Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Molecular Determinants of α7 Nicotinic Acetylcholine Receptor Allosteric Activation

The α7 nicotinic acetylcholine receptors (nAChRs) are uniquely sensitive to selective positive allosteric modulators (PAMs), which increase the efficiency of channel activation to a level greater than that of other nAChRs. Although PAMs must work in concert with “orthosteric” agonists, compounds such as GAT107 ((3aR,4S,9bS)-4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide) have the combined properties of agonists and PAMs (ago-PAM) and produce very effective channel activation (direct allosteric activation (DAA)) by operating at two distinct sites in the absence of added agonist. One site is likely to be the same transmembrane site where PAMs like PNU-120596 function. We show that the other site, required for direct activation, is likely to be solvent-accessible at the extracellular domain vestibule. We identify key attributes of molecules in this family that are able to act at the DAA site through variation at the aryl ring substituent of the tetrahydroquinoline ring system and with two different classes of competitive antagonists of DAA. Analyses of molecular features of effective allosteric agonists allow us to propose a binding model for the DAA site, featuring a largely non-polar pocket accessed from the extracellular vestibule with an important role for Asp-101. This hypothesis is supported with data from site-directed mutants. Future refinement of the model and the characterization of specific GAT107 analogs will allow us to define critical structural elements that can be mapped onto the receptor surface for an improved understanding of this novel way to target α7 nAChR therapeutically.
Lateralized interactive social content and valence processing within the human amygdala

In the past, the amygdala has generally been conceptualized as a fear-processing module. Recently, however, it has been proposed to respond to all stimuli that are relevant with respect to the current needs, goals, and values of an individual. This raises the question of whether the human amygdala may differentiate between separate kinds of relevance. A distinction between emotional (vs. neutral) and social (vs. non-social) relevance is supported by previous studies showing that the human amygdala preferentially responds to both emotionally and socially significant information, and these factors might even display interactive encoding properties. However, no investigation has yet probed a full 2 (positive vs. negative valence) × 2 (social vs. non-social content) processing pattern, with neutral images as an additional baseline. Applying such an extended orthogonal factorial design, our fMRI study demonstrates that the human amygdala is (1) more strongly activated for neutral social vs. non-social information, (2) activated at a similar level when viewing social positive or negative images, but (3) displays a valence effect (negative vs. positive) for non-social images. In addition, this encoding pattern is not influenced by cognitive or behavioral emotion regulation mechanisms, and displays a hemispheric lateralization with more pronounced effects on the right side. Finally, the same valence × social content interaction was found in three additional cortical regions, namely the right fusiform gyrus, right anterior superior temporal gyrus, and medial orbitofrontal cortex. Overall, these findings suggest that valence and social content processing represent distinct kinds of relevance that interact within the human amygdala as well as in a more extensive cortical network, likely subserving a key role in relevance detection.
The preferences for everyday living inventory: scale development and description of psychosocial preferences responses in community-dwelling elders.

PURPOSE OF THE STUDY Assessing preferences for daily life is the foundation for person-centered care delivery. This study tested a new measure, the Preferences for Everyday Living Inventory (PELI), with a large sample of community-dwelling older adults. We sought to evaluate the tool's convergent and divergent validity, identify the most commonly held preferences within the sample, and explore relationships between gender and race and strength of preferences. DESIGN AND METHODS Randomly selected African American and Caucasian home health agency clients (N = 437) were interviewed using the PELI. Respondents self-reported functional ability, physical health, affect, mental health, and five domains of psychosocial preferences. The study examined correlations among descriptive variables and preference items and used logistic regression to estimate relationships between gender and race and 55 PELI items and 10 descriptive covariates. RESULTS The study found support for the PELI's construct validity, identified seniors' most strongly held preferences across domains, and revealed significant differences in preferences by gender and race. IMPLICATIONS The PELI captures strongly held personal preferences and shows promise as a practical tool that allows providers to document client preferences and customize care accordingly.
Professional Development and Its Impact on Children in Early Childhood Education and Care: A Meta-Analysis Based on European Studies

ABSTRACT This study reviews the European evidence on the impact of professional development (PD) of pre-school educators on child outcomes. A meta-analysis investigates how PD of pre-school educators in formal pre-school centers in Europe affects child outcomes. The European studies are quite recent and limited in numbers, and our results show a significant positive effect of PD on child outcomes with an overall effect size of 0.35 (with a 95% confidence interval from 0.20 to 0.51). The magnitude is slightly smaller than corresponding results based on US studies, but indicates a general positive effect of PD on child outcomes.
Labour Supply and Taxes: New Estimates of the Responses of Wives to Husbands' Wages

In this paper, we estimate income- and substitution- labour supply and participation elasticities for Canadian married women using data from the Survey of Labour and Income Dynamics 1996-2005. We use the Canadian Tax and Credit Simulator (CTaCS) and detailed information on the structure of income at the household level to compute the marginal tax rates faced by each individual. We then use these marginal tax rates to compute net own-wage, spouse-wage, and non-labour income. We show how the magnitude of the estimated elasticities varies depending on whether net or gross wages and income are used in the estimation procedure, and quantify biases caused by using average instead of marginal tax rates. Finally, because marginal tax rates vary significantly over the sample, we use quantile regressions to compare elasticities at different points of the hours distribution. Overall, our results show that public policies now have, on average, less scope for influencing hours of work than 10 years ago. However, the quantile results show that wives working fewer hours per week are more sensitive to changes in their own or spouses' wages.
Seasonal patterns of tissue biomass and densities of symbiotic dinoflagellates in reef corals and relation to coral bleaching

Tissue biomass (ash‐free dry weight) and symbiotic dinoflagellates (density, chlorophyll a cell−1 or cm−2 of coral surface area) of five species of reef‐building corals were monitored seasonally for up to 4 yr at three different depths in the Bahamas. The lowest values of all tissue biomass and algal symbiont parameters occurred during the late summer–fall sample periods. In contrast, the highest densities and pigment content of symbionts usually occurred during the winter, whereas tissue biomass peaked most often in the spring, the time lag implying a functional relationship between these variables. Corals living in shallow water often (but not always) had higher levels of all parameters measured compared to deeper corals, except chlorophyll a content, which usually displayed the opposite trend. The results show that corals from all depths exhibited bleaching (loss of symbiotic dinoflagellates and/or their pigments) every year, regardless of whether they appeared white, tan, or mottled to the human eye. We speculate that these patterns are driven by seasonal changes in light and temperature on algal and animal physiology. Furthermore, we hypothesize that all tropical reef‐building corals, world‐wide, exhibit similar predictable cycles in their tissue biomass and symbiotic algae.
Healing Fears, Conquering Challenges: Narrative Outcomes From a Wilderness Therapy Program

ABSTRACT Despite the number of studies containing evaluations of the effectiveness of wilderness therapy, in the extant literature there is little research regarding participant views that account for the successful outcomes reported. This qualitative study contains an investigation of the narratives of staff and residents at a youth-focused therapeutic community who took part in a wilderness program. The researchers of this study seek to identify what the participants consider meaningful and the most significant change that took place within the participants as a result of taking part in the wilderness program. Data analysis reveals a sequential stage-model emphasizing the importance of relationship to: (a) professional staff; (b) nature as a healing modality; (c) peers; and (d) self, with all four categories contributing to improved mental health in specific ways. Links bridging these relationships and the factors influencing the strength of those links are also discussed. Findings inform design and practice of future wilderness programs, staff training, and directions for further research.
Strutting Hero, Sneaking Villain: Utilizing Body Motion Cues to Predict the Intentions of Others

A better understanding of how intentions and traits are perceived from body movements is required for the design of more effective virtual characters that behave in a socially realistic manner. For this purpose, realistic body motion, captured from human movements, is being used more frequently for creating characters with natural animations in games and entertainment. However, it is not always clear for programmers and designers which specific motion parameters best convey specific information such as certain emotions, intentions, or traits. We conducted two experiments to investigate whether the perceived traits of actors could be determined from their body motion, and whether these traits were associated with their perceived intentions. We first recorded body motions from 26 professional actors, who were instructed to move in a “hero”-like or a “villain”-like manner. In the first experiment, 190 participants viewed individual video recordings of these actors and were required to provide ratings to the body motion stimuli along a series of different cognitive dimensions (intentions, attractiveness, dominance, trustworthiness, and distinctiveness). The intersubject ratings across observers were highly consistent, suggesting that social traits are readily determined from body motion. Moreover, correlational analyses between these ratings revealed consistent associations across traits, for example, that perceived “good” intentions were associated with higher ratings of attractiveness and dominance. Experiment 2 was designed to elucidate the qualitative body motion cues that were critical for determining specific intentions and traits from the hero- and villain-like body movements. The results revealed distinct body motions that were readily associated with the perception of either “good” or “bad” intentions. Moreover, regression analyses revealed that these ratings accurately predicted the perception of the portrayed character type. These findings indicate that intentions and social traits are communicated effectively via specific sets of body motion features. Furthermore, these results have important implications for the design of the motion of virtual characters to convey desired social information.
Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels

Plant polyphenols have been shown to enhance the differentiation of acute myeloid leukemia (AML) cells induced by the hormonal form of vitamin D3 (1α,25-dihydroxyvitamin D3; 1,25D). However, how these agents modulate 1,25D effects in different subtypes of AML cells remains poorly understood. Here, we show that both carnosic acid (CA) and silibinin (SIL) synergistically enhancd 1,25D-induced differentiation of myeloblastic HL60 cells. However, in promonocytic U937 cells, only CA caused potentiation while SIL attenuated 1,25D effect. The enhanced effect of 1,25D+CA was accompanied by increases in both the vitamin D receptor (VDR) and retinoid X receptor alpha (RXRα) protein levels and vitamin D response element (VDRE) transactivation in both cell lines. Similar increases were observed in HL60 cells treated with 1,25D + SIL. In U937 cells, however, SIL inhibited 1,25D-induced VDRE transactivation concomitant with downregulation of RXRα at both transcriptional and posttranscriptional levels. These inhibitory effects correlated with the inability of SIL, with or without 1,25D, to activate the Nrf2/antioxidant response element signaling pathway in U937 cells. These results suggest that opposite effects of SIL on 1,25D-induced differentiation of HL60 and U937 cells may be determined by cell-type-specific signaling and transcriptional responses to this polyphenol resulting in differential modulation of RXRα expression.
Manual GO annotation of predictive protein signatures: the InterPro approach to GO curation

InterPro amalgamates predictive protein signatures from a number of well-known partner databases into a single resource. To aid with interpretation of results, InterPro entries are manually annotated with terms from the Gene Ontology (GO). The InterPro2GO mappings are comprised of the cross-references between these two resources and are the largest source of GO annotation predictions for proteins. Here, we describe the protocol by which InterPro curators integrate GO terms into the InterPro database. We discuss the unique challenges involved in integrating specific GO terms with entries that may describe a diverse set of proteins, and we illustrate, with examples, how InterPro hierarchies reflect GO terms of increasing specificity. We describe a revised protocol for GO mapping that enables us to assign GO terms to domains based on the function of the individual domain, rather than the function of the families in which the domain is found. We also discuss how taxonomic constraints are dealt with and those cases where we are unable to add any appropriate GO terms. Expert manual annotation of InterPro entries with GO terms enables users to infer function, process or subcellular information for uncharacterized sequences based on sequence matches to predictive models. Database URL: http://www.ebi. ac.uk/interpro. The complete InterPro2GO mappings are available at: ftp://ftp.ebi. ac.uk/pub/databases/GO/goa/external2go/interpro2go
Candidate Milky Way satellites in the Galactic halo

Aims. Sloan Digital Sky Survey (SDSS) DR5 photometric data with 120 ◦ <α <270 ◦ ,2 5 ◦ <δ< 70 ◦ were searched for new Milky Way companions or substructures in the Galactic halo. Methods. Five candidates are identified as overdense faint stellar sources that have color-magnitude diagrams similar to those of known globular clusters, or dwarf spheroidal galaxies. The distance to each candidate is estimated by fitting suitable stellar isochrones to the color-magnitude diagrams. Geometric properties and absolute magnitudes are roughly measured and used to determine whether the candidates are likely dwarf spheroidal galaxies, stellar clusters, or tidal debris. Results. SDSSJ1000+5730 and SDSSJ1329+2841 are probably faint dwarf galaxy candidates while SDSSJ0814+5105, SDSSJ0821+5608, and SDSSJ1058+2843 are very likely extremely faint globular clusters. Conclusions. Follow-up study is needed to confirm these candidates.
On normal subgroups in the fundamental groups of complex surfaces

We show that for each aspherical compact complex surface X whose funda- mental groupfits into a short exact sequence 1 → K → � → �1(S) → 1 where S is a compact hyperbolic Riemann surface and the group K is finitely- presentable, there is a complex structure on S and a nonsingular holomorphic fibration f : X → S which induces the above short exact sequence. In partic- ular, the fundamental groups of compact complex-hyperbolic surfaces cannot fit into the above short exact sequence. As an application we give the first example of a non-coherent uniform lattice in Isom(H 2 ).
Migration, identity and risk: the experiences of migrant male sex workers in London

This dissertation explores the experiences of migration and sex work amongst migrant males operating in London. Twenty-five non-UK born males, who were working as independent internet-based escorts, contributed to this study. This investigation used convenience sampling selection to recruit participants from two sexual health programmes specialising in male sex workers in London. The data was compiled through in-depth interviews and analysed using thematic analysis. This study provides connections between the trajectories that participants reported towards the UK and the routes of entry in to sex work. It also delivers insights about their experiences operating as independent internet-based escorts in London. Finally, it contributes information about their risk perception and unprotected sex experiences in the context of commercial sex, which allows the contemplation of risky sexual behaviour from the perspective of an occupational risk.
“He Is Just the Nowhere Man of British Politics”: Personal Attacks in Prime Minister’s Questions

Views from the media, the public, and from inside Parliament have expressed discontent with, reportedly, recent high levels of personally antagonistic behavior in Prime Minister’s Questions. The focus of this study is a fine-grained analysis of language classified as a personal attack. A personal attack coding system was devised, and significant individual differences between Prime Ministers and increases across individual premierships were observed. Of the five Prime Ministers between 1979 and 2016, David Cameron was the most personally aggressive, though a significant decrease followed Jeremy Corbyn’s appointment as Leader of the Opposition. Potential explanations for recent highs include heightened TV and social media attention coupled with sports-like reporting and party expectation, and not discounting individual personalities or intergroup theories. Suggestions for the functions of personal attacks include highlighting differences, disarming or deconstructing adversaries, and equivocation. Further explanations are offered for the relative politeness of Cameron versus Corbyn.
Voltage-sensitive dye imaging reveals improved topographic activation of cortex in response to manipulation of thalamic microstimulation parameters

Voltage-sensitive dye imaging was used to quantify in vivo, network level spatiotemporal cortical activation in response to electrical microstimulation of the thalamus in the rat vibrissa pathway. Thalamic microstimulation evoked a distinctly different cortical response than natural sensory stimulation, with response to microstimulation spreading over a larger area of cortex and being topographically misaligned with the cortical column to which the stimulated thalamic region projects. Electrical stimulation with cathode-leading asymmetric waveforms reduced this topographic misalignment while simultaneously increasing the spatial specificity of the cortical activation. Systematically increasing the asymmetry of the microstimulation pulses revealed a continuum between symmetric and asymmetric stimulation that gradually reduced the topographic bias. These data strongly support the hypothesis that manipulation of the electrical stimulation waveform can be used to selectively activate specific neural elements. Specifically, our results are consistent with the prediction that cathode-leading asymmetric waveforms preferentially stimulate cell bodies over axons, while symmetric waveforms preferentially activate axons over cell bodies. The findings here provide some initial steps toward the design and optimization of microstimulation of neural circuitry, and open the door to more sophisticated engineering tools, such as nonlinear system identification techniques, to develop technologies for more effective control of activity in the nervous system.
Effect of Drought and Topographic Position on Depth of Soil Water Extraction of Pinus sylvestris L. var. mongolica Litv. Trees in a Semiarid Sandy Region, Northeast China

Drought and topographic position are the most important factors influencing tree growth and survival in semiarid sandy regions of Northeast China. However, little is known about how trees respond to drought in combination with topographic position by modifying the depth of soil water extraction. Therefore, we identified water sources for 33-year-old Mongolian pine (Pinus sylvestris L. var. mongolica Litv.) trees growing at the top and bottom of sand dunes by comparing stable isotopes δ2H and δ18O in twig xylem water, soil water at various depths and groundwater during dry and wet periods. Needle carbon isotope composition (δ13C) was simultaneously measured to assess water use efficiency. Results showed that when soil moisture was low during the dry period, trees at the top used 40–300 cm soil water while trees at the bottom utilized both 40–300 cm soil water and possibly groundwater. Nevertheless, when soil moisture at 0–100 cm depth was higher during the wet period, it was the dominant water sources for trees at both the top and bottom. Moreover, needle δ13C in the dry period were significantly higher than those in the wet period. These findings suggested that trees at both the top and bottom adjust water uptake towards deeper water sources and improve their water use efficiency under drought condition. Additionally, during the dry period, trees at the top used shallower water sources compared with trees at the bottom, in combination with significantly higher needle δ13C, indicating that trees at the bottom applied a relatively more prodigal use of water by taking up deeper water (possibly groundwater) during drought conditions. Therefore, Mongolian pine trees at the top were more susceptible to suffer dieback under extreme dry years because of shallower soil water uptake and increased water restrictions. Nevertheless, a sharp decline in the groundwater level under extreme dry years had a strong negative impact on the growth and survival of Mongolian pine trees at the bottom due to their utilization of deeper water sources (possibly groundwater).
Neuroprotective Effects of Methyl 3,4-Dihydroxybenzoate against TBHP-Induced Oxidative Damage in SH-SY5Y Cells

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB or N-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 μM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2′,7′-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells.