Miracle-dz/UniFAR-FTUs huggingface dataset:
A developmental conundrum

Wnt signaling orchestrates morphogenetic processes in which changes in gene expression are associated with dramatic changes in cell organization within developing tissue/organss. Upon signaling, excess β-catenin not utilized at cell–cell junctions becomes stabilized, where it can provide the transcriptional activating domain for Lef/Tcf DNA binding proteins. In skin epithelium, forced stabilization of β-catenin in epidermis promotes hair follicle morphogenesis, whereas conditional removal of β-catenin in hair progenitor cells specifies an epidermal fate. We now report that a single protein, a stabilized version of β-catenin lacking the COOH-terminal transactivation domain, acts in epidermis to promote hair fates and in hair cells to promote epidermal fate. This reveals fundamental differences in ways that epidermal and hair cells naturally respond to β-catenin signaling. In exploring the phenotype, we uncovered mechanistic insights into the complexities of Lef1/Tcf/β-catenin signaling. Importantly, how a cell will respond to the transgene product, where it will be localized, and whether it can lead to activation of endogenous β-catenin/Tcf/Lef complexes is specifically tailored to skin stem cells, their particular lineage and their relative stage of differentiation. Finally, by varying the level of β-catenin signaling during a cell fate program, the skin cell appears to be pliable, switching fates multiple times.
Beneficial effects of the micronized purified flavonoid fraction (MPFF*, Daflon® 500 mg) on microvascular damage elicited by sclerotherapy

Objectives To evaluate if the micronized purified flavonoid fraction (MPFF) treatment could reduce the side effects of sclerotherapy (a procedure frequently used to treat venous disease manifestations) by minimizing the inflammatory response within the surrounding tissues. Method Twenty-two male New Zealand rabbits were treated by gavage with micronized purified flavonoid fraction (MPFF; 300 mg/kg/day) or vehicle (10% lactose solution) during 21 consecutive days, starting 7 days before sclerotherapy. The sclerotherapy consisted of an injection containing 5% ethanolamine oleate solution in the rabbit’s dorsal ear vein. Before and after sclerotherapy, venular and arteriolar diameters, microvascular permeability, functional capillary density (FCD), number of rolling and sticking leukocytes were evaluated on ear microcirculation. Images of the sclerotherapy site were taken before and after the procedure. Results Compared to placebo, MPFF treatment prevented the increase in venular diameter, preserved FCD (P < 0.001) and reduced the number of leaky sites (P < 0.001) and sticking leukocytes (P < 0.001). Imaging confirmed these effects on thrombosis and perivascular edema of the sclerosed vein, 14 days after procedure. Conclusion MPFF treatment limited the postsclerotherapy inflammation in surrounding microvascular network, suggesting that MPFF may prevent undesirable secondary effects of the procedure in this animal model. This study warrants further investigation for its use in clinical conditions.
Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide (18F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18F-GE180 PET in (older) healthy controls. Methods: Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. Results: 18F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (VT) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a VT highly consistent with VT in the kinetic model, which could be used for voxelwise analysis. Conclusion: We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low VT, the methodology presented here forms the basis for quantification for future PET studies using 18F-GE180 in different pathologies.
Early subjective response and acquired tolerance as predictors of alcohol use and related problems in a clinical sample.

BACKGROUND Previous studies have demonstrated that a low subjective response (SR) to alcohol is a risk factor for alcohol use disorders (AUDs), and a recent study suggests that acquired tolerance can be differentiated from initial SR and is also significantly associated with drinking problems. Because the prior study of SR and tolerance focused on a sample of moderate drinkers, the goal of the current study was to examine relations between early SR, acquired tolerance, alcohol use, and alcohol-related problems in a sample of young adults with clinically significant alcohol problems. METHODS The current study examined associations between early SR and acquired tolerance and both drinking behavior and alcohol-related problems within a sample of 113 heavy drinking young adults (66.1% male) volunteering for a clinical trial of naltrexone in combination with brief motivational counseling. RESULTS Consistent with the 1 prior study examining simultaneous effects of early SR and tolerance, both early SR and acquired tolerance were positively associated with typical drinking behavior, although tolerance was a much stronger predictor within this clinical sample. In contrast to the prior study, early SR was inversely associated with risk for alcohol-related problems, and tolerance was not a significant predictor of problems. CONCLUSIONS The results suggested that, controlling for weekly drinking, a low early SR protected against acute negative consequences within a sample of heavy drinkers who had acquired significant tolerance to alcohol effects. It is possible that this protective effect may eventually shift to a risk factor by allowing individuals with a low SR to persist in a pattern of hazardous drinking.
Please Scroll down for Article Journal of Sports Sciences Motion Analysis of Match-play in Elite U12 to U16 Age-group Soccer Players Motion Analysis of Match-play in Elite U12 to U16 Age-group Soccer Players

(2010) 'Motion analysis of match-play in elite U12 to U16 age-group soccer players', This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Abstract The aim of this study was to quantify the motion demands of match-play in elite U12 to U16 age-group soccer players. Altogether, 112 players from two professional soccer clubs at five age-group levels (U12–U16) were monitored during competitive matches (n ¼ 14) using a 5 Hz non-differential global positioning system (NdGPS). Velocity thresholds were normalized for each age-group using the mean squad times for a flying 10 m sprint test as a reference point. Match performance was reported as total distance, high-intensity distance, very high-intensity distance, and sprint distance. Data were reported both in absolute (m) and relative (m Á min 71) terms due to a rolling substitute policy. The U15 (1.35 + 0.09 s) and U16 (1.31 + 0.06 s) players were significantly quicker than the U12 (1.58 + 0.10 s), U13 (1.52 + 0.07 s), and U14 (1.51 + 0.08 s) players in the flying 10 m sprint test (P 5 0.001). The U16 age-group covered significantly more absolute total distance (U16 4 U12, U13, U14), high-intensity distance (U16 4 U12, U13, U14, U15), very high-intensity distance (U16 4 U12, U13), and sprint distance (U16 4 U12, U13) than their younger counterparts (P 5 0.05). When the data are considered relative to match exposure, few differences are apparent. Training prescription for youth soccer players should consider the specific demands of competitive match-play in each age-group.
Pointing and naming are not redundant: children use gesture to modify nouns before they modify nouns in speech.

Nouns form the first building blocks of children's language but are not consistently modified by other words until around 2.5 years of age. Before then, children often combine their nouns with gestures that indicate the object labeled by the noun, for example, pointing at a bottle while saying "bottle. " These gestures are typically assumed to be redundant with speech. Here we present data challenging this assumption, suggesting that these early pointing gestures serve a determiner-like function (i.e., point at bottle + "bottle" = that bottle). Using longitudinal data from 18 children (8 girls), we analyzed all utterances containing nouns and focused on (a) utterances containing an unmodified noun combined with a pointing gesture and (b) utterances containing a noun modified by a determiner. We found that the age at which children first produced point + noun combinations predicted the onset age for determiner + noun combinations. Moreover, point + noun combinations decreased following the onset of determiner + noun constructions. Importantly, combinations of pointing gestures with other types of speech (e.g., point at bottle + "gimme" = gimme that) did not relate to the onset or offset of determiner + noun constructions. Point + noun combinations thus appear to selectively predict the development of a new construction in speech. When children point to an object and simultaneously label it, they are beginning to develop their understanding of nouns as a modifiable unit of speech.
Associations Between Adding a Radial Artery Graft to Single and Bilateral Internal Thoracic Artery Grafts and Outcomes: Insights From the Arterial Revascularization Trial

Background: Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART. Methods: Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies. Results: Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1–3.4), 3.5% (95% CI, 2.1–5.0), and 4.4% (95% CI, 2.8–6.0) in the RA group and 3.4% (95% CI, 2.0–4.8), 4.0% (95% CI, 2.5–5.6), and 7.6% (95% CI, 5.5–9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5–11.0) compared with the SVG group (13.6%; 95% CI, 10.8–16.3; P=0.005). This association was present when an RA graft was used to supplement both SITA and BITA grafts (interaction P=0.62). Conclusions: This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts. Clinical Trial Registration: URL: https://www.situ. ox.ac. uk/surgical-trials/art. Unique identifier: ISRCTN46552265.
Toward software defined smart home

In recent years, the smart home field has caught wide attention and witnessed rapid development. Smart devices, continuously increasing in number, make user management and implementation more difficult while promoting the development of the smart home. How to design an efficient smart home management platform is one of the great challenges the current smart home field faces. This article refers to the core idea of SDN, and proposed the software defined smart home platform, SDSH for short. The design features of virtualization, openness, and centralization can effectively integrate the heterogeneous network devices in the smart home platform, and flexibly adapt to the great difference between family scenes and user demands. At the same time, this article brings up the core technology of SDSH, and discusses the application value of the four core technologies and the new challenges the current technology is facing in a smart home scenario. In the end, regarding the SDSH application scenarios, this article analyzes the household experience innovation brought by this kind of smart home management platform, and the opportunities and challenges the SDSH platform faces.
Foraging Value, Risk Avoidance, and Multiple Control Signals: How the Anterior Cingulate Cortex Controls Value-based Decision-making

Recent work on the role of the ACC in cognition has focused on choice difficulty, action value, risk avoidance, conflict resolution, and the value of exerting control among other factors. A main underlying question is what are the output signals of ACC, and relatedly, what is their effect on downstream cognitive processes? Here we propose a model of how ACC influences cognitive processing in other brain regions that choose actions. The model builds on the earlier Predicted Response Outcome model and suggests that ACC learns to represent specifically the states in which the potential costs or risks of an action are high, on both short and long timescales. It then uses those cost signals as a basis to bias decisions to minimize losses while maximizing gains. The model simulates both proactive and reactive control signals and accounts for a variety of empirical findings regarding value-based decision-making.
Attention Focusing for Neural Machine Translation by Bridging Source and Target Embeddings

In neural machine translation, a source sequence of words is encoded into a vector from which a target sequence is generated in the decoding phase. Differently from statistical machine translation, the associations between source words and their possible target counterparts are not explicitly stored. Source and target words are at the two ends of a long information processing procedure, mediated by hidden states at both the source encoding and the target decoding phases. This makes it possible that a source word is incorrectly translated into a target word that is not any of its admissible equivalent counterparts in the target language. In this paper, we seek to somewhat shorten the distance between source and target words in that procedure, and thus strengthen their association, by means of a method we term bridging source and target word embeddings. We experiment with three strategies: (1) a source-side bridging model, where source word embeddings are moved one step closer to the output target sequence; (2) a target-side bridging model, which explores the more relevant source word embeddings for the prediction of the target sequence; and (3) a direct bridging model, which directly connects source and target word embeddings seeking to minimize errors in the translation of ones by the others. Experiments and analysis presented in this paper demonstrate that the proposed bridging models are able to significantly improve quality of both sentence translation, in general, and alignment and translation of individual source words with target words, in particular.
Identification of a DEF-type Docking Domain for Extracellular Signal-regulated Kinases 1/2 That Directs Phosphorylation and Turnover of the BH3-only Protein BimEL*

The BH3-only protein, Bim, exists as three splice variants (BimS, BimL, and BimEL) of differing pro-apoptotic potency. BimEL, the least effective killer, is degraded by the proteasome in response to phosphorylation by extracellular signal-regulated kinases 1 and 2 (ERK1/2). ERK1/2-dependent phosphorylation correlates with the presence of a domain unique to the BimEL splice variant that includes the major ERK1/2 phosphorylation site Ser65. However, efficient phosphorylation by ERK1/2, c-Jun N-terminal kinase, or p38 requires the presence in the substrate of a discrete kinase-docking domain as well as the phosphoacceptor site. Here we show that the region unique to BimEL (amino acids 41–97) harbors two potential DEF-type ERK1/2 kinase-docking domains, DEF1 and DEF2. Peptide competition assays revealed that the DEF2 peptide could act autonomously to bind active ERK1/2, whereas the DEF1 peptide did not. Truncation analysis identified a minimal region, residues 80–97, containing the DEF2 motif as sufficient for ERK1/2 binding. Mutation of key residues in the DEF2 motif abolished the interaction of ERK1/2 and BimEL and also abolished ERK1/2-dependent phosphorylation of BimEL in vivo, thereby stabilizing the protein and enhancing cytotoxicity. Our results identify a new physiologically relevant functional motif in BimEL that may account for the distinct biological properties of this splice variant.
Computerised cognitive behaviour therapy (cCBT) as treatment for depression in primary care (REEACT trial): large scale pragmatic randomised controlled trial

Study question How effective is supported computerised cognitive behaviour therapy (cCBT) as an adjunct to usual primary care for adults with depression? Methods This was a pragmatic, multicentre, three arm, parallel randomised controlled trial with simple randomisation. Treatment allocation was not blinded. Participants were adults with symptoms of depression (score ≥10 on nine item patient health questionnaire, PHQ-9) who were randomised to receive a commercially produced cCBT programme (“Beating the Blues”) or a free to use cCBT programme (MoodGYM) in addition to usual GP care. Participants were supported and encouraged to complete the programme via weekly telephone calls. Control participants were offered usual GP care, with no constraints on the range of treatments that could be accessed. The primary outcome was severity of depression assessed with the PHQ-9 at four months. Secondary outcomes included health related quality of life (measured by SF-36) and psychological wellbeing (measured by CORE-OM) at four, 12, and 24 months and depression at 12 and 24 months. Study answer and limitations Participants offered commercial or free to use cCBT experienced no additional improvement in depression compared with usual GP care at four months (odds ratio 1.19 (95% confidence interval 0.75 to 1.88) for Beating the Blues v usual GP care; 0.98 (0.62 to 1.56) for MoodGYM v usual GP care). There was no evidence of an overall difference between either programme compared with usual GP care (0.99 (0.57 to 1.70) and 0.68 (0.42 to 1.10), respectively) at any time point. Commercially provided cCBT conferred no additional benefit over free to use cCBT or usual GP care at any follow-up point. Uptake and use of cCBT was low, despite regular telephone support. Nearly a quarter of participants (24%) had dropped out by four months. The study did not have enough power to detect small differences so these cannot be ruled out. Findings cannot be generalised to cCBT offered with a much higher level of guidance and support. What this study adds Supported cCBT does not substantially improve depression outcomes compared with usual GP care alone. In this study, neither a commercially available nor free to use computerised CBT intervention was superior to usual GP care. Funding, competing interests, data sharing Commissioned and funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project No 06/43/05). The authors have no competing interests. Requests for patient level data will be considered by the REEACT trial management group Trial registration Current Controlled Trials ISRCTN91947481.
Language as a social reality: The effects of the infantilization of women

The current study examined how people’s perceptions can be affected by various terms used to describe women. Participants from a Midwestern university read a script describing 26-year-old Erin either as a “woman,” a “girl,” or “person. ” Participants then rated Erin on eighteen different traits (e.g., mature, forceful). They also completed an ambivalent sexism scale and answered three questions about their use and interpretations of the terms “girl” and “woman. ” It was predicted that the participants in the “woman” condition would rate Erin as more mature, responsible, warm, understanding, and successful than the participants in the “girl” condition. Also, it was predicted that those in the “girl” condition would rate Erin as more feminine, gullible, and childlike. A research question asked how differing levels of ambivalent sexism might affect the ratings of Erin. Only 34% of participants were able to correctly recall how Erin was described in the scenario (i.e., girl, woman, person). There were few effects of gender or interactions, with no main effects of condition. Overall, higher levels of ambivalent sexism did significantly correlate with a few trait ratings of Erin. The qualitative results showed that over half of the participants reported using “girl” and less than a third reported using “woman” as their main term for adult females. Additionally, “girl” is often interpreted as more childlike, whereas “woman” is often interpreted as more adult-like. Although the manipulation did not seem to be effective, there was some evidence that there is some sort of effect of whether a woman is referred to as a “woman,” “girl,” or “person. ” LANGUAGE AS A SOCIAL REALITY: THE EFFECTS OF THE INFANTILIZATION OF WOMEN A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree Master of Arts