Publications by authors named "Langen P"

The large diversity of functional genomic assays allows for the characterization of non-coding and coding events at the tissue level or at a single-cell resolution. However, this diversity also leads to protocol differences, widely varying sequencing depths, substantial disparities in sample sizes, and number of features. In this work, we have built a Python package, MUFFIN, which offers a wide variety of tools suitable for a broad range of genomic assays and brings many tools that were missing from the Python ecosystem.

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Intergenic transcription in normal and cancerous tissues is pervasive but incompletely understood. To investigate this, we constructed an atlas of over 180,000 consensus RNA polymerase II (RNAPII)-bound intergenic regions from 900 RNAPII chromatin immunoprecipitation sequencing (ChIP-seq) experiments in normal and cancer samples. Through unsupervised analysis, we identified 51 RNAPII consensus clusters, many of which mapped to specific biotypes and revealed tissue-specific regulatory signatures.

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The continuous change in observed key indicators such as increasing nitrogen deposition, temperatures and precipitation will have marked but uncertain consequences for the ecosystem carbon (C) sink-source functioning of the Arctic. Here, we use multiple in-situ data streams measured by the Greenland Ecosystem Monitoring programme in tight connection with the Soil-Plant-Atmosphere model and climate projections from the high-resolution HIRHAM5 regional model. We apply this modelling framework with focus on two climatically different tundra sites in Greenland (Zackenberg and Kobbefjord) to assess how sensitive the net C uptake will expectedly be under warmer and wetter conditions across the 21st century and pin down the relative contribution to the overall C sink strength from climate versus plant trait variability.

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Background: Primary radio(chemo)therapy [R(C)T] is a treatment option for advanced oropharyngeal squamous cell carcinoma (OSCC). Nevertheless, early diagnostics of treatment failure is problematic. Cytokeratin fragment 19 (CYFRA 21-1), an established marker in the management of pulmonary cancer, might be helpful here.

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ReMap (https://remap.univ-amu.fr) aims to provide manually curated, high-quality catalogs of regulatory regions resulting from a large-scale integrative analysis of DNA-binding experiments in Human, Mouse, Fly and Arabidopsis thaliana for hundreds of transcription factors and regulators.

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In recent decades, meltwater runoff has accelerated to become the dominant mechanism for mass loss in the Greenland ice sheet. In Greenland's high-elevation interior, porous snow and firn accumulate; these can absorb surface meltwater and inhibit runoff, but this buffering effect is limited if enough water refreezes near the surface to restrict percolation. However, the influence of refreezing on runoff from Greenland remains largely unquantified.

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Multimodel ensembles are widely analyzed to estimate the range of future regional climate change projections. For an ensemble of climate models, the result is often portrayed by showing maps of the geographical distribution of the multimodel mean results and associated uncertainties represented by model spread at the grid point scale. Here we use a set of CMIP5 models to show that presenting statistics this way results in an overestimation of the projected range leading to physically implausible patterns of change on global but also on regional scales.

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The recent decades of accelerating mass loss of the Greenland ice sheet have arisen from an increase in both surface meltwater runoff and ice flow discharge from tidewater glaciers. Despite the role of the Greenland ice sheet as the dominant individual cryospheric contributor to sea level rise in recent decades, no observational record of its mass loss spans the 30-year period needed to assess its climatological state. We present for the first time a 40-year (1975-2014) time series of observed meltwater discharge from a >6500-km catchment of the southwestern Greenland ice sheet.

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Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.

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Terrestrial freshwater runoff strongly influences physical and biogeochemical processes at the fjord scale and can have global impacts when considered at the Greenland scale. We investigate the performance of the HIRHAM5 regional climate model over the catchments delivering freshwater to Tyrolerfjord and Young Sound by comparing to the unique Greenland Ecological Monitoring database of in situ observations from this region. Based on these findings, we estimate and discuss the fraction of runoff originating from glacierized and non-glacierized land delivered at the daily scale between 1996 and 2008.

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Objective: To estimate whether a strategy of immediate surgery was noninferior to a strategy based on discordant urodynamic findings followed by individually tailored therapy in women with stress urinary incontinence (SUI).

Methods: A multicenter diagnostic cohort study with an embedded noninferiority randomized controlled trial was conducted in six academic and 24 nonacademic Dutch hospitals. Women with predominant SUI eligible for surgical treatment based on clinical assessment were included between January 2009 and November 2010.

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Laser acupuncture is a painless, non-invasive, and cost effective treatment for children with therapy resistant monosymptomatic nocturnal enuresis. This kind of acupuncture is an alternative treatment with positive results. Currently, we are treating 24 children (22 males, 2 females) out of a planned 200 children aged between 5 and 12 years.

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In a prospective study, from September 2000 to September 2001, all ureteroscopies ( n=140) were performed under local and intravenous patient controlled analgesia using continuous infusion of remifentanil (Ultiva). The dosage of 0.15 micro g/kg/min was adapted to changing intraoperative pain (range 0.

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Acute urinary retention in children may be associated with a broad spectrum of different causes. Acute appendicitis or acute ovarian torsion are rare and complicate the diagnosis. The case of a 6-year-old girl with urinary retention caused by ovarian torsion is reported, in which clinical presentation showed nonspecific complaints and ultrasound demonstrated a retrovesical mass.

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Purpose: We evaluated the results and complications of children with reflux treated with the Politano-Leadbetter ureteroneocystostomy. In particular, we evaluated pre- and postoperative renal parenchymal scarring and the late development of hypertension.

Materials And Methods: From 1965 through 1996, 666 children (814 renal units) were reimplanted by nine urologists.

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Three novel alkylphospholipid and four novel O-alkylglycerophospholipid derivatives of fludarabine (F-ara-AMP), known as a drug for the clinical treatment of chronic lymphocytic leukemia, were synthesized. The antiproliferative activity was determined in comparison to the parent nucleoside fludarabine in an immortalized but nontumorigenic human mammary epithelial cell line (H 184 A1N4), in two human breast tumor cell lines (MaTu and MCF7), and in two leukemic cell lines (HL 60 and Daudi). Fludarabine inhibited the growth of the leucemic cell lines very effectively.

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Purpose: Prepubic urethrectomy is a simple, safe alternative to perineal urethrectomy. The lithotomy position can be avoided and, thus, operative time and risk of deep venous thrombosis are decreased. We developed a simple modification because of difficulty in dissecting the bulbous urethra.

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The ability of four different antitumor phospholipids, 1-O-hexadecyl-2-chloro-2-deoxyglycero-3-phosphocholine (ET16CIPC), hexadecylphosphocholine (C16OPC), hexadecylphospho-L-serine analogs (C16OPS, C16OPS-N-Ac) and cytidine-5'-hexadecylphosphonophosphate (C16PCMP) to modulate the cytosolic Ca2+ concentration [Ca2+]i was studied in an immortalized human mammary epithelial cell line H184 A1N4. The compounds induced different modes of activity depending on their structure and concentration. ET16CIPC induced between 0.

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ara-Cytidine-5'-alkylphosphonophosphates and the corresponding -diphosphates were found to be cytostatically active in vitro against the human mammary epithelial cell line H184 A1N4 and the human mammary tumor cell line MaTu. Our results indicate that the replacement of the diphosphate by the phosphonophosphate group has no influence on antiproliferative activity in this case. The compounds were more active than the corresponding cytidine phospholipid conjugates and related compounds lacking a cytostatically active nucleoside, the ara-C prodrug Cytoros, and were slightly less active than ara-C.

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Recent studies have shown that phosphono analogs of cytidine-5'-diphosphate diacylglycerol (CDP-DAG) possessing a structurally modified lipid moiety exhibit antiproliferative activity in vitro. As an extension of our previous work we tried to elucidate whether the presence of the cytidine component is necessary for cytostatic activity. In this context we have synthesized similarly structured nucleoside-phospholipid conjugates containing nucleoside components other than cytidine, which also do not exhibit cytostatic properties as such.

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Antiproliferative alkyllysophospholipid (ALP) analogs produced multiple effects on the cytosolic Ca++ concentration ([Ca++]i) in an immortalized human breast epithelial cell line (H 184). The addition of small concentrations resulted in a short transient [Ca++]i response. With higher concentrations the transient rise was followed by a sustained increase.

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The chemical synthesis of cytidine-5'-alkyl- and cytidine-5'-alkyl (acyl)deoxyglycerophosphonophosphates is reported. The compounds obtained represent a novel class of cytostatically active agents based on phospholipids, which inhibit the growth of various tumor cell lines in vitro. They are phosphono analogs of the cytidine-5'-diphosphate-diacylglycerol (CDP-DAG) possessing a structurally modified lipid moiety and a phospholipase C-resistant P-C bond.

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