julilili42/papers huggingface dataset:
Large-scale mitogenomic analysis of the phylogeography of the Late Pleistocene cave bear
2019-08-15

Abstract The cave bear ( Ursus spelaeus ) is one of the Late Pleistocene megafauna species that faced extinction at the end of the last ice age. Although it is represented by one of the largest fossil records in Europe and has been subject to several interdisciplinary studies including palaeogenetic research, its fate remains highly controversial. Here, we used a combination of hybridisation capture and next generation sequencing to reconstruct 59 new complete cave bear mitochondrial genomes (mtDNA) from 14 sites in Western, Central and Eastern Europe. In a Bayesian phylogenetic analysis, we compared them to 64 published cave bear mtDNA sequences to reconstruct the population dynamics and phylogeography during the Late Pleistocene. We found five major mitochondrial DNA lineages resulting in a noticeably more complex biogeography of the European lineages during the last 50,000 years than previously assumed. Furthermore, our calculated effective female population sizes suggest a drastic cave bear population decline starting around 40,000 years ago at the onset of the Aurignacian, coinciding with the spread of anatomically modern humans in Europe. Thus, our study supports a potential significant human role in the general extinction and local extirpation of the European cave bear and illuminates the fate of this megafauna species.
Conductance Model for Single-Crystalline/Compact Metal Oxide Gas-Sensing Layers in the Nondegenerate Limit: Example of Epitaxial SnO2(101)
2019-08-15

Semiconducting metal oxide (SMOX)-based gas sensors are indispensable for safety and health applications, for example, explosive, toxic gas alarms, controls for intake into car cabins, and monitor for industrial processes. In the past, the sensor community has been studying polycrystalline materials as sensors where the porous and random microstructure of the SMOX does not allow a separation of the phenomena involved in the sensing process. This led to conduction models that can model and predict the behavior of the overall response, but they were not capable of giving fundamental information regarding the basic mechanisms taking place. The study of epitaxial layers is a definite improvement, allowing clarifying the different aspects and contributions of the sensing mechanisms. A detailed analytical model of the transduction function for n- and p-type single-crystalline/compact metal oxide gas sensors was developed that directly relates the conductance of the sample with changes in the surface electrostatic potential. Combined dc resistance and work function measurements were used in a compact SnO<sub>2</sub>(101) layer in operando conditions that allowed us to check the validity of our model in the region where Boltzmann approximation holds to determine the surface and bulk properties of the material.
A real-time ex vivo model (eIBUB) for optimizing intraperitoneal drug delivery as an alternative to living animal models
2019-08-15

Abstract Background Optimization of intraperitoneal drug delivery systems requires functional models. We proposed the Inverted Bovine Urinary Bladder Model (IBUB), but IBUB does not allow repeated measurements over time and there is a significant biological variability between organs. Methods A further development of IBUB is presented, based on the physical principle of communicating vessels. Fresh bovine bladders were inverted so that the peritoneum lines up the inner surface. The IBUB and a second vessel were then interconnected under the same CO 2 pressure and placed on two scales. The therapeutic solution (Doxorubicin 2.7 mg and Cisplatin 13.5 mg) was delivered via an aerosolizer. All experiments were in triplicate and blinded to the origin of samples, measurements in a GLP-certified laboratory. Results The enhanced IBUB (eIBUB) model allows measurements of tissue drug concentration, depth of tissue penetration and spatial distribution. The homogeneous morphology of the peritoneum enables standardized, multiple tissue sampling. eIBUB minimizes biological variability between different bladders and eliminates the bias caused by the liquid collecting at the bottom of the model. Concentration of doxorubicin in the eIBUB (mean ± STDV: 18.5 ± 22.6 ng/mg) were comparable to clinical peritoneal biopsies (19.2 ± 38.6 ng/mg), as was depth of drug penetration (eIBUB: mean (min-max) 433 (381–486) μm, clinical ~ 500 μm). Conclusions The eIBUB model is a simple and powerful ex vivo model for optimizing intraperitoneal drug delivery and represents an attractive alternative to animal models. Results obtained are similar to those obtained in the human patient.
Factor endowments on the ‘frontier’: Algerian settler agriculture at the beginning of the 1900s
2019-08-15

Abstract This article examines rural settlement in Constantine, a département in French Algeria, at the beginning of the 1900s. By taking into account the timing of colonial settlement for almost 100 municipalities, it shows how the changing geographical conditions and the relative quantities of land and labour shaped the colonial land policy and settler modes of production. As fertile land grew scarcer on the settlement ‘frontier’, the ability of settlers to participate in the export market was increasingly dependent on the capacity to make use of modern agricultural techniques that required larger fields and intensive labour. Thus, the outcome of rural settlement was determined by the relative abundance of indigenous labour and the adaptation of the land policy to Algeria's agricultural needs. The results demonstrate that—even within a country itself and during the settlement process—the colonial land policy and settler modes of production change significantly, depending on the region being occupied.
Ni(NHC) Catalyzed Rearrangement of 1‐Acyl‐2‐vinylcyclopropanes: Tackling a Mechanistic Puzzle by Combined Experimental and Computational Studies
2019-08-15

The Ni(NHC) catalyzed rearrangement of 1‐acyl‐2‐vinylcyclopropanes to the corresponding 4‐acyl‐cyclopent‐1‐enes is highly promising for the synthesis of keto‐functionalized annelated bi‐ and tricyclic subunits of natural products. Therefore, we investigated the catalytic activity of Ni(NHC) complexes in the rearrangement of 1‐acyl‐2‐vinylcyclopropanes with different ring sizes and substitution patterns. Surprising effects regarding substrate scope and stereoselectivity of the Ni(NHC) catalyzed vinylcyclopropane‐cyclopentene rearrangement were observed. Only vinylcyclopropanes with 1‐methyl, 1‐phenyl, 1,2‐dialkyl or 2‐phenyl‐substitution at the vinyl moiety could be rearranged successfully. Moreover, an endo ‐configuration on the cyclopropane ring was required for successful rearrangement. By treatment of the vinylcyclopropanes with Rh catalysts or Lewis acids, the involvement of Lewis acid catalysis could be ruled out. In order to understand these experimental results and to rationalize the reactivity of the Ni(NHC) complexes computational studies were performed, which provided insights into mechanistic details.
Common variants in breast cancer risk loci predispose to distinct tumor subtypes
2019-08-15

Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER), but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate &lt;5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at P&lt;0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Effects of forest management on the phenology of early-flowering understory herbs
2019-08-15

Abstract Many organisms respond to anthropogenic environmental change through shifts in their phenology. In plants, flowering is largely driven by temperature, and therefore affected by climate change. However, on smaller scales climatic conditions are also influenced by other factors, including habitat structure. A group of plants with a particularly distinct phenology are the understorey herbs in temperate forests. In these forests, management alters tree species composition and stand structure and, as a consequence, light conditions and microclimate. Forest management should thus also affect the phenology of understorey herbs. To test this, we recorded the flowering phenology of 20 early-flowering herbs on 100 forest plots varying in management intensity, from near-natural to intensely managed forests, in Central and Southern Germany. We found that in forest stands with a high management intensity the plants flowered on average about two weeks later than in unmanaged forests. This was largely because management also affected microclimate (e.g. spring temperatures of 5.9 °C in managed coniferous, 6.7 in managed deciduous and 7.0 °C in unmanaged deciduous plots), which in turn affected phenology, with plants flowering later on colder and moister forest stands (+4.5 days per −1°C and 2.7 days per 10 % humidity increase). Among forest characteristics, the main tree species as well as the age, overall crown projection area, structural complexity and spatial distribution of trees had the greatest influence on microclimate. Our study demonstrates that forest management alters plant phenology, with potential far-reaching consequences for the ecology and evolution of understorey communities. More generally, our study suggests that besides climate change other drivers of environmental change, too, can influence the phenology of organisms.
Geographical variation of the merging between dental and retroflex sibilants in Taiwan Mandarin
2019-08-15

This study investigates the geographical distribution of pronunciation variation of voiceless dental and retroflex sibilants in Taiwan Mandarin. Previous studies indicated that the merging of the two sibi- lants is geographically dependent [17, 6]. How- ever, the geographical effects in these studies are not easy to interpret due to the limited number of speakers and regions. For the current study, we recruited 331 native speakers of Taiwan Mandarin from 120 regions in Taiwan. In a picture-naming task, 30 dental/retroflex-initial words were elicited from each speaker. The data were analysed with Generalized Additive Mixed models [26]. The anal- ysis revealed a robust effect of geographical loca- tion, with merging being less common in metropoli- tan cities as compared to the surrounding areas.
EPIFANY – A method for efficient high-confidence protein inference
2019-08-15

Abstract Accurate protein inference under the presence of shared peptides is still one of the key problems in bottom-up proteomics. Most protein inference tools employing simple heuristic inference strategies are efficient, but exhibit reduced accuracy. More advanced probabilistic methods often exhibit better inference quality but tend to be too slow for large data sets. Here we present a novel protein inference method, EPIFANY, combining a loopy belief propagation algorithm with convolution trees for efficient processing of Bayesian networks. We demonstrate that EPIFANY combines the reliable protein inference of Bayesian methods with significantly shorter runtimes. On the 2016 iPRG protein inference benchmark data EPIFANY is the only tested method which finds all true-positive proteins at a 5% protein FDR without strict pre-filtering on PSM level, yielding an increase in identification performance (+10% in the number of true positives and +35% in partial AUC) compared to previous approaches. Even very large data sets with hundreds of thousands of spectra (which are intractable with other Bayesian and some non-Bayesian tools) can be processed with EPIFANY within minutes. The increased inference quality including shared peptides results in better protein inference results and thus increased robustness of the biological hypotheses generated. EPIFANY is available as open-source software for all major platforms at https://OpenMS.de/epifany .
Physical activity promotion in daily exercise therapy: The perspectives of exercise therapists in German rehabilitation settings
2019-08-15

Abstract 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).
Black holes, gravitational waves and fundamental physics: a roadmap
2019-08-16

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis
2019-08-16

Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental <i>in vivo</i> mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice <i>in vivo</i> ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.
Treatment options for postural instability and gait difficulties in Parkinson’s disease
2019-08-16

<b>Introduction</b>: Gait and balance disorders in Parkinson's disease (PD) represent a major therapeutic challenge as frequent falls and freezing of gait impair quality of life and predict mortality. Limited dopaminergic therapy responses implicate non-dopaminergic mechanisms calling for alternative therapies.<b>Areas covered</b>: The authors provide a review that encompasses pathophysiological changes involved in axial motor impairments in PD, pharmacological approaches, exercise, and physical therapy, improving physical activity levels, invasive and non-invasive neurostimulation, cueing interventions and wearable technology, and cognitive interventions.<b>Expert opinion</b>: There are many promising therapies available that, to a variable degree, affect gait and balance disorders in PD. However, not one therapy is the 'silver bullet' that provides full relief and ultimately meaningfully improves the patient's quality of life. Sedentariness, apathy, and emergence of frailty in advancing PD, especially in the setting of medical comorbidities, are perhaps the biggest threats to experience sustained benefits with any of the available therapeutic options and therefore need to be aggressively treated as early as possible. Multimodal or combination therapies may provide complementary benefits to manage axial motor features in PD, but selection of treatment modalities should be tailored to the individual patient's needs.
Species composition of arbuscular mycorrhizal communities changes with elevation in the Andes of South Ecuador
2019-08-16

Arbuscular mycorrhizal fungi (AMF) are the most prominent mycobionts of plants in the tropics, yet little is known about their diversity, species compositions and factors driving AMF distribution patterns. To investigate whether elevation and associated vegetation type affect species composition, we sampled 646 mycorrhizal samples in locations between 1000 and 4000 m above sea level (masl) in the South of Ecuador. We estimated diversity, distribution and species compositions of AMF by cloning and Sanger sequencing the 18S rDNA (the section between AML1 and AML2) and subsequent derivation of fungal OTUs based on 99% sequence similarity. In addition, we analyzed the phylogenetic structure of the sites by computing the mean pairwise distance (MPD) and the mean nearest taxon difference (MNTD) for each elevation level. It revealed that AMF species compositions at 1000 and 2000 masl differ from 3000 and 4000 masl. Lower elevations (1000 and 2000 masl) were dominated by members of Glomeraceae, whereas Acaulosporaceae were more abundant in higher elevations (3000 and 4000 masl). Ordination of OTUs with respect to study sites revealed a correlation to elevation with a continuous turnover of species from lower to higher elevations. Most of the abundant OTUs are not endemic to South Ecuador. We also found a high proportion of rare OTUs at all elevations: 79-85% of OTUs occurred in less than 5% of the samples. Phylogenetic community analysis indicated clustering and evenness for most elevation levels indicating that both, stochastic processes and habitat filtering are driving factors of AMF community compositions.
Peripheral PD-1+CD56+ T-cell frequencies correlate with outcome in stage IV melanoma under PD-1 blockade
2019-08-16

Immune checkpoint blockade with anti-PD-1 antibodies is showing great promise for patients with metastatic melanoma and other malignancies, but despite good responses by some patients who achieve partial or complete regression, many others still do not respond. Here, we sought peripheral blood T-cell biomarker candidates predicting treatment outcome in 75 stage IV melanoma patients treated with anti-PD-1 antibodies. We investigated associations with clinical response, progression-free survival (PFS) and overall survival (OS). Univariate analysis of potential biological confounders and known biomarkers, and a multivariate model, was used to determine statistical independence of associations between candidate biomarkers and clinical outcomes. We found that a lower than median frequency of peripheral PD-1+CD56+ T-cells was associated with longer OS (p = 0.004), PFS (p = 0.041) and superior clinical benefit (p = 0.009). However, neither frequencies of CD56-CD4+ nor CD56-CD8+ T-cells, nor of the PD-1+ fraction within the CD4 or CD8 subsets was associated with clinical outcome. In a multivariate model with known confounders and biomarkers only the M-category (HR, 3.11; p = 0.007) and the frequency of PD-1+CD56+ T-cells (HR, 2.39; p = 0.028) were identified as independent predictive factors for clinical outcome under PD-1 blockade. Thus, a lower than median frequency of peripheral blood PD-1+CD56+ T-cells prior to starting anti-PD-1 checkpoint blockade is associated with superior clinical response, longer PFS and OS of stage IV melanoma patients.