julilili42/papers huggingface dataset:
Generation of an induced pluripotent stem cell line from a patient with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): HIHCNi003-A
2018-06-21

An induced pluripotent stem cell line, HIHCNi003-A (iPSC-ALSP), was created from a skin biopsy of a patient with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) caused by a heterozygous c.2512G&gt;C, p.Val838Leu mutation in the CSF1R gene. Skin fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC, and hLIN28. The iPSC-ALSP line exhibits chromosomal stability with conservation of the CSF1R mutation, expresses pluripotency markers and differentiates into endo-, meso-, and ectodermal cells in vitro.
The forgotten effects of thyrotropin-releasing hormone: Metabolic functions and medical applications
2018-06-22

Thyrotropin-releasing hormone (TRH) causes a variety of thyroidal and non-thyroidal effects, the best known being the feedback regulation of thyroid hormone levels. This was employed in the TRH stimulation test, which is currently little used. The role of TRH as a cancer biomarker is minor, but exaggerated responses to TSH and prolactin levels in breast cancer led to the hypothesis of a potential role for TRH in the pathogenesis of this disease. TRH is a rapidly degraded peptide with multiple targets, limiting its suitability as a biomarker and drug candidate. Although some studies reported efficacy in neural diseases (depression, spinal cord injury, amyotrophic lateral sclerosis, etc.), therapeutic use of TRH is presently restricted to spinocerebellar degenerative disease. Regulation of TRH production in the hypothalamus, patterns of expression of TRH and its receptor in the body, its role in energy metabolism and in prolactin secretion are addressed in this review.
Efficient Bethe-Salpeter equation treatment in dynamical mean-field theory
2018-06-22

We present here two alternative schemes designed to correct the\\nhigh-frequency truncation errors in the numerical treatment of the\\nBethe-Salpeter equations. The schemes are applicable to all Bethe-Salpeter\\ncalculations with a local two-particle irreducible local, which is relevant,\\ne.g., for the dynamical mean-field theory (DMFT) and its diagrammatic\\nextensions. In particular, within a purely diagrammatic framework, we could\\nextend existing algorithms for treating the static case in the particle-hole\\nsector to more general procedures applicable to all bosonic frequencies and all\\nchannels. After illustrating the derivation and the theoretical interrelation\\nof the two proposed schemes, these have been applied to the Bethe-Salpeter\\nequations for the auxiliary Anderson impurity models of selected DMFT\\ncalculations, where results can be compared against a numerically "exact"\\nsolution. The successful performance of the proposed schemes suggests that\\ntheir implementation can significantly improve the accuracy of dynamical\\nmean-field theory (DMFT) calculations at the two-particle level, in particular\\nfor more realistic multi-orbital calculations where the large number of degrees\\nof freedom substantially restricts the actual frequency range for numerical\\ncalculations, as well as -on a broader perspective- of the diagrammatic\\nextensions of DMFT.\\n
Phytophthora infestans RXLR effector SFI5 requires association with calmodulin for PTI/MTI suppressing activity
2018-06-22

Summary Pathogens secrete effector proteins to interfere with plant innate immunity, in which Ca 2+ /calmodulin (CaM) signalling plays key roles. Thus far, few effectors have been identified that directly interact with CaM for defence suppression. Here, we report that SFI 5, an RXLR effector from Phytophthora infestans , suppresses microbe‐associated molecular pattern ( MAMP )‐triggered immunity ( MTI ) by interacting with host CaMs. We predicted the CaM‐binding site in SFI 5 using in silico analysis. The interaction between SFI 5 and CaM was tested by both in vitro and in vivo assays. MTI suppression by SFI 5 and truncated variants were performed in a tomato protoplast system. We found that both the predicted CaM‐binding site and the full‐length SFI 5 protein interact with CaM in the presence of Ca 2+ . MTI responses, such as FRK 1 upregulation, reactive oxygen species accumulation, and mitogen‐activated protein kinase activation were suppressed by truncated SFI 5 proteins containing the C‐terminal CaM‐binding site but not by those without it. The plasma membrane localization of SFI 5 and its ability to enhance infection were also perturbed by loss of the CaM‐binding site. We conclude that CaM‐binding is required for localization and activity of SFI 5. We propose that SFI 5 suppresses plant immunity by interfering with immune signalling components after activation by CaMs.
Using ancestral state reconstruction methods for onomasiological reconstruction in multilingual word lists
2018-06-22

Abstract Current efforts in computational historical linguistics are predominantly concerned with phylogenetic inference. Methods for ancestral state reconstruction have only been applied sporadically. In contrast to phylogenetic algorithms, automatic reconstruction methods presuppose phylogenetic information in order to explain what has evolved when and where. Here we report a pilot study exploring how well automatic methods for ancestral state reconstruction perform in the task of onomasiological reconstruction in multilingual word lists, where algorithms are used to infer how the words evolved along a given phylogeny, and reconstruct which cognate classes were used to express a given meaning in the ancestral languages. Comparing three different methods, Maximum Parsimony, Minimal Lateral Networks, and Maximum Likelihood on three different test sets (Indo-European, Austronesian, Chinese) using binary and multi-state coding of the data as well as single and sampled phylogenies, we find that Maximum Likelihood largely outperforms the other methods. At the same time, however, the general performance was disappointingly low, ranging between 0.66 (Chinese) and 0.79 (Austronesian) for the F -Scores. A closer linguistic evaluation of the reconstructions proposed by the best method and the reconstructions given in the gold standards revealed that the majority of the cases where the algorithms failed can be attributed to problems of independent semantic shift (homoplasy), to morphological processes in lexical change, and to wrong reconstructions in the independently created test sets that we employed.
Assessing the Efficiency of Cultivation Techniques To Recover Natural Product Biosynthetic Gene Populations from Sediment
2018-06-22

Despite decades of cultivating microorganisms for use in drug discovery, few attempts have been made to measure the extent to which common cultivation techniques have accessed existing chemical space. Metagenomic studies have shown that cultivable bacteria represent a fraction of those that exist in the environment, and that uncultivated populations in sediment have genes that encode for a high diversity of novel natural product (NP) biosynthetic enzymes. Quantifying these genes in both sediment and cultivatable bacterial populations allows us to assess how much diversity is present on nutrient agar and is critical to guiding the trajectory of future NP discovery platforms. Herein, we employed next-generation amplicon sequencing to assess the NP biosynthetic gene populations present in two Lake Huron sediment samples, and compared these with populations from their corresponding cultivatable bacteria. We highlight three findings from our study: (1) after cultivation, we recovered between 7.7% and 23% of three common types of NP biosynthetic genes from the original sediment population; (2) between 76.3% and 91.5% of measured NP biosynthetic genes from nutrient agar have yet to be characterized in known biosynthetic gene cluster databases, indicating that readily cultivatable bacteria harbor the potential to produce new NPs; and (3) even though the predominant taxa present on nutrient media represented some of the major producers of bacterial NPs, the sediment harbored a significantly greater pool of NP biosynthetic genes that could be mined for structural novelty, and these likely belong to taxa that typically have not been represented in microbial drug discovery libraries.
Maintenance and continuous therapy for multiple myeloma
2018-06-22

In multiple myeloma (MM), maintenance therapy is a longer, less intensive treatment course than initial therapy that is administered postinduction to delay disease progression. Maintenance and continuous therapy have been shown to suppress minimal residual disease and deepen and prolong responses, with the goal of improving progression-free survival and overall survival. Areas covered: In this review, we have summarized current clinical trial data on maintenance and continuous therapy in newly diagnosed MM and relapsed/refractory MM (RRMM), focusing on lenalidomide and bortezomib. We have also analyzed the potential uses of newer agents, including carfilzomib, daratumumab, elotuzumab, pomalidomide, and ixazomib. Expert commentary: Although lenalidomide- and bortezomib-containing regimens have demonstrated safety and efficacy, only lenalidomide is approved for maintenance; it is the preferred agent in the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines. Furthermore, results from the FIRST trial support lenalidomide plus low-dose dexamethasone (Rd) as a standard of care for continuous therapy. In RRMM, newer agents have been successfully added to Rd and data from additional trials are awaited. The vital roles of maintenance and continuous therapy and their benefits are now more clearly understood, but important questions remain regarding optimal duration of therapy and regimens.
Moonfalls: collisions between the Earth and its past moons
2018-06-22

During the last stages of the terrestrial planet formation, planets grow mainly through giant-impacts with large planetary embryos. The Earth's Moon was suggested to form through one of these impacts. However, since the proto-Earth has experienced many giant-impacts, several moons are naturally expected to form through a sequence of multiple (including smaller scale) impacts. Each impact potentially forms a sub-Lunar mass moonlet that interacts gravitationally with the proto-Earth and possibly with previously-formed moonlets. Such interactions result in either moonlet-moonlet mergers, moonlet ejections or infall of moonlets on the Earth. The latter possibility, leading to low-velocity moonlet-Earth collisions is explored here for the first time. We make use of SPH simulations and consider a range of moonlet masses, collision impact-angles and initial proto-Earth rotation rates. We find that grazing/tidal-collisions are the most frequent and produce comparable fractions of accreted-material and debris. The latter typically clump in smaller moonlets that can potentially later interact with other moonlets. Other collision geometries are more rare. Head-on collisions do not produce much debris and are effectively perfect mergers. Intermediate impact angles result in debris mass-fractions in the range of 2-25% where most of the material is unbound. Retrograde collisions produce more debris than prograde collisions, whose fractions depend on the proto-Earth initial rotation rate. Moonfalls can slightly change the rotation-rate of the proto-Earth. Accreted moonfall material is highly localized, potentially explaining the isotopic heterogeneities in highly siderophile elements in terrestrial rocks, and possibly forming primordial super-continent topographic features. Our results can be used for simple scaling laws and applied to n-body studies of the formation of the Earth and Moon.
The effect of dictionary omissions on phylogenies computationally inferred from lexical data
2018-06-22

Abstract Lexical datasets used for computational phylogenetic inference suffer a unique type of data error. Some words actually present in a language may be absent from the dataset at no fault of its curators: especially for lesser-studied languages, a word may be missing from all available sources such as dictionaries. It is thus important to be able to (i) check how robust one’s inferences are to dictionary omission errors, and (ii) incorporate the knowledge that such errors may be present into one’s inference. I introduce two simple techniques that work towards those goals, and study the possible effects of dictionary omission errors in two real-life case studies on the Lezgian and Uralic datasets from Kassian (2015) and Syrjänen et al. (2013), respectively. The effects of dictionary omission turn out to be moderate (Lezgian) to negligible (Uralic), and certainly far less significant than the possible effects of modeling choices, including priors, on the inferred phylogeny, as demonstrated in the Uralic case study. Assessing the possible effects of dictionary omissions is advisable, but severe problems are unlikely. Collecting significantly larger lexical datasets, in order to overcome sensitivity to priors, is likely more important than expending resources on verifying data against dictionary omissions.
Swelling and aggregation of Leonardite upon pH change and PbII binding: an AFM study
2018-06-24

Environmental context Natural organic materials, such as humic substances, play key roles in the binding and environmental fate of metals. We study the interaction of protons and metal ions with humic acids, and show changes to the mechanical properties of the particles and their capability to fix metal pollutants. The results will help refine current models of metal behaviour in the environment. Abstract The swelling and aggregation of Leonardite humic acid, due to acid–base and PbII binding interactions, was studied through atomic force microscopy (AFM) tapping mode measurements and correlated with potentiometric experiments. These experiments allowed determination of parameters for the non-ideal competitive adsorption (NICA)-elastic polyelectrolyte network (EPN) model, which predicts size and electrostatic potential changes. AFM observations showed growth of agglomerates at low pH values. Height distribution analysis allowed discrimination of single particles from agglomerates. The size of individual particles increased slightly with pH increase. Agglomeration was evaluated through the dispersity, which increased at pH &amp;lt; 5, concomitant with a decrease of the electrostatic repulsion and an increase of protonated carboxylic groups, thus the agglomeration is attributed to both factors. In the presence of PbII, agglomeration is observed to rise strongly with the increase in metal concentration, which is attributed to bridging of humic particles by PbII ions. The AFM ex situ results suggest consistency between NICA-EPN predictions and experimental behaviour.
Antiviral and Antioxidant Potential of Fungal Endophytes of Egyptian Medicinal Plants
2018-06-25

This study aimed to explore the antioxidant potential and antiviral activity of endophytic fungi which were isolated from healthy living tissues of medicinal plants. Endophytic strains (29 different taxa) were isolated from 18 Egyptian medicinal plants collected from Saint Katherine Protectorate, Egypt. The fungal endophytes were identified based on morphological characters. All isolates were identified as ascomycetes, except two Zygomycetes strains (Absidia corymbifera and Mucor fuscus). Isolated endophytes were cultivated on potato dextrose media. The fungal metabolites were extracted by ethyl acetate and examined for their biological activities. Among 99 total extracts, only Chaetomium globosum, which was isolated from Adiantum capillus, showed a promising DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging activity (99% at 100 μg/mL). Fifteen extracts prohibited the reproduction of HSV-2 virus. On the other hand, the reproduction of VSV-virus was inhibited by sixteen endophytic extracts. The promising anti-(HSV-2 and VSV) extract of endophytic Pleospora tarda strain; that was originally isolated from the medicinal plant Ephedra aphylla, showed viral inhibitory activity of 40.7% and 15.2%, respectively. Two compounds, for which antiviral activates could be attributed, were isolated and identified as alternariol and alternariol-(9)-methyl ether using different NMR techniques from P. tarda extract. For the first time, we report here the ability of the endophytic fungus P. tarda to produce alternariol and alternariol-(9)-methyl ether. The results indicate that the endophytic fungi from medicinal plants are promising sources of bioactive compounds.
Distance and size matters: A comparison of six wildlife camera traps and their usefulness for wild birds
2018-06-25

Abstract Camera traps are increasingly used in ecological research. However, tests of their performance are scarce. It is already known from previous work that camera traps frequently fail to capture visits by animals. This can lead to a misinterpretation of ecological results such as density estimates or predation events. While previous work is mainly based on mammals, for birds, no data about if and how camera traps can be successfully used to estimate species diversity or density are available. Hence, the goal of our study was an empirical validation of six different camera traps in the field. We observed a total number of N = 4567 events (independent visits of a bird) in 100 different sessions from March 2017 until January 2018 while camera traps were deployed. In addition, N = 641 events are based on a comparison of the two close‐up camera traps especially designed for birds. These events were all directly observed by the authors. Thus, the cameras can be compared against the human observer. To give an overall assessment and a more generalizable result, we combined the data from the six camera traps and showed that bird size category (effect size = 0.207) and distance (effect size = 0.132) are the most important predictors for a successful trigger. Also, temperature had a small effect, and flock size had an impact with larger flocks being captured more often. The approach of the bird, whether it approached the camera frontally or laterally had no influence. In Table , we give some recommendations, based on our results, at which distances camera traps should be placed to get a 25%, 50%, and 75% capture rate for a given bird size.
On the magnetic field of the first Galactic ultraluminous X-ray pulsar Swift J0243.6+6124
2018-06-25

Abstract We report on the monitoring of the final stage of the outburst from the first Galactic ultraluminous X-ray pulsar Swift J0243.6+6124, which reached ∼40 Eddington luminosities. The main aim of the monitoring program with the Swift/XRT telescope was to measure the magnetic field of the neutron star using the luminosity of transition to the ‘propeller’ state. The visibility constraints, unfortunately, did not permit us to observe the source down to the fluxes low enough to detect such a transition. The tight upper limit on the propeller luminosity Lprop &amp;lt; 6.8 × 1035 erg s−1 implies the dipole component of the magnetic field B &amp;lt; 1013 G. On the other hand, the observed evolution of the pulse profile and of the pulsed fraction with flux points to a change of the emission region geometry at the critical luminosity Lcrit ∼ 3 × 1038 erg s−1 both in the rising and declining parts of the outburst. We associate the observed change with the onset of the accretion column, which allows us to get an independent estimate of the magnetic field strength close to the neutron stars surface of B &amp;gt; 1013 G. Given the existing uncertainty in the effective magnetosphere size, we conclude that both estimates are marginally compatible with each other.
Cellular Uptake Kinetics of Neutral and Charged Chemicals inin VitroAssays Measured by Fluorescence Microscopy
2018-06-25

Cellular uptake kinetics are key for understanding time-dependent chemical exposure in in vitro cell assays. Slow cellular uptake kinetics in relation to the total exposure time can considerably reduce the biologically effective dose. In this study, fluorescence microscopy combined with automated image analysis was applied for time-resolved quantification of cellular uptake of 10 neutral, anionic, cationic, and zwitterionic fluorophores in two reporter gene assays. The chemical fluorescence in the medium remained relatively constant during the 24-h assay duration, emphasizing that the proteins and lipids in the fetal bovine serum (FBS) supplemented to the assay medium represent a large reservoir of reversibly bound chemicals with the potential to compensate for chemical depletion by cell uptake, growth, and sorption to well materials. Hence FBS plays a role in stabilizing the cellular dose in a similar way as polymer-based passive dosing, here we term this process as serum-mediated passive dosing (SMPD). Neutral chemicals accumulated in the cells up to 12 times faster than charged chemicals. Increasing medium FBS concentrations accelerated uptake due to FBS-facilitated transport but led to lower cellular concentrations as a result of increased sorption to medium proteins and lipids. In vitro cell exposure results from the interaction of several extra- and intracellular processes, leading to variable and time-dependent exposure between different chemicals and assay setups. The medium FBS plays a crucial role for the thermodynamic equilibria as well as for the cellular uptake kinetics, hence influencing exposure. However, quantification of cellular exposure by an area under the curve (AUC) analysis illustrated that, for the evaluated bioassay setup, current in vitro exposure models that assume instantaneous equilibrium between medium and cells still reflect a realistic exposure because the AUC was typically reduced less than 20% compared to the cellular dose that would result from instantaneous equilibrium.
Trends in corneal transplantation at the University Eye Hospital in Tübingen, Germany over the last 12 years: 2004 – 2015
2018-06-25

This research showed major changes in the preferred corneal transplantation techniques and leading indications for keratoplasty over the last 12 years. More importantly, it seems that the rapid development and implementation of endothelial keratoplasty, especially the Descemet's membrane endothelial keratoplasty, has had a profound effect on and begun a new era in corneal transplantation.
Character definition and tempus optimum in comparative chondrocranial research
2018-06-25

Abstract Here, we define a research program using primordial skull characters for broad scale phylogenetic comparisons, particularly for amniotes. There are many chondrocranium descriptions in the literature, encompassing many clades of vertebrates. The definition of a comparable “tempus optimum” for fully formed chondrocrania, as developed herein, will enable discrete character definition in the sense of phylogenetic systematics. The “tempus optimum” is a time period in which the nose region shows full chondrification and the basicranium has not yet changed in its anatomy by ossification processes. For studies on heterochrony, changes in the developmental timing through evolution, the available data in the literature are insufficient. Anatomical standardizations, traceable methodological approaches and clear definitions of comparable developmental stages are needed. Moreover, for profound homology assertions of chondrocranial structures, ontogeny needs to be traced from early mesenchymal condensation, through several stages of cartilage development, up to postnatal stages, in which ossifications are already present. A holistic observation, including hard and soft tissue anatomy, is of paramount importance to generate hypotheses of homology with much explanatory power and to derive conclusions on functional morphology. For that, traditional histological methodology is needed. We exemplify the suggested approach in two case studies on the disputed laterosphenoid in turtles and crocodiles and on the homology of pila antotica in a pleurodire turtle, and, using here defined criteria, we formulate hypotheses on their homology.