Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemoprevention of Skin Cancer with 1,1-Bis (3′-Indolyl)-1-(Aromatic) Methane Analog through Induction of the Orphan Nuclear Receptor, NR4A2 (Nurr1)

Background The objective of this study was to demonstrate the anti-skin cancer and chemopreventive potential of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl methane) (DIM-D) using an in vitro model. Methods In vitro cell cytotoxicity and viability assays were carried out in A431 human epidermoid carcinoma cell line and normal human epidermal keratinocytes (NHEK) respectively by crystal violet staining. Apoptosis induction in A431 cells (DIM-D treated) and NHEK cells pretreated with DIM-D (2 hr) prior to UVB irradiation, were assessed. The accumulation of reactive oxygen species (ROS) in DIM-D pretreated NHEK cells (2 hr) prior to UVB exposure was also determined. Immunocytochemistry and western blot analysis was performed to determine cleaved caspase 3 and DNA damage markers in DIM-D treated A431 cells and in DIM-D pretreated NHEK cells prior to UVB irradiation. Results The IC50 values of DIM-D were 68.7±7.3, 48.3±10.1 and 11.5±3.1 μM whilst for Epigallocatechin gallate (EGCG) were 419.1±8.3, 186.1±5.2 and 56.7±3.1 μM for 24, 48 and 72 hr treatments respectively. DIM-D exhibited a significantly (p<0.05) greater induction of DNA fragmentation in A431 cells compared to EGCG with percent cell death of 38.9. In addition, DIM-D induced higher expression in A431 cells compared to EGCG of cleaved caspase 3 (3.0-fold vs. 2.4-fold changes), Nurr1 (2.7-fold vs. 1.7-fold changes) and NFκB (1.3-fold vs. 1.1-fold changes). DIM-D also exhibited chemopreventive activity in UVB-irradiated NHEK cells by significantly (p<0.05) reducing UVB-induced ROS formation and apoptosis compared to EGCG. Additionally, DIM-D induced expression of Nurr1 but reduced expression of 8-OHdG significantly in UVB-irradiated NHEK cells compared to EGCG and UV only. Conclusion Our results suggest that DIM-D exhibits Nurr1-dependent transactivation in the induction of apoptosis in A431 cells and it protects NHEK cells against UVB-induced ROS formation and DNA damage.
Melatonin in Epilepsy: A New Mathematical Model of Diurnal Secretion

Purpose. The main objective of the study was to create a mathematical model that describes the melatonin circadian secretion and, then the functionality of the model was tested by a comparison of the melatonin secretions in children with and without epilepsy. Material and Methods. The patients were divided into the epilepsy group (EG, n = 52) and the comparison group (CG, n = 30). The melatonin level was assessed by a radioimmunoassay method. The diurnal melatonin secretion was described using a nonlinear least squares method. Spearman's rank correlation coefficient was chosen to estimate the dependence of the acquired data. The model reproduces blood concentration profiles and its parameters were statistically analyzed using the Mann-Whitney-Wilcoxon test and logistic regression. Results. The correlation analysis performed for the EG and CG groups showed moderate correlations between age and the melatonin secretion model parameters. Patients with epilepsy are characterized by an increased phase shift of melatonin release.
Functional assessment of the NMDA receptor variant GluN2A R586K

Background: The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that has important roles in synaptogenesis, synaptic transmission, and synaptic plasticity. Recently, a large number of rare genetic variants have been found in NMDAR subunits in people with neurodevelopmental disorders, and also in healthy individuals. One such is the GluN2A R586K variant ( GRIN2A G1757A), found in a person with intellectual disability. Identifying the functional consequences, if any, of such variants allows their potential contribution to pathogenesis to be assessed. Here, we assessed the effect of the GluN2A R586K variant on NMDAR pore properties. Methods: We expressed recombinant NMDARs with and without the GluN2A R586K variant in Xenopus laevis oocytes and in primary cultured mouse neurons, and made electrophysiological recordings assessing Mg 2+ block, single-channel conductance, mean open time and current density. Results: The GluN2A R586K variant was not found to influence any of the properties assessed. Conclusions: Our findings suggest it is unlikely that the GluN2A R586K variant contributes to the pathogenesis of neurodevelopmental disorder.
Optical Control of Muscle Function by Transplantation of Stem Cell–Derived Motor Neurons in Mice

Optogenetics Applied to Motorneuron Control Nerves damaged by disease or injury do not always regenerate. In such cases, therapies involving transplanted stem cells show some promise. However, the new neurons derived from transplanted cells cannot communicate with the central control systems that would normally regulate movement. To avoid the need for such communication, in a proof-of-principle study, Bryson et al. (p. 94; see the Perspective by Iyer and Delp) added optogenetic control to differentiation and transplantation of motor neurons. In the mouse, these engineered neurons were able to reestablish connections within a damaged sciatic nerve and, when activated by localized light stimulation, could drive muscle contractions. Transplanted neurons controlled by light can drive muscle function in damaged mouse sciatic nerves. [Also see Perspective by Iyer and Delp] Damage to the central nervous system caused by traumatic injury or neurological disorders can lead to permanent loss of voluntary motor function and muscle paralysis. Here, we describe an approach that circumvents central motor circuit pathology to restore specific skeletal muscle function. We generated murine embryonic stem cell–derived motor neurons that express the light-sensitive ion channel channelrhodopsin-2, which we then engrafted into partially denervated branches of the sciatic nerve of adult mice. These engrafted motor neurons not only reinnervated lower hind-limb muscles but also enabled their function to be restored in a controllable manner using optogenetic stimulation. This synthesis of regenerative medicine and optogenetics may be a successful strategy to restore muscle function after traumatic injury or disease.
Subgradient Optimization in Nonsmooth Optimization (including the Soviet Revolution)

Convex nondifferentiable, also known as convex nonsmooth, optimization (NDO) looks at problems where the functions involved are not continuously differentiable. The gradient does not exist, implying that the function may have kinks or corner points, and thus cannot be approximated locally by a tangent hyperplane, or by a quadratic approximation. Directional derivatives still exist because of the convexity property. NDO problems are widespread, often resulting from reformulations of smooth, or linear problems, that are formulated in a space with much smaller number of variables than in the original problem. Examples of this are the reformulation implicit in Dantzig-Wolfe decomposition or column generation [4] and [5], which are equivalent by duality to Cheney’s cutting plane method [20]. These methods do not work well if an aggregated formulation is used. Shor’s subgradient method [35, 36] provided a superior alternative, leading to a true Soviet revolution. His work was expanded both in theory and in practice by numerous authors. Held and Karp [17], unaware of the work of Shor, developed a method for the traveling salesman problem that uses subgradient optimization to compute a bound in a Lagrangean relaxation scheme. This seminal contribution also led to a huge following; see for instance Fisher [11].
Practical consensus recommendations on management of HR + ve early breast cancer with specific reference to genomic profiling

Abstract Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.
Evaluating the plausibility of edited throwing animations

Animation budget constraints during the development of a game often call for the use of a limited set of generic motions. Editing operations are thus generally required to animate virtual characters with a sufficient level of variety. Evaluating the perceptual plausibility of edited animations can therefore contribute greatly towards producing visually plausible animations. In this paper we study observers' sensitivity to manipulations of overarm and underarm biological throwing animations. In our first experiment, we used Dynamic Time Warping to edit the biological throwing motions, and modified the release velocity of the ball accordingly. We found that observers are more tolerant to speeding up of the original throwing motion than to slowing down, and that slowed down underarm throws are perceived as particularly unnatural. In our second experiment, we modified separately horizontal and vertical components of the release velocity of the ball, while leaving the motion of the thrower unchanged. We found that observers are more sensitive to manipulations of the horizontal component in overarm throws, and of the vertical component in underarm throws. As in the first experiment, we found that observers are most disturbed by decreases in the velocity of the ball in underarm throws. Our results provide valuable insights for developers of games and VR applications by specifying thresholds for the perceptual plausibility of throwing manipulations.
α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro

α-Synuclein and Aging Transgenic α-synuclein can reverse the otherwise lethal neurodegeneration of cysteine string protein-α knockout mice via changes in SNARE proteins, which mediate synaptic vesicle release. Using experiments with purified recombinant proteins, triple αβγ-synuclein knockout mice, and studies of mouse aging, Burré et al. (p. 1663, published online 26 August) now demonstrate that α-synuclein directly interacts with the SNARE protein synaptobrevin and functions as a catalyst for SNARE-complex assembly. The role of synucleins is fully dispensable in young animals, but becomes essential late in life, which suggests that α-synuclein maintains normal synaptic function during aging. A protein implicated in neurodegeneration promotes the assembly of membrane fusion complexes. Presynaptic nerve terminals release neurotransmitters repeatedly, often at high frequency, and in relative isolation from neuronal cell bodies. Repeated release requires cycles of soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE)–complex assembly and disassembly, with continuous generation of reactive SNARE-protein intermediates. Although many forms of neurodegeneration initiate presynaptically, only few pathogenic mechanisms are known, and the functions of presynaptic proteins linked to neurodegeneration, such as α-synuclein, remain unclear. Here, we show that maintenance of continuous presynaptic SNARE-complex assembly required a nonclassical chaperone activity mediated by synucleins. Specifically, α-synuclein directly bound to the SNARE-protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and promoted SNARE-complex assembly. Moreover, triple-knockout mice lacking synucleins developed age-dependent neurological impairments, exhibited decreased SNARE-complex assembly, and died prematurely. Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging.
A finite rate of innovation algorithm for fast and accurate spike detection from two-photon calcium imaging

Objective. Inferring the times of sequences of action potentials (APs) (spike trains) from neurophysiological data is a key problem in computational neuroscience. The detection of APs from two-photon imaging of calcium signals offers certain advantages over traditional electrophysiological approaches, as up to thousands of spatially and immunohistochemically defined neurons can be recorded simultaneously. However, due to noise, dye buffering and the limited sampling rates in common microscopy configurations, accurate detection of APs from calcium time series has proved to be a difficult problem. Approach. Here we introduce a novel approach to the problem making use of finite rate of innovation (FRI) theory (Vetterli et al 2002 IEEE Trans. Signal Process. 50 1417–28). For calcium transients well fit by a single exponential, the problem is reduced to reconstructing a stream of decaying exponentials. Signals made of a combination of exponentially decaying functions with different onset times are a subclass of FRI signals, for which much theory has recently been developed by the signal processing community. Main results. We demonstrate for the first time the use of FRI theory to retrieve the timing of APs from calcium transient time series. The final algorithm is fast, non-iterative and parallelizable. Spike inference can be performed in real-time for a population of neurons and does not require any training phase or learning to initialize parameters. Significance. The algorithm has been tested with both real data (obtained by simultaneous electrophysiology and multiphoton imaging of calcium signals in cerebellar Purkinje cell dendrites), and surrogate data, and outperforms several recently proposed methods for spike train inference from calcium imaging data.
Giant cavities, cooling and metallicity substructure in Abell 2204

We present results from deep Chandra and XMM-Newton observations of the relaxed X-ray luminous galaxy cluster Abell 2204. We detect metallicity inhomogeneities in the intracluster medium on a variety of distance scales, from a ∼12 kpc enhancement containing a few times 10 7 M ⊙ of iron in the centre to a region at 400 kpc radius with an excess of a few times 10 9 M ⊙ . Subtracting an average surface brightness profile from the X-ray image yields two surface brightness depressions to the north and south of the cluster. Their morphology is similar to the cavities observed in the cluster cores, but they have radii of 240 and 160 kpc and a total enthalpy of 2 x 10 62 erg. If they are fossil radio bubbles, their buoyancy time-scales imply a total mechanical heating power of 5 x 10 46 erg s -1 , the largest such bubble heating power known. More likely, they result from the accumulation of many past bubbles. Energetically this is more feasible, as the enthalpy of these regions could combat X-ray cooling in this cluster to 500 kpc radius for around 2 Gyr. The core of the cluster also contains five to seven ∼4 kpc radius surface brightness depressions that are not associated with the observed radio emission. If they are bubbles generated by the nucleus, they are too small to balance cooling in the core by an order of magnitude. However, if the radio axis is close to the line of sight, projection effects may mask more normal bubbles. Using reflection grating spectrometer (RGS) spectra, we detect a Fe XVII line. Spectral fitting reveals temperatures down to ∼0.7 keV; the cluster, therefore, shows a range in X-ray temperature of at least a factor of 15. The quantity of low temperature gas is consistent with a mass deposition rate of 65 M ⊙ yr -1 .
Effects of Service-Learning on Kinesiology Students' Attitudes Toward Children With Disabilities

Contact theory (Allport, 1954) served as the framework to investigate undergraduate kinesiology students’ attitudes toward children with disabilities after a service-learning (SL) experience. Fifty-one undergraduate kinesiology students enrolled in an adapted physical education (APE) course served as the experimental group, and 31 undergraduate kinesiology students enrolled in an introductory kinesiology course served as the control group. The Attitudes Toward Disabled Persons Scale–Form A (Yuker, Block, & Younng, 1970) was administered at three different times: before, during, and after the SL. A mixed-design ANOVA revealed that there were no statistically significant main or interaction effects for gender, group, and time on the attitude scores of kinesiology students toward children with disabilities. The results suggest that the quantity and quality of contact time with children with disabilities may be important to consider when designing and structuring SL experiences in APE courses.
Cell Cycle Progression in the Pericycle Is Not Sufficient for SOLITARY ROOT/IAA14-Mediated Lateral Root Initiation in Arabidopsis thalianaw⃞

To study the mechanisms behind auxin-induced cell division, lateral root initiation was used as a model system. By means of microarray analysis, genome-wide transcriptional changes were monitored during the early steps of lateral root initiation. Inclusion of the dominant auxin signaling mutant solitary root1 (slr1) identified genes involved in lateral root initiation that act downstream of the auxin/indole-3-acetic acid (AUX/IAA) signaling pathway. Interestingly, key components of the cell cycle machinery were strongly defective in slr1, suggesting a direct link between AUX/IAA signaling and core cell cycle regulation. However, induction of the cell cycle in the mutant background by overexpression of the D-type cyclin (CYCD3;1) was able to trigger complete rounds of cell division in the pericycle that did not result in lateral root formation. Therefore, lateral root initiation can only take place when cell cycle activation is accompanied by cell fate respecification of pericycle cells. The microarray data also yielded evidence for the existence of both negative and positive feedback mechanisms that regulate auxin homeostasis and signal transduction in the pericycle, thereby fine-tuning the process of lateral root initiation.
Development and Examination of the Linguistic Category Model in a Computerized Text Analysis Method

The linguistic category model (LCM) seeks to understand social psychological processes through the lens of language use. Its original development required human judges to analyze natural language to understand how people assess actions, states, and traits. The current project sought to computerize the LCM assessment based on an idea of language abstraction with a previously published data set. In the study, a computerized LCM analysis method was built using an LCM verb dictionary and a part-of-speech tagging program that identified relevant adjectives and nouns. This computerized method compared open-ended texts written in first-person and third-person perspectives from 130 college students. Consistent with construal-level theory, third-person writing resulted in higher levels of abstraction than first-person writing. Implications of relying on an automated LCM method are discussed.
Do Age-Disparate Relationships Drive HIV Incidence in Young Women? Evidence from a Population Cohort in Rural KwaZulu-Natal, South Africa

Background:Based on ethnographic investigations and mathematical models, older sexual partners are often considered a major risk factor for HIV for young women in sub-Saharan Africa. Numerous public health campaigns have been conducted to discourage young women from relationships with older men. However, longitudinal evidence relating sex partner age disparity to HIV acquisition in women is limited. Methods:Using data from a population-based open cohort in rural KwaZulu-Natal, South Africa, we studied 15- to 29-year-old women who were HIV seronegative at first interview between January 2003 and June 2012 (n = 2444). We conducted proportional hazards analysis to establish whether the age disparity of women's most recent sexual partner, updated at each surveillance round, was associated with subsequent HIV acquisition. Results:A total of 458 HIV seroconversions occurred over 5913 person-years of follow-up (incidence rate: 7.75 per 100 person-years). Age disparate relationships were common in this cohort; 37.7% of women reported a partner 5 or more years older than themselves. The age disparity of women's partners was not associated with HIV acquisition when measured either continuously [hazard ratio (HR) for 1-year increase in partner's age: 1.00, 95% confidence interval (CI): 0.97 to 1.03] or categorically (man ≥5 years older: HR, 0.98; 95% CI: 0.81 to 1.20; man ≥10 years older: HR, 0.98; 95% CI: 0.67 to 1.43). These results were robust to adjustment for known sociodemographic and behavioral HIV risk factors and did not vary significantly by women's age, marital status, education attainment, or household wealth. Conclusions:HIV incidence in young women was very high in this rural community in KwaZulu-Natal. Partner age disparity did not predict HIV acquistion. Campaigns to reduce age-disparate sexual relationships may not be a cost-effective use of HIV prevention resources in this setting.
A Soft Trading Service for COTS Components Using Parametric Contracts

Currently, various efforts are concerned with the creation of domainspecific components. However, the use of repositories of such components requires efficient methods for component selection. Current component retrieval and trading services are limited when dealing with mismatches between components and architectural requirements. In this paper, we analyze the required features that soft trading services should have, and describe soft trading algorithms used to implement a soft trading service based on parametric contracts. In addition, we validate our approach by presenting soft trading experiments and an analysis of the results. The results show an significant improvement against existing approaches for component selection which do not use parametric contracts.
Selectivity of content and language integrated learning programmes in German secondary schools

ABSTRACT Despite its increasing popularity and adoption across Europe, Content and Language Integrated Learning (CLIL) is not without its critics. It has been argued that CLIL programmes are highly selective, that is, the students possess more favourable learning prerequisites than their monolingually taught peers. The present study contributes to this debate by investigating possible differences in learning prerequisites between CLIL and non-CLIL students in German CLIL secondary schools. We assessed figural and verbal cognitive skills, family background (immigration background, parents’ education, socio-economic status, and cultural capital), and achievement and motivation in the soon-to-be bilingually taught content subject History and in the foreign language of 1362 CLIL and non-CLIL eighth graders. Results indicated significant advantages of CLIL students regarding their verbal cognitive skills, parents’ education, socio-economic status, cultural capital, and achievement and motivation in History and in the foreign language. Additionally, it was investigated whether differences in students’ foreign language performance would diminish after possible differences in learning prerequisites were taken into account. Multiple regression analyses showed distinct selection effects but CLIL students still outperformed their monolingually taught peers by one to almost two school years (listening comprehension resp. C-test). These results can lay the foundation for an evaluation of the effectiveness of CLIL programmes.