julilili42/papers huggingface dataset:
Kinematic response of ice-rise divides to changes in ocean and atmosphere forcing
2019-10-14

Abstract. The majority of Antarctic ice shelves are bounded by grounded ice rises. These ice rises exhibit local flow fields that partially oppose the flow of the surrounding ice shelves. Formation of ice rises is accompanied by a characteristic upward-arching internal stratigraphy (“Raymond arches”), whose geometry can be analysed to infer information about past ice-sheet changes in areas where other archives such as rock outcrops are missing. Here we present an improved modelling framework to study ice-rise evolution using a satellite-velocity calibrated, isothermal, and isotropic 3-D full-Stokes model including grounding-line dynamics at the required mesh resolution (&lt;500 m). This overcomes limitations of previous studies where ice-rise modelling has been restricted to 2-D and excluded the coupling between the ice shelf and ice rise. We apply the model to the Ekström Ice Shelf, Antarctica, containing two ice rises. Our simulations investigate the effect of surface mass balance and ocean perturbations onto ice-rise divide position and interpret possible resulting unique Raymond arch geometries. Our results show that changes in the surface mass balance result in immediate and sustained divide migration (&gt;2.0 m yr−1) of up to 3.5 km. In contrast, instantaneous ice-shelf disintegration causes a short-lived and delayed (by 60–100 years) response of smaller magnitude (&lt;0.75 m yr−1). The model tracks migration of a triple junction and synchronous ice-divide migration in both ice rises with similar magnitude but differing rates. The model is suitable for glacial/interglacial simulations on the catchment scale, providing the next step forward to unravel the ice-dynamic history stored in ice rises all around Antarctica.
Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles
2019-10-14

Abstract The genetic background of follicular lymphomas (FLs) diagnosed in advanced clinical stages III/IV, and which are frequently characterized by t(14;18), has been substantially unraveled. Molecular features, as exemplified in the clinicogenetic risk model m7FLIPI, are important tools in risk stratification. In contrast, little information is available concerning localized-stage FL (clinical stages I/II), which accounts for ∼20% of newly diagnosed FL in which the detection rate of t(14;18) is only ∼50%. To investigate the genetic background of localized-stage FL, patient cohorts with advanced-stage FL or localized-stage FL, uniformly treated within phase 3 trials of the German Low-Grade Lymphoma Study Group, were comparatively analyzed. Targeted gene expression (GE) profiling of 184 genes using nCounter technology was performed in 110 localized-stage and 556 advanced-stage FL patients. By penalized Cox regression, a prognostic GE signature could not be identified in patients with advanced-stage FL, consistent with results from global tests and univariate regression. In contrast, it was possible to define robust GE signatures discriminating localized-stage and advanced-stage FL (area under the curve, 0.98) by penalized logistic regression. Of note, 3% of samples harboring an “advanced-stage signature” in the localized-stage cohort exhibited inferior failure-free survival (hazard ratio [HR], 7.1; P = .0003). Likewise, in the advanced-stage cohort, 7% of samples with a “localized-stage signature” had prolonged failure-free survival (HR, 2.3; P = .017) and overall survival (HR, 3.4; P = .072). These data support the concept of a biological difference between localized-stage and advanced-stage FL that might contribute to the superior outcome of localized FL.
An extinction event in planktonic Foraminifera preceded by stabilizing selection
2019-10-14

Unless they adapt, populations facing persistent stress are threatened by extinction. Theoretically, populations facing stress can react by either disruption (increasing trait variation and potentially generating new traits) or stabilization (decreasing trait variation). In the short term, stabilization is more economical, because it quickly transfers a large part of the population closer to a new ecological optimum. However, stabilization is deleterious in the face of persistently increasing stress, because it reduces variability and thus decreases the ability to react to further changes. Understanding how natural populations react to intensifying stress reaching terminal levels is key to assessing their resilience to environmental change such as that caused by global warming. Because extinctions are hard to predict, observational data on the adaptation of populations facing extinction are rare. Here, we make use of the glacial salinity rise in the Red Sea as a natural experiment allowing us to analyse the reaction of planktonic Foraminifera to stress escalation in the geological past. We analyse morphological trait state and variation in two species across a salinity rise leading to their local extinction. Trilobatus sacculifer reacted by stabilization in shape and size, detectable several thousand years prior to extinction. Orbulina universa reacted by trait divergence, but each of the two divergent populations remained stable or reacted by further stabilization. These observations indicate that the default reaction of the studied Foraminifera is stabilization, and that stress escalation did not lead to the emergence of adapted forms. An inherent inability to breach the global adaptive threshold would explain why communities of Foraminifera and other marine protists reacted to Quaternary climate change by tracking their zonally shifting environments. It also means that populations of marine plankton species adapted to response by migration will be at risk of extinction when exposed to stress outside of the adaptive range.
Treatment and outcome of the patients with rhabdomyosarcoma of the biliary tree: Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS)
2019-10-14

Abstract Background Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The management of affected patients contains unique challenges because of the rarity of this tumor entity and its critical location at the porta hepatis, which can make achievement of a radical resection very difficult. Methods In a retrospective chart analysis we analysed children suffering from biliary RMS who were registered in three different CWS trials (CWS-96, CWS-2002P, and SoTiSaR registry). Results Seventeen patients (12 female, 5 male) with a median age of 4.3 years were assessed. The median follow-up was 42.2 months (10.7–202.5). The 5-year overall (OS) and event free survival (EFS) rates were 58% (45–71) and 47% (34–50), respectively. Patients &gt; 10 years of age and those with alveolar histology had the worst prognosis (OS 0%). Patients with botryoid histology had an excellent survival (OS 100%) compared to those with non-botryoid histology (OS 38%, 22–54, p = 0.047). Microscopic complete tumor resection was achieved in almost all patients who received initial tumor biopsy followed by chemotherapy and delayed surgery. Conclusion Positive predictive factors for survival of children with biliary RMS are age ≤ 10 years and botryoid tumor histology. Primary surgery with intention of tumor resection should be avoided.
A Facile Route toward Ceric Silylamide [Ce{N(SiHMe2)2}4]
2019-10-14

Treatment of the ate complex [Ce{N(SiHMe 2 ) 2 } 4 Li(thf)] with neutral donor molecules (do) gave several solvent(do)‐separated ion‐pair complexes of the composition [Ce{N(SiHMe 2 ) 2 } 4 ][Li(do) n ] (do = thf, pyridine, tmeda, dme, 12‐crown‐4). Their solid‐state structures have been analyzed by X‐ray diffraction and DRIFTS. Displacement of the [Li(do) n ] entity, resulting in a solvent‐separated ion pair with a symmetric environment around the Ce(III) center, was also revealed in solution by 7 Li NMR spectroscopy. The oxidation of [Ce{N(SiHMe 2 ) 2 } 4 ][Li(do) n ] with 1,4‐benzoquinone to afford homoleptic ceric [Ce{N(SiHMe 2 ) 2 } 4 ] has been investigated and screened. Overall, the separated ion pairs [Ce{N(SiHMe 2 ) 2 } 4 ][Li(do) n ] performed better than the intramolecular ate complex [Ce{N(SiHMe 2 ) 2 } 4 Li(thf)], with pyridine as donor giving the best results.
The Symmetry of Viral Sialic Acid Binding Sites–Implications for Antiviral Strategies
2019-10-14

Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number of diverse viruses. Structural biology research has helped to establish the molecular bases for many virus–sialic acid interactions. Due to the icosahedral 532 point group symmetry that underlies many viral capsids, the receptor binding sites are frequently arranged in a highly symmetric fashion and linked by five-fold, three-fold, or two-fold rotation axes. For the inhibition of viral attachment, one emerging strategy is based on developing multivalent sialic acid-based inhibitors that can simultaneously engage several of these binding sites, thus binding viral capsids with high avidity. In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors.
Immersive VR Experience of Redeveloped Post-industrial Sites: The Example of “Zeche Holland” in Bochum-Wattenscheid
2019-10-15

Abstract Modern hardware and software innovations in the field of virtual reality (VR), such as VR headsets and accessible game engines, allow cartographers to create 3D environments which can be experienced from the ego perspective in real time and with a simulated illusion of physical presence (immersion) in the virtual representation. The new immersive experience of these virtual environments requires new ideas on how to present and orchestrate geographical information for the benefit of planning applications. This paper intends to present examples how VR-based 3D environments use can be enriched (based on the game engine Unreal Engine 4) to support the district development of a restructured post-industrial area. A VR model of a representative former industrial area in the German Ruhr district which was revitalized and part of a large urban transformation programme (IBA Emscher Park), serves an example. Today, the area of “Zeche Holland” in Bochum-Wattenscheid is characterized by a mix of residential and commercial uses. The area is used as a leisure route for locals and tourists, with an old winding tower as an important urban landmark in its centre. VR techniques allow to transport additional spatial information which cannot be experienced when visiting the real physical area. This paper addresses the potential of immersive VR environments representing a multifaceted and redeveloped area for planning and related usage scenarios. It shows how peculiarities of game engine-based VR can help to extend the immersive (3D) experience of geographic information.
Effect-Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water
2019-10-15

Abstract Effect-based monitoring is increasingly applied to detect and—in conjunction with chemical analysis—to identify endocrine-disrupting compounds (EDCs) in the environment. Although this approach of effect-directed analysis has been successfully demonstrated for estrogenicity and androgenicity, data on progestogens and glucocorticoids driving endocrine disruption are quite limited. We investigated progestogenic and glucocorticoid activities in Danube River water receiving untreated wastewater from Novi Sad, Serbia. After a 2-step fractionation, all fractions were tested with reporter gene bioassays for agonistic and antagonistic hormonal responses at progestogenic and glucocorticoid hormone receptors as well as with target and nontarget analytical screening of active fractions by liquid chromatography–high-resolution mass spectrometry. Due to masking by cytotoxic mixture components, the effects could not be detected in the raw water extract but were unraveled only after fractionation. Target chemical screening of the fraction that was active in the progesterone receptor (PR) assay revealed that progesterone and megestrol acetate were predominant drivers of PR-mediated activity along with medroxyprogesterone, dihydrotestosterone, androsterone, and epiandrosterone. Hydrocortisone was detected at sub-ng/L concentration in the active fraction in the glucocorticoid receptor (GR) assay but could not explain a significant fraction of the observed GR activity. The present study indicates that effect-based monitoring is a powerful tool to detect EDCs in the aquatic environment but that fractionation may be required to avoid masking effects of mixture components. Future effect-directed analysis studies are required to better understand the occurrence of EDCs and masking compounds in different lipophilicity windows, to finally reduce fractionation requirements for monitoring to a smart clean-up. Environ Toxicol Chem 2019;39:189–199. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. Abstract Summary of the work flow of effect-directed analysis of wastewater-impacted Danube River water and the results specifying the main drivers of progestogenic effects.
Enriched Environmental Conditions Modify the Gut Microbiome Composition and Fecal Markers of Inflammation in Parkinson’s Disease
2019-10-15

Recent findings suggest an implication of the gut microbiome in Parkinson's disease (PD) patients. PD onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors. In this study, we used a mouse model, overexpressing the complete human SNCA gene (SNCA-TG mice) modeling familial and sporadic forms of PD to study whether environmental conditions such as standard <i>vs.</i> enriched environment changes the gut microbiome and influences disease progression. We performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and SNCA-TG mice kept under standard environment (SE) and enriched environment (EE) conditions. The overall composition of the gut microbiota was not changed in SNCA-TG mice compared with WT in EE with respect to SE. However, individual gut bacteria at genus level such as <i>Lactobacillus</i> sp. was a significant changed in the SNCA-TG mice. EE significantly reduced colon fecal inflammatory calprotectin protein in WT and SNCA-TG EE compared to SE. Moreover, EE reduces the pro-inflammatory cytokines in the feces and inflammation inducing genes in the colon. Our data suggest that an enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine and by modulating anti-inflammatory gut bacteria.
Invariant natural killer T cells are functionally impaired in patients with systemic sclerosis
2019-10-15

Abstract Background Systemic sclerosis (SSc) is a potentially fatal autoimmune disease that leads to extensive fibrosis of the skin and internal organs. Invariant natural killer T (iNKT) cells are potent immunoregulatory T lymphocytes being able to orchestrate dysregulated immune responses. The purpose of this study was to evaluate numbers and function of iNKT cells in patients with SSc and to analyze their correlation with disease parameters. Methods Human iNKT cells from 88 patients with SSc and 33 healthy controls were analyzed by flow cytometry. Their proliferative capacity and cytokine production were investigated following activation with CD1d ligand α-galactosylceramide (α-GalCer). Results We observed an absolute and relative decrease of iNKT cells in patients with SSc compared with healthy controls. Interestingly, the subtype of SSc, disease severity, or treatment with immunosuppressive drugs did not affect iNKT cell numbers. However, T helper (Th) cell immune polarization was biased towards a Th17 immunophenotype in SSc patients. Moreover, iNKT cells from patients with SSc showed a significantly decreased expansion capacity upon stimulation with α-GalCer. Conclusion iNKT cells are deficient and functionally impaired in patients with SSc. Therefore, adoptive transfer strategies using culture-expanded iNKT cells could be a novel approach to treat SSc patients.
C–H-Bond Activation and Isoprene Polymerization Studies Applying Pentamethylcyclopentadienyl-Supported Rare-Earth-Metal Bis(Tetramethylaluminate) and Dimethyl Complexes
2019-10-15

As previously shown for lutetium and yttrium, 1,2,3,4,5-pentamethylcyclopentadienyl (C5Me5 = Cp*)-bearing rare-earth metal dimethyl half-sandwich complexes [Cp*LnMe2]3 are now also accessible for holmium, dysprosium, and terbium via tetramethylaluminato cleavage of [Cp*Ln(AlMe4)2] with diethyl ether (Ho, Dy) and tert-butyl methyl ether (TBME) (Tb). C–H-bond activation and ligand redistribution reactions are observed in case of terbium and are dominant for the next larger-sized gadolinium, as evidenced by the formation of mixed methyl/methylidene clusters [(Cp*Ln)5(CH2)(Me)8] and metallocene dimers [Cp*2Ln(AlMe4)]2 (Ln = Tb, Gd). Applying TBME as a “cleaving” reagent can result in both TBME deprotonation and ether cleavage, as shown for the formation of the 24-membered macrocycle [(Cp*Gd)2(Me)(CH2OtBu)2(AlMe4)]4 or monolanthanum complex [Cp*La(AlMe4){Me3Al(CH2)OtBu}] and monoyttrium complex [Cp*Y(AlMe4)(Me3AlOtBu)], respectively. Complexes [Cp*Ln(AlMe4)2] (Ln = Ho, Dy, Tb, Gd) and [Cp*LnMe2]3 (Ln = Ho, Dy) are applied in isoprene and 1,3-butadiene polymerization, upon activation with borates [Ph3C][B(C6F5)4] and [PhNHMe2][B(C6F5)4], as well as borane B(C6F5)3. The trans-directing effect of AlMe3 in the binary systems [Cp*Ln(AlMe4)2]/borate is revealed and further corroborated by the fabrication of high-cis-1,4 polybutadiene (97%) with “aluminum-free” [Cp*DyMe2]3/[Ph3C][B(C6F5)4]. The formation of multimetallic active species is supported by the polymerization activity of pre-isolated cluster [(Cp*Ho)3Me4(CH2)(thf)2].
Physical activity promotion in daily exercise therapy: The perspectives of exercise therapists in German rehabilitation settings
2019-10-15

<title>Abstract</title> Abstract Background This study aims to explore exercise therapists’ perspectives on the topic of physical activity promotion (PAP) with a focus on identifying (i) the intervention content and methodological approaches used for promoting physical activity (PA) in daily practice and (ii) the barriers and facilitators that affect PAP. Methods This qualitative study comprised the heads of exercise therapy departments (n = 58; 41% women; mean age = 45 years) from different rehabilitation clinics in Germany. Each participant took part in a semi-structured focus-group discussion on PAP in exercise therapy. The findings of the focus groups were processed and interpreted using a conventional qualitative content analysis. Results The exercise therapists demonstrated detailed didactic–methodological strategies and action orientations for PAP. The identified core topics of the content and methods of PAP were (1) conceptualization, (2) exercise and PA for enjoyment and pleasure, (3) education with practice–theory combinations, (4) media and materials for self-directed training, and (5) strategies to enhance personal responsibility and independence. The core topics for the associated barriers and facilitators were (1) structural conditions, (2) the role of exercise therapists, (3) the interdisciplinary rehabilitation team, (4) rehabilitant experiences and expectations, and (5) aftercare services. Conclusion The topic of PAP is addressed with a high level of variability; exercise therapists involved in this study identify various methods and content for the promotion of PA within their individual practices. However, they display a limited awareness of existing evidence- and theory-based concepts for the promotion of PA as well as underlying theories of behavioural change. This variability may be due to the lack of a defined common framework for promoting PA, insufficient emphasis being placed on PA promotion in the current curricula and training, or extensive conceptual differences within German exercise therapy departments (e.g. different weighting of PAP).
Muscarinic receptors promote pacemaker fate at the expense of secondary conduction system tissue in zebrafish
2019-10-16

Deterioration or inborn malformations of the cardiac conduction system (CCS) interfere with proper impulse propagation in the heart and may lead to sudden cardiac death or heart failure. Patients afflicted with arrhythmia depend on antiarrhythmic medication or invasive therapy, such as pacemaker implantation. An ideal way to treat these patients would be CCS tissue restoration. This, however, requires precise knowledge regarding the molecular mechanisms underlying CCS development. Here, we aimed to identify regulators of CCS development. We performed a compound screen in zebrafish embryos and identified tolterodine, a muscarinic receptor antagonist, as a modifier of CCS development. Tolterodine provoked a lower heart rate, pericardiac edema, and arrhythmia. Blockade of muscarinic M3, but not M2, receptors induced transcriptional changes leading to amplification of sinoatrial cells and loss of atrioventricular identity. Transcriptome data from an engineered human heart muscle model provided additional evidence for the contribution of muscarinic M3 receptors during cardiac progenitor specification and differentiation. Taken together, we found that muscarinic M3 receptors control the CCS already before the heart becomes innervated. Our data indicate that muscarinic receptors maintain a delicate balance between the developing sinoatrial node and the atrioventricular canal, which is probably required to prevent the development of arrhythmia.