Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations

Background: Activating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion. Objectives: To study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA. Patients and methods: Twenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed. Results: Heterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 µmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified. Conclusion: Patients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations

ARPES studies of cuprate Fermiology: superconductivity, pseudogap, and quasiparticle dynamics

We present angle-resolved photoemission spectroscopy (ARPES) studies of the cuprate high-temperature superconductors which elucidate the relation between superconductivity and the pseudogap and highlight low-energy quasiparticle dynamics in the superconducting state. Our experiments suggest that the pseudogap and superconducting gap represent distinct states, which coexist below T$_c$. Studies on Bi-2212 demonstrate that the near-nodal and near-antinodal regions behave differently as a function of temperature and doping, implying that different orders dominate in different momentum-space regions. However, the ubiquity of sharp quasiparticles all around the Fermi surface in Bi-2212 indicates that superconductivity extends into the momentum-space region dominated by the pseudogap, revealing subtlety in this dichotomy. In Bi-2201, the temperature dependence of antinodal spectra reveals particle-hole asymmetry and anomalous spectral broadening, which may constrain the explanation for the pseudogap. Recognizing that electron-boson coupling is an important aspect of cuprate physics, we close with a discussion of the multiple 'kinks' in the nodal dispersion. Understanding these may be important to establishing which excitations are important to superconductivity.Comment: To appear in a focus issue on 'Fermiology of Cuprates' in New Journal of Physic

Examining the effects of celebrity trust on advertising credibility, brand credibility, and corporate credibility

Drawing on signalling theory, this study aims to fill a gap in knowledge by examining the effects of celebrity trust on advertising credibility, brand credibility and corporate credibility, both directly and based on the moderating variables of age, gender and ethnicity. The research has three objectives: (i) to explore the effects of celebrity trust on advertising credibility, brand credibility and corporate credibility; (ii) to explore the effects of celebrity trust on advertising credibility, brand credibility and corporate credibility, based on the moderating effects of consumer demographics; and (iii) to explore the effects of the other constructs on each other, i.e. advertising credibility on brand credibility and corporate credibility, and brand credibility on corporate credibility. For this purpose, a survey of 625 respondents was conducted in London. The empirical results show that celebrity trust has a positive effect on both advertising credibility and brand credibility, and that these effects are moderated by consumers’ ethnicity, with no obvious effects of age or gender. No effect was found on corporate credibility. The effects of advertising credibility on brand credibility and corporate credibility, and of brand credibility on corporate credibility, were found to be significant. The significant implications for managers and researchers are highlighted

Examining the effects of advertising credibility on brand credibility, corporate credibility and corporate image: a qualitative approach

Purpose – The aim of this study is to understand the concept of advertising credibility and examine its effects on brand credibility, corporate credibility and corporate image. Design/methodology/approach – A qualitative approach was used. Ten interviews and four mini focus groups were conducted among participants drawn from the 32 London boroughs. Data was analysed by using thematic analysis. Findings - The findings suggest that advertising credibility is defined using terms like accurate, caring, competent, complete, convincing, ethical, honest, impressive, reliable and warranted; and on the basis that it delivers what it promises about the products/service. The findings also suggest that advertising credibility has a positive effect on brand credibility, corporate credibility and corporate image. Originality/value – Advertising credibility has received little attention in the literature. This is the first study, which has exploratory examined its effects on brand credibility, corporate credibility, and corporate image

Nifedipine in Congenital Hyperinsulinism - A Case Report.

PublishedJournal ArticleThis is the final version of the article. Available from Galenos Yayınevi via the DOI in this record.Congenital hyperinsulinism (CHI) is the commonest cause of persistent hypoglycemia in neonates. Diazoxide is the first-line drug in its treatment, but the more severe cases are usually diazoxide-resistant. Recessive ABCC8 and KCNJ11 mutations are responsible for most (82%) of the severe diazoxide-unresponsive CHI. Oral nifedipine has been effective in isolated cases of CHI. Successful treatment of diazoxide-unresponsive CHI with a combination of octreotide and nifedipine has been reported in a single isolated case so far. We report here a case of diazoxide-resistant CHI due to homozygous ABCC8 nonsense mutation. In this case, hypoglycaemia uncontrolled by pancreatectomy and octreotide alone showed a good response to a combination of nifedipine and octreotide. Octreotide was tapered off by one year age and thereafter the child is euglycaemic on oral nifedipine alone. Continuous glucose monitoring sensor was used as an aid to monitor glycaemic control and was found to be a safe and reliable option reducing the number of needle-pricks in small children

Celebrity endorsement and the attitude towards luxury brands for a sustainable consumption

Taking into consideration the increasing role of sustainability in the luxury industry, our study investigates the role of celebrity credibility, celebrity familiarity, luxury brand value, and brand sustainability awareness on attitude towards celebrity, brand, and purchase intention for a sustainable consumption. For this, we explored relationships among these variables to test a conceptual model which is developed using existing knowledge available in academic research on this topic. Data for testing were collected from high-end retail stores in UK about the world top luxury brands by brand value in 2019, also acknowledged for their major engagement in sustainability. Findings from a survey of 514 consumers suggest that celebrity credibility is a very strong key to increase purchase intentions of luxury sustainable goods. The study has important implications for the expansion of current literature, theory development and business practices. Limitations of the study are also outlined and directions for future research are considered too

EFFECT OF INBREEDING ON PRE-WEANING GROWTH TRAITS IN THALLI SHEEP

Pedigree records of 17250 Thalli sheep with 17030 lambings maintained at the Livestock Experiment Station, Rakh Ghulaman, Distt. Bhakkar, Pakistan during the period from 1975 to 2004 were utilized in the present study. Average values for birth weight, weights at 60 and 90 days of age, weaning weight and pre-weaning average daily gain were 4.11 ± 0.82, 11.58 ± 3.57, 14.92 ± 4.56, 18.95 ± 4.56 and 0.12 ± 0.04 kg, respectively. Coefficients of inbreeding ranged from 10.15 to 37.50 percent for 295 animals, being 1.70 percent of the flock. Inbreeding significantly (P<0.01) affected birth and 60 days weight. Birth weight and 60 days weight decreased by 0.051 and 0.048 kg for each 1 percent increase in the level of inbreeding. However, inbreeding had non significant effect on weight at 90 days of age, weaning weight and pre-weaning average daily gain. The regression values for these traits were 0.010, 0.083 and 0.105, respectively. It was concluded that inbreeding showed deleterious effects only in early stages of life but as the lambs grew older the effect of inbreeding on pre-weaning traits diminished

Development of Optical Parametric Oscillator Tunable in the Range 970-1460 nm

Optical parametric oscillator (OPO) tunable in the range 970-1460 nm has been developed using bet barium borate (BBO) crystal as the gain medium and second harmonic of Nd:YAG laser as pump source. Two sets of resonators were used to cover the range; first was nearly degenerate (970-1180 nm) and the second was nondegenerate (1240-1460 nm). The measured threshold pump pulse energy was nearly 8 mJ. Maximum signal pulse energy of about 14 mJ was obtained for pump pulse energy of nearly 31 mJ. Power scaling efficiency was about 70 per cent. The signal pulse width was ~5 ns corresponding to the pump pulse width of ~ 9 ns. OPO signal beam quality was Gaussian although the pump beam was top-hat multimode.Defence Science Journal, 2011, 61(4), pp.377-382, DOI:http://dx.doi.org/10.14429/dsj.61.56

Exploring the Hidden Challenges Associated with the Evaluation of Multi-class Datasets using Multiple Classifiers

The optimization and evaluation of a pattern recognition system requires different problems like multi-class and imbalanced datasets be addressed. This paper presents the classification of multi-class datasets which present more challenges when compare to binary class datasets in machine learning. Furthermore, it argues that the performance evaluation of a classification model for multi-class imbalanced datasets in terms of simple “accuracy rate” can possibly provide misleading results. Other parameters such as failure avoidance, true identification of positive and negative instances of a class and class discrimination are also very important. We, in this paper, hypothesize that “misclassification of true positive patterns should not necessarily be categorized as false negative while evaluating a classifier for multi-class datasets”, a common practice that has been observed in the existing literature. In order to address these hidden challenges for the generalization of a particular classifier, several evaluation metrics are compared for a multi-class dataset with four classes; three of them belong to different neurodegenerative diseases and one to control subjects. Three classifiers, linear discriminant, quadratic discriminant and Parzen are selected to demonstrate the results with examples