julilili42/papers huggingface dataset:
H.E.S.S. observations of the flaring gravitationally lensed galaxy PKS 1830–211
2019-04-19

PKS 1830–211 is a known macrolensed quasar located at a redshift of z = 2.5. Its high-energy gamma-ray emission has been detected with the Fermi-Large Area Telescope (LAT) instrument and evidence for lensing was obtained by several authors from its high-energy data. Observations of PKS 1830–211 were taken with the High Energy Stereoscopic System (H.E.S.S.) array of Imaging Atmospheric Cherenkov Telescopes in 2014 August, following a flare alert by the Fermi-LAT Collaboration. The H.E.S.S observations were aimed at detecting a gamma-ray flare delayed by 20–27 d from the alert flare, as expected from observations at other wavelengths. More than 12 h of good-quality data were taken with an analysis threshold of ∼67 GeV. The significance of a potential signal is computed as a function of the date and the average significance over the whole period. Data are compared to simultaneous observations by Fermi-LAT. No photon excess or significant signal is detected. An upper limit on PKS 1830–211 flux above 67 GeV is computed and compared to the extrapolation of the Fermi-LAT flare spectrum
CIELO-RGS: a catalog of soft X-ray ionized emission lines
2019-04-19

Context. High-resolution X-ray spectroscopy has advanced our understanding of the hot Universe by revealing physical properties like kinematics, temperature, and abundances of the astrophysical plasmas. Despite technical and scientific achievements, the lack of scientific products at a level higher than count spectra is hampering complete scientific exploitation of high-quality data. This paper introduces the Catalog of Ionized Emission Lines Observed by the Reflection Grating Spectrometer (CIELO-RGS) onboard the XMM-Newton space observatory. Aims. The CIELO-RGS catalog aims to facilitate the exploitation of emission features in the public RGS spectra archive. In particular, we aim to analyze the relationship between X-ray spectral diagnostics parameters and measurements at other wavelengths. This paper focuses on the methodology of catalog generation, describing the automated line-detection algorithm. Methods. A moderate sample (∼2400 observations) of high-quality RGS spectra available at XMM-Newton Science Archive is used as our starting point. A list of potential emission lines is selected based on a multi-scale peak-detection algorithm in a uniform and automated way without prior assumption on the underlying astrophysical model. The candidate line list is validated via spectral fitting with simple continuum and line profile models. We also compare the catalog content with published literature results on a small number of exemplary sources. Results. We generate a catalog of emission lines (1.2 × 10 4 ) detected in ∼1600 observations toward stars, X-ray binaries, supernovae remnants, active galactic nuclei, and groups and clusters of galaxies. For each line, we report the observed wavelength, broadening, energy and photon flux, equivalent width, and so on.
Establishment of a human induced pluripotent stem cell (iPSC) line (HIHDNEi002-A) from a patient with developmental and epileptic encephalopathy carrying a KCNA2 (p.Arg297Gln) mutation
2019-04-19

Developmental and epileptic encephalopathies (DEE) can be caused by mutations in the KCNA2 gene, coding for the voltage-gated K+ channel K<sub>v</sub>1.2. This ion channel belongs to the delayed rectifier class of potassium channels and plays a role during the repolarization phase of an action potential. In this study we reprogrammed fibroblasts from a 30-year-old male patient with DDE carrying a point mutation (c.890G > A, p.Arg297Gln) in KCNA2 to induced pluripotent stem cells. Pluripotency state of the cells was verified by the capability to differentiate into all three germ layers and the expression of several pluripotency markers on RNA and protein levels.
Drosophila Homeodomain-Interacting Protein Kinase (Hipk) Phosphorylates the Homeodomain Proteins Homeobrain, Empty Spiracles, and Muscle Segment Homeobox
2019-04-19

The Drosophila homeodomain-interacting protein kinase (Hipk) is the fly representative of the well-conserved group of HIPKs in vertebrates. It was initially found through its characteristic interactions with homeodomain proteins. Hipk is involved in a variety of important developmental processes, such as the development of the eye or the nervous system. In the present study, we set Hipk and the Drosophila homeodomain proteins Homeobrain (Hbn), Empty spiracles (Ems), and Muscle segment homeobox (Msh) in an enzyme-substrate relationship. These homeoproteins are transcription factors that function during Drosophila neurogenesis and are, at least in part, conserved in vertebrates. We reveal a physical interaction between Hipk and the three homeodomain proteins in vivo using bimolecular fluorescence complementation (BiFC). In the course of in vitro phosphorylation analysis and subsequent mutational analysis we mapped several Hipk phosphorylation sites of Hbn, Ems, and Msh. The phosphorylation of Hbn, Ems, and Msh may provide further insight into the function of Hipk during development of the Drosophila nervous system.
PHB is Produced from Glycogen Turn-over during Nitrogen Starvation in Synechocystis sp. PCC 6803
2019-04-20

Polyhydroxybutyrate (PHB) is a polymer of great interest as a substitute for conventional plastics, which are becoming an enormous environmental problem. PHB can be produced directly from CO2 in photoautotrophic cyanobacteria. The model cyanobacterium Synechocystis sp. PCC 6803 produces PHB under conditions of nitrogen starvation. However, it is so far unclear which metabolic pathways provide the precursor molecules for PHB synthesis during nitrogen starvation. In this study, we investigated if PHB could be derived from the main intracellular carbon pool, glycogen. A mutant of the major glycogen phosphorylase, GlgP2 (slr1367 product), was almost completely impaired in PHB synthesis. Conversely, in the absence of glycogen synthase GlgA1 (sll0945 product), cells not only produced less PHB, but were also impaired in acclimation to nitrogen depletion. To analyze the role of the various carbon catabolic pathways (EMP, ED and OPP pathways) for PHB production, mutants of key enzymes of these pathways were analyzed, showing different impact on PHB synthesis. Together, this study clearly indicates that PHB in glycogen-producing Synechocystis sp. PCC 6803 cells is produced from this carbon-pool during nitrogen starvation periods. This knowledge can be used for metabolic engineering to get closer to the overall goal of a sustainable, carbon-neutral bioplastic production.
Proto-Urban Establishments in Inner Asia: Surveys of an Iron Age Walled Site in Eastern Mongolia
2019-04-21

Walled sites attributed to the Xiongnu steppe empire (2nd century b.c.–1st century a.d.) constitute the earliest investments in explicitly non-mortuary built environments among pastoralists of the Mongolian Steppe. These permanent constructions are important precedents to the medieval towns of subsequent steppe empires, yet very little of the complete layouts and surrounding remains of the large enclosures are understood. Our investigations of the walled site at Kherlen-Bars in eastern Mongolia are among the first surveys to fully document all aspects above and below ground across an entire Iron Age walled site area. In addition to detailed documentation of the large structures, our geomagnetic prospections and digital elevation modeling brought to light numerous small sub-surface and subtle-surface features that show such early walled sites, often deemed virtually empty, to be far more complex and diachronic in their formation processes and possible functions.
Vegetation, land, and wood use at the sites of Bat and Al‐Khashbah in Oman (fourth–third millennium BC)
2019-04-22

Abstract About 4200 charcoal fragments have been identified from the fourth‐ to third‐millennium BC archaeological sites of Bat and Al‐Khashbah in order to gain an understanding of plant resources available at the sites. Acacia sp., Ziziphus sp., and Tamarix sp. were the main taxa identified at both sites and indicate a similar vegetation composition as today. Phoenix sp. (date palm) charcoal also has been found at both sites. Whereas the cultivation of date palm for the 2700–2300 BC layers from Bat was likely, given other circumstantial evidence (i.e. local cereal cultivation and floodwater irrigation), it is unclear whether date palm was cultivated at Al‐Khashbah. Especially for the older periods (3300–2700 BC ) it is possible that nomadic pastoralists were exploiting and/or managing wild date palms. The find of Avicennia marina at Al‐Khashbah indicates long‐distance contacts with the coast.
Noninvasive diagnosis of urothelial cancer in urine using DNA hypermethylation signatures—Gender matters
2019-04-22

Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa‐associated hypermethylated sites were identified in urine of a male screening cohort ( n = 24) applying Infinium‐450K‐methylation arrays and verified in two separate mixed‐gender study groups ( n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples ( n = 56) of mixed‐gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/μl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.
Enriched environmental conditions modify the gut microbiome composition and fecal markers of inflammation in Parkinson’s disease
2019-04-22

Abstract Background Recent findings suggest an implication of the gut microbiome in Parkinson’s disease patients. Parkinson’s disease onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors. Objectives In this study, we used a transgenic mouse model overexpressing the complete human SNCA genes modeling familial and sporadic forms of Parkinson’s disease to study whether environmental conditions such as standard versus enriched environment changes the gut microbiome and influences disease progression. Methods We performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and transgenic mice kept under standard environment and enriched environment conditions. Results The overall composition of the gut microbiota was not changed in transgenic mice compared with wild-type in enriched environment, however, individual gut bacteria at genus level such as Lactobacillus sp. were significantly changed in transgenic mice. Furthermore, enriched environment significantly reduced colon fecal inflammatory calprotectin protein in wild-type and transgenic enriched environment conditions compared to standard environment. Conclusion Our data suggest that enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine by changing anti-inflammatory gut bacteria.
Deep convolutional models improve predictions of macaque V1 responses to natural images
2019-04-23

Despite great efforts over several decades, our best models of primary visual cortex (V1) still predict spiking activity quite poorly when probed with natural stimuli, highlighting our limited understanding of the nonlinear computations in V1. Recently, two approaches based on deep learning have emerged for modeling these nonlinear computations: transfer learning from artificial neural networks trained on object recognition and data-driven convolutional neural network models trained end-to-end on large populations of neurons. Here, we test the ability of both approaches to predict spiking activity in response to natural images in V1 of awake monkeys. We found that the transfer learning approach performed similarly well to the data-driven approach and both outperformed classical linear-nonlinear and wavelet-based feature representations that build on existing theories of V1. Notably, transfer learning using a pre-trained feature space required substantially less experimental time to achieve the same performance. In conclusion, multi-layer convolutional neural networks (CNNs) set the new state of the art for predicting neural responses to natural images in primate V1 and deep features learned for object recognition are better explanations for V1 computation than all previous filter bank theories. This finding strengthens the necessity of V1 models that are multiple nonlinearities away from the image domain and it supports the idea of explaining early visual cortex based on high-level functional goals.
The neural dynamics of hierarchical Bayesian causal inference in multisensory perception
2019-04-23

Abstract Transforming the barrage of sensory signals into a coherent multisensory percept relies on solving the binding problem – deciding whether signals come from a common cause and should be integrated or, instead, segregated. Human observers typically arbitrate between integration and segregation consistent with Bayesian Causal Inference, but the neural mechanisms remain poorly understood. Here, we presented people with audiovisual sequences that varied in the number of flashes and beeps, then combined Bayesian modelling and EEG representational similarity analyses. Our data suggest that the brain initially represents the number of flashes and beeps independently. Later, it computes their numbers by averaging the forced-fusion and segregation estimates weighted by the probabilities of common and independent cause models (i.e. model averaging). Crucially, prestimulus oscillatory alpha power and phase correlate with observers’ prior beliefs about the world’s causal structure that guide their arbitration between sensory integration and segregation.
Phage tail-like particles are versatile bacterial nanomachines – A mini-review
2019-04-23

Type VI secretion systems and tailocins, two bacterial phage tail-like particles, have been reported to foster interbacterial competition. Both nanostructures enable their producer to kill other bacteria competing for the same ecological niche. Previously, type VI secretion systems and particularly R-type tailocins were considered highly specific, attacking a rather small range of competitors. Their specificity is conferred by cell surface receptors of the target bacterium and receptor-binding proteins on tailocin tail fibers and tail fiber-like appendages of T6SS. Since many R-type tailocin gene clusters contain only one tail fiber gene it was appropriate to expect small R-type tailocin target ranges. However, recently up to three tail fiber genes and broader target ranges have been reported for one plant-associated <i>Pseudomonas</i> strain. Here, we show that having three tail fiber genes per R-type tailocin gene cluster is a common feature of several strains of Gram-negative (often plant-associated) bacteria of the genus <i>Kosakonia</i>. Knowledge about the specificity of type VI secretion systems binding to target bacteria is even lower than in R-type tailocins. Although the mode of operation implicated specific binding, it was only published recently that type VI secretion systems develop tail fiber-like appendages. Here again <i>Kosakonia</i>, exhibiting up to three different type VI secretion systems, may provide valuable insights into the antagonistic potential of plant-associated bacteria. Current understanding of the diversity and potential of phage tail-like particles is fragmentary due to various synonyms and misleading terminology. Consistency in technical terms is a precondition for concerted and purposeful research, which precedes a comprehensive understanding of the specific interaction between bacteria producing phage tail-like particles and their targets. This knowledge is fundamental for selecting and applying tailored, and possibly engineered, producer bacteria for antagonizing plant pathogenic microorganisms.
Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
2019-04-23

A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17 months) and 6537 infants (enrolled at 6-12 weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score ≤2 (cerebral malaria [CM]) and gender-specific mortality were assessed <i>post-hoc</i>. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%-28.4% and 1.5%-2.5%, respectively across groups; 0.0%-0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2-3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that - given their severity - warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.
Targeting self- and neoepitopes with a modular self-adjuvanting cancer vaccine
2019-04-23

Induction of a potent CD4 and CD8 T-cell response against tumor-specific and tumor-associated antigen is critical for eliminating tumor cells. Recent vaccination strategies have been hampered by an inefficacious and low amplitude immune response. Here we describe a self-adjuvanted chimeric protein vaccine platform to address these challenges, characterized by a multidomain construction incorporating (i) a cell penetrating peptide (CPP) allowing internalization of several multiantigenic Major Histocompatibility Complex (MHC)-restricted peptides within (ii) the multiantigenic domain (Mad) and (iii) a TLR2/4 agonist domain (TLRag). Functionality of the resulting chimeric protein is based on the combined effect of the above-mentioned three different domains for simultaneous activation of antigen presenting cells and antigen cross-presentation, leading to an efficacious multiantigenic and multiallelic cellular immune response. Helper and cytotoxic T-cell responses were observed against model-, neo- and self-antigens, and were highly potent in several murine tumor models. The safety and the immunogenicity of a human vaccine candidate designed for colorectal cancer treatment was demonstrated in a non-human primate model. This newly engineered therapeutic vaccine approach is promising for the treatment of poorly infiltrated tumors that do not respond to currently marketed immunotherapies.
THE IMPACT OF ORGANISATIONAL SUPPORT AND INDIVIDUAL ACHIEVEMENT ORIENTATION ON CREATIVE DEVIANCE
2019-04-23

Innovation-oriented firms encourage their staff to generate ideas, but lack the resources to sponsor them all. Entrepreneurially minded employees may respond to this discrepancy with creative deviance, i.e., pursue ideas despite managerial orders to stop. We elucidate this understudied flipside of corporate entrepreneurship by theorising and testing organisational and individual antecedents to creative deviance. Strain theory leads us to hypothesise that organisational support for innovation reduces creative deviance. Based on achievement goal theory, we conjecture that mastery goals foster creative deviance. These predictors are expected to interact in their impact on creative deviance. Data from 659 employees support our hypotheses. Our study contributes to corporate entrepreneurship theory by expounding an important, but so far understudied form of innovative behaviour, extends strain theory by showing how individual traits can reinforce or mitigate the structural strain created by organisations, and advances research on achievement goals by connecting mastery achievement orientation to deviant behaviour. In terms of practical implications, our study indicates how leaders may promote compliant innovation through organisational support and how they can increase person-job fit by screening candidates’ achievement goals during recruitment.
Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum
2019-04-23

Abstract Cyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure–activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin‐inspired analogues. Optimization via side chain modifications of the non‐canonical amino acids led to potent lead structures for each pathogen.
Out of Africa by spontaneous migration waves
2019-04-23

Hominin evolution is characterized by progressive regional differentiation, as well as migration waves, leading to anatomically modern humans that are assumed to have emerged in Africa and spread over the whole world. Why or whether Africa was the source region of modern humans and what caused their spread remains subject of ongoing debate. We present a spatially explicit, stochastic numerical model that includes ongoing mutations, demic diffusion, assortative mating and migration waves. Diffusion and assortative mating alone result in a structured population with relatively homogeneous regions bound by sharp clines. The addition of migration waves results in a power-law distribution of wave areas: for every large wave, many more small waves are expected to occur. This suggests that one or more out-of-Africa migrations would probably have been accompanied by numerous smaller migration waves across the world. The migration waves are considered "spontaneous", as the current model excludes environmental or other extrinsic factors. Large waves preferentially emanate from the central areas of large, compact inhabited areas. During the Pleistocene, Africa was the largest such area most of the time, making Africa the statistically most likely origin of anatomically modern humans, without a need to invoke additional environmental or ecological drivers.