julilili42/papers huggingface dataset:
Minimal genetically encoded tags for fluorescent protein labeling in living neurons
2021-01-16

Abstract Modern light microscopy, including super-resolution techniques, brought about a demand for small labeling tags that bring the fluorophore closer to the target. This challenge can be addressed by labeling unnatural amino acids (UAAs) with click chemistry. UAAs are site-specifically incorporated into a protein of interest by genetic code expansion. If the UAA carries a strained alkene or alkyne moiety it can be conjugated to a tetrazine-bearing fluorophore via a strain-promoted inverse-electron-demand Diels–Alder cycloaddition (SPIEDAC), a variant of bioorthogonal click chemistry. The minimal size of the incorporated tag and the possibility to couple the fluorophores directly to the protein of interest with single-residue precision make SPIEDAC live-cell labeling unique. However, until now, this type of labeling has not been used in complex, non-dividing cells, such as neurons. Using neurofilament light chain as a target protein, we established SPIEDAC labeling in living primary neurons and applied it for fixed-cell, live-cell, dual-color pulse—chase and super-resolution microscopy. We also show that SPIEDAC labeling can be combined with CRISPR/Cas9 genome engineering for tagging endogenous NFL. Due to its versatile nature and compatibility with advanced microscopy techniques, we anticipate that SPIEDAC labeling will contribute to novel discoveries in neurobiology.
A multicentre study of naevus‐associated melanoma vs. de novo melanoma, tumour thickness and body site differences*
2021-01-17

Clinicopathological and body site differences between de novo melanoma and NAM support the divergent pathway model of development. These differences were also found in thin melanomas, suggesting that de novo melanomas are different from NAM and their differences are not due to the obliteration of naevus remnants in thicker tumours.
Marginal Adaptation and Microbial Leakage at Conometric Prosthetic Connections for Implant-Supported Single Crowns: An In Vitro Investigation
2021-01-17

Encouraging clinical results were reported on a novel cone-in-cone coupling for the fixation of dental implant-supported crowns (Acuris, Dentsply Sirona Implants, Mölndal, Sweden). However, the presence or absence of a microgap and a potential bacterial leakage at the conometric joint has not yet been investigated. A misfit and a resulting gap between the conometric components could potentially serve as a bacterial reservoir that promotes plaque formation, which in turn may lead to inflammation of the peri-implant tissues. Thus, a two-fold study set-up was designed in order to evaluate the bidirectional translocation of bacteria along conometrically seated single crowns. On conometric abutments filled with a culture suspension of anaerobic bacteria, the corresponding titanium nitride-coated (TiN) caps were fixed by friction. Each system was sterilized and immersed in culture medium to provide an optimal environment for microbial growth. Positive and negative controls were prepared. Specimens were stored in an anaerobic workstation, and total and viable bacterial counts were determined. Every 48 h, samples were taken from the reaction tubes to inoculate blood agar plates and to isolate bacterial DNA for quantification using qrt-PCR. In addition, one Acuris test system was subjected to scanning electron microscopy (SEM) to evaluate the precision of fit of the conometric coupling and marginal crown opening. Throughout the observational period of one week, blood agar plates of the specimens showed no viable bacterial growth. qrt-PCR, likewise, yielded a result approaching zero with an amount of about 0.53 × 10−4 μg/mL DNA. While the luting gap/marginal opening between the TiN-cap and the ceramic crown was within the clinically acceptable range, the SEM analysis failed to identify a measurable microgap at the cone-in-cone junction. Within the limits of the in-vitro study it can be concluded that the Acuris conometric interface does not allow for bacterial translocation under non-dynamic loading conditions.
Effects of alliance ruptures and repairs on outcomes
2021-01-17

CBASP was not associated with more or fewer ruptures or repairs as compared to SP in the treatment of chronic depression. The study highlights the need to resolve ruptures to avoid poor outcomes.<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT00970437.
Long‐term remission of small cell lung cancer after reactivation of tuberculosis following immune‐checkpoint blockade: A case report
2021-01-17

Abstract Immune‐checkpoint inhibitors (ICIs) provide a promising treatment option for advanced tumors including small cell lung cancer (SCLC). Nevertheless, in addition to immune‐related adverse events (irAEs), an increased risk of infection including tuberculosis has been previously described. Here, we report a case of long‐term remission of a patient with SCLC after reactivation of lung tuberculosis following ICI therapy. Our case illustrates the complexity of ICI‐associated immune modulation in tuberculosis. Since new lesions in lung cancer patients are commonly associated with tumor progression, infections with mycobacterial tuberculosis may be underdiagnosed in lung cancer.
Dopamine enhances model-free credit assignment through boosting of retrospective model-based inference
2021-01-17

Abstract Dopamine is implicated in signalling model-free (MF) reward prediction errors and various aspects of model-based (MB) credit assignment and choice. Recently, we showed that cooperative interactions between MB and MF systems include guidance of MF credit assignment by MB inference. Here, we used a double-blind, placebo-controlled, within-subjects design to test the hypothesis that enhancing dopamine levels, using levodopa, boosts the guidance of MF credit assignment by MB inference. We found that levodopa enhanced retrospective guidance of MF credit assignment by MB inference, without impacting on MF and MB influences per se. This drug effect positively correlated with working memory, but only in a context where reward needed to be recalled for MF credit assignment. The dopaminergic enhancement in MB-MF interactions correlated negatively with a dopamine-dependent change in MB credit assignment, possibly reflecting a potential trade-off between these two components of behavioural control. Thus, our findings demonstrate that dopamine boosts MB inference during guidance of MF learning, supported in part by working memory, but trading-off with a dopaminergic enhancement of MB credit assignment. The findings highlight a novel role for a DA influence on MB-MF interactions.
Investigating Genre Distinctions through Discourse Distance and Discourse Network
2021-01-17

The notion of genre has been widely explored using quantitative methods from both lexical and syntactical perspectives. However, discourse structure has rarely been used to examine genre. Mostly concerned with the interrelation of discourse units, discourse structure can play a crucial role in genre analysis because genre is closely related to discourse (text). Nevertheless, few quantitative studies have explored genre distinctions from a discourse structure perspective. Here, we use two English discourse corpora (RST-DT and GUM) to investigate the hierarchical and relational dimensions of discourse structure from a novel viewpoint. The RST-DT is divided into four small subcorpora distinguished according to genre, and another corpus (GUM) containing seven genres is used for cross-verification. An RST (rhetorical structure theory) tree is converted into dependency representations by taking information from RST annotations to calculate the discourse distance through a process similar to that used to calculate syntactic dependency distance. Moreover, the data on dependency representations stemming from the two corpora is readily convertible into network data. Afterwards, we examine different genres in the two corpora by combining discourse distance and discourse network. The two methods are mutually complementary in comprehensively revealing the distinctiveness of various genres. Accordingly, we propose an effective quantitative method for assessing genre differences using discourse distance and discourse network. This quantitative study can help us better understand the nature of genre and develop effective strategies for genre-based writing.
Sustainable data analysis with Snakemake
2021-01-18

<ns4:p>Data analysis often entails a multitude of heterogeneous steps, from the application of various command line tools to the usage of scripting languages like R or Python for the generation of plots and tables. It is widely recognized that data analyses should ideally be conducted in a reproducible way. Reproducibility enables technical validation and regeneration of results on the original or even new data. However, reproducibility alone is by no means sufficient to deliver an analysis that is of lasting impact (i.e., sustainable) for the field, or even just one research group. We postulate that it is equally important to ensure adaptability and transparency. The former describes the ability to modify the analysis to answer extended or slightly different research questions. The latter describes the ability to understand the analysis in order to judge whether it is not only technically, but methodologically valid.</ns4:p><ns4:p>Here, we analyze the properties needed for a data analysis to become reproducible, adaptable, and transparent. We show how the popular workflow management system Snakemake can be used to guarantee this, and how it enables an ergonomic, combined, unified representation of all steps involved in data analysis, ranging from raw data processing, to quality control and fine-grained, interactive exploration and plotting of final results.</ns4:p>
Energy and mass balance dynamics of the seasonal snowpack at two high-altitude sites in the Himalaya
2021-01-18

Snow dynamics play a crucial role in the hydrology of alpine catchments in the Himalaya. However, studies based on in-situ observations that elucidate the energy and mass balance of the snowpack at high altitude in this region are scarce. In this study, we use meteorological and snow observations at two high-altitude sites in the Nepalese Himalaya to quantify the mass and energy balance of the seasonal snowpack. Using a data driven experimental set-up we aim to understand the main meteorological drivers of snowmelt, illustrate the importance of accounting for the cold content dynamics of the snowpack, and gain insight into the role that snow meltwater refreezing plays in the energy and mass balance of the snowpack. Our results show an intricate relation between the sensitivity of melt and refreezing on the albedo, the importance of meltwater refreezing, and the amount of positive net energy used to overcome the cold content of the snowpack. The net energy available at both sites is primarily driven by the net shortwave radiation, and is therefore extremely sensitive to snow albedo measurements. We conclude that, based on observed snowpack temperatures, 21% of the net positive energy is used to overcome the cold content build up during the night. We also show that at least 32–34% of the snow meltwater refreezes again for both sites. Even when the cold content and refreezing are accounted for, excess energy is available beyond what is needed to melt the snowpack. We hypothesize that this excess energy may be explained by uncertainties in the measurement of shortwave radiation, an underestimation of refreezing due to a basal ice layer, a cold content increase due to fresh snowfall and the ground heat flux. Our study shows that in order to accurately simulate the mass balance of seasonal snowpacks in Himalayan catchments, simple temperature index models do not suffice and refreezing and the cold content needs to be accounted for.
Examining teacher recruitment strategies in England
2021-01-18

For national education systems, the goal of an effective teacher recruitment strategy is not simply to attract more applicants, but to attract high-quality applicants who are well suited to teaching and are likely to remain in the profession. The goal of this article is to examine teacher recruitment strategies in England and to propose new models to understand and improve these strategies. We began by reviewing personnel recruitment theories and research from education and related fields. Next, we analysed publicly available teacher recruitment strategies and messages from two key education organisations in England: the Department for Education (DfE) and Teach First. We then compared teacher recruitment strategies with strategies and models developed in health professions (as presented by the National Health Service). The findings highlight that recruitment strategy documents for DfE and Teach First emphasise administrative/system changes and personal utility messages, whereas the public-facing advertisements focus on personal utility, social utility, and to a lesser extent, the personal attributes deemed to be important for teaching. We conclude by proposing how teacher recruitment strategies in England could be more strongly grounded in relevant theoretical and empirical work.
Outcomes of Transsphenoidal Microsurgery for Prolactinomas – A Contemporary Series of 162 Cases
2021-01-18

Abstract Introduction Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged. This study is aimed at defining the current role of pituitary surgery in the management of prolactinomas. Materials and Methods In this retrospective, consecutive single-center study, 162 patients who underwent primary microscopic TSS for prolactinomas between 2006 and 2019 were analyzed regarding surgical indication, previous dopamine-agonist (DA) treatment, early remission rates (3 months postoperatively), surgical complications and pituitary function. Results Seventy-four microprolactinomas and 88 macroprolactinomas were operated by TSS. 62.3% of the patients had received prior DA treatment. For microprolactinomas, the predominant indication for surgery was patient’s wish (41.9%), while indications for macroprolactinomas varied. For enclosed microprolactinomas, the initial remission rate was 92.1%, while for macroprolactinomas, the rate was 70.4%. No significant difference of remission rates was found between DA-pretreated (65.3%) and non-pretreated (72.1%) patients (p=0.373).None of the patients suffered a significant complication. Re-operation for a postoperative cerebrospinal fluid leak was required in one patient (0.6%). Permanent postoperative deterioration of pituitary function was only observed in one of 158 patients with surgery for a prolactinoma (0.6%). Improvement of pituitary function was observed in 8 of 25 patients (32%) with preoperative deficits. Conclusion Transsphenoidal microsurgery is safe and efficient for treatment of prolactinomas. It is particularly suitable for enclosed prolactinomas. The patient should be well informed of the pros and cons of the treatment options, which include DA medication and TSS, and the patient’s preference should be taken into account during decision-making.
Precessing magnetars as central engines in short gamma-ray bursts
2021-01-18

ABSTRACT Short gamma-ray bursts that are followed by long-duration X-ray plateaus may be powered by the birth, and hydrodynamic evolution, of magnetars from compact binary coalescence events. If the rotation and magnetic axes of the system are not orthogonal to each other, the star will undergo free precession, leading to fluctuations in the luminosity of the source. In some cases, precession-induced modulations in the spin-down power may be discernible in the X-ray flux of the plateau. In this work, 25 X-ray light curves associated with bursts exhibiting a plateau are fitted to luminosity profiles appropriate for precessing, oblique rotators. Based on the Akaike Information Criterion, 16 of the magnetars within the sample display either moderate or strong evidence for precession. Additionally, since the precession period of the star is directly tied to its quadrupolar ellipticity, the fits allow for an independent measure of the extent to which the star is deformed by internal stresses. Assuming these deformations arise due to a mixed poloidal–toroidal magnetic field, we find that the distribution of magnetic-energy ratios is bimodal, with data points clustering around energetically equal and toroidally dominated partitions. Implications of this result for gravitational-wave emission and dynamo activity in newborn magnetars are discussed.
Designing Visual-Arts Education Programs for Transfer Effects: Development and Experimental Evaluation of (Digital) Drawing Courses in the Art Museum Designed to Promote Adolescents’ Socio-Emotional Skills
2021-01-18

An active engagement with arts in general and visual arts in particular has been hypothesized to yield beneficial effects beyond arts itself. So-called cognitive and socio-emotional “transfer” effects into other domains have been claimed. However, the empirical basis of these hopes is limited. This is partly due to a lack of experimental comparisons, theory-based designs, and objective measurements in the literature on transfer effects of arts education. Therefore, the aim of the present study was to design and experimentally investigate a theory-based visual-arts education program for adolescents aged between 12 and 19 years ( M age = 15.02, SD age = 1.75). The program was delivered in a museum context in three sessions and was expected to yield specific and objectively measurable transfer effects. To conduct a randomized field trial, three strictly parallelized and standardized art courses were developed, all of which addressed the topic of portrait drawing. The courses mainly differed regarding their instructional focus, which was either on periods of art history, on the facial expression of emotions, or on the self-perception of a person in the context of different social roles. In the first and more “traditional” course portrait drawing was used to better understand how portraits looked like in former centuries. The two other courses were designed in a way that the artistic engagement in portrait drawing was interwoven with practicing socio-emotional skills, namely empathy and emotion recognition in one course and understanding complex self-concept structures in the other. We expected positive socio-emotional transfer effects in the two “psychological” courses. We used an animated morph task to measure emotion recognition performance and a self-concept task to measure the self-complexity of participants before and after all three courses. Results indicate that an instructional focus on drawing the facial expressions of emotions yields specific improvements in emotion recognition, whereas drawing persons in different social roles yields a higher level of self-complexity in the self-concept task. In contrast, no significant effects on socio-emotional skills were found in the course focussing on art history. Therefore, our study provides causal evidence that visual-arts programs situated in an art-museum context can advance socio-emotional skills, when designed properly.
Lung organoids and other preclinical models of pulmonary fibrosis
2021-01-18

Summary Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease affecting over 100 000 people in Europe with an increasing incidence. Available treatments offer only slowing of disease progression and are poorly tolerated by patients leading to cessation of therapy. Lung transplant remains the only cure. Therefore, alternative treatments are urgently required. The pathology of IPF is complex and poorly understood and thus creates a major obstacle to the discovery of novel treatments. Additionally, preclinical assessment of new treatments currently relies upon animal models where disparities with human lung biology often hamper drug development. At a cellular level, IPF is characterized by persistent and abnormal deposition of extracellular matrix by fibroblasts and alveolar epithelial cell injury which is seen as a key event in initiation of disease progression. In-depth investigation of the role of alveolar epithelial cells in health and disease has been impeded due to difficulties in primary cell isolation and culture ex vivo. Novel strategies employing patient-derived induced pluripotent stem cells engineered to produce type 2 alveolar epithelial cells (iAEC2) cultured as three-dimensional organoids have the potential to overcome these hurdles and inform new effective precision treatments for IPF leading to improved survival and quality of life for patients worldwide.
Gearing Time Toward Musical Creativity: Conceptual Integration and Material Anchoring in Xenakis’ Psappha
2021-01-18

Understanding compositional practices is a major goal of musicology and music theory. Compositional practices have been traditionally viewed as disembodied and idiosyncratic. This view makes it hard to integrate musical creativity into our understanding of the general cognitive processes underlying meaning construction. To overcome this unnecessary isolation of musical composition from cognitive science, in this conceptual analysis, we approach compositional processes with the analytic tools of blending theory, material anchoring, and enaction. Our case study is Iannis Xenakis’ use of sieves for distributing rhythmic patterns in Psappha . Though disregarded in previous accounts, the timeline and the gearwheel provide crucial conceptual templates for anchoring Xenakis’ idea of time for this score. This case study of conceptual integration templates for temporal representation seeks to gain insight into musical creativity, embodiment, and blending, especially into how virtual interactions with material structures facilitate the construction of complex meanings.
N-(6-Chloro-3-nitropyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)isoquinolin-3-amine
2021-01-18

Here we describe the synthesis of N-(6-chloro-3-nitropyridin-2-yl)5-(1-methyl-1H-pyrazol-4-yl)isoquinolin-3-amine via a three-step procedure including a Buchwald–Hartwig arylamination with benzophenone imine and a highly regioselective nucleophilic aromatic substitution. The title compound was analyzed by nuclear magnetic resonance spectroscopy (1H, 13C, HSQC, HMBC, COSY, DEPT90 and NOESY), high resolution mass spectrometry (ESI-TOF-HRMS) and infrared spectroscopy (ATR-IR) and its structure was confirmed by single crystal X-ray diffraction. The inhibitory potency of the title compound was evaluated for selected kinases harboring a rare cysteine in the hinge region (MPS1, MAPKAPK2 and p70S6Kβ/S6K2).