julilili42/papers huggingface dataset:
Cutaneous B-Cell Lymphoproliferative Disorders
2013-03-22

Abstract The diagnosis and classification of the cutaneous B-cell lymphomas can be quite a challenge, with a definitive diagnosis sometimes being elusive, even when an extensive workup has been performed. Distinction of benign from neoplastic disorders can be difficult, with some hyperplasias mimicking lymphomas and vice versa. There are only a limited number of skin-specific B-cell lymphomas, including primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type. Cutaneous marginal zone lymphomas have distinctive features but are classified with the other mucosa-associated lymphoid tissue lymphomas. It is important, however, to also remember that many other B-cell lymphomas/ plasma cell neoplasms can primarily, or more often secondarily, involve the skin. Some may mimic one of the skin-specific lymphomas but have very different clinical implications. Iatrogenic and senescent immunodeficiency-associated lymphoproliferative disorders that are often Epstein-Barr virus (EBV) positive can also primarily involve the skin, including cases also known as EBV-positive mucocutaneous ulcer.
Response Evaluation of Musculoskeletal Involvement in Patients With Deep Morphea Treated With Methotrexate and Prednisolone: A Combined MRI and Clinical Approach
2013-03-22

MRI findings were sensitive to changes in musculoskeletal manifestations in patients with deep morphea undergoing systemic treatment with methotrexate and prednisolone. Thus, MRI can be recommended as an additional tool for response monitoring.
Therapy Monitoring of Magnetic Resonance–Guided Radiofrequency Ablation Using T1- and T2-Weighted Sequences at 1.5 T
2013-03-22

In examinations performed directly after the intervention, the T2-weighted images tend to underestimate the ablation zone, whereas T1-weighted images clearly better reflect the ablation zone. T1-weighted images therefore seem more adequate for repetitive monitoring of MR-guided RFA at 1.5 T.
INTRAVITREAL BEVACIZUMAB FOR JUXTAFOVEAL CHOROIDAL NEOVASCULARIZATION SECONDARY TO MULTIFOCAL CHOROIDITIS
2013-03-22

Intravitreal bevacizumab is a beneficial treatment for juxtafoveal choroidal neovascularization associated with multifocal choroiditis. Further studies are warranted to confirm these preliminary results.
Vemurafenib reverses immunosuppression by myeloid derived suppressor cells
2013-03-23

Myeloid derived suppressor cells (MDSCs) suppress innate and adaptive immunity, thereby limiting anti‐tumor immune responses in cancer patients. In patients with advanced melanoma, the phenotype and function of MDSCs remains controversial. In our study, we further explored two distinct subpopulations of MDSCs and investigated the impact of Vemurafenib on these cells. Flow cytometry analysis revealed that in comparison to healthy donors and patients with localized disease, PBMCs from patients with metastatic melanoma showed an increased frequency of CD14 + HLA‐DR −/low monocytic MDSCs (moMDSCs) and of a previously unrecognized population of CD14 − CD66b + Arginase1 + granulocytic MDSCs (grMDSCs). In vitro , both populations suppressed autologous T‐cell proliferation, which was tested in CFSE‐based proliferation assays. Vemurafenib treatment of melanoma patients reduced the frequency of both moMDSCs and grMDSCs. According to our in vivo finding, conditioned medium (CM) from Vemurafenib treated melanoma cells was less active in inducing moMDSCs in vitro than CM from untreated melanoma cells. In conclusion, patients with advanced melanoma show increased levels of moMDSCs, and of a population of CD14 − CD66b + Arginase1 + grMDSCs. Both MDSCs are distinct populations capable of suppressing autologous T‐cell responses independently of each other. In vitro as well as in vivo , Vemurafenib inhibits the generation of human moMDSCs. Thus, Vemurafenib decreases immunosuppression in patients with advanced melanoma, indicating its potential as part of future immunotherapies.
High magnitude and rapid incision from river capture: Rhine River, Switzerland
2013-03-23

Abstract Landscape evolution is controlled by the development and organization of drainage basins. As a landscape evolves, drainage reorganization events can occur via river capture or piracy, whereby one river basin grows at the expense of another. The river downstream of a capture location will generate a transient topographic response as the added water discharge increases sediment transport and erosion efficiency. This erosional response will propagate upstream through both the captured and original river basins. Here we focus on quantifying the impact of drainage reorganization along the Rhine/Aare River system (~45,000 km 2 ) during the late Pliocene/early Pleistocene, where gravel remnants indicate total incision of ~650 m during the last ~4.2 Myr in the region of the recent Aare‐Rhine confluence. We develop a numerical model of drainage capture to quantify the range of possible magnitudes of erosion and the transient river response resulting from the reorganization of the Rhine River. The model accounts for both fluvial incision and sediment transport. Our model estimates 400–800 m of river elevation change (lowering profiles) during the last ~4 Myr due to river capture events, providing an important component to the recent exhumation budget of the Swiss Alpine Foreland. The model indicates a rapid response to capture events (re‐equilibration timescale of ~1 Myr). The predicted incision magnitudes are consistent with incision measured from the elevation of Pliocene and early Pleistocene river gravels, suggesting that across northern Switzerland, a significant amount of incision can be explained by drainage reorganization.
Engraftment of low numbers of pediatric acute lymphoid and myeloid leukemias into NOD/SCID/IL2Rcγnull mice reflects individual leukemogenecity and highly correlates with clinical outcome
2013-03-23

Although immortalized cell lines have been extensively used to optimize treatment strategies in cancer, the usefulness of such in vitro systems to recapitulate primary disease is limited. Therefore, the design of in vivo models ideally utilizing patient‐derived material is of critical importance. In this regard, NOD.Cg‐ Prkdc scid IL2rg tmWjl /Sz (NSG) mice have been reported to provide superior engraftment rates. However, limited data exist on the validity of such a model to constitute a surrogate marker for clinical parameters. We studied primary and serial engraftment on more than 200 NSG mice with 54 primary pediatric B cell precursor acute lymphatic leukemia (B‐ALL), myeloid leukemia (AML) and T cell leukemia (T‐ALL) samples, characterized the leukemogenic profile and correlated engraftment kinetics with clinical outcome. Median time to engraftment was 7–10 weeks and 90% of the mice engrafted. Male recipients conferred significantly higher engraftment levels than female recipients ( p ≤ 0.004). PCR‐based minimal residual disease marker expression and fluorescence in situ hybridization confirmed the presence of patient‐specific genetic aberrations in mice. Transcriptome cluster analysis of genes known to be important in the leukemogenesis of all three diseases revealed that well‐known tumor‐regulating genes were expressed to a comparable extent in mice and men. The extent of engraftment and overall survival of NSG mice highly correlated with the individual prognosis of B‐ALL, AML and T‐ALL patients. Thus, we propose an in vivo model that provides a valuable preclinical tool to explore the heterogeneity of leukemic disease and exploit patient‐tailored leukemia‐targeting strategies within multivariate analyses.
Evidence for Age-Dependent in Vivo Conformational Rearrangement within Aβ Amyloid Deposits
2013-03-25

Deposition of aggregated Aβ peptide in the brain is one of the major hallmarks of Alzheimer's disease. Using a combination of two structurally different, but related, hypersensitive fluorescent amyloid markers, LCOs, reporting on separate ultrastructural elements, we show that conformational rearrangement occurs within Aβ plaques of transgenic mouse models as the animals age. This important mechanistic insight should aid the design and evaluation of experiments currently using plaque load as readout.
Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis
2013-03-25

The Bacillus subtilis glutamine synthetase (GS) plays a dual role in cell metabolism by functioning as catalyst and regulator. GS catalyses the ATP‐dependent synthesis of glutamine from glutamate and ammonium. Under nitrogen‐rich conditions, GS becomes feedback‐inhibited by high intracellular glutamine levels and then binds transcription factors GlnR and TnrA, which control the genes of nitrogen assimilation. While GS‐bound TnrA is no longer able to interact with DNA, GlnR–DNA binding is shown to be stimulated by GS complex formation. In this paper we show a new physiological feature of the interaction between glutamine synthetase and TnrA. The transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in vivo and in vitro , while the GlnR protein does not affect the activity of the enzyme.
Tissue Inhibitor of Metalloproteinase 1 Is Preferentially Expressed in Th1 and Th17 T-Helper Cell Subsets and Is a Direct Stat Target Gene
2013-03-26

CD4(+) T helper (Th) cells differentiate into distinct effector subsets that are critical for host defense, but are also implicated in the pathogenesis of autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as important drivers of multiple diseases including psoriasis, spondyloarthropathy and multiple sclerosis. To gain insight into the function of Th17 cells, we performed transcriptional profiling in hopes of elucidating products not previously recognized as being functionally relevant in these T cells. Herein, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted protein with pleiotropic effects on cellular growth, survival and integrity of the extracellular matrix, is preferentially produced by Th17 and Th1 cells. We further show that Th1 and Th17 cell TIMP1 regulation follows separate mechanisms with a requirement for STAT4 in the former and STAT3 in the latter. Finally, we demonstrate that when restricted to T cells, expression of TIMP1 promotes neuropathology in experimental allergic encephalomyelitis.
Optimization and visualization of the edge weights in optimal assignment methods for virtual screening
2013-03-26

The optimization of the edge weights in optimal assignment methods is a valuable approach for ligand-based virtual screening experiments. The approach can be applied to any similarity function that employs the optimal assignment method, which includes a variety of similarity measures that have proven to be valuable in various cheminformatic tasks. The proposed visualization helps to get a better understanding of the binding mode of the analyzed query molecule.
Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity
2013-03-27

The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-Kit(CreERT2) knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.
Evidence of Gene–Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors
2013-03-27

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.
Sex Determining Region Y-Box 2 (SOX2) Amplification Is an Independent Indicator of Disease Recurrence in Sinonasal Cancer
2013-03-27

This is the first study assessing SOX2 amplification and expression in a large cohort of sinonasal carcinomas. As opposed to AD and ACC, SOX2 amplifications were detected in more than 1/3 of all SCCs, SNUCs and INVCs. We therefore suggest that SNUCs are molecularly closely related to SCCs and INVCs and that these entities represent a subgroup of sinonasal carcinomas relying on SOX2 acquisition during oncogenesis. SOX2 amplification appears to identify sinonasal carcinomas that are more likely to relapse after primary therapy, suggesting that these patients might benefit from a more aggressive therapy regime.
UV MCP Detectors for WSO-UV: Cross Strip <newline/>Anode and Readout Electronics
2013-03-27

The main instrument of the WSO-UV satellite covers the wavelength range of 102-176 nm and 174-310 nm with two high resolution echelle spectrographs. The essential requirements for the associated detectors are high quantum efficiency, solar blindness, and single photon detection. To achieve this, we are developing microchannel plate (MCP) detectors in sealed tubes. It is planned to use cesium activated gallium nitride as semitransparent photocathode, a stack of two microchannel plates in chevron configuration, and a 33 mm × 44 mm cross strip anode with 64 horizontal and 64 vertical electrodes. This type of anode requires a lower gain of the MCPs ( ≈ 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> ) compared to other types of anodes. Therefore, it extends the expected lifetime of the detectors to about five to ten years. The challenge for the use of a cross strip anode onboard the WSO-UV satellite is the combination of contradictory constraints on the readout electronics: On the one hand it should be able to handle a maximum count rate of 3·10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> s <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> with a spatial resolution better than 15 μm . On the other hand the power consumption is limited to about 8 W. One feasible solution is the so-called Beetle chip. This chip provides 128 input channels with charge-sensitive preamplifiers and shapers. It stores the sampled data temporarily in a ring buffer and multiplexes it to four analogue readout channels. The output is then digitized by four ADCs and processed in a radiation hard FPGA, which also contains the space-wire interface to the satellite bus.
Analysing diversity and community structures usingPCR‐RFLP: a new software application
2013-03-27

Abstract Restriction fragment length polymorphism tools is an R application which supports a complete workflow of polymerase chain reaction‐restriction fragment length polymorphism ( PCR ‐ RFLP ), dealing with the problems which accompany analysis when PCR ‐ RFLP is used in diversity studies. Large numbers of different RFLP samples obtained from multiple electrophoresis runs might lead to limitations or misidentifications due to the need for band matching in most existing software applications. Due to the common problem of variation in the density of bands (i.e. distances between bands or visual intensity) in the electropherograms, it is desirable to have options for handling samples with uncertain or faint bands. As a further step in the workflow, scientists often use DNA sequencing to identify individual genotypes, so that the use of specific software to combine these tasks might be helpful. With this background, we here present an application that supports a complete workflow, starting with the analysis of single species samples by PCR ‐ RFLP , to PCR ‐ RFLP genotype identification based on a reference data set and DNA sequencing followed by similarity analysis. RFLP tools is a freely available, platform‐independent application which provides analysis functions for DNA fragment molecular weights (e.g. by RFLP analysis), including similarity calculations without the need for band matching. As it is written for the statistical software R, other statistical analyses might also be easily applied.
17 FUNCTIONAL DETRUSOR MYOPLASTY IN BLADDER HYPOCONTRACTILITY- EXTENDED FOLLOW-UP
2013-03-27

You have accessJournal of UrologyTrauma/Reconstruction: Traum & Reconstructive Surgery (1)1 Apr 201317 FUNCTIONAL DETRUSOR MYOPLASTY IN BLADDER HYPOCONTRACTILITY- EXTENDED FOLLOW-UP Georgios Gakis, Milomir Ninkovic, and Arnulf Stenzl Georgios GakisGeorgios Gakis Tuebingen, Germany , Milomir NinkovicMilomir Ninkovic Tuebingen, Germany , and Arnulf StenzlArnulf Stenzl Tuebingen, Germany View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1391AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To report the extended long-term results of the Latissimus Dorsi Detrusor Myoplasty (LDDM) procedure in patients with bladder hypocontractility caused by a lower motor neuron lesion. METHODS From 06/2003 until 05/2011, a total of 16 patients (mean age: 40 years, range: 17-63; 10 males, 6 females) underwent LDDM surgery for urodynamically proven bladder hypocontractility. All patients required complete clean intermittent catheterization (CIC) 6 times per day (3-7) preoperatively with a mean postvoid residual urine volume (PVR) of 550 ml (250-800). Preoperatively, patients performed CIC over a mean time period of 4.9 years (0.6-12.4). Median follow-up was 64 months (3-71 mo.) and included history, uroflowmetry with measurement of PVR. RESULTS Of the 16 patients, 13 (81%) gained complete spontaneous voiding after a median time period of 6 months (1.4-16.2) with a mean PVR of 10ml (range: 0-100ml) and maximum uroflow of 27ml/s (range: 10-46ml/s). In one patient the frequency of CIC was reduced from 5-6/24h preoperatively to 2-4/24h postoperatively with a PVR of 180ml and a maximum uroflow of 10ml/s. Two patients (13%) are still continuing to perform CIC 4-6/24h. The mean rate of recurrent urinary tract infections was 6/year preoperatively and 0.3/year postoperatively (p<0.001). No postoperative vesicoureteral reflux was observed in any patient. CONCLUSIONS After a median follow-up of 64 months spontaneous voiding with a PVR less than 100ml was achieved in approximately 80% of the patients. Due to these results persistent over a long-term follow-up period LDDM can be regarded as an effective treatment option alternative to CIC in a select group of patients with bladder hypocontractility. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e7 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Georgios Gakis Tuebingen, Germany More articles by this author Milomir Ninkovic Tuebingen, Germany More articles by this author Arnulf Stenzl Tuebingen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
School Life and Adolescents' Self‐Esteem Trajectories
2013-03-28

This study investigates heterogeneity in adolescents' trajectories of global self‐esteem ( GSE ) and the relations between these trajectories and facets of the interpersonal, organizational, and instructional components of students' school life. Methodologically, this study illustrates the use of growth mixture analyses, and how to obtain proper student‐level effects when there are multiple schools, but not enough to support multilevel analyses. This study is based on a 4‐year, six‐measurement‐point, follow‐up of 1,008 adolescents ( M age = 12.6 years, SD = 0.6 at Time 1.) The results show four latent classes presenting elevated, moderate, increasing, and low trajectories defined based on GSE levels and fluctuations. The results show that GSE becomes trait‐like as it increases and that school life effects, moderated by gender, played an important role in predicting membership in these trajectories.
Backward difference time discretization of parabolic differential equations on evolving surfaces
2013-03-28

Journal Article Backward difference time discretization of parabolic differential equations on evolving surfaces Get access Christian Lubich, Christian Lubich * Mathematisches Institut, University of Tübingen, Auf der Morgenstelle 10, D-72076 Tübingen, Germany *Corresponding author: lubich@na.uni-tuebingen.de Search for other works by this author on: Oxford Academic Google Scholar Dhia Mansour, Dhia Mansour Mathematisches Institut, University of Tübingen, Auf der Morgenstelle 10, D-72076 Tübingen, Germany Search for other works by this author on: Oxford Academic Google Scholar Chandrasekhar Venkataraman Chandrasekhar Venkataraman Department of Mathematics, Universty of Sussex, Falmer near Brighton, BN1 9QH, UK Search for other works by this author on: Oxford Academic Google Scholar IMA Journal of Numerical Analysis, Volume 33, Issue 4, October 2013, Pages 1365–1385, https://doi.org/10.1093/imanum/drs044 Published: 28 March 2013 Article history Received: 24 February 2012 Revision received: 18 July 2012 Published: 28 March 2013