cTEC) is achieved by depletion of hematopoietic (CD45(hi)) cells from the low-density Percoll cell fraction allowing their subsequent isolation via fluorescence activated cell sorting (FACS) using specific cell markers. The isolated cells can be used for different downstream applications.
Isolation of Myeloid Dendritic Cells and Epithelial Cells from Human Thymus
2013-09-19

In this protocol we provide a method to isolate dendritic cells (DC) and epithelial cells (TEC) from the human thymus. DC and TEC are the major antigen presenting cell (APC) types found in a normal thymus and it is well established that they play distinct roles during thymic selection. These cells are localized in distinct microenvironments in the thymus and each APC type makes up only a minor population of cells. To further understand the biology of these cell types, characterization of these cell populations is highly desirable but due to their low frequency, isolation of any of these cell types requires an efficient and reproducible procedure. This protocol details a method to obtain cells suitable for characterization of diverse cellular properties. Thymic tissue is mechanically disrupted and after different steps of enzymatic digestion, the resulting cell suspension is enriched using a Percoll density centrifugation step. For isolation of myeloid DC (CD11c+), cells from the low-density fraction (LDF) are immunoselected by magnetic cell sorting. Enrichment of TEC populations (mTEC, cTEC) is achieved by depletion of hematopoietic (CD45hi) cells from the low-density Percoll cell fraction allowing their subsequent isolation via fluorescence activated cell sorting (FACS) using specific cell markers. The isolated cells can be used for different downstream applications.
Health Risk Evaluation of Disinfection By-Products (DBPs) for Indoor Swimming Pool Users via Life Cycle Impact Assessment Approach
2013-09-19

Due to continuous disinfection and constant organic load from swimmers, indoor swimming pools constitute environments with high levels of DBPs in water and air, some of which are linked to human health concerns. The purpose of this study is to customize current global-scale or continental scale life cycle human health impact assessment models to indoor swimming pool applications and subsequently use the model to compare different operation scenarios, which can provide relatively straight forward ideas for possible mitigation strategies. A comparison study is carried out between "baseline" scenario and four specific 'what-if' scenarios (using alternative disinfectant, reducing precursors, increasing ventilation, and changing characteristics of the air-water surface). We build the indoor-scale model based on USEtox, the consensus environmental model for characterisation of human and ecotoxicological impacts in Life Cycle Impact Assessment (LCIA). The model estimates the potential health risks for adults and children for 20 years during which age-specific intake factors change over time. The primary results indicated the impact from inhalation dominates the overall human health impact, while the dermal adsorption during swimming also makes significant contribution. The chloroform and trichloramine are identified as major stressors for inhalation human impact, while chloroform for dermal absorption impact. Through the scenario comparison, improving the ventilation of indoor swimming pools is an effect way to reduce the human health impact for all subjects. Another promising method is to control the precursors through increasing freshwater exchange, especially for the heavily-used pools. This study implies the choice of mitigation strategies should depend on the function and operation time of the pool. Through incorporating the proposed life cycle human health impact assessment model to the cradle-to-grave life cycle assessment studies, a systematic and comprehensive environmental profile of indoor swimming usage can be available.
Genetic comorbidities in Parkinson's disease
2013-09-20

Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain.
Charge and Spin Confinement to the Amine Site in 3-Connected Triarylamine Vinyl Ruthenium Conjugates
2013-09-20

The triarylamine vinyl ruthenium conjugate (4-OMeC6H4)2N{C6H4-3-CH═CH-RuCl(CO)(PiPr3)2} (m-1) has been prepared and investigated in its neutral and one-electron-oxidized states. Comparison with tris(4-anisylamine), An3N, and the related 4-methoxystyryl complex 4-OMeC6H4-CH═CH-RuCl(CO)(PiPr3)2, 2, shows that the intrinsic formal potentials of the two nonidentical redox-active subunits of complex m-1 (triarylamine and vinyl ruthenium) are very similar. Complex m-1 is oxidized in two consecutive one-electron waves with a half-wave potential splitting of 320 mV. Detailed investigations of the one-electron-oxidized radical cation m-1•+ by IR and EPR spectroscopy and by quantum chemical calculations as well as comparison to An3N•+ and 2•+ indicate that the charge and the unpaired spin of m-1•+ are dominantly located on the triarylamine site. This is in stark contrast to the previously published para isomer p-1•+, which, despite the nonidentical redox sites, is a fully delocalized mixed-valent system of Class III. As a consequence of partial charge localization, the low-energy absorption bands in the near-infrared assume the character of ruthenium or styryl ruthenium to triarylamine intervalence charge-transfer (IVCT) transitions with significantly diminished absorptivities compared to the highly intense charge resonance bands of p-1•+. Hush analysis of the IVCT bands indicates that m-1•+ is a significantly coupled mixed-valent system of Class II. The crystallographically determined structures of complexes m-1 and 2 and of the amine precursor (4-OMeC6H4)2N(C6H4Br-3) (An2N-Br) are also reported.
Single-Step Ugi Multicomponent Reaction for the Synthesis of Phosphopeptidomimetics
2013-09-20

This article describes the design and optimization of an effective microwave-assisted multicomponent reaction to produce a novel class of phosphopeptidomimetic compounds. When using aminophosphonic acids (α, β, γ), aldehydes, and isocyanides as reactants and alcohols as solvents, these building blocks are merged to functionalized amido-aminophosphonate structures in a novel Ugi-type one-pot transformation reaction. A high level of structural diversity can be achieved with this synthetic approach, providing a platform for the production of functionalized building blocks for novel bioactive molecules. The general scope of this multicomponent synthetic protocol is explored by variation of reaction parameters together with an evaluation of a diverse set of reaction substrates. The applicability of this reaction has been demonstrated by the synthesis of 17 distinct compounds giving yields in the range of 20-92%.
Zone coulometry and ion-release analysis of degradable magnesium alloys
2013-09-20

Zone coulometry and determination of ion release of an electrolyte from anodic polarization measurements are the established calculation modes for the electrochemical behavior of dental and biomedical alloys. The aim of the study was to compare the electrochemical corrosion behavior of six different experimental magnesium alloys without manganese using artificial plasma (AP) and in phosphate-buffered saline (PBS − ) as simulated body fluids through anodic polarization measurements. In addition, determination of the magnesium release of the electrolytes was performed using inductively coupled plasma optical emission spectrometry and zone coulometry. Six specimens were prepared from each alloy. Anodic polarization measurements ranging from –150 mV ~E corr to –1200 mV were performed with both of the electrolytes. From each measurement, corrosion current density, the breakdown or pitting potential and its corresponding current density, zero potential, the polarization resistance, the corrosion rate were calculated. The magnesium release of the electrolytes was compared with the calculated values using Faraday’s law. For zone coulometry, five different trials were completed, and the electrical charge was calculated for each potential range of all magnesium alloys tested and for both electrolytes. Lower corrosion values were found in AP than in PBS − for all measurements. However, the rankings of the alloys are similar in both the electrolytes. Zone coulometry using small potential ranges and determination of ion release can be additional evaluation tools for magnesium alloys.
Correction: LPS Structure and PhoQ Activity Are Important for Salmonella Typhimurium Virulence in the Gallleria mellonella Infection Model
2013-09-20

The larvae of the wax moth, Galleria mellonella, have been used experimentally to host a range of bacterial and fungal pathogens.In this study we evaluated the suitability of G. mellonella as an alternative animal model of Salmonella infection.Using a range of inoculum doses we established that the LD 50 of Salmonella Typhimurium strain NCTC 12023 was 3.6 × 10 3 bacteria per larva.Further, a set of isogenic mutant strains depleted of known virulence factors was tested to identify determinants essential for S. Typhimurium pathogenesis.Mutants depleted of one or both of the type III secretion systems encoded by Salmonella Pathogenicity Islands 1 and 2 showed no virulence defect.In contrast, we observed reduced pathogenic potential of a phoQ mutant indicating an important role for the PhoPQ two-component signal transduction system.Lipopolysaccharide (LPS) structure was also shown to influence Salmonella virulence in G. mellonella.A waaL (rfaL) mutant, which lacks the entire O-antigen (OAg), was virtually avirulent, while a wzz ST /wzz fepE double mutant expressing only a very short OAg was highly attenuated for virulence.Furthermore, shortly after infection both LPS mutant strains showed decreased replication when compared to the wild type in a flow cytometry-based competitive index assay.In this study we successfully established a G. mellonella model of S. Typhimurium infection.By identifying PhoQ and LPS OAg length as key determinants of virulence in the wax moth larvae we proved that there is an overlap between this and other animal model systems, thus confirming that the G. mellonella infection model is suitable for assessing aspects of Salmonella virulence function.
Association of the Yeast RNA-binding Protein She2p with the Tubular Endoplasmic Reticulum Depends on Membrane Curvature
2013-09-21

Localization of mRNAs contributes to the generation and maintenance of cellular asymmetry in a wide range of organisms. In Saccharomyces cerevisiae, the so-called locasome complex with its core components Myo4p, She2p, and She3p localizes more than 30 mRNAs to the yeast bud tip. A significant fraction of these mRNAs encodes membrane or secreted proteins. Their localization requires, besides the locasome, a functional segregation apparatus of the cortical endoplasmic reticulum (ER), including the machinery that is involved in the movement of ER tubules into the bud. Colocalization of RNA-containing particles with these tubules suggests a coordinated transport of localized mRNAs and the cortical ER to the bud. Association of localized mRNAs to the ER requires the presence of the locasome component She2p. Here we report that She2p is not only an RNA-binding protein but can specifically bind to ER-derived membranes in a membrane curvature-dependent manner in vitro. Although it does not contain any known curvature recognizing motifs, the protein shows a binding preference for liposomes with a diameter resembling that of yeast ER tubules. In addition, membrane binding depends on tetramerization of She2p. In an in vivo membrane-tethering assay, She2p can target a viral peptide GFP fusion protein to the cortical ER, indicating that a fraction of She2p associates with the ER in vivo. Combining RNA- and membrane-binding features makes She2p an ideal coordinator of ER tubule and mRNA cotransport.
Oxytocin's impact on social face processing is stronger in homosexual than heterosexual men
2013-09-21

Oxytocin is an evolutionarily highly preserved neuropeptide that contributes to the regulation of social interactions including the processing of facial stimuli. We hypothesized that its improving effect on social approach behavior depends on perceived sexual features and, consequently, on sexual orientation. In 19 homosexual and 18 heterosexual healthy young men, we investigated the acute effect of intranasal oxytocin (24IU) and placebo, respectively, on the processing of social stimuli as assessed by ratings of trustworthiness, attractiveness and approachability for male and female faces. Faces were each presented with a neutral, a happy, and an angry expression, respectively. In heterosexual subjects, the effect of oxytocin administration was restricted to a decrease in ratings of trustworthiness for angry female faces (p<0.02). In contrast, in homosexual men oxytocin administration robustly increased ratings of attractiveness and approachability for male faces regardless of the facial expression (all p ≤ 0.05), as well as ratings of approachability for happy female faces (p<0.01). Results indicate that homosexual in comparison to heterosexual men display higher sensitivity to oxytocin's enhancing impact on social approach tendencies, suggesting that differences in sexual orientation imply differential oxytocinergic signaling.
Interactive and Multi-modal Visualization for Neuroendoscopic Interventions
2013-09-21

Based on the VIVENDI-framework for virtual endoscopy, we present a system for the interactive and multi-modal representation of important anatomical structures for neuroendoscopic interventions. A serious problem of neuroendoscopic interventions is the possibility of injuring a blood vessel while performing endoscopic surgery inside the human brain. Besides the sudden loss of optical visibility due to the red-out of the injured vessel, a potential lethal mass bleeding can be the fatal outcome of the intervention. To avoid accidental lesions, we represent the relevant information using multiple volumetric MRI-based representations of the respective organs.
The Setup for Triangle Rasterization
2013-09-21

Integrating the slope and setup calculationsfor triangles to the rasterizer offloads the host processor from intensive calculations and can significantly increase 3D system performance. The processing on the host is greatly reduced and much less data is passed from the host to the graphics subsystem. A setup architecture handling generalized triangle meshes and computing all necessary parameters for a high-end raster pipeline to generate Gouraud shaded, texture- and bumpmapped triangles is described and its benefits on the final bandwidth are shown. To efficiently compute the slopes and color gradients for each triangle, some implementation aspects on division and multiplicationpipelines are discussed.