julilili42/papers huggingface dataset:
Boon and bane of studying the multiple cyclotron source 4U 0115+63
2013-07-18

We present a study of RXTE and INTEGRAL spectra of the transient 3.6 s X-ray pulsar 4U 0115+634 taken during a giant outburst in 2008 March/April. The spectra can be almost equally well modeled by two different semi-empirical continuum models, modified by an Fe Kα fluorescence line, interstellar absorption, and cyclotron resonance scattering features (CRSFs) located at ∼10.7, 21.8, 35.5, 46.7, and 59.7 keV. One of these two models, the so called NPEX model, leads to an anticorrelation between the centroid energy of the fundamental CRSF E0 and the X-ray flux FX, in agreement with previous works. The other model, consisting of a simple exponentially cutoff power law modified by a Gaussian emission feature around 10 keV, however, leads to a constant value for E0 for the observed fluxes and a comparatively narrow line shape. We show that the cyclotron line model component resulting from the NPEX fits rather contribute to the broadband continuum model. We conclude that the previously reported anticorrelation is probably due to an artifact of the particular modeling of the continuum.
SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma
2013-07-19

Abstract The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. Cancer Res; 73(17); 5544–55. ©2013 AACR.
Allelic variation in two distinct Pseudomonas syringae flagellin epitopes modulates the strength of plant immune responses but not bacterial motility
2013-07-19

Summary The bacterial flagellin (FliC) epitopes flg22 and flg II ‐28 are microbe‐associated molecular patterns ( MAMP s). Although flg22 is recognized by many plant species via the pattern recognition receptor FLS 2, neither the flg II ‐28 receptor nor the extent of flg II ‐28 recognition by different plant families is known. Here, we tested the significance of flg II ‐28 as a MAMP and the importance of allelic diversity in flg22 and flg II ‐28 in plant–pathogen interactions using purified peptides and a Pseudomonas syringae ∆ fliC mutant complemented with different fliC alleles. The plant genotype and allelic diversity in flg22 and flg II ‐28 were found to significantly affect the plant immune response, but not bacterial motility. The recognition of flg II ‐28 is restricted to a number of solanaceous species. Although the flg II ‐28 peptide does not trigger any immune response in Arabidopsis, mutations in both flg22 and flg II ‐28 have FLS 2 ‐dependent effects on virulence. However, the expression of a tomato allele of FLS 2 does not confer to Nicotiana benthamiana the ability to detect flg II ‐28, and tomato plants silenced for FLS 2 are not altered in flg II ‐28 recognition. Therefore, MAMP diversification is an effective pathogen virulence strategy, and flg II ‐28 appears to be perceived by an as yet unidentified receptor in the Solanaceae, although it has an FLS 2 ‐dependent virulence effect in Arabidopsis.
The Impact of Thin‐Capitalization Rules on External Debt Usage – A Propensity Score Matching Approach
2013-07-19

Abstract Thin‐capitalization rules (TCRs) aim at limiting the tax advantage of internal debt financing by restricting the tax deductibility of the corresponding interest expenses. This article examines how subsidiaries of multinational firms respond to a change in the German thin‐capitalization legislation. The empirical analysis not only demonstrates that the TCR effectively restricts internal debt financing, it also suggests that firms are able to avoid taxation of interest by substituting external for internal debt. The empirical approach applies propensity score matching techniques and exploits the German tax reform 2001 to solve endogeneity problems.
Predictors of survival in patients with disease recurrence after radical nephroureterectomy
2013-07-19

Objectives To evaluate the prognostic value of the B ajorin criteria in a multi‐institutional cohort of patients with disease recurrence after radical nephroureterectomy ( RNU ) for upper tract urothelial carcinoma ( UTUC ). To investigate whether clinical, pathological and/or biological factors at time of disease recurrence are also associated with cancer‐specific outcomes in these patients. Patients and Methods We identified 242 patients with disease recurrence after RNU for UTUC from 11 centres. With regard to the B ajorin criteria, patients were categorized into three groups based on two risk factors: K arnofsky performance status &lt;80% and the presence of visceral metastasis. Assessed variables included pathological characteristics, time to disease recurrence, age‐adjusted C harlson comorbidity index ( ACCI ), A merican S ociety of A nesthesiologists ( ASA ) score, and laboratory tests at time of disease recurrence. Results Overall, 185 patients died from their disease; the median survival was 9 months. The survival rates at 1 year were 53, 33, and 39% for patients with no (n = 18), one (n = 109) and two (n = 115) risk factors, respectively, with no significant difference between the groups. In univariable analyses, higher pT ‐stage, tumour necrosis, non‐administered salvage chemotherapy, higher ACCI score, higher ASA score, lower albumin level and higher white blood cell count were significantly associated with a shorter time to cancer‐specific mortality. Conclusions We confirmed the poor yet variable outcomes of patients with disease recurrence after RNU . While the B ajorin criteria seem to have limited prognostic value in this specific cohort, we found several other clinical variables to be associated with worse cancer‐specific mortality. If validated, these factors should be taken into consideration for clinical trial design.
Aryl‐Phosphonate Lanthanide Complexes and Their Fluorinated Derivatives: Investigation of Their Unusual Relaxometric Behavior and Potential Application as Dual Frequency 1H/19F MRI Probes
2013-07-19

Abstract A series of low molecular weight lanthanide complexes were developed that have high 1 H longitudinal relaxivities ( r 1 ) and the potential to be used as dual frequency 1 H and 19 F MR probes. Their behavior was investigated in more detail through relaxometry, pH‐potentiometry, luminescence, and multinuclear NMR spectroscopy. Fitting of the 1 H NMRD and 17 O NMR profiles demonstrated a very short water residence lifetime (&lt;10 ns) and an appreciable second sphere effect. At lower field strengths (20 MHz), two of the complexes displayed a peak in r 1 (21.7 and 16.3 m M −1 s −1 ) caused by an agglomeration, that can be disrupted through the addition of phosphate anions. NMR spectroscopy revealed that at least two species are present in solution interconverting through an intramolecular binding process. Two complexes provided a suitable signal in 19 F NMR spectroscopy and through the selection of optimized imaging parameters, phantom images were obtained in a MRI scanner at concentrations as low as 1 m M . The developed probes could be visualized through both 1 H and 19 F MRI, showing their capability to function as dual frequency MRI contrast agents.
New Aspects of Gene-Silencing for the Treatment of Cardiovascular Diseases
2013-07-19

Coronary heart disease (CHD), mainly caused by atherosclerosis, represents the single leading cause of death in industrialized countries. Besides the classical interventional therapies new applications for treatment of vascular wall pathologies are appearing on the horizon. RNA interference (RNAi) represents a novel therapeutic strategy due to sequence-specific gene-silencing through the use of small interfering RNA (siRNA). The modulation of gene expression by short RNAs provides a powerful tool to theoretically silence any disease-related or disease-promoting gene of interest. In this review we outline the RNAi mechanisms, the currently used delivery systems and their possible applications to the cardiovascular system. Especially, the optimization of the targeting and transfection procedures could enhance the efficiency of siRNA delivery drastically and might open the way to clinical applicability. The new findings of the last years may show the techniques to new innovative therapies and could probably play an important role in treating CHD in the future.
Linguistic Tests for Discourse Relations
2013-07-19

Discourse structure and discourse relations are an important ingredient in systems for the analysis of text that go beyond the boundary of single clauses. Discourse relations often indicate important additional information about the connection between two clauses, such as causality, and are widely believed to have an influence on aspects of reference resolution.In this article, we first present the general design choices that are to be made in the design of an annotation scheme for discourse structure and discourse relations. In a second part, we present the scheme used in our annotation of selected articles from the TüBa-D/Z treebank of German (Telljohann et al., 2009). The scheme used in the annotation is theory-neutral, but informed by more detailed linguistic knowledge in the way of linguistic tests that can help disambiguate between several plausible relations.
Heptacene: Increased Persistence of a 4n+2 π‐Electron Polycyclic Aromatic Hydrocarbon by Oxidation to the 4n π‐Electron Dication
2013-07-22

An unexpectedly stable dication: Heptacene (a 4n+2 π-electron compound) is so highly reactive that it cannot be isolated. Its dication (a 4n π-electron compound) can be obtained from heptacene dimers/oligomers in sulfuric acid at room temperature and can be kept for more than one year in the absence of oxygen. (See picture for the UV/Vis-NIR spectra of the dications of tetracene to heptacene.) As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cytosolic calcium, hydrogen peroxide and related gene expression and protein modulation in Arabidopsis thaliana cell cultures respond immediately to altered gravitation: parabolic flight data
2013-07-22

Abstract Callus cell cultures of A rabidopsis thaliana (cv. C olumbia) were exposed to parabolic flights in order to assess molecular, short‐term responses to altered gravity fields. Using transgenic cell lines, hydrogen peroxide ( H 2 O 2 ) and cytosolic C a 2+ were continuously monitored. In parallel, the metabolism of samples was chemically quenched ( RNA later, A mbion for RNA ; acid/base for NADPH , NADP ) at typical stages of a parabola [1 g before pull up; end of pull up (1.8 g ), end of microgravity (20 s) and end of pull out (1.8 g )]. Cells exhibited an increase in both C a 2+ and H 2 O 2 with the onset of microgravity, and a decline thereafter. This behaviour was accompanied by a decrease of the NADPH / NADP redox ratio, indicating C a 2+ ‐dependent activation of a NADPH oxidase. Microarray analyses revealed concomitant expression profiles. At the end of the microgravity phase, 396 transcripts were specifically up‐, while 485 were down‐regulated. Up‐regulation was dominated by C a 2+ ‐ and ROS ‐related gene products. The same material was also used for analysis of phosphopeptides with 2‐ D SDS PAGE . Relevant spots were identified by liquid chromatography– MS . With the exception of a chaperone ( HSP 70‐3), hypergravity (1.8 g ) and microgravity modified different sets of proteins. These are partly involved in primary metabolism (glycolysis, gluconeogenesis, citrate cycle) and detoxification of ROS . Taken together, these data show that both gene expression and protein modulation jointly respond within seconds to alterations in the gravity field, with a focus on metabolic adaptation, signalling and control of ROS .
The V471A Polymorphism in Autophagy-Related Gene ATG7 Modifies Age at Onset Specifically in Italian Huntington Disease Patients
2013-07-22

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.
Epigenetic effects of natural polyphenols: A focus on SIRT1‐mediated mechanisms
2013-07-23

Polyphenols are a class of natural compounds widely distributed in fruits, vegetables, and plants. They have been reported to possess a wide range of activities in prevention and alleviation of various diseases like cancer, neuroinflammation, diabetes, and aging. Polyphenols are effective against chronic diseases and recent reports indicated strong epigenetic effects of polyphenols. Most of the studies investigating epigenetic effects of natural polyphenols have focused on their beneficial effects in cancer treatment. However, epigenetic defects have been demonstrated in many other diseases as well, and application of polyphenols to modulate the epigenome is becoming an interesting field of research. This review summarizes the effects of natural polyphenols in modulating epigenetic‐related enzymes as well as their effect in prevention and treatment of chronic diseases with a focus on SIRT1 modulation. We have also discussed the relation between the structure and function of epigenetic‐modifying polyphenols.
The GPVI-Fc Fusion Protein Revacept Improves Cerebral Infarct Volume and Functional Outcome in Stroke
2013-07-23

Revacept reduces arterial thrombus formation, reduces cerebral infarct size and edema after ischemic stroke, improves functional and prognostic outcome without intracranial bleeding. Revacept not only prevents GPVI-mediated, but probably also vWF-mediated platelet adhesion and aggregate formation. Therefore Revacept might be a potent and safe tool to treat ischemic complications of stroke.
Loschmidt Echo and the Many-Body Orthogonality Catastrophe in a Qubit-Coupled Luttinger Liquid
2013-07-23

We investigate the many-body generalization of the orthogonality catastrophe by studying the generalized Loschmidt echo of Luttinger liquids (LLs) after a global change of interaction. It decays exponentially with system size and exhibits universal behavior: the steady state exponent after quenching back and forth n times between 2 LLs (bang-bang protocol) is 2n times bigger than that of the adiabatic overlap and depends only on the initial and final LL parameters. These are corroborated numerically by matrix-product state based methods of the XXZ Heisenberg model. An experimental setup consisting of a hybrid system containing cold atoms and a flux qubit coupled to a Feshbach resonance is proposed to measure the Loschmidt echo using rf spectroscopy or Ramsey interferometry.
Potential Capacity of Aptamers to Trigger Immune Activation in Human Blood
2013-07-23

Target specific short single-stranded DNA (ssDNA) molecules, called aptamers, are auspicious ligands for numerous in vivo applications. However, aptamers are synthetic molecules, which might be recognized by the immune cells in vivo and induce an activation of the innate immune system. Thus, immune activation potential of synthetic ssDNA oligonucleotides (ODNs) was determined using a well established closed-loop circulation model. Fresh human blood was incubated at 37°C for 2 or 4 hours with ssDNA ODNs (SB_ODN) or CpG ODN as positive control. Transcriptional changes were determined by microarray analyses. Blood samples containing SB_ODN demonstrated after 4 hours a significant regulation of 295 transcripts. Amongst others, CCL8, CXCL10, CCL7 and CXCL11 were highest regulated genes. Gene Ontology terms and KEGG pathway analyses exhibited that the differentially expressed genes belong to the transcripts that are regulated during an immune and inflammatory response, and were overrepresented in TLR signaling pathway. This study shows for the first time the potential of aptamers to activate immune system after systemic application into the human blood. Thus, we highly recommend performing of these preclinical tests with potential aptamer-based therapeutics.
Evaluation of a Novel Spine and Surface Topography System for Dynamic Spinal Curvature Analysis during Gait
2013-07-23

A novel rasterstereographic measurement device that allows surface and spine topography under dynamic conditions was assessed. The accuracy of this system was with one millimeter on a solid plate and during dynamic measurements, to the gold standard for motion detection. The advantage of rasterstereography is that it can be used to determine a three-dimensional surface map and also allows the analysis of the underlying spine.
Antimicrobial Activity of High-Mobility-Group Box 2: a New Function to a Well-Known Protein
2013-07-23

ABSTRACT The human intestinal tract is highly colonized by a vast number of microorganisms. Despite this permanent challenge, infections remain rare, due to a very effective barrier defense system. Essential effectors of this system are antimicrobial peptides and proteins (AMPs), which are secreted by intestinal epithelial and lymphoid cells, balance the gut microbial community, and prevent the translocation of microorganisms. Several antimicrobial proteins have already been identified in the gut. Nonetheless, we hypothesized that additional AMPs are yet to be discovered in this setting. Using biological screening based on antimicrobial function, here we identified competent antibacterial activity of high-mobility-group box 2 (HMGB2) against Escherichia coli . By recombinant expression, we confirmed this biologically new antimicrobial activity against different commensal and pathogenic bacteria. In addition, we demonstrated that the two DNA-binding domains (HMG boxes A and B) are crucial for the antibiotic function. We detected HMGB2 in several gastrointestinal tissues by mRNA analysis and immunohistochemical staining. In addition to the nuclei, we also observed HMGB2 in the cytoplasm of intestinal epithelial cells. Furthermore, HMGB2 was detectable in vitro in the supernatants of two different cell types, supporting an extracellular function. HMGB2 expression was not changed in inflammatory bowel disease but was detected in certain stool samples of patients, whereas it was absent from control individuals. Taken together, we characterized HMGB2 as an antimicrobial protein in intestinal tissue, complementing the diverse repertoire of gut mucosal defense molecules.
Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha‐2b in metastatic melanoma (phase II DeCOG trial)
2013-07-23

Summary Background and objectives During a clinical study with combined therapy of sorafenib and pegylated interferon alpha‐2b (SoraPeg study) of the German Dermatologic Oncology Group (ADO/DeCOG), multiple and severe cutaneous side effects were observed. This study sought to analyze these cutaneous side effects, particularly because future studies with combinations of interferon alpha and targeted therapies are planned. Patients and methods In a multicenter phase‐II‐DeCOG study (NCT00623402) in 10 dermato‐oncology centers, 55 patients with metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally) and pegylated interferon alpha‐2b (3 μg/kg body weight 1 x/week subcutaneously). All cutaneous side effects were documented. Results Forty‐one patients (74.5 %) developed cutaneous side effects, particularly exanthems (51.2 %), hand‐foot syndrome (36.5 %), alopecia (36.5 %) and pruritus (24.4 %). Due to the cutaneous side effects, dose reductions were required in 10 patients, interruption of therapy in 10 cases and permanent discontinuation of therapy and in one patient with extensive follicular‐cystic lesions. Exanthems were seen more frequently in women (76.2 %) than in men (23.8 %). The occurrence of cutaneous side effects was not correlated with clinical outcome or prognosis. Conclusions The combination of sorafenib/pegylated interferon alpha‐2b caused more cutaneous side effects than have been reported for single agents. Despite intensive dermatologic management of the cutaneous side effects 24 % of patients required a dose modification.
Observations of TeV binary systems with the H.E.S.S. telescope
2013-07-23

Recent observations of binary systems obtained with the High Energy Stereoscopic System of Cherenkov telescopes are providing crucial information on the physics of relativistic outflows and the engines powering them. We report here on new H.E.S.S. results on HESS J0632+057, PSR B1259-63/LS 2883, Eta Carinae and the recently discovered source HESS J1018-589. Despite the high-quality data obtained in the last years through both ground and space-based gamma-ray detectors, many questions on the mechanisms that permit binary systems to emit at gamma-rays remain open. In particular, it is becoming apparent that emission at high and very- high energies is uncorrelated in some gamma-ray binary systems, with bright GeV flares not observed at TeV energies (e.g. PSR B1259-63), and sources periodically detected at VHEs which are lacking its HE counterpart (e.g. HESS J0632+057). Our results mainly confirm the predictions derived previously for the studied sources, but unexpected results are also found in a few cases, which are discussed in the context of contemporaneous observations at lower energies.