julilili42/papers huggingface dataset:
A Rare-Earth-Metal Ensemble of the Tebbe Reagent: Scope of Coligands and Carbonyl Olefination
2020-09-23

Treatment of the half-sandwich complexes CpRLn(AlMe4)2 (CpR = C5Me5, C5Me4SiMe3; Ln = Y, La, Lu) with the mild halogenido transfer reagents SiMe3X (X = Cl, Br, I) resulted in efficient and selective halogenido/tetramethylaluminato exchange. Depending on the size of the rare-earth metal, dimeric [CpRLn(AlMe4)(μ-X)]2 (Ln = Y, Lu) and decametallic [CpR3La3(AlMe4)2(μ-X)4]2 could be obtained. Donor (THF)-induced tetramethylaluminato cleavage gave access to "methyl-free" mixed methylidene/halogenido complexes CpR3Ln3(μ-X)3(μ3-X)(μ3-CH2)(THF)3 for yttrium (X = Cl, Br) and lanthanum (X = Cl, Br, I) in good yields. Additionally, mixed methylidene/halogenido Y(III) complexes could be obtained via methyl/halogenido exchange employing (C5Me5)3Y3(μ-Me)3(μ3-Me)(μ3-CH2)(THF)2 and SiMe3X via tetramethylsilane elimination. All methylidene complexes were probed in olefination reactions and found to act as efficient Schrock-type nucleophilic carbenes converting ketones and aldehydes into the respective terminal alkenes. Such reactivity is as high as that of the prominent Tebbe reagent but is less tolerant toward sterically demanding and functionalized substrates (such as esters). In contrast to the Tebbe reagent, complexes CpR3Ln3(μ-X)3(μ3-X)(μ3-CH2)(THF)3 polymerize δ-valerolactone in an efficient manner, generating polylactones with molecular weight distributions Mw/Mn as low as 1.13. Moreover, the bromido variant of the Tebbe reagent, Cp2Ti(μ-CH2)(μ-Br)AlMe2, is described, underlying similar synthesis limitations: that is, the coformation (and hence cocrystallization) of the trivalent species Cp2Ti(μ-Br)2AlMe2.
Can physical activity protect against depression and anxiety during the COVID-19 pandemic? A rapid systematic review
2020-09-23

Abstract The Covid-19 pandemic is affecting the entire world population. During the first spread, most governments have implemented quarantine and strict social distancing procedures. Similar measures during recent pandemics resulted in an increase in post-traumatic stress, anxiety and depression symptoms. The development of novel interventions to mitigate the mental health burden are of outmost importance. In this rapid review, we aimed to provide a systematic overview of the literature with regard to associations between physical activity (PA) and depression and anxiety during the COVID-19 pandemic. We searched major databases (PubMed, EMBASE, Sportdiscus, Web of Science) and preprint servers (MedRxivs, SportRxiv, ResearchGate and Google scholar), for relevant papers up to 25/07/2020. We identified a total of 21 observational studies (4 longitudinal, one cross-sectional with retrospective analysis and 16 cross-sectional), including information of 42,293 (age range = 6-70 years, median female = 68%) participants from 5 continents. The early evidence suggests that people who performed PA on a regular basis with higher volume and frequency and kept the PA routines stable, showed less symptoms of depression and anxiety. For instance, those reporting a higher total time spent in moderate to vigorous PA had 12% to 32% lower chances of presenting depressive symptoms and 15% to 34% of presenting anxiety. In order to maintain PA routines during Covid-19, specific volitional and motivational skills might be paramount to overcome Covid-19 specific barriers. Particularly, web-based technologies could be an accessible way to increase motivation and volition for PA and maintain daily PA routines.
Novel Harmicines with Improved Potency against Plasmodium
2020-09-23

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents.
Refined Analysis of a Cross-Sectional Doping Survey Among Recreational Triathletes: Support for the Nutritional Supplement Gateway Hypothesis
2020-09-23

<b>Introduction:</b> The current literature provides no consensus that nutritional supplements (NS) may provide a gateway to doping. In particular, studies in recreational athletes are lacking. Within a previous cross-sectional empirical study, our group provided first evidence that the use of NS may provide a gateway for the use of doping substances in recreational triathletes. For the present paper, we refine the analysis of the triathletes' survey in order to provide evidence for a NS gateway hypothesis in recreational athletes. <b>Methods:</b> A self-report, paper-and-pencil questionnaire was distributed to a sample of 2,997 competitive ironman and half-ironman (<i>n</i> = 1,076; 36.1%) triathletes. The randomized response technique (RRT) was used to assess the 12-month prevalence estimate for the use of doping substances. The prevalence for the use of NS was assessed by using direct questioning. Two-tailed (<i>α</i> = 0.05) large-sample <i>z</i>-tests were performed to assess whether the estimated prevalence for the use of doping substances differs significantly between users and nonusers of NS. <b>Results:</b> The 12-month prevalence estimate for the use of doping substances is significantly higher in athletes who report using NS (20.6%) compared to those who do not (11.4%; <i>z</i> = 2.595, <i>p</i> = 0.0097). <b>Conclusion:</b> The present results are consistent with the hypothesis that the use of NS provides a gateway to the use of doping substances. Therefore, doping prevention concepts should not primarily focus on preventing the use of doping substances <i>per se</i>, but should start one step earlier, namely by the use of NS.
Temperature-Driven Grafted Nanoparticle Penetration into Polymer Melt: Role of Enthalpic and Entropic Interactions
2020-09-23

Understanding the fundamentals of nanoparticle (NP) penetration into soft matter systems is indispensable for numerous applications ranging from targeted nanoparticle-based drug delivery to generating hybrid polymer nanocomposite materials. Hence, it is crucial to identify the parameters which control the extent of NP penetration. Here we study the penetration of polystyrene-grafted Au nanoparticles (PGNPs) into an entropically/enthalpically coupled soft polymer film. The system consists of two layers: ultrathin monolayer of ordered grains of PGNPs on top of a bulk polymer film. To study enthalpic effects on nanoparticle penetration, PGNP monolayer was coupled to two different polymers, polystyrene (PS) and poly(tert-butyl acrylate) (PtBA). When the temperature of the system is increased toward the glass transition temperature of underlying films, the width and extent of penetration of the PGNP layer depends on the Flory-Huggins parameter between the graft chain of the PGNPs and the underlying matrix polymer. In athermal cases (PGNP/PS) (Ï� = 0), the initially compact monolayer undergoes structural disordering and individual PGNPs penetrate into PS films to form a broad layer. However, in the second case (PGNP/PtBA) (Ï� â�� 0.26), unfavorable enthalpic interactions results in PGNPs penetrating together as a monolayer into PtBA leading to the formation of a narrow layer of PGNP. The extent of PGNP penetration is improved upon increasing the entropic and enthalpic compatibility between PGNPs and underlying bulk layer. The experimental findings are corroborated by molecular dynamics simulation studies, where the time evolution of PGNP penetration into a bottom polymer layer is found to be similar to that in experiments. Â© Copyright Â© 2020 American Chemical Society.
Can Functionalised Play Make Children Happy? A Critical Sociology Perspective
2020-09-23

The functionalisation of play basically stems from the diagnosis of a global childhood inactivity crisis, the so-called "children's obesity pandemic." Hence, in the context of the activity-related guidelines, children's play appears no longer to be unproductive and purpose-free. It is rather considered an anti-obesity tool that will help children to meet physical activity recommendations. It is questionable whether such a functionalised tool can also provide what has been called the salience of the pleasures of free-play for children. Furthermore, a "normalization" of functionalised practices of play, in turn, could stigmatize children who do not or cannot adhere to these practices. Based upon this background, this paper will take a critical sociology perspective to analyse the functionalisation and medicalisation of children's play in an individualized, mediatized, and pedagogised society. In this sense, the paper aims to pay attention to how the primary goal of play in the sense of "simply make children happy" has given way to the goal of making them healthy and functional.
Reduction of visual stimulus artifacts using a spherical tank for small, aquatic animals
2020-09-23

Abstract Delivering appropriate stimuli remains a challenge in vision research, particularly for aquatic animals such as zebrafish. Due to the shape of the water tank and the associated optical paths of light rays, the stimulus can be subject to unwanted refraction or reflection artifacts, which may spoil the experiment and result in wrong conclusions. Here, we employ computer graphics simulations and calcium imaging in the zebrafish optic tectum to show, how a spherical glass container optically outperforms many previously used water containers, including Petri dish lids. We demonstrate that aquatic vision experiments suffering from total internal reflection artifacts at the water surface or at the flat container bottom may result in the erroneous detection of visual neurons with bipartite receptive fields and in the apparent absence of neurons selective for vertical motion. Our results and demonstrations will help aquatic vision neuroscientists on optimizing their stimulation setups.
Predicting Native Chinese Readers’ Perception of Sentence Boundaries in Written Texts
2020-09-23

It is well known that sentence boundaries in Mandarin Chinese texts are to some extent flexible and subjective. Sentence boundaries are used parsimoniously in Mandarin Chinese and they often do not occur until the end of a block of clauses and so express the completeness of a meaning or an idea. Nonetheless, our hypothesis is that native Chinese depends on unspoken principles for judging the degree of completeness of meaning within a block of clauses. The concern on perceiving sentence boundaries by Chinese readers is similar as the issue of how Chinese readers segment words boundaries which has been investigated extensively. The former topic has, however, seldom been examined. The concern of our investigation is the kinds of unspoken principles or factors that play a role in detecting sentence boundaries (the practice of periods). Tackling these problems is an essential prerequisite to understanding the nature of this fundamental unit in Chinese, and gaining further insight into how Chinese readers perceive the completeness of meaning in this language. In order to clarify these issues, we conducted the re-punctuation experiments in the two separate groups (the training set vs. the testing set) that use different stimuli. Annotation data was also collected from the stimuli texts annotated by linguistic information at different levels. Logistic regression and the Bayesian statistical methods were then applied so as to test the effects of independent variables on the response variable. It turns out that the syntactic information does not affect the response variable. The logistic regression model works well in making good predictions about the data of the testing set. We propose that the sentence boundaries in Chinese are most probably semantically and textually conceptualized rather than syntactically defined.
Faculty Opinions recommendation of Efficient rational modification of non-ribosomal peptides by adenylation domain substitution.
2020-09-23

Non-ribosomal peptide synthetase (NRPS) enzymes form modular assembly-lines, wherein each module governs the incorporation of a specific monomer into a short peptide product.Modules are comprised of one or more key domains, including adenylation (A) domains, which recognise and activate the monomer substrate; condensation (C) domains, which catalyse amide bond formation; and thiolation (T) domains, which shuttle reaction intermediates between catalytic domains.This arrangement offers prospects for rational peptide modification via substitution of substrate-specifying domains.For over 20 years, it has been considered that C domains play key roles in proof-reading the substrate; a presumption that has greatly complicated rational NRPS redesign.Here we present evidence from both directed and natural evolution studies that any substrate-specifying role for C domains is likely to be the exception rather than the rule, and that novel non-ribosomal peptides can be generated by substitution of A domains alone.We identify permissive A domain recombination boundaries and show that these allow us to efficiently generate modified pyoverdine peptides at high yields.We further demonstrate the transferability of our approach in the PheATE-ProCAT model system originally used to infer C domain substrate specificity, generating modified dipeptide products at yields that are inconsistent with the prevailing dogma.
Comparison of Bead-Based Fluorescence Versus Planar Electrochemiluminescence Multiplex Immunoassays for Measuring Cytokines in Human Plasma
2020-09-24

This study compared two 96-well multiplex immunoassay platforms for analytical performance in assessing cytokine concentrations in standards, quality controls and human plasma samples (<i>n</i> = 62), and evaluated assay time requirements. Assays included a bead-based fluorescence MILLIPLEX<sup>®</sup> assay/Luminex fluorescence platform (LMX) and three kits from Meso Scale Discovery (MSD) in planar electrochemiluminescence format. The LMX kit evaluated 21 cytokines and the MSD kits evaluated 10 cytokines each, with 16 overlapping cytokines between platforms. Both assays provided good reproducibility in standard curves for all analytes. Interassay CVs of shared analytes showed average kit quality control CVs ranging 1.9-18.2% for LMX and 2.4-13.9% for MSD. The MSD platform had lower LLoQs than LMX for 14/16 shared cytokines. For IL-17, the LLoQ was lower with LMX than MSD, and the LLoQs for IL-6 were similar. Although MSD calibration curves indicated lower LLoQs for most of those analytes, many more cytokines in human plasma samples were not detected by MSD than by LMX. The ULoQs were higher in LMX versus MSD assays for 13/16 shared analytes, lower than MSD for IL-17, and equivalent between assays for IL-6 and MIP-1α. Bland-Altman plots indicated that MSD classified 13/16 shared analytes as concentrations lower than by LMX. Time and motion analysis indicated that total mean assay times were 20 h 28 m and 21 h 33 m for LMX and MSD, respectively, including an overnight (17 h) incubation. The MSD assays employed a manufacturer-approved overnight incubation instead of the standard 2-h incubation, which kit instructions suggest might increase detection sensitivity. Hands-on labor time averaged 1 h 37 m for LMX and 2 h 33 m for MSD. In summary, assay selection factors should include selection of specific markers of interest, time and cost considerations, and anticipated cytokine concentrations in prospective samples.
Transferring a Community-Based Participatory Research Project to Promote Physical Activity Among Socially Disadvantaged Women—Experiences From 15 Years of BIG
2020-09-24

<b>Introduction:</b> Community-based participatory research (CBPR) is an effective approach to health promotion, especially in relation to socially disadvantaged groups. However, the long-term implementation of CPBR-based projects on a broad scale is often challenging, and research regarding the sustainable transfer of participatory research is lacking. This limits the scaling-up and public health impact of CBPR. Therefore, this study examines the mechanisms utilized to transfer and sustain the BIG project, a multifaceted CBPR project aimed at promoting physical activity among women in difficult life situations. <b>Materials and Methods:</b> Borrowing from the RE-AIM framework, we analyzed project documentation and conducted a reflection workshop to investigate methods of transferring BIG to new sites as well as strategies from researchers to support project implementation and the maintenance of program activities at those sites. Moreover, we analyzed the reasons for discontinuing program activities at some former BIG sites and the costs involved in transferring BIG. <b>Results:</b> Since its establishment in 2005, BIG was transferred to and implemented at 17 sites. As of the winter of 2019, the program activities were maintained at eight sites. The average duration of sites that continue to offer program activities was more than 9 years. Discontinued sites maintained project activities for an average of 4 years. According to the study findings, the extent of scientific support, the provision of seed funding, and the local project coordinator, the person managing the project at the site, all have a significant impact on the sustainability of the transfer. A patchwork of funding agencies was needed to finance scientific support and seed funding in BIG. The transfer of BIG projects accrued annual costs of approximately EUR20,000 per site; however, long-term project implementation resulted in a decline in the annual transfer costs of BIG. <b>Discussion and Conclusion:</b> The sustainable transfer of CBPR is challenging but possible, and increased support of research and seed funding can facilitate long-term transfer. Nevertheless, other factors in the implementation setting are beyond scientific control. With scarce financial resources, researchers need to carefully balance the efforts of the sustainability and transfer of CBPR projects. To address this issue, there is a need for further research into the interrelationship of the sustainability and transfer of CBPR projects as well as increased long-term funding.
Network Localization of Alien Limb in Patients with Corticobasal Syndrome
2020-09-24

Objective Perirolandic atrophy occurs in corticobasal syndrome (CBS) but is not specific versus progressive supranuclear palsy (PSP). There is heterogeneity in the locations of atrophy outside the perirolandic cortex and it remains unknown why atrophy in different locations would cause the same CBS‐specific symptoms. In prior work, we used a wiring diagram of the brain called the human connectome to localize lesion‐induced disorders to symptom‐specific brain networks. Here, we use a similar technique termed “atrophy network mapping” to localize single‐subject atrophy maps to symptom‐specific brain networks. Methods Single‐subject atrophy maps were generated by comparing cortical thickness in patients with CBS versus controls. Next, we performed seed‐based functional connectivity using a large normative connectome to determine brain regions functionally connected to each patient's atrophied locations. Results Patients with CBS had perirolandic atrophy versus controls at the group level, but locations of atrophy in CBS were heterogeneous outside of the perirolandic cortex at the single‐subject level (mean spatial correlation = 0.04). In contrast, atrophy occurred in locations functionally connected to the perirolandic cortex in all patients with CBS (spatial correlation = 0.66). Compared with PSP, patients with CBS had atrophy connected to a network of higher‐order sensorimotor regions beyond perirolandic cortex, matching a CBS atrophy network from a recent meta‐analysis. Finally, atrophy network mapping identified a symptom‐specific network for alien limb, matching a lesion‐induced alien limb network and a network associated with agency in healthy subjects. Interpretation We identified a syndrome‐specific network for CBS and symptom‐specific network for alien limb using single‐subject atrophy maps and the human connectome. ANN NEUROL 2020;88:1118–1131
Comparative Transcriptional Profiling of Motor Neuron Disorder-Associated Genes in Various Human Cell Culture Models
2020-09-24

Disease modeling requires appropriate cellular models that best mimic the underlying pathophysiology. Human origin and an adequate expression of the disease protein are pre-requisites that support information from a model to be meaningful. In this study we investigated expression profiles of (i) PBMCs and (ii) fibroblasts as patient derived cells as well as (iii) lymphoblasts and (iv) induced pluripotent stem cells (iPSC) as immortalized sources, and (v) iPSC-derived cortical neurons to assess their aptitude to model motor neuron diseases (MNDs) including hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). We generated all five different cell types from two healthy donors and performed RNA sequencing to display expression patterns in MND-related genes. For the ten most common HSP genotypes we validated gene expression by qPCR. To verify the results on protein level, proteome analysis of fibroblasts, iPSCs and cortical neurons was performed. Depending on the specific MND gene we found largely different expression patterns. Out of 168 MND-related genes, 50 had their highest expression in iPSC-derived cortical neurons, 41 were most strongly expressed in fibroblasts, 26 in lymphoblasts, 22 in iPSCs, and 14 in PBMCs. Pathophysiologically related MNDs like HSPs associated with axonal transport deficits shared highest expression in cortical neurons. 15 MND-related genes were not detectable in any of the analyzed cell types. This may reflect the critical dependency of motor neurons on support of other cell types like oligodendrocytes which express myelin proteins like L1CAM (SPG1), PLP1 (SPG2) and MAG (SPG75) which are lacking in neurons but cause MNDs if mutated. This study provides comprehensive information on expression of genes associated with a large spectrum of MNDs. Expression profiles can be used to inform on appropriate cell models for genotype specific motor neuron research.