julilili42/papers huggingface dataset:
Combining Ultracentrifugation and Peptide Termini Group-specific Immunoprecipitation for Multiplex Plasma Protein Analysis
2012-04-24

Blood plasma is a valuable source of potential biomarkers. However, its complexity and the huge dynamic concentration range of its constituents complicate its analysis. To tackle this problem, an immunoprecipitation strategy was employed using antibodies directed against short terminal epitope tags (triple X proteomics antibodies), which allow the enrichment of groups of signature peptides derived from trypsin-digested plasma. Isolated signature peptides are subsequently detected using MALDI-TOF/TOF mass spectrometry. Sensitivity of the immunoaffinity approach was, however, compromised by the presence of contaminant peaks derived from the peptides of nontargeted high abundant proteins. A closer analysis of the enrichment strategy revealed nonspecific peptide binding to the solid phase affinity matrix as the major source of the contaminating peptides. We therefore implemented a sucrose density gradient ultracentrifugation separation step into the procedure. This yielded a 99% depletion of contaminating peptides from a sucrose fraction containing 70% of the peptide-antibody complexes and enabled the detection of the previously undetected low abundance protein filamin-A. Assessment of this novel approach using 15 different triple X proteomics antibodies demonstrated a more consistent detection of a greater number of targeted peptides and a significant reduction in the intensity of nonspecific peptides. Ultracentrifugation coupled with immunoaffinity MS approaches presents a powerful tool for multiplexed plasma protein analysis without the requirement for demanding liquid chromatography separation techniques.
Mesh‐related complications in urogynecology – a multidisciplinary challenge
2012-04-24

Abstract Diagnoses of complications in women who underwent pelvic floor surgery using meshes and the multidisciplinary management of these cases at two national referral urogynecological centers between January and June 2011 are presented in a series of cases of mesh complications, which provide an indication of the wide range of symptoms and, at times, the long time span over which they may be encountered. Complications included infection, erosion (extrusion/exposure), fistulas, perforation into the surrounding organs (such as urethra, bladder and/or bowel), chronic pelvic pain (often radiating into buttocks, groins and/or thighs), dysuria, dyschezia, voiding difficulties, constipation, stool evacuation difficulties, de novo overactive bladder, urinary and fecal incontinence and prolapse recurrences. Although meshes have the ability to provide adequate anatomical support, the emergence of such a multitude of complications has resulted in restrictions for their use, as well as being a multidisciplinary challenge.
Diagnosis-Related Groups in Hand Surgery – a comparison of six European countries
2012-04-24

Diagnosis-Related Group (DRG) is a classification system, which groups patients according to their diagnosis and resource consumption. Common hand surgical diagnoses and procedures were processed using national DRG-groupers of six European countries. The upper thresholds of length of stay (LoS) are indicated for every country with the exception of Spain. The mean value in the series was 9.9 days for Germany, 4.5 days for Austria, 10.7 days for Italy, 9.7 days for Sweden and 9.4 days for the United Kingdom (UK). Germany and Austria also have lower thresholds of LoS and the average LoS. Multiple finger replantation presented the highest single case reimbursement in Germany, Austria and the UK (13,825 €, 10,576 € and 9,198 €). Scaphoid non-union had the highest single case reimbursement in Italy (2,676 €), flap coverage of wounds in Spain (5,506 €) and trapeziometacarpal arthritis in Sweden (5,350 €). The mean values for single case reimbursement were as follows: Germany 3,211 €, Austria 2,821 €, Italy 1,947 €, Spain 3,594 €, Sweden 2,403 € and the UK 3,253 €. Ten out of 19 cases showed the highest reimbursement in Spain, followed by the UK (5 cases), Sweden (2 cases), Germany and Austria (1 case each). Applying the case numbers of our clinic to the reimbursement system of each country, total proceeds would be 2.25 million € in Spain, 1.79 million € in Germany as well as the UK, 1.75 million € in Austria, 1.63 million € in Sweden and 1.22 million € in Italy. The consequences of international differences in efficiency and reimbursement are hard to assess as they are influenced by multiple factors that are seldom purely market-driven. However, the consideration of international data for benchmarking and refinement of national compensation systems should be a useful instrument.
Malignant ectomesenchymoma in children and adolescents: Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)
2012-04-25

Abstract Background Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited. Methods Six patients with MEM were registered 1996–2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed. Results The median age of the three females and three males was 0.6 years (range, 0.2–13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow‐up of 5 years (range: 2.1–13.7). Conclusions Risk‐factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma‐like soft tissue sarcoma. Pediatr Blood Cancer 2013;60:224–229. © 2012 Wiley Periodicals, Inc.
Neutrophils Express Distinct RNA Receptors in a Non-canonical Way
2012-04-25

RNAs are capable of modulating immune responses by binding to specific receptors. Neutrophils represent the major fraction of circulating immune cells, but receptors and mechanisms by which neutrophils sense RNA are poorly defined. Here, we analyzed the mRNA and protein expression patterns and the subcellular localization of the RNA receptors RIG-I, MDA-5, TLR3, TLR7, and TLR8 in primary neutrophils and immortalized neutrophil-like differentiated HL-60 cells. Our results demonstrate that both neutrophils and differentiated HL-60 cells express RIG-I, MDA-5, and TLR8 at the mRNA and protein levels, whereas TLR3 and TLR7 are not expressed at the protein level. Subcellular fractionation, flow cytometry, confocal laser scanning microscopy, and immuno-transmission electron microscopy provided evidence that, besides the cytoplasm, RIG-I and MDA-5 are stored in secretory vesicles of neutrophils and showed that RIG-I and its ligand, 3p-RNA, co-localize at the cell surface without triggering neutrophil activation. In summary, this study demonstrates that neutrophils express a distinct pattern of RNA recognition receptors in a non-canonical way, which could have essential implications for future RNA-based therapeutics.
Covalent attachment of pyridoxal-phosphate derivatives to 14-3-3 proteins
2012-04-25

Small-molecule inhibitors of 14-3-3 protein–protein interactions could serve as valuable chemical biology tools and starting points for drug development. The article by Zhao et al. (1) described FOBISIN101 (1) (Fig. 1A), a pyridoxal-phosphate (PLP) derivative that inhibits 14-3-3 protein–protein interactions. The authors provided a crystal structure of 14-3-3¿ with PLP covalently bound to K120 [Protein Data Bank (PDB) ID code 3RDH] lacking the p-amino-benzoate moiety. As a mechanism, they propose X-ray–induced cleavage of the N=N bond. They suggest this mechanism could serve as a radiation-triggered anticancer prodrug concept.
Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Cav1.3−/−, and Cav1.2DHP−/− mice
2012-04-26

Voltage-gated Ca 2+ (Ca v )1.3 α-subunits of high voltage-activated Ca 2+ channels (HVACCs) are essential for Ca 2+ influx and transmitter release in cochlear inner hair cells and therefore for signal transmission into the central auditory pathway. Their absence leads to deafness and to striking structural changes in the auditory brain stem, particularly in the lateral superior olive (LSO). Here, we analyzed the contribution of various types of HVACCs to the total Ca 2+ current ( I Ca ) in developing mouse LSO neurons to address several questions: do LSO neurons express functional Ca v 1.3 channels? What other types of HVACCs are expressed? Are there developmental changes? Do LSO neurons of Ca v 1.3 −/− mice show any compensatory responses, namely, upregulation of other HVACCs? Our electrophysiological and pharmacological results showed the presence of functional Ca v 1.3 and Ca v 1.2 channels at both postnatal days 4 and 12. Aside from these L-type channels, LSO neurons also expressed functional P/Q-type, N-type, and, most likely, R-type channels. The relative contribution of the four different subtypes to I Ca appeared to be 45%, 29%, 22%, and 4% at postnatal day 12, respectively. The physiological results were flanked and extended by quantitative RT-PCR data. Altogether, LSO neurons displayed a broad repertoire of HVACC subtypes. Genetic ablation of Ca v 1.3 resulted in functional reorganization of some other HVACCs but did not restore normal I Ca properties. Together, our results suggest that several types of HVACCs are of functional relevance for the developing LSO. Whether on-site loss of Ca v 1.3, i.e., in LSO neurons, contributes to the recently described malformation of the LSO needs to be determined by using tissue-specific Ca v 1.3 −/− animals.
Structural and Optical Properties of Mixed Diindenoperylene–Perfluoropentacene Thin Films
2012-04-26

Mixed films of perfluorinated pentacene and diindenoperylene are studied for their structural and optical properties on SiO 2 and glass substrates. Grazing incidence X-ray diffraction shows that the compounds mix on the molecular level. Two structures are identified. Their out-of-plane lattice spacing is determined by X-ray reflectivity, and their growth morphology is characterized using atomic force microscopy. It is found that one structure consists of molecules in a standing-up and the other in a lying-down orientation. The uniaxial dielectric function of mixed films is determined with spectroscopic ellipsometry, and the in-plane optical extinction coefficient is measured by real-time differential reflectance spectroscopy during growth. The question of intermolecular coupling between perfluorinated pentacene and diindenoperylene is discussed.
Vacuum nature of the QCD condensates
2012-04-26

Recently it was claimed that QCD condensates were associated with the internal dynamics of the hadrons. We challenge this "in-hadron" picture of the QCD condensates and show that it conflicts with well established concepts and experimental facts for the example of the quark condensate. We explicitly demonstrate the vacuum nature of the quark condensate by a model calculation. © 2012 American Physical Society.
Novel Gastrin Receptor-Directed Contrast Agents - Potential in Brain Tumor Magnetic Resonance Imaging
2012-04-26

Magnetic resonance imaging (MRI) is presently the method of choice for detection of brain tumors. However, MRI alone is not conclusive. As the commonly used contrast agents do not bind to the cells and are not taken up into the cells, they generally do accumulate in regions where the blood-brain-barrier is disrupted. While this can be brain tumors (WHO grade II-III and above), it can also be inflammations. A cell-directed contrast agent would be a great asset not only to avoid unnecessary brain biopsies, but also to achieve sharper tumor margins during intraoperative MRI. The gastrin/cholecystockinin receptor found in the brain and the intestinal tract is a potential target for a cell-directed contrast agent. The receptor has already been found in human glioma cell lines and autocrine stimulation has also been demonstrated for the receptor and its ligand gastrin. We coupled the correct and a mutant 17-amino-acid gastrin to gadolinium -1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (an MRI contrast agent) and rhodamine isothiocyanate (a fluorescent dye). Using confocal laser scanning microscopy and magnetic resonance relaxometry experiments we found cytoplasmic uptake of the correct gastrin conjugate into human U373 glioma cells. Surprisingly, the mutant conjugate was also taken up into the cells in a similar pattern, albeit to a lesser degree. Both conjugates showed no cytotoxicity. These conjugates show potential for future use in magnetic resonance imaging studies of brain tumors after systemic or intraoperative local application. The cytoplasm specificity of the conjugates also makes it a potential building block for the design of future cytoplasmdirected imaging and therapeutic conjugates.
Treatment of chronic tinnitus with theta burst stimulation
2012-04-27

<h3>Objective:</h3> To test whether 4 weeks of bilateral repetitive transcranial magnetic stimulation (rTMS) to the temporal or temporoparietal cortex is effective and safe in the treatment of chronic tinnitus. <h3>Methods:</h3> In this controlled 3-armed trial, 48 patients with chronic tinnitus were treated with 4 weeks (20 sessions) of bilateral continuous theta burst stimulation (cTBS) at the Tübingen University Hospital. They were randomized to stimulation above the temporal cortex, the temporoparietal cortex, or as sham condition behind the mastoid. Patients were masked for the stimulation condition. Tinnitus severity was assessed after 2 and primarily 4 weeks of treatment and at 3 months follow-up with the tinnitus questionnaire and by a tinnitus change score. Audiologic safety was monitored by pure-tone and speech audiometry after 2 and 4 weeks of cTBS. <h3>Results:</h3> Tinnitus severity was slightly reduced from baseline by a mean (SD) 2.6 (8.2) after sham, 2.4 (8.0) after temporoparietal, 2.2 (8.3) after temporal treatment of 16 patients each, but there was no significant difference between sham treatments and temporal (confidence interval [CI] −5.4 to +6.7) or temporoparietal cTBS (CI −5.9 to +6.3) or real cTBS (CI −7 to +5.1). Patients9 global evaluation of tinnitus change after treatment did not indicate any effects. Audiologic measures were unaffected by treatment. <h3>Conclusions:</h3> Treating chronic tinnitus for 4 weeks by applying cTBS to the temporal or temporoparietal cortex of both hemispheres appears to be safe but not more effective than sham stimulation. However, these results are not to be generalized to all forms of rTMS treatments for tinnitus. <h3>Classification of Evidence:</h3> This study provides Class I evidence that bilateral cTBS is not effective in the treatment of chronic tinnitus.
Paleoclimatic implications of magnetic susceptibility in Late Pliocene–Quaternary sediments from deep drilling core SG‐1 in the western Qaidam Basin (NE Tibetan Plateau)
2012-04-27

Lake sediments are important archives of paleoclimate change and erosion history. A 938.5 m long core (SG‐1) of lacustrine sediments, dated at 2.77 Ma to 0.1 Ma, was obtained from the western Qaidam Basin in the northeastern Tibetan Plateau, consisting of dark grayish mudstone and grayish siltstone, intercalated with salts and fine sandstones in the upper part. Magnetic susceptibility data, combined with detailed rock magnetic properties, were analyzed for revealing the significance of ferro(i)magnetic concentration for past changes of climate and erosion. Mass‐specific susceptibility ( χ ) shows a striking cyclic and long‐term variation. Samples with high χ values are dominated by magnetite and maghemite with pseudo‐single‐domain properties. In contrast, samples with low χ values contain maghemite from single‐domain to multidomain and, additionally, a significant fraction of hematite. The driving mechanism of χ variation can be explained by three alternative models: (1) different source regions with alternations of wind and cryoclastic erosion in a wider hinterland (dry‐cold climate) and surface runoff erosion from a narrower area (more humid climate) and (2 and 3) low‐temperature oxidation, occurring either in the lake sediments (dry climate) or in the catchment area during weathering (more humid climate). Trends of χ match with changes in sedimention rates and are roughly synchronous with the deep‐sea δ 18 O record on a glacial‐interglacial timescale. Therefore, the concentration of magnetic minerals in the western Qaidam Basin sediments is likely controlled by both tectonic influence and paleoenvironmental changes but can be best interpreted by alternations and trends of dry‐cold and more humid periods due to Asian drying and global cooling.
Establishment of a Coculture Model for Studying Inflammation After Pediatric Cardiopulmonary Bypass: from Bench to Bedside
2012-04-27

Cardiopulmonary bypass (CPB) has been known to induce an inflammatory response that is influenced by various factors. Hypothermia is supposed to reduce inflammation after CPB. We developed an in vitro coculture model for CPB and compared the effects of hypothermia on the inflammatory response in the coculture model with results from a clinical prospective randomized trial. The coculture model consisted of endothelial cells and monocytes. Cells were stimulated with tumor necrosis factor (TNF)-α and exposed to deep hypothermia (20°C) or normothermia (37°C). In the clinical trial, 20 patients undergoing CPB for ventricular septum defect receive either normothermic (37°C) or mild hypothermic (32°C) CPB. We observed a significant interleukin (IL)-6 and IL-8 release in the coculture model 2 and 24 h after the experimental start. In the clinical trial, cytokines were significantly increased directly after weaning from CPB and remained elevated until 24 h. IL-8 and IL-6 secretions were similar in the hypothermic and normothermic group of the coculture model and the patients after 24 h. These results demonstrate that the inflammatory reaction observed in our coculture model is comparable with the cytokine increase in the blood of children undergoing CPB. Our coculture model could be useful for studies on the mechanisms of CPB-induced inflammation.
Insight in schizophrenia–course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder
2012-04-28

Abstract Background To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight. Methods Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale (“lack of insight and judgement”). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients. Results Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment ( p &lt;0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms ( p = 0.0004), less suicidality ( p = 0.0218), suffering from multiple illness-episodes ( p &lt;0.0001) and worse adherence ( p = 0.0012) at admission were identified to be significant predictors of poor insight at discharge. Conclusion The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.
Two Preferentially Expressed Proteins Protect Vascular Endothelial Cells from an Attack by Peptide-Specific CTL
2012-04-29

Abstract Vascular endothelial cells (EC) are an exposed tissue with intimate contact with circulating Ag-specific CTL. Experimental in vitro and clinical data suggested that endothelial cells present a different repertoire of MHC class I-restricted peptides compared with syngeneic leukocytes or epithelial cells. This endothelial-specific peptide repertoire might protect EC from CTL-mediated cell death. The HLA-A*02-restricted peptide profile of human EC and syngeneic B lymphoblastoid cells was biochemically analyzed and compared. For EC selective peptides, source protein expression, peptide binding affinity, and peptide–HLA-A*02 turnover were measured. The significance of abundant peptide presentation for target cell recognition by immunodominant CTL was tested by small interfering RNA treatment of EC to knock down the source proteins. High amounts of two peptides, PTRF56–64 and CD59106–114, were consistently detected in EC. This predominance of two endothelial peptides was explained by cell type-specific source protein expression that compensated for poor HLA-A*02 binding affinity and short half-live of peptide/HLA-A*02 complexes. Knocking down the source proteins containing the abundant endothelial peptide motifs led to a nearly 100-fold increase of surface expression of SMCY311–319, an immunodominant minor histocompatibility Ag, as detected by cytotoxicity assays using SMCY311–319-specific CTL. We conclude that EC express and present preferentially two distinct HLA-A*02-restricted peptides at extraordinary high levels. These abundant self-peptides may protect EC from CTL-mediated lysis by competing for HLA-A*02 binding sites with immunodominant scarcely expressed antigenic peptides.
Motion statistics at the saccade landing point: attentional capture by spatiotemporal features in a gaze-contingent reference
2012-04-29

Motion is known to play a fundamental role in attentional capture, still it is not always included in computational models of visual attention. A wealth of literature in the past years has investigated natural image statistics at the centre of gaze to assess static low-level features accounting for fixation capture on images. A motion counterpart describing which features trigger saccades on dynamic scenes has been less looked into, whereas it would provide significant insight on the visuomotor behaviour when attending to events instead of less realistic still images. Such knowledge would be paramount to devise active vision systems that can spot interesting or malicious activities and disregard less relevant patterns. In this paper, we present an analysis of spatiotemporal features at the future centre of gaze to extract possible regularities in the fixation distribution to contrast with the feature distribution of non-fixated points. A substantial novelty in the methodology is the evaluation of the features in a gaze-contingent reference. Each video sequence fragment is indeed foveated with respect to the current fixation, while features are collected at the next saccade landing point. This allows us to estimate covertly selected motion cues in a retinotopic fashion. We consider video sequences and eye-tracking data from a recent state-of-the art dataset and test a bottom-up motion saliency measure against human performance. Obtained results can be used to further tune saliency computational models and to learn to predict human fixations on video sequences or generate meaningful shifts of active sensors in real world scenarios.