julilili42/papers huggingface dataset:
Whither systems medicine?
2018-03-01

New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails. Based on our analysis of current developments in medicine and healthcare and associated research needs, we emphasize the role of systems medicine as a multilevel and multidisciplinary methodological framework for informed data acquisition and interdisciplinary data analysis to extract previously inaccessible knowledge for the benefit of patients.
Phylogeny, biogeography and diversification patterns of side-necked turtles (Testudines: Pleurodira)
2018-03-01

Pleurodires or side-necked turtles are today restricted to freshwater environments of South America, Africa–Madagascar and Australia, but in the past they were distributed much more broadly, being found also on Eurasia, India and North America, and marine environments. Two hypotheses were proposed to explain this distribution; in the first, vicariance would have shaped the current geographical distribution and, in the second, extinctions constrained a previously widespread distribution. Here, we aim to reconstruct pleurodiran biogeographic history and diversification patterns based on a new phylogenetic hypothesis recovered from the analysis of the largest morphological dataset yet compiled for the lineage, testing which biogeographical process prevailed during its evolutionary history. The resulting topology generally agrees with previous hypotheses of the group and shows that most diversification shifts were related to the exploration of new niches, e.g. littoral or marine radiations. In addition, as other turtles, pleurodires do not seem to have been much affected by either the Cretaceous–Palaeogene or the Eocene–Oligocene mass extinctions. The biogeographic analyses highlight the predominance of both anagenetic and cladogenetic dispersal events and support the importance of transoceanic dispersals as a more common driver of area changes than previously thought, agreeing with previous studies with other non-turtle lineages.
Onchocerca volvulus infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of Simulium damnosum s.l. vector control and mass drug administration of ivermectin
2018-03-01

In the northern and central river basins in Togo, interruption of O. volvulus transmission has not yet been attained. Patent O. volvulus infections, positive antibody responses, progressive ocular onchocerciasis were diagnosed, and parasite transmission by S. damnosum s.l. occurred close to the survey locations. Future interventions may require approaches selectively targeted to non-complying endemic populations, to the seasonality of parasite transmission and national onchocerciasis control programs should harmonize cross-border MDA as a coordinated intervention.
Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli
2018-03-01

Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M. bovis AF2122/97 and M. tuberculosis H37Rv at both the global transcriptional and the translational level via RNA-sequencing and SWATH MS. Furthermore, a bovine alveolar macrophage infection time course model was used to investigate the shared and divergent host transcriptomic response to infection with M. tuberculosis H37Rv or M. bovis AF2122/97. Significant differential expression of virulence-associated pathways between the two bacilli was revealed, including the ESX-1 secretion system. A divergent transcriptional response was observed between M. tuberculosis H37Rv and M. bovis AF2122/97 infection of bovine alveolar macrophages, in particular cytosolic DNA-sensing pathways at 48 h post-infection, and highlights a distinct engagement of M. bovis with the bovine innate immune system. The work presented here therefore provides a basis for the identification of host innate immune mechanisms subverted by virulent host-adapted mycobacteria to promote their survival during the early stages of infection.
The Evolution of GX 339-4 in the Low-hard State as Seen by NuSTAR and Swift
2018-03-01

Abstract We analyze 11 Nuclear Spectroscopic Telescope Array and Swift observations of the black hole X-ray binary GX 339–4 in the hard state, 6 of which were taken during the end of the 2015 outburst and 5 during a failed outburst in 2013. These observations cover luminosities from 0.5% to 5% of the Eddington luminosity. Implementing the most recent version of the reflection model relxillCp , we perform simultaneous spectral fits on both data sets to track the evolution of the properties in the accretion disk, including the inner edge radius, the ionization, and the temperature of the thermal emission. We also constrain the photon index and electron temperature of the primary source (the “corona”). We observe a maximum truncation radius of 37 R g in the preferred fit for the 2013 data set, and a marginal correlation between the level of truncation and luminosity. We also explore a self-consistent model under the framework of coronal Comptonization, and find consistent results regarding the disk truncation in the 2015 data, providing a more physical preferred fit for the 2013 observations.
Subcellular Compartmentation of Alternatively Spliced Transcripts Defines SERINE/ARGININE-RICH PROTEIN30 Expression
2018-03-01

Alternative splicing (AS) is prevalent in higher eukaryotes, and generation of different AS variants is tightly regulated. Widespread AS occurs in response to altered light conditions and plays a critical role in seedling photomorphogenesis, but despite its frequency and effect on plant development, the functional role of AS remains unknown for most splicing variants. Here, we characterized the light-dependent AS variants of the gene encoding the splicing regulator Ser/Arg-rich protein SR30 in Arabidopsis (<i>Arabidopsis thaliana</i>). We demonstrated that the splicing variant <i>SR30.2</i>, which is predominantly produced in darkness, is enriched within the nucleus and strongly depleted from ribosomes. Light-induced AS from a downstream 3' splice site gives rise to <i>SR30.1</i>, which is exported to the cytosol and translated, coinciding with SR30 protein accumulation upon seedling illumination. Constitutive expression of SR30.1 and SR30.2 fused to fluorescent proteins revealed their identical subcellular localization in the nucleoplasm and nuclear speckles. Furthermore, expression of either variant shifted splicing of a genomic <i>SR30</i> reporter toward <i>SR30.2</i>, suggesting that an autoregulatory feedback loop affects <i>SR30</i> splicing. We provide evidence that <i>SR30.2</i> can be further spliced and, unlike <i>SR30.2</i>, the resulting cassette exon variant <i>SR30.3</i> is sensitive to nonsense-mediated decay. Our work delivers insight into the complex and compartmentalized RNA processing mechanisms that control the expression of the splicing regulator SR30 in a light-dependent manner.
MY English: a social constructivist perspective on ELF
2018-03-01

Abstract In this article, I address issues, concepts and empirical insights that have profoundly shaped my view of English as a lingua franca (ELF) and of the pedagogical lessons to be learned for English Language Teaching (ELT). Starting from discrepancies in my ELF identity as a speaker of English with ELT roots in a German secondary school, I argue for the social constructivist concept of MY English as a basis for understanding ELF competence development and the tensions surrounding the relationship between ELT and ELF. Continually shaped by speakers’ participation in ELF communication, relevant dimensions of their MY English profiles include linguistic-communicative-communal repertoires and requirements of performance, individual and social identity orientations, and confidence in their ELF creativity. Against this backdrop, I discuss topics I consider relevant for a much-needed pedagogical reconciliation of ELT with ELF. Special attention is given to teachers’ ELF apprehension and the distinction between a “strict” (quasi-behaviouristic) and an “open” (social constructivist) target language orientation, speaker satisfaction as a criterion of success in ELF communication, and teaching towards ELF competence from awareness raising to comprehension, production and interaction to non-native speaker emancipation. Successful ELF implementation in both ELT practice and ELT teacher education requires extensive and authentic involvement of students and teachers in ELF communication. Intercultural telecollaboration provides innovative means for creating a space for ELF communication in the ELT classroom. Pedagogical case studies about video and text chat conversations strongly support the assumption that using their common target language as a lingua franca significantly enables learners of English to develop an emancipated non-native speaker identity and thus to become speakers of English in their own right. And what is more, the pedagogical lingua franca approach can be successfully transferred to other foreign target languages as well. I conclude my article with a brief contextualization of the MY English concept in relation to translingual practice and ELF languaging.
CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival
2018-03-01

Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line.We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74<sup>high</sup> and TIL<sup>high</sup> tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected.In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.
Update Breast Cancer 2018 (Part 2) – Advanced Breast Cancer, Quality of Life and Prevention
2018-03-01

Abstract The treatment of metastatic breast cancer has become more complicated due to increasing numbers of new therapies which need to be tested. Therapies are now being developed to treat special clinical or molecular subgroups. Even though intrinsic molecular subtypes play a major role, more and more new therapies for subgroups and histological subtypes are being developed, such as the use of PARP inhibitors to treat patients with BRCA mutations (breast and ovarian cancer). Supportive therapies are also evolving, allowing problems such as alopecia or nausea and vomiting to be treated more effectively. Treatment-related side effects have a direct impact on the prognosis of patients with metastatic breast cancer, and supportive therapy can improve compliance. Digital tools could be useful to establish better patient management systems. This overview provides an insight into recent trials and how the findings could affect routine treatment. Current aspects of breast cancer prevention are also presented.
Update Breast Cancer 2018 (Part 1) – Primary Breast Cancer and Biomarkers
2018-03-01

Abstract This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.
Characterization and Management of Borderline Ovarian Tumors – Results of a Retrospective, Single-center Study of Patients Treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald
2018-03-01

Our study critically demonstrated that until a few years ago, BOTs were not usually treated according to international therapy recommendations. Nevertheless, the rate of tumor recurrence was very low.
Triggering the Activation of Main-belt Comets: The Effect of Porosity
2018-03-01

Abstract It has been suggested that the comet-like activity of Main-belt comets (MBCs) is due to the sublimation of sub-surface water-ice that is exposed when these objects are impacted by meter-sized bodies. We recently examined this scenario and showed that such impacts can, in fact, excavate ice and present a plausible mechanism for triggering the activation of MBCs. However, because the purpose of that study was to prove the concept and identify the most viable ice-longevity model, the porosity of the object and the loss of ice due to the heat of impact were ignored. In this paper, we extend our impact simulations to porous materials and account for the loss of ice due to an impact. We show that for a porous MBC, impact craters are deeper, reaching to ∼15 m, implying that if the activation of MBCs is due to the sublimation of sub-surface ice, this ice has to be within the top 15 m of the object. Results also indicate that the loss of ice due to the heat of impact is negligible, and the re-accretion of ejected ice is small. The latter suggests that the activities of current MBCs are most probably from multiple impact sites. Our study also indicates that for sublimation from multiple sites to account for the observed activity of the currently known MBCs, the water content of MBCs (and their parent asteroids) needs to be larger than the values traditionally considered in models of terrestrial planet formation.
Haves and Have nots must find a better way: The case for Open Scientific Hardware
2018-03-01

Although many efforts are being made to make science more open and accessible, they aremostly concentrated on issues that appear before and after experiments are performed: Open accessjournals, open databases for data and code sharing, and many other tools to increase replicability ofscience and access to information. While great, these initiatives do not directly increase the access tothe scientific equipment necessary to perform experiments and to generate new data. Unfortunately,their availability has always been uneven around the world, mostly due to monetary constraints andaffecting mostly low income countries and institutions. In this paper a case is made for the use offree/open source hardware in research and education even in countries and institutions where fundswere never a problem.
Novel Ligands for Platelet Glycoprotein VI
2018-03-01

Platelet hyperreactivity is a major risk factor for thrombo-ischaemic events such as myocardial infarction and stroke.[1] Antiplatelet therapy has substantially improved morbidity and mortality in patients with acute and chronic cardiovascular diseases. In patients with high risk for thrombo-ischaemic events, dual-antiplatelet therapy (DAPT) consisting of acetyl salicylic acid and P2Y12 inhibitors has become the standard antithrombotic therapy for secondary prevention.[2] However, current antiplatelet therapy (especially with DAPT) is associated with increased bleeding complications, which is associated with various clinical risk factors[3] [4] but also with enhanced mortality.[5]
Is Mistletoe Treatment Beneficial in Invasive Breast Cancer? A New Approach to an Unresolved Problem
2018-03-01

Based on a "similar case" model we did not observe any differences in the overall survival (OS), recurrence-free survival (RFS), and quality of life data between breast cancer patients with standard treatment and those who in addition to standard treatment received ML-I treatment.
Will People Like Your Image? Learning the Aesthetic Space
2018-03-01

Rating how aesthetically pleasing an image appears is a highly complex matter and depends on a large number of different visual factors. Previous work has tackled the aesthetic rating problem by ranking on a 1-dimensional rating scale, e.g., incorporating handcrafted attributes. In this paper, we propose a rather general approach to automatically map aesthetic pleasingness with all its complexity into an "aesthetic space" to allow for a highly fine-grained resolution. In detail, making use of deep learning, our method directly learns an encoding of a given image into this high-dimensional feature space resembling visual aesthetics. Additionally to the mentioned visual factors, differences in personal judgments have a large impact on the likeableness of a photograph. Nowadays, online platforms allow users to "like" or favor certain content with a single click. To incorporate a huge diversity of people, we make use of such multi-user agreements and assemble a large data set of 380K images (AROD) with associated meta information and derive a score to rate how visually pleasing a given photo is. We validate our derived model of aesthetics in a user study. Further, without any extra data labeling or handcrafted features, we achieve state-of-the art accuracy on the AVA benchmark data set. Finally, as our approach is able to predict the aesthetic quality of any arbitrary image or video, we demonstrate our results on applications for resorting photo collections, capturing the best shot on mobile devices and aesthetic key-frame extraction from videos.
Knowledge Spaces in VR: Intuitive Interfacing with a Multiperspective Hypermedia Environment
2018-03-01

Virtual reality technologies, along with motion based input devices allow for the design of innovative interfaces between learners and digital knowledge resources. These interfaces might facilitate knowledge work in educational and scientific contexts. Compared to 2D interfaces, immersive 3D environments provide greater flexibility regarding the interface design, however, so far no general, theory-driven and validated design principles are available. Seeing that complex learning environments can foster the development of various cognitive abilities, like multiperspective reasoning skills (MPRS), such design principles are highly desirable. Using multiperspective hypermedia environments (MHEs) as a testbed, the presented project aims to identify and evaluate design principles, derived from cognitive science. We will create and study interactive, immersive 3D-interface to MHEs using virtual reality technology. To evaluate the developed system, we will contrast the acquisition of MPRS in 2D and 3D learning environments. We expect that the developed design principles will be directly applicable for enhancing the accessibility of other knowledge environments.
Advancing source-level timing simulation using loop acceleration
2018-03-01

Source-level timing simulation (STLS) is an important technique for early examination of timing behavior, as it is very fast and accurate. A factor occasionally more important than precision is simulation speed, especially in design space exploration or very early phases of development. Additionally, practices like rapid prototyping also benefit from high-performance timing simulation. Therefore, we propose to further reduce simulation run-time by utilizing a method called loop acceleration. Accelerating a loop in the context of SLTS means deriving the timing of a loop prior to simulation to increase simulation speed of that loop. We integrated this technique in our SLTS framework and conducted an comprehensive evaluation using the Malardalen benchmark suite. We were able to reduce simulation time by up to 43% of the original time, while the introduced accuracy loss did not exceed 8 percentage points.
Auxin and Vesicle Traffic.
2018-03-01

Dear Editor, The plant hormone auxin (indole-3-acetic acid [IAA]) controls almost every aspect of plant development and growth. Auxin is transported within the plant from cell to cell through auxin transporters, including the PIN-FORMED (PIN) efflux transporters ([Geisler et al., 2017][1]; [
Air pollution-associated fly ash particles induce fibrotic mechanisms in primary fibroblasts
2018-03-01

Air pollution is associated with a variety of respiratory and cardiovascular disorders, including fibrosis. To understand the possible molecular mechanisms underlying this observation, we examined the effect of particulate matter on primary fibroblasts, the key regulators of the extracellular matrix. Fly ash collected in an experimental waste incinerator was used as model particles for fine and ultrafine pollution components. Brief treatment of fibroblasts isolated from adult male Wistar rat hearts with fly ash triggered the immediate formation of intracellular reactive oxygen species (ROS). Using phospho-specific antibodies we observed activation of p38 MAP kinase, p44/42 MAP kinase (ERK1/2) and p70S6 kinase. Prolonged incubation with fly ash increased the expression of collagen 1 and TGF-β1, but decreased mRNA levels of MMP9 and TNF-α. Cell proliferation was inhibited at high concentrations of fly ash. An increase in the level of advanced glycation endproduct (AGE) modification of various cellular proteins after long-term treatment of cultured fibroblasts with fly ash was observed. The results of our study demonstrate that direct activation of fibroblasts by combustion-derived particles is a mechanism that may contribute to the adverse health effects of particulate air pollution.