Miracle-dz/UniFAR-FTUs huggingface dataset:
Signaling through Tyr985 of Leptin Receptor as an Age/Diet-Dependent Switch in the Regulation of Energy Balance

ABSTRACT Leptin regulates energy homeostasis through central activation of multiple signaling pathways mediated by Ob-Rb, the long form of leptin receptor. Leptin resistance underlies the pathogenic development of obesity, which is closely associated with environmental factors. To further understand the physiological function of leptin signaling mechanisms, we generated a knock-in line of mice (Y985F) expressing a mutant Ob-Rb with a phenylalanine substitution for Tyr985, one of the three intracellular tyrosines that mediate leptin's signaling actions. Surprisingly, whereas young homozygous Y985F animals were slightly leaner, they exhibit adult-onset or diet-induced obesity. Importantly, both age-dependent and diet-induced deterioration of energy balance was paralleled with pronounced leptin resistance, which was largely attributable to attenuation of leptin-responsive hypothalamic STAT3 activation as well as prominently elevated expression of hypothalamic SOCS3, a key negative regulator of leptin signaling. Thus, these results unmask distinct binary roles for Try985-mediated signaling in energy metabolism, acting as an age/diet-dependent regulatory switch to counteract age-associated or diet-induced obesity.
The Cambridge Introduction to Literature and the Environment: Interdisciplinarity and science

Preface Introduction: the challenge Part I. Romantic and Anti-Romantic: 1. Old World Romanticism 2. New World Romanticism 3. Genre and the ethics of nonfiction 4. Language beyond the human? 5. The inherent violence of Western thought? 6. Posthumanism and the 'end of nature' Part II. The Boundaries of the Political: 7. Thinking like a mountain? 8. Environmental justice and the move 'beyond nature writing' 9. European eco-justice 10. Liberalism and Green moralism 11. Ecofeminism 12. 'Postcolonial' eco-justice 13. Questions of scale: the local, the national and the global Part III. Science and the Struggle for Intellectual Authority: 14. Science and the crisis of authority 15. Science studies 16. Evolutionary theories of literature 17. Interdisciplinarity and science: two essays on human evolution Part IV. The Animal Mirror: 18. Ethics and the nonhuman animal 19. Anthropomorphism 20. The future of ecocriticism Further reading Index.
A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias

Objective: The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus. Methods: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. Results: The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects. Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 0.02). 4AP was well-tolerated. Conclusions: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. Level of evidence: This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias.
Effects of age on proximal gastric motor and sensory function.

BACKGROUND Healthy aging is associated with a reduction in appetite and food intake, which may predispose to pathologic weight loss and malnutrition. Changes in intragastric mechanisms mediating satiation in the elderly have not been studied. The aim of this study was to evaluate the effects of aging on i) fasting gastric compliance and the perception of gastric distension, and ii) food intake and gastric accommodation to a meal. METHODS Five healthy older (aged 68-73 years) and five healthy young (aged 22-27 years) men, matched for body mass index, were each studied on three occasions after an overnight fast. On one day ('barostat day'), isovolumetric and isobaric distensions of the proximal stomach were performed, and meal-induced changes in intrabag volume were measured with an electronic barostat. On another day ('tube-only day') subjects were intubated with a nasogastric tube without an intragastric bag before the meal. On the 3rd day (control day) subjects were given the meal without intubation. Energy intake from the buffet meal was quantified, and perceptions assessed using visual analogue questionnaires. RESULTS During both isobaric and isovolumetric distensions the pressure-volume relationship did not differ significantly between older and young subjects. During gastric distensions perceptions of fullness (P < 0.01), abdominal discomfort (P < 0.05), and bloating (P < 0.05) were less in older than young subjects, whereas the perception of hunger (P < 0.05) was less in the young than in older subjects. There was no difference in energy intake (P = 0.44) between young and older subjects. Food intake was less on the barostat day (P < 0.01) and the tube-only day (P < 0.01) than on the control day in young subjects but was not affected by the different study conditions in the older subjects. After the meal the maximum intrabag volume occurred later in the older than in the young subjects (105 +/- 4 min versus 36 +/- 8 min; P < 0.05), and the intrabag volume change was greater (P = 0.05) in the older than the young subjects later in the postprandial period. CONCLUSIONS Healthy aging is associated with decreased perception of gastric distension without any change in fasting gastric compliance and with reduced gastric tone late in the postprandial period when compared with the young. Control of food intake is less sensitive to external stimuli in older than in young subjects.
Reliability in Pragmatics

1. Introduction PART I - REPUTATION AND COOPERATION 2. Cooperation 3. Trust and reputations 4. Hedging beyond truth 5. Deriving hedged interpretations PART II - EVIDENTIALS AND RELIABILITY 6. The nature of evidentials 7. Evidentials and reliability 8. Using priorities 9. Testimonial evidence 10. Conclusion Appendix: Formal system References Index
Assessment of the relationship between maxillary rotation and nasal morphology in males

Background: Nasal features are important in treatment planning for orthodontic treatment. Aims and Objectives: The purpose of the study was to assess the relationship between maxillary inclination and nasal morphology in males. Materials and Methods: Forty-five samples were selected for the study between the age group of 18 and 30 years. Selected individuals were subjected to cephalometric radiography. These lateral cephalograms were traced and divided into three groups on the basis of the angle given by Schwarz for rotation of the maxilla. The nasal features of these groups were evaluated and compared using mean, standard deviation, Student's t-test and analysis of variance. Results: The results suggest that there was statistically significant difference in nasal height, nasal bone length (NBL), nasal depth, nasolabial angle (NLA), nasal tip angle and upper lip inclination angle in different maxillary inclination group. Conclusion: The nasal height, NBL, NLA and nasal tip angle had a maximum value in retro inclination group.
Adverse drug reactions associated with the use of liraglutide in patients with type 2 diabetes – focus on pancreatitis and pancreas cancer

Introduction: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, is a widely used drug for the treatment of type 2 diabetes. Liraglutide is one of several incretin-based agents that have been suggested to be associated with pancreatitis and pancreas cancer. The suspicion accelerated after publication of an autopsy study claiming increased incidences of several pathological changes in pancreata from patients with diabetes treated with incretin-based drugs. Areas covered: The aim of the present review is to give an overview of the pharmacology of liraglutide and provide a review of adverse reactions associated with liraglutide with a focus on the risk of pancreatitis and pancreas cancer. Expert opinion: When comprehensively reviewing the available literature, no clear and significant associations between liraglutide and pancreatitis and/or pancreas cancer seem evident. However, a recently published analysis suggests a trend toward a slightly elevated risk of pancreatitis with GLP-1 receptor agonists (including liraglutide), which may become statistical significant as more data become available. Well-established side effects are of gastrointestinal origin, typical mild-to-moderate and of transient character. The risk of hypoglycemia associated with liraglutide treatment is low.
Ghee Whiz! the Growing Evidence for the Benefits of the Modified Atkins Diet

Commentary It has now been a decade since the modified Atkins diet (MAD), a less restrictive, outpatient-initiated version of the ketogenic diet (KD), was first published in the medical literature (1). Although still inducing ketosis, the MAD does not restrict protein, calories, or fluids—solely measuring daily carbohydrates and encouraging high fat intake. In the ten years since its introduction, there have been 27 articles published, reporting 355 children and adults. Results to date suggest similar efficacy but fewer side effects in comparison to the KD. The scientific evidence behind the MAD is strong; however, until this article, there had not been any randomized and controlled trials to support its use. This is similar to the situation prior to 2008 for the classic KD, following which two studies, one blinded, were published (2, 3). The most widely publicized—a randomized and controlled study by Neal and colleagues from United Kingdom—tested the ketogenic diet (both the classic and the medium-chain triglyceride versions) versus 3 months of continued status quo anticonvulsants in children ages 2–16 years with refractory epilepsy (2). The randomization occurred following a 4-week baseline period for all children. As of the writing of this review, according to Google Scholar, this publication has been cited 205 times in the literature in just 5 years, demonstrating its impact. Perhaps seeking to replicate the fame and impact of this landmark study, Dr. Sharma and her colleagues from India utilized an essentially identical study design to evaluate the MAD in children ages 2–14 years with intractable epilepsy. There were some differences compared to the Neal study, primarily in regard to patient demographics: 78% were male, all from a single tertiary center, and a larger percentage (approximately half ) had the diagnosis of Lennox-Gastaut syndrome (2). The study was completed successfully with a lower dropout rate than the Neal study; in fact, with a remarkable 8% discontinuation rate with MAD (versus 15% in the Neal KD study arm) (2). The results certainly suggest both a similarity to the KD based on the Neal outcomes, as well as seizure improvement dramatically better than the control. The likelihood of > 50% seizure reduction at 3 months was 52% with the MAD versus 11.5% in the control group. Similarly, > 90% seizure reduction occurred in 30% versus 7.7%. This is similar, if not slightly better, than the Neal findings with the KD, in which they found 38% versus 6% (for > 50% seizure reduction) and 7% versus 0% (> 90% seizure reduction) (2). These studies can and should not be directly compared, and the high placebo rate in the current study is surprising, yet the results are intriguing. The MAD was very well-tolerated, with adverse effects primarily constipation, weight loss, and vomiting, as would be Use of the Modified Atkins Diet for Treatment of Refractory Childhood Epilepsy: A Randomized Controlled Trial.
The family context and residential choice: a challenge for new research

Even in today's Western societies, a substantial influence can be expected on residential choice (behaviour with respect to residential mobility, migration, location choice and housing quality) from the wider family context (parents, children and siblings living outside the household). In this paper, an agenda is presented for research investigating the influence of the wider family context on the residential choices of households and the feedback of these choices to segregation with regard to socioeconomic status and ethnicity. The results of the research will contribute to the academic literature on residential choice, family migration, family solidarity, and to societal and policy debates on social inequality and residential segregation. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis and Characterization of a Laminated Hydroxyapatite/Gelatin Nanocomposite Scaffold with Controlled Pore Structure for Bone Tissue Engineering

In this study, a nanostructured scaffold was designed for bone repair using hydroxyapatite (HA) and gelatin (GEL) as its main components. Nanopowders of HA were synthesized, and together with GEL, used to engineer a 3-dimensional nanocomposite combining 3 techniques of layer solvent casting, freeze-drying, and lamination. The results show that the scaffold possesses a 3-dimensional interconnected homogenous porous structure with a porosity of 82% and pore sizes ranging from 300 to 500 μm. It has also been shown that mechanical indices are in the range of spongy bones. Cultured osteoblast-like cells (SaOS-2) have shown an excellent level of cell attachment, migration, and penetration into the porosities of the nanocomposite scaffold. Here, we have shown that by a combination of widely available methods with simple experimental operations, nano-HA powders can be synthesized and used to make 3-dimensional HA/GEL nanocomposites in any desired shape, with mechanical properties comparable to spongy bone.
A Two-Stage Moment Robust Optimization Model and its Solution Using Decomposition ∗

Moment robust optimization models formulate a stochastic problem with an uncertain probability distribution of parameters described by its moments. In this paper we study a two-stage stochastic convex programming model using moments to define the probability ambiguity set for the objective function coefficients in both stages. A decomposition based algorithm is given. We show that this two-stage model can be solved to any precision in polynomial time. We consider a special case where the probability ambiguity sets are described by the exact information of the first two moments and the convex functions are piece-wise linear utility functions. A two-stage stochastic semidefinite programming formulation is given of this problem and we provide computational results on the performance of this problem using a portfolio optimization application. Results show that the two stage modeling is effective when forecasting models have predictive power.
Weak Spatial and Temporal Population Genetic Structure in the Rosy Apple Aphid, Dysaphis plantaginea, in French Apple Orchards

We used eight microsatellite loci and a set of 20 aphid samples to investigate the spatial and temporal genetic structure of rosy apple aphid populations from 13 apple orchards situated in four different regions in France. Genetic variability was very similar between orchard populations and between winged populations collected before sexual reproduction in the fall and populations collected from colonies in the spring. A very small proportion of individuals (∼2%) had identical multilocus genotypes. Genetic differentiation between orchards was low (F ST <0.026), with significant differentiation observed only between orchards from different regions, but no isolation by distance was detected. These results are consistent with high levels of genetic mixing in holocyclic Dysaphis plantaginae populations (host alternation through migration and sexual reproduction). These findings concerning the adaptation of the rosy apple aphid have potential consequences for pest management.
Patient-reported medication symptoms in primary care.

BACKGROUND Little is known about the prevalence and character of medication-related symptoms in primary care and their relationship to adverse drug events (ADEs) or about factors that affect patient-physician communication regarding medication symptoms. METHODS The study included 661 patients who received prescriptions from physicians at 4 adult primary care practices. We interviewed patients 2 weeks and 3 months after the index visit, reviewed patients' medical records, and surveyed physicians whose patients identified medication-related symptoms. Physician reviewers determined whether medication symptoms constituted true ADEs. We used multivariable regression to examine factors associated with patients' decision to discuss symptoms with a physician and with physicians' decision to alter therapy. RESULTS A total of 179 patients identified 286 medication-related symptoms but discussed only 196 (69%) with their physicians. Physicians changed therapy in response to 76% of reported symptoms. Patients' failure to discuss 90 medication symptoms resulted in 19 (21%) ameliorable and 2 (2%) preventable ADEs. Physicians' failure to change therapy in 48 cases resulted in 31 (65%) ameliorable ADEs. In multivariable analyses, patients who took more medications (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.04-1.08; P<.001) and had multiple medication allergies (OR = 1.07; 95% CI = 1.03-1.11; P = .001) were more likely to discuss symptoms. Male physicians (OR = 1.20, 95% CI = 1.09-1.26; P = .002) and physicians at 2 practices were more likely to change therapy (OR = 1.24; 95% CI = 1.17-1.28; P<.001; and OR = 1.17; 95% CI = 1.08-1.24; P = .002). CONCLUSION Primary care physicians may be able to reduce the duration and/or the severity of many ADEs by eliciting and addressing patients' medication symptoms.
PENERAPAN MODEL PEMBELAJARAN CONTEXTUAL TEACHING AND LEARNING (CTL) UNTUK MENINGKATKAN HASIL BELAJAR PKN

Tujuan Penelitian ini untuk meningkatkan peran serta belajar siswa dan meningkatkan prestasi belajar siswa pada mata pelajaran PKn. Jenis penelitian ini adalah penelitian tindakan kelas (PTK) dengan dua siklus, setiap siklus meliputi perencanaan, pelaksanaan tindakan observasi-evaluasi dan refleksi. Subjek penelitian adalah siswa kelas X-1 MAN Popongan Kabupaten Klaten di Prambanan tahun pelajaran 2011/2012 yang berjumlah 19 siswa. Dalam penelitian ini terdapat dua jenis data yaitu kuantitatif dan kualitatif. Data kuantitatif yang berupa hasil tes kognitif siswa dianalisis dengan deskriptif kuantitatif, sedangkan data kualitatif berupa hasil observasi terhadap aktivitas belajar siswa dianalisis dengan deskriptif kualitatif. Hasil penelitian menunjukkan bahwa penggunaan metode CTL dapat meningkatkan peran serta belajar siswa dalam pembelajaran PKn, hal itu terlihat pada siklus I, skor peran serta belajar siswa sebesar 53,17, pada siklus II sebesar 78,86. Peningkatan peran serta siswa ternyata berdampak positif terhadap prestasi belajar siswa, pada siklus I, rata-rata hasil tes kognitif sebesar 66,05; pada siklus II sebesar 72,85
‘Blair's Children’: Young Women as ‘Aspirational Subjects’ in the Psychic Landscape of Class

This paper engages with the subjective experience of ‘doing’ aspiration, teasing out the psychic and social costs that accompany this as a classed process. It draws on a qualitative study of young women located in further education and contemplating their futures under New Labour, locating how the political rhetoric of aspiration gets institutionalized within school practices; how it intersects with maternal expectations and practices of involvement; and how these are lived and managed by subjects located in different positions in class-inflected social space. In attending to the tangled web of institutional, intergenerational and affective practices which shape young women's aspirations, the paper seeks to interrupt the celebratory and simplistic rhetoric of aspiration that characterizes the contemporary socio-political register of neoliberalism. As these ideals become further entrenched by the current Coalition government, there is an even greater urgency for such sociological enquiries.
Pragmatics in Language Teaching: The role of input enhancement in developing pragmatic competence

Introduction Input enhancement in second language acquisition (SLA) has been addressed in studies of form-focused instruction at morphosyntactic levels, known as Focus on Form (FonF) research (e.g., White, Spada, Lightbown & Ranta, 1991; Carroll, Swain & Roberge, 1992; Fotos, 1993; Spada & Lightbown, 1993; Trahey & White, 1993; see Doughty & Williams, 1998; Long & Robinson, 1998, for an overview). Following Sharwood Smith's (1991, 1993) definition of input enhancement, researchers experimentally manipulated instructional input on L2 structures in various ways: some form of corrective feedback with or without metalinguistic information (e.g., Doughty & Varela, 1998), visual enhancement (textual modification) with the use of bold or italic face (e.g., Alanen, 1995; Jourdenais, Ota, Stauffer, Boyson, & Doughty, 1995; J. White, 1998), and task manipulation directing learners to notice and attend to target structures (e.g., Hulstijn, 1989; Robinson, 1996; Williams & Evans, 1998). All of these studies provided evidence that high levels of attention-drawing activities, as represented by presenting metalinguistic information and corrective feedback, are more helpful for learners in gaining the mastery of target-language structures than simple exposure to positive evidence. These findings thus provide the basis for theoretical verification of Schmidt's (1993a, 1995, 1998) Noticing Hypothesis, which states that conscious noticing is the necessary and sufficient condition for converting input to intake. In contrast to the rich array of input enhancement research into morphosyntactic features, there have been considerably fewer studies specifically focusing on the role of input enhancement in developing L2 pragmatic competence.
PRIMARY MECHANISMS OF ERYTHROCYTE PHOTOLYSIS INDUCED BY BIOLOGICAL SENSITIZERS AND PHOTOTOXIC DRUGS

Abstract— The elucidation of the molecular mechanism of photosensitized hemolysis of red blood cells may give important clues to the primary events underlying the phototoxic reactions observed in pathological conditions such as porphyria and induced by photosensitizing drugs. Sensitizers effective in photo‐hemolysis are porphyrins, the tryptophan metabolite kynurenic acid, and phototoxic drugs such as chlor‐promazine and demethylchlortetracycline. Utilizing the singlet oxygen quenchers. jS‐carotene and histi‐dine and the large deuterium effect on the lifetime of singlet oxygen previously described by us, good evidence of the participation of this excited molecular species in the photohemolysis in the presence of kynurenic acid was obtained. Chlorpromazine and demethylchlortetracycline clearly act by a non‐singlet oxygen pathway. The situation observed with haematoporphyrin is less clear and may represent a mixed Type I‐Type II mechanism.