Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolism and Pharmacokinetics of EAPB0203 and EAPB0503, Two Imidazoquinoxaline Compounds Previously Shown to Have Antitumoral Activity on Melanoma and T-Lymphomas

For several years, our group has been developing quinoxalinic compounds. Two of them, N-methyl-1-(2-phenethyl)imidazo[1,2-a]quinoxalin-4-amine (EAPB0203) and 1-(3-methoxyphenyl)-N-methylimidazo[1,2-a]quinoxalin-4-amine (EAPB0503), have emerged as the most promising anticancer drugs. In the present work, we determined metabolism pathways using liver microsomes from four mammalian species including human. We identified the cytochrome P450 isoform(s) involved in the metabolism and then investigated the pharmacokinetics and metabolism of EAPB0203 and EAPB0503 in rat after intravenous and intraperitoneal administration. Biotransformation of the compounds involved demethylation and hydroxylation reactions. Rat and dog metabolized the compounds at a higher rate than mouse and human. In all species, CYP1A1/2 and CYP3A isoforms were the predominant enzymes responsible for the metabolism. From human liver microsomes, unbound intrinsic clearances were approximately 56 ml/(min · g) protein. EAPB0203 and EAPB0503 were extensively bound to human plasma proteins, mainly human serum albumin (HSA) (∼98–99.5%). Thus, HSA could act as carrier of these compounds in human plasma. Scatchard plots showed patterns in which the plots yielded upwardly convex hyperbolic curves. On the basis of the Hill coefficients, there appears to be interaction between the binding sites of HSA, suggesting positive cooperativity. The main in vitro metabolites were identified in vivo. Total clearances of EAPB0203 and EAPB0503 [3.2 and 2.2 l/(h · kg), respectively] were notably lower than the typical cardiac plasma output in rat. The large volumes of distribution of these compounds (4.3 l/kg for EAPB0203 and 2.5 l/kg for EAPB0503) were consistent with extensive tissue binding. After intraperitoneal administration, bioavailability was 22.7% for EAPB0203 and 35% for EAPB0503 and a significant hepatic first-pass effect occurred.
On finding a minimum spanning tree in a network with random weights

We investigate Prim's standard “tree-growing” method for finding a minimum spanning tree, when applied to a network in which all degrees are about d and the edges e have independent identically distributed random weights w(e). We find that when the kth edge ek is added to the current tree, where k=o(\sqrt{d}), the probability that this edge ek is incident to the node that was most recently added to the tree equals {1\over 2}+{1\over 2k}+o(1) as d∞. We also find for example that, if the edge weights are uniformly distributed on (0, 1), then the expected value of w(ek) is asymptotic to ({1\over 2}+{1\over 2k})/d. © 1997 John Wiley & Sons, Inc. Random Struct. Alg. ,10, 187–204 (1997)
Inactivation of the Phloem-Specific Dof Zinc Finger GeneDAG1 Affects Response to Light and Integrity of the Testa of Arabidopsis Seeds1

We show here that seeds from the knockout mutant of the Arabidopsis DAG1 gene encoding a Dof zinc finger transcription factor have an altered response to red and far-red light. Mutant dag1 seeds are induced to germinate by much lower red light fluence rates, and germination reaches more quickly a point where it is independent of phytochrome signaling. Moreover, although microscopic analysis reveals no obvious structural alterations in the seed coat (testa) of dag1 seeds, staining assays with different dyes point to an abnormal fragility of the testa. By extensive in situ mRNA hybridization analysis we show here that the gene, which is not expressed in the embryo, is specifically expressed in the phloem of all organs of the mother plant.
Exploring Resilience and Adaptation in Adolescents with Sickle Cell Disease

Living with sickle cell disease (SCD) can be a significant adversity due to disease-related symptoms and complications. Compounding these challenges, SCD predominantly affects ethnic minority populations already vulnerable to societal stigmatization, discrimination, and health disparities. It is important to recognize the negative impact of this chronic illness on psychosocial functioning; however, there is value in utilizing a strengths-based approach to determine how to promote adaptation to a challenging life-long disease. The current study explored the association among pain characteristics, adolescent, caregiver, and family protective factors, and functioning outcomes. Another primary aim of this study was to apply the protective factor model of resilience based in resilience theory to pediatric SCD by evaluating the moderating effect of adolescent, caregiver, and family protective factors on the relation between SCD pain burden and functioning outcomes. 93 12to 18-year-olds with SCD and their caregivers were recruited from a large Southeastern children’s hospital. Adolescents completed measures assessing pain intensity and frequency, general and pain-specific protective factors, and functional outcomes. Caregivers completed measures assessing demographic and disease variables, psychological flexibility, and family functioning. Correlation analyses revealed that the majority of variables were related in expected directions and supported previous research. Adolescent protective factors were generally associated with one another and increased functional ability and quality of life. With the exception of family functioning, caregiver and family variables were not related to primary outcomes. After controlling for demographic, pain, and disease variables, moderation analyses showed that adolescent pain acceptance buffered the relation between SCD pain burden and quality of life. Contrary to hypotheses, moderating effects were not significant for the remaining adolescent, caregiver, and family protective factors. Findings highlight the importance of continuing to identify individual, caregiver, family, and broader environmental protective factors and evaluate resilience mechanisms among adolescents with SCD. Pain acceptance may also be a critical variable to target in future pain-focused interventions. Utilizing a strengths-based approach might lead to novel clinical avenues to empower youth to positively adapt to a chronic illness characterized by pain. INDEX WORDS: Resilience, Adolescents, Sickle cell disease, Pain management EXPLORING RESILIENCE AND ADAPATATION IN ADOLESCENTS WITH SICKLE CELL DISEASE
Must analysis of meaning follow analysis of form? A time course analysis

Many models of word recognition assume that processing proceeds sequentially from analysis of form to analysis of meaning. In the context of morphological processing, this implies that morphemes are processed as units of form prior to any influence of their meanings. Some interpret the apparent absence of differences in recognition latencies to targets (SNEAK) in form and semantically similar (sneaky-SNEAK) and in form similar and semantically dissimilar (sneaker-SNEAK) prime contexts at a stimulus onset asynchrony (SOA) of 48 ms as consistent with this claim. To determine the time course over which degree of semantic similarity between morphologically structured primes and their targets influences recognition in the forward masked priming variant of the lexical decision paradigm, we compared facilitation for the same targets after semantically similar and dissimilar primes across a range of SOAs (34–100 ms). The effect of shared semantics on recognition latency increased linearly with SOA when long SOAs were intermixed (Experiments 1A and 1B) and latencies were significantly faster after semantically similar than dissimilar primes at homogeneous SOAs of 48 ms (Experiment 2) and 34 ms (Experiment 3). Results limit the scope of form-then-semantics models of recognition and demonstrate that semantics influences even the very early stages of recognition. Finally, once general performance across trials has been accounted for, we fail to provide evidence for individual differences in morphological processing that can be linked to measures of reading proficiency.
Efficient Learning of Image Super-Resolution and Compression Artifact Removal with Semi-Local Gaussian Processes

Improving the quality of degraded images is a key problem in image processing, but the breadth of the problem leads to domain-specific approaches for tasks such as super-resolution and compression artifact removal. Recent approaches have shown that a general approach is possible by learning application-specific models from examples; however, learning models sophisticated enough to generate high-quality images is computationally expensive, and so specific per-application or per-dataset models are impractical. To solve this problem, we present an efficient semi-local approximation scheme to large-scale Gaussian processes. This allows efficient learning of task-specific image enhancements from example images without reducing quality. As such, our algorithm can be easily customized to specific applications and datasets, and we show the efficiency and effectiveness of our approach across five domains: single-image super-resolution for scene, human face, and text images, and artifact removal in JPEG- and JPEG 2000-encoded images.
Fall prevention for people with learning disabilities: key points and recommendations for practitioners and researchers

Purpose This article provides a narrative review of what is currently known about the high rates of falls, and fall injuries, which are experienced by people with learning disabilities throughout their lives. Current evidence is summarised as key points and recommendations for practitioners and researchers. Design/methodology/approach Narrative review. Findings People with learning disabilities experience similar rates of falls as older adults in the wider population, but throughout their lives, or at an earlier age. Originality/value Key points and recommendations are summarised for practitioners and researchers, to promote fall prevention strategies and interventions for people with learning disabilities.
Right temporal cortical hypertrophy in resilience to trauma: an MRI study

Background In studies employing physiological measures such as magnetic resonance imaging (MRI), it is often hard to distinguish what constitutes risk-resilience factors to posttraumatic stress disorder (PTSD) following trauma exposure and what the effects of trauma exposure and PTSD are. Objective We aimed to investigate whether there were observable morphological differences in cortical and sub-cortical regions of the brain, 7–8 years after a single potentially traumatic event. Methods Twenty-four participants, who all directly experienced the 2004 Indian Ocean Tsunami, and 25 controls, underwent structural MRI using a 3T scanner. We generated cortical thickness maps and parcellated sub-cortical volumes for analysis. Results We observed greater cortical thickness for the trauma-exposed participants relative to controls, in a right lateralized temporal lobe region including anterior fusiform gyrus, and superior, middle, and inferior temporal gyrus. Conclusions We observed greater thickness in the right temporal lobe which might indicate that the region could be implicated in resilience to the long-term effects of a traumatic event. We hypothesize this is due to altered emotional semantic memory processing. However, several methodological and confounding issues warrant caution in interpretation of the results. Highlights of the article Following a traumatic event, most people do not develop long-lasting trauma-related symptoms. In a group who experienced a traumatic event 8 years prior, but showed low levels of trauma-related symptoms, we observed increased cortical thickness in the right temporal lobe. The right temporal lobe is implicated in emotional semantic memory processing, and thus might be associated with resilience to the long-term effects of a traumatic event.
Telomere Length as an Indicator of Biological Aging: The Gender Effect and Relation With Pulse Pressure and Pulse Wave Velocity

Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56±11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67±0.09 versus 8.37±0.07 kb;P =0.016). In both genders, telomere length was inversely correlated with age (P <0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.
Gravitational Memory Charges of Supertranslation and Superrotation on Rindler Horizons

In a Rindler-type coordinate system spanned in a region outside of a black hole horizon, we have nonvanishing classical holographic charges as soft hairs on the horizon for stationary black holes. Taking a large black hole mass limit, the spacetimes with the charges are described by asymptotic Rindler metrics. We construct a general theory of gravitational holographic charges for a ($1+3$)-dimensional linearized gravity field in the Minkowski background with Rindler horizons. Although matter crossing a Rindler horizon causes horizon deformation and a time-dependent coordinate shift\char22{}that is, gravitational memory\char22{}the supertranslation and superrotation charges on the horizon can be defined during and after its passage through the horizon. It is generally proven that holographic states on the horizon cannot store any information about absorbed perturbative gravitational waves. However, matter crossing the horizon really excites holographic states. By using gravitational memory operators, which consist of the holographic charge operators, we suggest a resolution of the no-cloning paradox of quantum information between matter falling into the horizon and holographic charges on the horizon from the viewpoint of the contextuality of quantum measurement.
Board task performance: An exploration of micro- and macro-level determinants of board effectiveness

This paper addresses recent calls to narrow the micro–macro gap in management research (Bamberger, 2008), by incorporating a macro-level context variable (country) in exploring micro-level determinants of board effectiveness. Following the integrated model proposed by Forbes and Milliken (1999), we identify three board processes as micro-level determinants of board effectiveness. Specifically, we focus on effort norms, cognitive conflicts and the use of knowledge and skills as determinants of board control and advisory task performance. Further, we consider how two different institutional settings influence board tasks, and how the context moderates the relationship between processes and tasks. Our hypotheses are tested on a survey-based dataset of 535 medium-sized and large industrial firms in Italy and Norway, which are considered to substantially differ along legal and cultural dimensions. The findings show that: (i) Board processes have a larger potential than demographic variables to explain board task performance; (ii) board task performance differs significantly between boards operating in different contexts; and (iii) national context moderates the relationships between board processes and board task performance. Copyright © 2010 John Wiley & Sons, Ltd.
The Role of Diverse Beliefs in Asset Pricing and Equity Premia

by Mordecai Kurz and Maurizio Motolese A very preliminary draft: February 2, 2010 Summary: Why do risk premia vary over time? We examine this problem theoretically and empirically by studying the effect of market belief on risk premia. Individual belief is taken as a fundamental, primitive, state variable. Market belief which is the distribution of individual beliefs is observable, it is central to the empirical evaluation and we show how to measure it. Our asset pricing model is familiar from the noisy REE literature but we adapt it to an economy with diverse beliefs. We derive equilibrium asset prices and implied risk premium. Our approach permits a closed form solution of prices hence we trace the exact effect of market belief on the time variability of asset prices and risk premia. We test empirically the theoretical conclusions. We study premia on long positions of S&P500 for investment periods of 6 -12 months and find that, on average, a change in the mean market belief by 1 standard deviation changes equity premia by about 0.4 standard deviation of excess returns. We also find that the introduction of belief variables reduces the effect of the traditional Fama and French (1989) variables used to forecast excess returns. More specifically we find that given information about market belief the term premium, the default premium and Lattau and Ludvigson’s (2001) CAY variables have no significant effect. As to the structure of the premium we show that when the market holds abnormally favorable belief about the future payoff on the S&P500 the market views the long position as less risky hence the equity risk premium declines. We also find that in a VAR model of asset and consumption growth, our market belief variables have a significant effect. We thus conclude that market belief has significant independent effect on economic fluctuations and risk premia. JEL classification: C53, D8, D84, E27, E4, G12, G14.
PEMAHAMAN MASYARAKAT MENGENAI GANGGUAN JIWA DAN KETERBELAKANGAN MENTAL

Pemahaman masyarakat mengenai gangguan jiwa dan keterbelakangan mental sangat minim. Minimnya pengetahuan masyarakat mengenai gangguan jiwa dan keterbelakangan mental menyebabkan penderita kerap kali mendapatkan perilaku yang tidak menyenangkan dari masyarakat bahkan dari keluarga penderita sendiri. Salah satunya di negara Indonesia, perlakuan yang di dapatkan oleh penderita gangguan jiwa dan keterbelakangan seperti diskriminasi, mereka terisolasi, dikucilkan bahkan hingga dipasung, padahal penderita gangguan jiwa dan cacat mental adalah warga negara Indonesia yang berhak mendapatkan hak-hak mereka sebagai warga negara Indonesia dan sebagai seorang manusia yang dapat mengembangkan diri dan mengasah potensi-potensi yang dimilikinya. Penyakit gangguan jiwa dan keterbelakangan mental memiliki pemahaman yang berbeda akan tetapi penderita sering kali mendapatkan perlakuan yang serupa dari masyarakat maupun keluarga penderita. Gangguan jiwa merupakan suatu penyakit yang dapat menyerang seseorang kapan saja dan dimana saja dan penyakit ini dapat disembuhkan dengan mendapatkan penanganan yang tepat, sedangkan cacat mental bukanlah suatu penyakit akan tetapi cacat mental merupakan suatu keadaan yang telah dialami seseorang dari semenjak dikandungan, akan tetapi bukan berarti mereka tidak dapat mengembangkan diri sebagai manusia, penanganan sejak dini dan dengan tepat juga diperlukan oleh penderita cacat mental. Maka dari itu, peran dari masyarakat sangat dibutuhkan guna untuk membantu penderita dalam bekreasi hingga dapat mengembangkan potensi-potensi yang dimilikinya dengan cara mengetahui bagaimana harus bersikap kepada mereka dengan tidak memandang penderita sebelah mata. Peran dari seorang pekerja sosial dalam hal ini dapat membantu masyarakat dan keluarga penderita gangguan jiwa atau cacat mental sebagai educator, motivator dan sebagai konselor.
An importance-driven radiosity algorithm

We present a new radiosi[y algorithm for efficiently computing global solutions with respect to a constrained set of views. Radiosi - ties of directly visible surfaces are computed to high accuracy, while those ot’ surfaces having only an indirect effect are computed to an accuracy commensurate with their contribution. The algorithm uses an adaptive subdivision scheme that is guided by the interplay between two closely related transport processes: one propagating power from the light sources, and the other propagating imporrarwc from the visible surfaces. By simultaneously refining approximate solutions to the dud transport equations, computation is significantly reduced in areas that contribute little to the region of interest. This approach is very effective for complex environments in which only a small fraction is visible at any time. Our statistics show dramatic speedups over the fastest previous radiosity algorithms for diffuse environments with details at a wide range of scales.
Negotiators Who Give Too Much: Unmitigated Communion, Relational Anxieties, and Economic Costs in Distributive and Integrative Bargaining

A series of studies found that the personality dimension of unmitigated communion (H. L. Fritz & V. S. Helgeson, 1998) leads negotiators to make concessions to avoid straining relationships. Results indicate that even within the population of successful business executives, this dimension of relational anxiety can be identified distinctly from more general relational orientations, such as agreeableness, and that it distinctly predicts accommodating tendencies in everyday conflicts. In economic games, unmitigated communion predicts giving in contexts in which the relational norm of reciprocity applies, but not in contexts tapping instrumental or altruistic motives for cooperation. In distributive negotiations, the effect of unmitigated communion in lowering a negotiator's outcome is mediated by prenegotiation anxieties about relational strain and plans to make large concessions if needed to avoid impasse (lower reservation points). In integrative negotiations, high unmitigated communion on both sides of the negotiation dyad results in relational accommodation, evidenced by decreased success in maximizing economic joint gain but increased subjective satisfaction with the relationship.
Sensitivity of Performance in the Erlang-A Queueing Model to Changes in the Model Parameters

This paper studies the M/M/s +M queue, i.e., the M/M/s queue with customer abandonment, also called the Erlang-A model, having independent and identically distributed customer abandon times with an exponential distribution (the +M), focusing on the case in which the arrival rate and the number of servers are large. The goal is to better understand the sensitivity of performance to changes in the model parameters: the arrival rate, the service rate, the number of servers, and the abandonment rate. Elasticities are used to show the percentage change of a performance measure caused by a small percentage change in a parameter. Elasticities are calculated using an exact numerical algorithm and simple finite-difference approximations. Insight is gained by applying fluid and diffusion approximations. The analysis shows that performance is quite sensitive to small percentage changes in the arrival rate or the service rate, but relatively insensitive to small percentage changes in the abandonment rate.