julilili42/papers huggingface dataset:
Galleria mellonella: A Novel Invertebrate Model to Distinguish Intestinal Symbionts From Pathobionts
2018-09-19

Insects and mammals share evolutionary conserved innate immune responses to maintain intestinal homeostasis. We investigated whether the larvae of the greater wax moth <i>Galleria mellonella</i> may be used as an experimental organism to distinguish between symbiotic <i>Bacteroides vulgatus</i> and pathobiotic <i>Escherichia coli</i>, which are mammalian intestinal commensals. Oral application of the symbiont or pathobiont to <i>G. mellonella</i> resulted in clearly distinguishable innate immune responses that could be verified by analyzing similar innate immune components in mice <i>in vivo</i> and <i>in vitro</i>. The differential innate immune responses were initiated by the recognition of bacterial components <i>via</i> pattern recognition receptors. The pathobiont detection resulted in increased expression of reactive oxygen and nitrogen species related genes as well as antimicrobial peptide gene expression. In contrast, the treatment/application with symbiotic bacteria led to weakened immune responses in both mammalian and insect models. As symbionts and pathobionts play a crucial role in development of inflammatory bowel diseases, we hence suggest <i>G. mellonella</i> as a future replacement organism in inflammatory bowel disease research.
The small GTPase RAB28 is required for phagocytosis of cone outer segments by the murine retinal pigmented epithelium
2018-09-19

RAB28, a member of the RAS oncogene family, is a ubiquitous, farnesylated, small GTPase of unknown function present in photoreceptors and the retinal pigmented epithelium (RPE). Nonsense mutations of the human <i>RAB28</i> gene cause recessive cone-rod dystrophy 18 (CRD18), characterized by macular hyperpigmentation, progressive loss of visual acuity, RPE atrophy, and severely attenuated cone and rod electroretinography (ERG) responses. In an attempt to elucidate the disease-causing mechanism, we generated <i>Rab28</i><sup>-/-</sup> mice by deleting exon 3 and truncating RAB28 after exon 2. We found that <i>Rab28</i><sup>-/-</sup> mice recapitulate features of the human dystrophy (<i>i.e.</i> they exhibited reduced cone and rod ERG responses and progressive retina degeneration). Cones of <i>Rab28</i><sup>-/-</sup> mice extended their outer segments (OSs) to the RPE apical processes and formed enlarged, balloon-like distal tips before undergoing degeneration. The visual pigment content of WT and <i>Rab28</i><sup>-/-</sup> cones was comparable before the onset of degeneration. Cone phagosomes were almost absent in <i>Rab28</i><sup>-/-</sup> mice, whereas rod phagosomes displayed normal levels. A protein-protein interaction screen identified several RAB28-interacting proteins, including the prenyl-binding protein phosphodiesterase 6 δ-subunit (PDE6D) and voltage-gated potassium channel subfamily J member 13 (KCNJ13) present in the RPE apical processes. Of note, the loss of PDE6D prevented delivery of RAB28 to OSs. Taken together, these findings reveal that RAB28 is required for shedding and phagocytosis of cone OS discs.
Impact of Intrauterine Growth Restriction on Cognitive and Motor Development at 2 Years of Age
2018-09-19

Intrauterine growth restriction (IUGR), which is already known to be a risk factor for pathological intrauterine development, perinatal mortality, and morbidity, is now also assumed to cause both physical and cognitive alterations in later child development. In the current study, effects of IUGR on infantile brain function were investigated during the fetal period and in a follow-up developmental assessment during early childhood. During the fetal period, visual and auditory event-related responses (VER and AER) were recorded using fetal magnetoencephalography (fMEG). VER latencies were analyzed in 73 fetuses (14 IUGR fetuses) while AER latencies were analyzed in 66 fetuses (11 IUGR fetuses). Bayley Scales of Infant Development, Second Edition (BSID-II) were used to assess the developmental status of the infants at the age of 24 months. The Mental Development Index (MDI) was available from 66 children (8 IUGR fetuses) and the Psychomotor Development Index (PDI) from 63 children (7 IUGR fetuses). Latencies to visual stimulation were more delayed in IUGR than in small for gestational age (SGA) or appropriate for gestational age (AGA) fetuses, albeit not to any significant extent (<i>p</i> = 0.282). The MDI in former IUGR infants was significantly lower (<i>p</i> = 0.044) than in former SGA and AGA infants. However, IUGR had no impact on PDI (<i>p</i> = 0.213). These findings support the hypothesis that IUGR may constitute a risk factor for neurodevelopmental delay. Further investigation of the possible underlying mechanisms, as well as continued long-term developmental research, is therefore necessary.
Chromobodies to Quantify Changes of Endogenous Protein Concentration in Living Cells
2018-09-19

Understanding cellular processes requires the determination of dynamic changes in the concentration of genetically nonmodified, endogenous proteins, which, to date, is commonly accomplished by end-point assays <i>in vitro</i> Molecular probes such as fluorescently labeled nanobodies (chromobodies, CBs) are powerful tools to visualize the dynamic subcellular localization of endogenous proteins in living cells. Here, we employed the dependence of intracellular levels of chromobodies on the amount of their endogenous antigens, a phenomenon, which we termed antigen-mediated CB stabilization (AMCBS), for simultaneous monitoring of time-resolved changes in the concentration and localization of native proteins. To improve the dynamic range of AMCBS we generated turnover-accelerated CBs and demonstrated their application in visualization and quantification of fast reversible changes in antigen concentration upon compound treatment by quantitative live-cell imaging. We expect that this broadly applicable strategy will enable unprecedented insights into the dynamic regulation of proteins, <i>e.g.</i> during cellular signaling, cell differentiation, or upon drug action.
The starburst galaxy NGC 253 revisited by HESS and Fermi-LAT
2018-09-20

Context. NGC 253 is one of only two starburst galaxies found to emit γ-rays from hundreds of MeV to multi-TeV energies. Accurate measurements of the very-high-energy (VHE; E &gt; 100 GeV) and high-energy (HE; E &gt; 60 MeV) spectra are crucial to study the underlying particle accelerators, probe the dominant emission mechanism(s) and to study cosmic-ray interaction and transport.\\n\\nAims. The measurement of the VHE γ-ray emission of NGC 253 published in 2012 by H.E.S.S. was limited by large systematic uncertainties. Here, the most up to date measurement of the γ-ray spectrum of NGC 253 is investigated in both HE and VHE γ-rays. Assuming a hadronic origin of the γ-ray emission, the measurement uncertainties are propagated into the interpretation of the accelerated particle population.\\n\\nMethods. The data of H.E.S.S. observations are reanalysed using an updated calibration and analysis chain. The improved Fermi–LAT analysis employs more than 8 yr of data processed using pass 8. The cosmic-ray particle population is evaluated from the combined HE–VHE γ-ray spectrum using NAIMA in the optically thin case.\\n\\nResults. The VHE γ-ray energy spectrum is best fit by a power-law distribution with a flux normalisation of (1.34 ± 0.14stat ± 0.27sys) × 10−13 cm−2 s−1 TeV1 at 1 TeV – about 40% above, but compatible with the value obtained in Abramowski et al. (2012). The spectral index Γ = 2.39 ± 0.14stat ± 0.25sys is slightly softer than but consistent with the previous measurement within systematic errors. In the Fermi energy range an integral flux of F(E &gt; 60 MeV) = (1.56 ± 0.28stat ± 0.15sys) × 10−8 cm−2 s−1 is obtained. At energies above ∼3 GeV the HE spectrum is consistent with a power-law ranging into the VHE part of the spectrum measured by H.E.S.S. with an overall spectral index Γ = 2.22 ± 0.06stat.\\n\\nConclusions. Two scenarios for the starburst nucleus are tested, in which the gas in the starburst nucleus acts as either a thin or a thick target for hadronic cosmic rays accelerated by the individual sources in the nucleus. In these two models, the level to which NGC 253 acts as a calorimeter is estimated to a range of fcal = 0.1 to 1 while accounting for the measurement uncertainties. The presented spectrum is likely to remain the most accurate measurements until the Cherenkov Telescope Array (CTA) has collected a substantial set of data towards NGC 253.
Radiation Hydrodynamics Simulations of Photoevaporation of Protoplanetary Disks. II. Metallicity Dependence of UV and X-Ray Photoevaporation
2018-09-20

Abstract We perform a suite of radiation hydrodynamics simulations of photoevaporating disks, varying the metallicity in a wide range of . We follow the disk evolution for over ∼5000 years by solving hydrodynamics, radiative transfer, and nonequilibrium chemistry. Our chemistry model is updated from the first paper of this series by adding X-ray ionization and heating. We study the metallicity dependence of the disk photoevaporation rate and examine the importance of X-ray radiation. In the fiducial case with solar metallicity, including the X-ray effects does not significantly increase the photoevaporation rate when compared to the case with ultraviolet (UV) radiation only. At subsolar metallicities in the range of , the photoevaporation rate increases as metallicity decreases owing to the reduced opacity of the disk medium. The result is consistent with the observational trend that disk lifetimes are shorter in low metallicity environments. In contrast, the photoevaporation rate decreases at even lower metallicities of , because dust–gas collisional cooling remains efficient compared to far-UV photoelectric heating whose efficiency depends on metallicity. The net cooling in the interior of the disk suppresses the photoevaporation. However, adding X-ray radiation significantly increases the photoevaporation rate, especially at . Although the X-ray radiation itself does not drive strong photoevaporative flows, X-rays penetrate deep into the neutral region in the disk, increase the ionization degree there, and reduce positive charges of grains. Consequently, the effect of photoelectric heating by far-UV radiation is strengthened by the X-rays and enhances the disk photoevaporation.
Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis
2018-09-20

Background During treatment with direct oral anticoagulants ( DOAC ), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC ‐specific coagulation assays around the current safe‐for‐treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti‐Xa assay ( AXA ) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography–tandem mass spectrometry as reference. All dabigatran‐specific assays had high sensitivity to concentrations &gt;30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as &lt;30 ng/ mL ). If no DOAC ‐specific calibration for AXA is available, results 2‐fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC ‐specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe‐for‐treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070.
Superconducting coplanar microwave resonators with operating frequencies up to 50 GHz
2018-09-20

We demonstrate the operation of superconducting coplanar microwave resonators in a very large frequency range up to 50 GHz. The resonators are fabricated from niobium thin films on sapphire substrates and optimized for these high frequencies by small chip sizes. We study numerous harmonics of the resonators at temperatures between 1.5 K and 6 K, and we determine quality factors of up to 25000 at 1.5 K. As an example for spectroscopy applications of such resonators we detect the superconducting transition of a bulk tin sample at multiple probing frequencies.
Glucose tolerance and insulin sensitivity define adipocyte transcriptional programs in human obesity
2018-09-20

Our study showed that glucose intolerance and insulin resistance co-operate to remodel adipocyte transcriptome. We also identified the Nuclear Export Mediator Factor (NEMF) and the Ectoderm-Neural Cortex 1 (ENC1) as novel potential targets in the management of metabolic health in human obesity.
Simulations of photo-nuclear dijets with PYTHIA 8 and their sensitivity to nuclear PDFs
2018-09-20

In ultra-peripheral heavy-ion collisions the nuclei pass with such a large impact parameter that no strong interaction can take place. However, a photon emitted by one nucleus can still interact either with the other nucleus or with a photon from the another nucleus. The former event type corresponds to photoproduction, earlier studied e.g. in electron-proton collisions at HERA, but now with a nuclear target. This provides an unique opportunity to study the nuclear modifications of the PDFs with the photo-nuclear processes measured in lead-lead collisions at the LHC. Here we present our recent implementation of photoproduction processes in the Pythia 8 general-purpose Monte-Carlo event generator. The resulting simulations are compared to charged-hadron and dijet photoproduction data from the HERA experiments, and the theoretical uncertainties of the framework are studied. We discuss how the relevant part of the photon flux from heavy ions is obtained using the equivalent photon approximation and present predictions for photo-nuclear dijet cross section at the LHC. To estimate the potential of this data to further constrain the nuclear PDFs, the expected statistical uncertainty based on LHC luminosity is compared to uncertainties in the current nuclear PDF analyses.
Genome-wide active enhancer identification using cell type-specific signatures of epigenomic activity
2018-09-20

Abstract Recently enhancers have emerged as key players regulating crucial mechanisms such as cell fate determination and establishment of spatiotemporal patterns of gene expression during development. Due to their functional and structural complexity, an accurate in silico identification of active enhancers under specific conditions remain challenging. We present a novel machine learning based method that derives epigenomic patterns exclusively from experimentally characterized active enhancers contrasted with a weighted set of non-enhancer genomic regions. We demonstrate better predictive performance over previous methods, as well as wide generalizability by identifying and annotating active enhancers genome-wide across different tissues/cell types in human and mouse.
Unexpected malignant uterine pathology: incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease
2018-09-20

Hysterectomy presents a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to assess the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort, and to discuss implications for clinical routine.
Next-to-Leading Order QCD Corrections to Inclusive Heavy-Flavor Production in Polarized Deep-Inelastic Scattering
2018-09-20

We report on a recently completed, first calculation of the full\\nnext-to-leading order QCD corrections for heavy flavor contributions to the\\ninclusive structure function in longitudinally polarized deep-inelastic\\nscattering. All results are derived with largely analytical methods and retain\\nthe full dependence on the heavy quark's mass. As a first phenomenological\\napplication, inclusive charm production at a future electron-ion collider and\\nits sensitivity to the polarized gluon distribution is studied. Theoretical\\nuncertainties due to the residual dependence on unphysical factorization and\\nrenormalization scales are estimated.\\n
Prophylactic surgery among germline TP53 mutation carriers in Germany – a multicentric observational study
2018-09-20

Li-Fraumeni syndrome comprises a rare inherited cancer susceptibility disorder caused by germline TP53 variants. It is associated with an increased life-time risk of breast cancer (BC) in up to 79% of female carriers with a mean age of 35 at the time of onset. In healthy mutation carriers, intensified surveillance programs or prophylactic mastectomy (PM) are possible. If unilateral BC occurs, mastectomy, as a radiation-free alternative to lumpectomy, as well as contralateral PM due to an increased contralateral BC risk of up to 31% should be discussed. Data for carriers' perception are missing; this study addresses PM among female TP53 mutation carriers in Germany.
Late Miocene proboscideans from Samos Island (Greece) revisited: new specimens from old collections
2018-09-20

&amp;lt;p&amp;gt;In this article we present new proboscidean remains from the late Miocene (Turolian) of Samos Island (Greece), which are stored at the old Samos collections of Darmstadt, Frankfurt a. M. (Germany), Lausanne (Switzerland) and Vienna (Austria), and originate from the excavations or fossil collections that took place on the island at the end of the 19th and the beginning of the 20th century. The specimens belong to juvenile individuals of deinotheres, choerolophodonts and amebelodonts. The deinothere material is attributed to the last European huge-sized deinothere, Deinotherium proavum. The described skull from Samos is so far the most complete specimen of all known Miocene juvenile deinotheres from Eurasia and Africa. The majority of the Samos choerolophodont specimens represent the advanced morph of Choerolophodon pentelici, whereas one shows more archaic features and belongs to the primitive evolutionary stage of this species. This more primitive morph could originate from the lower fossiliferous&amp;lt;br&amp;gt;\\nhorizons of Samos, which are dated to the early Turolian. The third proboscidean is attributedto the tetralophodont shovel-tusker Konobelodon atticus, a rare taxon in the Samos fauna. Together with the previously described zygodont Mammut from Samos, these four proboscideans are typical for the Turolian proboscidean fauna of Southeastern Europe. We discuss the biostratigraphy of the Samos proboscideans aiming to unravel some aspects of the chronological range of the late Miocene proboscideans with emphasis in the Southern Balkans and Turkey.&amp;lt;/p&amp;gt;
Effectiveness of curvilinear approach in dissection of Descemet's membrane: first 500 cases – factors influencing graft preparation
2018-09-21

Abstract Purpose To confirm the reproducibility of manual graft preparation using curvilinear forceps and evaluate the incidence and type of structural abnormalities of Descemet's membrane ( DM ) preventing successful grafts preparation. Methods Five hundred corneo‐scleral buttons were prepared. Factors such as endothelial cell number before preparation, donor age, post‐mortem time, time in culture, pigmentation of the trabecular meshwork and preparation characteristics of the fellow eye were analysed. According to the preparation characteristics, three groups were formed: A, uncomplicated; B, complicated preparation with stripping from the contralateral side; and C, failure of preparation. Three failed grafts were examined by transmission electron microscopy ( TEM ). Results Using curvilinear forceps, manual separation of DM was achieved without any adverse effects in 457 of 500 corneas (91.4%). In 32 corneas (6.4%) with micro‐tears during preparation, stripping from the opposite side was possible. However, 11 of the 500 corneas (2.2%) showed extremely strong adhesion leading to multiple tears of DM and preventing successful preparation of the graft. Endothelial cell number, donor age, post‐mortem time, time in culture and pigmentation of the trabecular meshwork showed no significant correlation with failure to successfully obtain a DM graft. Complicated graft preparations of one eye showed a highly significant correlation with complicated graft preparations in the fellow eye. TEM analysis of failed grafts showed abnormal invasion of stromal parts into the DM , cell accumulation and pigmentation in the DM plane. Conclusion Using curvilinear forceps for dissecting of the graft shows valid and reproducible results in the vast majority (97.8%) of donor corneas.
Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review
2018-09-22

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.