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53 result(s) for "Wieser, Christoph"
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Birth of a comet magnetosphere: A spring of water ions
The Rosetta mission shall accompany comet 67P/Churyumov-Gerasimenko from a heliocentric distance of >3.6 astronomical units through perihelion passage at 1.25 astronomical units, spanning low and maximum activity levels. Initially, the solar wind permeates the thin comet atmosphere formed from sublimation, until the size and plasma pressure of the ionized atmosphere define its boundaries: A magnetosphere is born. Using the Rosetta Plasma Consortium ion composition analyzer, we trace the evolution from the first detection of water ions to when the atmosphere begins repelling the solar wind (~3.3 astronomical units), and we report the spatial structure of this early interaction. The near-comet water population comprises accelerated ions (<800 electron volts), produced upstream of Rosetta, and lower energy locally produced ions; we estimate the fluxes of both ion species and energetic neutral atoms.
Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment
Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.
Topo-Bathymetric LiDAR for Monitoring River Morphodynamics and Instream Habitats—A Case Study at the Pielach River
Airborne LiDAR Bathymetry (ALB) has been rapidly evolving in recent years and now allows fluvial topography to be mapped in high resolution (>20 points/m2) and height accuracy (<10 cm) for both the aquatic and the riparian area. This article presents methods for enhanced modeling and monitoring of instream meso- and microhabitats based on multitemporal data acquisition. This is demonstrated for a near natural reach of the Pielach River, with data acquired from April 2013 to October 2014, covering two flood events. In comparison with topographic laser scanning, ALB requires a number of specific processing steps. We present, firstly, a novel approach for modeling the water surface in the case of sparse water surface echoes and, secondly, a strategy for improved filtering and modeling of the Digital Terrain Model of the Watercourse (DTM-W). Based on the multitemporal DTM-W we discuss the massive changes of the fluvial topography exhibiting deposition/erosion of 103 m3 caused by the 30-years flood event in May 2014. Furthermore, for the first time, such a high-resolution data source is used for monitoring of hydro-morphological units (mesohabitat scale) including the consequences for the target fish species nase (Chondrostoma nasus, microhabitat scale). The flood events caused a spatial displacement of the hydro-morphological units but did not effect their overall frequency distribution, which is considered an important habitat feature as it documents resilience against disturbances.
NAD metabolism fuels human and mouse intestinal inflammation
ObjectiveNicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated in inflammation including IBD and counteracts an increased cellular NAD turnover mediated by NAD-depleting enzymes. These constitute an important mechanistic link between inflammatory, metabolic and transcriptional pathways and NAD metabolism.DesignWe investigated the impact of NAMPT inhibition by the small-molecule inhibitor FK866 in the dextran sulfate sodium (DSS) model of colitis and the azoxymethane/DSS model of colitis-associated cancer. The impact of NAD depletion on differentiation of mouse and human primary monocytes/macrophages was studied in vitro. Finally, we tested the efficacy of FK866 compared with dexamethasone and infliximab in lamina propria mononuclear cells (LPMNC) isolated from patients with IBD.ResultsFK866 ameliorated DSS-induced colitis and suppressed inflammation-associated tumorigenesis in mice. FK866 potently inhibited NAMPT activity as demonstrated by reduced mucosal NAD, resulting in reduced abundances and activities of NAD-dependent enzymes including PARP1, Sirt6 and CD38, reduced nuclear factor kappa B activation, and decreased cellular infiltration by inflammatory monocytes, macrophages and activated T cells. Remarkably, FK866 effectively supressed cytokine release from LPMNCs of patients with IBD. As FK866 was also effective in Rag1−⁄− mice, we mechanistically linked FK866 treatment with altered monocyte/macrophage biology and skewed macrophage polarisation by reducing CD86, CD38, MHC-II and interleukin (IL)-6 and promoting CD206, Egr2 and IL-10.ConclusionOur data emphasise the importance of NAD immunometabolism for mucosal immunity and highlight FK866-mediated NAMPT blockade as a promising therapeutic approach in acute intestinal inflammation.
Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients
Background Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment. Objective The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort. Methods Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan–Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival. Results A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM ( p  < 0.001). The median disease-specific survival was 99 months (95% confidence interval 60–138) and 19 months (95% confidence interval 16–22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant. Conclusions The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.
Array programming with NumPy
Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves 1 and in the first imaging of a black hole 2 . Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis. NumPy is the primary array programming library for Python; here its fundamental concepts are reviewed and its evolution into a flexible interoperability layer between increasingly specialized computational libraries is discussed.
Gynecologic Malignancies in Children and Adolescents: How Common is the Uncommon?
The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls ≤18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan–Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5–18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0–4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0–18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.
Interfragmentary compression in a feline sacroiliac luxation model: biomechanical comparison of cannulated compression headless screws and cortical screws applied in positional or lag fashion
Background The purpose of this study was to compare the efficacy of cannulated compression headless screws (CCHS) with cortical positional and lag screws in generating interfragmentary compression in a simulated feline sacroiliac luxation fracture (SILF) model. In this ex vivo biomechanical study thirty-six cadavers of adult domestic short-haired cats with simulated unilateral SILF were allocated to three groups. Pressure mapping sensors were inserted into the joint space prior to fracture reduction. The SILF models were stabilized with 2.5 mm CCHS ( n  = 12), 2.4 mm cortical position ( n  = 12) or lag screws ( n  = 12), each spanning 60% of the sacral width. Total force (N), area of compression (mm 2 ) and total pressure (N/mm 2 ) were recorded and compared between the three groups. Pairwise comparison (Dunn for Kruskal-Wallis, Student’s t-tests for Fisher’s ANOVA) determined post-hoc differences between groups. Results Total force ( p  = 0.23), area of compression ( p  = 0.62) and total pressure ( p  = 0.22) did not differ significantly between the three groups. Conclusion No statistically significant differences in interfragmentary compression were observed among the three screw types under the specific ex vivo static testing conditions used in the feline SILF model. These findings challenge the current recommendation for using compression screws in feline SILF from a biomechanical perspective.