Miracle-dz/UniFAR-FTUs huggingface dataset:
Crosstalk and Signaling Switches in Mitogen-Activated Protein Kinase Cascades

Mitogen-activated protein kinase (MAPK) cascades control cell fate decisions, such as proliferation, differentiation, and apoptosis by integrating and processing intra- and extracellular cues. However, similar MAPK kinetic profiles can be associated with opposing cellular decisions depending on cell type, signal strength, and dynamics. This implies that signaling by each individual MAPK cascade has to be considered in the context of the entire MAPK network. Here, we develop a dynamic model of feedback and crosstalk for the three major MAPK cascades; extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), c-Jun N-terminal kinase (JNK), and also include input from protein kinase B (AKT) signaling. Focusing on the bistable activation characteristics of the JNK pathway, this model explains how pathway crosstalk harmonizes different MAPK responses resulting in pivotal cell fate decisions. We show that JNK can switch from a transient to sustained activity due to multiple positive feedback loops. Once activated, positive feedback locks JNK in a highly active state and promotes cell death. The switch is modulated by the ERK, p38, and AKT pathways. ERK activation enhances the dual specificity phosphatase (DUSP) mediated dephosphorylation of JNK and shifts the threshold of the apoptotic switch to higher inputs. Activation of p38 restores the threshold by inhibiting ERK activity via the PP1 or PP2A phosphatases. Finally, AKT activation inhibits the JNK positive feedback, thus abrogating the apoptotic switch and allowing only proliferative signaling. Our model facilitates understanding of how cancerous deregulations disturb MAPK signal processing and provides explanations for certain drug resistances. We highlight a critical role of DUSP1 and DUSP2 expression patterns in facilitating the switching of JNK activity and show how oncogene induced ERK hyperactivity prevents the normal apoptotic switch explaining the failure of certain drugs to induce apoptosis.
‘I’m a researcher!’ Working together to gain ethical approval for a participatory research study

‘I’m a researcher! ’ These were the words used by one member of our research team when we left a meeting of our Local Research Ethics Committee having been granted approval for our research study. This participatory study aims to ask people with intellectual disabilities1 what they think about health and what helps them to be healthy. However, it also aims to enable people with intellectual disabilities to develop their skills as researchers. We felt that we had learnt a lot from the process of gaining ethical committee approval and, since ethical committee approval is something which many participatory studies may need to secure, we thought that our experiences would help other people both nationally and internationally who are planning to undertake similar work. We therefore decided to write this article.
The Role of the Antisocial Family in School Completion and Delinquency: A Three-Generation Study

THE OBSERVATION that deviant children have deviant parents has been made in a near-astronomical number of studies. ' The path to this conclusion has almost always been through the comparison of parents of deviant children (particularly juvenile delinquents) with parents of control subjects. Studies which have proceeded from the other end-i.e., by using the parents as the index case in order to estimate the probability that deviant behavior in the parent will be reflected in the child's behavior-have been negligible in number. Among the rare studies of this kind are Anne Roe's study of children of alcoholics, Wilson's study of delinquency in children whose parents were referred for child neglect, Geismar's study of juvenile delinquency in "multiproblem" families, and Lewis' study of mental illness in the offspring of mentally ill parents.2 Studies
Research on Food Allergy Information using Smart Mobile Media Devices to Enhance Communication at Restaurants

Dealing with food allergies in the restaurant industry is becoming important as more customers have needs and restaurants are concerned with corporate social responsibilitiy CSR. This research discusses how to provide information to facilitate the communication between the restaurant industry that is interested in dealing with food allergies and the patient's family who wants to enjoy eating at restaurants. The authors used a mixed method, combining qualitative and quantitative research, and divided the research into three steps Creswell, 2008. First, the authors researched patients' families and companies to organize communication. The authors conducted an interview with Company A, a big company in the restaurant industry, to parallel the research of patients' families. In the second step, they developed a tool and verified the method of obtaining information. Lastly, to verify the effectiveness of the information providing measure, they set up a focus group consisting of responders from the questionnaire given to parents who have children with food allergies. They found that the lack of information about ingredients and the lack of knowledge of the employees when patients' families are selecting from the menu are responsible for the inconsiderate customer service and misses in operation.
Farnesylthiosalicylic acid (salirasib) inhibits Rheb in TSC2‐null ELT3 cells: A potential treatment for lymphangioleiomyomatosis

The small GTPase proteins, Ras and Rheb, serve as molecular switches regulating cell proliferation, differentiation and apoptosis. Ras also regulates Rheb by inactivating the tuberous sclerosis complex (TSC), which includes products of the TSC1 and TSC2 genes encoding hamartin (TSC1) and tuberin (TSC2), respectively, and acts as a Rheb‐specific GTPase‐activating protein. Loss of function of TSC1 or TSC2 results in an increase in active Rheb.GTP with the consequent translational abnormalities and excessive cell proliferation characteristic of the genetic disorders, tuberous sclerosis and lymphangioleiomyomatosis (LAM). To determine whether inactivation of Rheb, Ras or both might be a potential treatment for LAM, we used TSC2‐null ELT3 cells as a LAM model. The cells were treated with the Ras inhibitor S‐trans,trans‐farnesylthiosalicylic acid (FTS; salirasib), which mimics the C‐terminal S‐farnesyl cysteine common to Ras and Rheb. This C‐terminus is critical for their attachment to cellular membranes and for their biological activities. Untreated, the ELT3 cells expressed significant amounts of Rheb but little Ras.GTP, and this phenotype was reversed by TSC2 reexpression. Treatment with FTS decreased Ras.GTP only slightly in the TSC2‐null cells, but reduced their overactive Rheb as well as their proliferation, migration and tumor growth. Notably, TSC2 reexpression in these ELT3 cells rescued them from the inhibitory effect of FTS. Evidently, therefore, FTS blocks active Rheb in TSC2‐null ELT3 cells and may have therapeutic potential for LAM.
Pushed for time or saving on fuel: fine-scale energy budgets shed light on currencies in a diving bird

Animals may forage using different currencies depending on whether time minimization or energy maximization is more pertinent at the time. Assessment of net energy acquisition requires detailed information on instantaneous activity-specific power use, which varies according to animal performance, being influenced, for example, by speed and prey loading, and which has not been measured before in wild animals. We used a new proxy for instantaneous energy expenditure (overall dynamic body acceleration), to quantify foraging effort in a model species, the imperial shag Phalacrocorax atriceps, during diving. Power costs varied nonlinearly with depth exploited owing to depth-related buoyancy. Consequently, solutions for maximizing the gross rate of gain and energetic efficiency differed for dives to any given depth. Dive effort in free-ranging imperial shags measured during the breeding season was consistent with a strategy to maximize the gross rate of energy gain. We suggest that the divergence of time and energy costs with dive depth has implications for the measurement of dive efficiency across diverse diving taxa.
Study on Risk Evaluation of Bank Financing Products Based on Analytical Network Process

The relative risk scale of bank financing products are extended nowadays, and lots of uncertain factors affects the evaluation process. In order to solve these problems, analytical network process (ANP) was utilized to estimate the risk possibility. Risk factors index system of bank financing products were built firstly. ANP considered all kinds of risk factors as well as influence among them. The feedback relation between every two factors were described and calculated. Finally all of the risk factors were sorted synthetically. The example shows that ANP is a suitable method.
Distribution of mu, delta, and kappa opiate receptor types in the forebrain and midbrain of pigeons

Ligands that are highly specific for the mu, delta, and kappa opiate receptor binding sites in mammalian brains have been identified and used to map the distribution of these receptor types in the brains of various mammalian species. In the present study, the selectivity and binding characteristics in the pigeon brain of three such ligands were examined by in vitro receptor binding techniques and found to be similar to those reported in previous studies on mammalian species. These ligands were then used in conjunction with autoradiographic receptor binding techniques to study the distribution of mu, delta, and kappa opiate receptor binding sites in the forebrain and midbrain of pigeons. The autoradiographic results indicated that the three opiate receptor types showed similar but not identical distributions. For example, mu, delta, and kappa receptors were all abundant within several parts of the cortical‐equivalent region of the telencephalon, particularly the hyperstriatum ventrale and the medial neostriatum. In contrast, in other parts of the cortical‐equivalent region of the avian telencephalon, such as the dorsal archistriatum and caudal neostriatum, only kappa receptors appeared to be abundant. Within the basal ganglia, all three types of opiate receptos were abundant in the striatum and low in the pallidum. Within the diencephalon, kappa and delta binding was high in the dorsal and dorsomedial thalamic nuclei, but the levels of all three receptor types were generally low in the specific sensory relay nuclei of the thalamus. Kappa binding and delta binding were high, but mu was low in the hypothalamus. Within the midbrain, all three receptor types were abundant in both the superficial and deep tectal layers, in periventricular areas, and in the tegmental dopaminergic cell groups.
Incretin and islet hormone responses to meals of increasing size in healthy subjects.

CONTEXT Postprandial glucose homeostasis is regulated through the secretion of glucagon-like peptide 1 (GLP-1) through the stimulation of insulin secretion and inhibition of glucagon secretion. However, how these processes dynamically adapt to demands created by caloric challenges achieved during daily life is not known. OBJECTIVE The objective of the study was to explore the adaptation of incretin and islet hormones after mixed meals of increasing size in healthy subjects. DESIGN Twenty-four healthy lean subjects ingested a standard breakfast after an overnight fast followed, after 4 hours, by a lunch of a different size (511, 743, and 1034 kcal) but with identical nutrient composition together with 1.5 g paracetamol. Glucose, insulin, C-peptide, glucagon, intact GLP-1, and glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured after the meals. MAIN OUTCOME MEASURE Area under the 180-minute curve (AUC) for insulin, C-peptide, glucagon, GLP-1, and GIP and model-derived β-cell function and paracetamol appearance were calculated. RESULTS Glucose profiles were similar after the two larger meals, whereas after the smaller meal, there was a postpeak reduction below baseline to a nadir of 3.8 ± 0.1 mmol/L after 75 minutes (P < .001). The AUC for GLP-1, GIP, insulin, and C-peptide were significantly higher by increasing the caloric load as was β-cell sensitivity to glucose. In contrast, the AUC glucagon was the same for all three meals, although there was an increase in glucagon after the postpeak glucose reduction in the smaller meal. The 0- to 20-minute paracetamol appearance was increased by increasing meal size. CONCLUSION Mixed lunch meals of increasing size elicit a caloric-dependent insulin response due to increased β-cell secretion achieved by increased GIP and GLP-1 levels. The adaptation at larger meals results in identical glucose excursions, whereas after a lower caloric lunch, the insulin response is high, resulting in a postpeak suppression of glucose below baseline.
Étude des approches de modélisation de la turbulence pour la simulation numérique d'un compresseur centrifuge à fort taux de pression. (Study of turbulence modelling for the numerical simulation of a high pressure centrifugal compressor)

Cette etude a pour objectif d’etudier differentes approches de modelisation de la turbulence sur un compresseur centrifuge industriel a fort taux de pression afin d’essayer d’elargir notre comprehension des differents phenomenes physiques mis en jeu et leur interaction avec la turbulence. D’abord, la sensibilite au maillage et au modele turbulence est evaluee sur des calculs RANS. Une analyse de simulations LES est ensuite effectuee. En particulier, une etude de l’effet de la turbulence sur l’ecoulement et une comparaison aux resultats RANS et experimentaux est realisee. Enfin, deux approches hybrides DES sont etudiees afin d’exposer les problemes rencontres par ces modeles sur cette configuration. Il en resulte une evaluation des differentes methodes et de leur applicabilite future dans un contexte industriel.
Phencyclidine disturbs relational memory in the transitive inference task

Transitive inference, that is, the ability to infer relationships among stimuli that are only indirectly associated, is impaired in schizophrenic patients and in rats with lesions of the prefrontal cortex. Symptoms of schizophrenia can be pharmacologically modeled by administration of the N-methyl-d-aspartate receptor antagonist, phencyclidine (PCP). Here, a subchronic administration of PCP (2.5 mg/kg for 5 days) to well-trained rats impaired the subsequent transitive inference judgment; the effect was observed 3 days, but not 10 days after the last dose. These results support the findings showing that PCP administration impairs cognitive domains specifically affected in schizophrenia in addition to mimicking the ‘positive’ and ‘negative’ symptoms of the disorder.
Matching as a non-cooperative game

With this paper we offer a game-theoretic perspective for the all-pervasive matching problem in computer vision. Specifically, we formulate the matching problem as a (population) non-cooperative game where the potential associations between the items to be matched correspond to (pure) strategies, while payoffs reflect the degree of compatibility between competing hypotheses. Within this formulation, the solutions of the matching problem correspond to evolutionary stable states (ESS's), a robust population-based generalization of the notion of a Nash equilibrium. In order to find ESS's of our matching game, we propose using a novel, fast evolutionary game dynamics motivated by Darwinian selection processes, which let the pure strategies play against each other until an equilibrium is reached. A distinguishing feature of the proposed framework is that it allows one to naturally deal with general many-to-many matching problems even in the presence of asymmetric compatibilities. The potential of the proposed approach is demonstrated via two sets of image matching experiments, both of which show that our results outperform those obtained using well-known domain-specific algorithms.
Employing the International Classification of Functioning, Disability and Health to enhance services for children and youth with chronic physical health conditions and disabilities.

PURPOSE In 2001, the World Health Organization published the International Classification of Functioning, Disability and Health (ICF). The ICF is just beginning to be used in a variety of clinical and research settings in Canada and worldwide. The purpose of the present article is to describe the initial use of the ICF at an Ontario children's rehabilitation centre, and to consider further uses both within and outside the centre for enhancing services for children and youth with chronic physical health conditions and disabilities, as well as for their families. METHOD A description is provided on how the ICF has been used at the centre to guide clinical thinking and practice, and to justify and steer research directions. Plans underway to use the ICF to collect and record functional data at the centre are also described. Finally, recommendations for the use of the ICF to enhance communication among child health professionals across service settings are provided. CONCLUSIONS Used in conjunction with the International Classification of Diseases - Tenth Revision, the ICF's conceptual framework and classification system shows great promise for enhancing the quality of services for children with chronic conditions and their families. This information may assist paediatric specialists, other child health professionals, researchers and administrators to use the ICF in similar settings. It may also stimulate exploration of the use of the ICF for general paediatricians and other service providers in the larger community.
Abasic DNA structure, reactivity, and recognition.

Loss of a base in DNA, i.e., creation of an abasic site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously, or under the action of radiations and alkylating agents, or enzymatically as an intermediate in the repair of modified or abnormal bases. The abasic site lesion is mutagenic or lethal if not repaired. From a chemical point of view,the abasic site is an alkali-labile residue that leads to strand breakage through beta- and delta- elimination. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of synthetic abasic duplexes. Several efficient synthetic methods have thus been developed to introduce the lesion (or a stable analogue) at defined position in the sequence. Physicochemical and spectroscopic examination of such duplexes, including calorimetry, melting temperature, high-field nmr and molecular modeling indicate that the lesion strongly destabilizes the duplex, although remaining in the canonical B-form with structural modifications strictly located at the site of the lesion. Probes have been developed to titrate the damage in DNA in vitro. Series of molecules have been devised to recognize specifically the abasic site, exhibiting a cleavage activity and mimicking the AP nucleases. Others have been prepared that bind strongly to the abasic site and show promise in potentiating the cytotoxic and antitumor activity of the clinically used nitrosourea (bis-chloroethylnitrosurea).
What is universal and what is language-specific in emotion words?: Evidence from Biblical Hebrew

This paper proposes a model for the analysis of emotions in which each emotion word in each language is made up of a universal component and a language-specific component; the universal component is drawn from a set of universal human emotions which underlie all emotion words in all languages, and the language-specific component involves a language-particular thought pattern which is expressed as part of the meanings of a variety of different words in the language. The meanings of a variety of emotion words of Biblical Hebrew are discussed and compared with the meanings of English words with the same general meaning; it is shown that a number of the Biblical Hebrew words (though by no means all) directly represent the biblical conception of God and the role of God combined with one or another of the proposed universal emotions.
Basic Genetic Principles Applied to Posterior Fossa Malformations

Abstract Recent advances in neuroimaging techniques turned possible for neuroradiologists to be frequently the first one to detect possible brain structural anomalies. However, with all the recent advances in genetics and embryology, understanding posterior fossa malformation’s principles is being hardest to be achieved than previously. Studies in vertebrate models provide a developmental framework in which to categorize human hindbrain malformations and serve to inform our thinking regarding candidate genes involved in disrupted developmental processes. The main focus of this review was to survey the basic principles of the rhombomere division, anteroposterior and dorsoventral patterning, alar and basal zone concept, and axonal path finding to integrate the knowledge of human hindbrain malformations for better understanding the genetic basis of hindbrain development.
Detecting Sodium-Sensitivity in Hypertensive Patients: Information From 24-Hour Ambulatory Blood Pressure Monitoring

Sodium sensitivity is an important cardiovascular risk factor for which a diagnosis requires a time-consuming protocol, the implementation of which is often challenging for patients and physicians. Our aim was to assess the reliability of an easier approach based on data from 24-hour ambulatory blood pressure monitoring performed in hypertensive subjects during daily-life conditions and habitual diet. We enrolled 46 mild to moderate hypertensive subjects who underwent 24-hour ambulatory blood pressure monitoring during usual sodium intake. Patients were divided into 3 classes of sodium sensitivity risk on the basis of ambulatory blood pressure monitoring data: low risk if dippers and a 24-hour heart rate ≤70 bpm; high risk if nondippers and a 24-hour heart rate of >70 bpm; intermediate risk with the remaining combinations (dippers with heart rate >70 bpm or nondippers with heart rate ≤70 bpm). Then patients underwent a traditional sodium sensitivity test for the dichotomous classification as sodium sensitive or sodium resistant and for evaluating the sodium sensitivity index. Prevalence of sodium-sensitive patients and mean value of sodium sensitivity index were calculated in the 3 risk classes. The sodium sensitivity index markedly and significantly increased from the low-risk to the high-risk class, being equal to 19.9±14.4, 37.8±8.3, and 68.3±17.0 mm Hg/(mol/day) in the low-risk, intermediate-risk, and high-risk classes, respectively (M±SEM). Also, the prevalence of sodium-sensitive patients increased significantly from the low-risk class (25%) to the intermediate-risk (40%) and high-risk (70%) classes. Thus, performance of 24-hour ambulatory blood pressure monitoring in daily-life conditions and habitual diet may give useful information on the sodium sensitivity condition of hypertensive subjects in an easier manner than with the traditional sodium sensitivity test approach.
GoHotDraw: evaluating the Go programming language with design patterns

Go, a new programming language backed by Google, has the potential for widespread use: it deserves an evaluation. Design patterns are records of idiomatic programming practice and inform programmers about good program design. In this study, we evaluate Go by implementing design patterns, and porting the "pattern-dense" drawing framework HotDraw into Go, producing GoHotDraw. We show how Go's language features affect the implementation of Design Patterns, identify some potential Go programming patterns, and demonstrate how studying design patterns can contribute to the evaluation of a programming language.