bluuebunny/crossref_metadata_2025 huggingface dataset:
ESTUDO COMPARATIVO ENTRE O MODELO DE NEGÓCIO TRADICIONAL E O MODELO DE NEGÓCIO DIGITAL PARA ACONSTRUÇÃO DE NEGÓCIOS SUSTENTÁVEIS
Authors: Ribeiro Gustavo Santos
Published: April 2024

O objetivo do presente trabalho é construir um estudo comparativo entre o modelo de negócio iniciado durante a revolução industrial, ou seja, aquele queexplora a produção seriada e o consumo em massa em relação aos novos modelos de negócio digitais que transformam os produtos em serviço. O tema levantado nesse estudo apresenta as diferentes ferramentas que indicam a tendência para antigas e novas empresas a transformarem seus produtos em serviços e assim permitir maior liberdade de escolha ao usuário, autonomia na publicidade e eliminação gradual do ponto de venda físico. Essa provável mudança tende, direta ou indiretamente, construir um ciclo produtivo mais sustentável, ou seja, através um relacionamento mais próximo com o cliente serão atendidas diferentes necessidades, novos compartilhamentos, adaptações ou atualizações de produtos, maior independência em relação à publicidade e menor dependência de atividades de alto consumo energético. Essa mudança de atitude permitirá que mudemos daera do possuir para a era do utilizar. Por fim, auxiliará no entendimento de como o designer deverá se comportar como agente essencial na desconstrução de barreiras criadas pelo consumo massivo.
Catia customization for Design and Modeling of Two stage spur Gearbox
Authors: Patwardhan Mayuresh V. , Nimbalkar Uddhavrao
Published: April 2024

In this paper, we describe how the customization of design task, in solid modeling with CATIA V5 for two stage spur gearbox can be approached, by means of macros (piece of code) and with GUI form. The user has to supply some basic requirements of the gearbox and rest of the different parameters for design of gearbox is calculated by formulas. And then with the help of these parameters, part model of gearbox is created.
Rationalization of the scope of work: evaluation of imbalances and opportunities of multi-tasking
Authors: Hamid Algamir , Ricopuerto Jenny , Sanson Kenneth
Published: April 2024

The purpose of this undertaking was to determine the imbalances and opportunities of multitasking of teachers in their workplace. Teachers have one of the most important jobs in the world. They fill in the shoes of too many different professions like a parent, disciplinarian, judge, administrator, academic experts, mentor, and more, and probably all-time. It’s no secret that our teachers get so many things done that it’s no wonder that they’ve become experts in multitasking. This study evaluates the imbalances and opportunities of multitasking of 60 teachers handled general education and major subject. Purposive surveys a descriptive quantitative and qualitative method was applied survey and interviews will be conducted; to rationalize the scope of work, were employed as research instruments to collect responses on imbalances and opportunities of multitasking. The research findings showed the majority of teachers strongly agreed with the opportunities of multitasking in terms of Integration of Diverse Work, and imparting knowledge to co-instructor. It further revealed that most of the respondents that practice multitasks were men. To divert the emphasis on the imbalances of multitasking, the administration should be able to motivate instructor in terms of giving honoraria to those who extend their working hours and acknowledging them also during the ceremonial events.
Assessing Secondary School Teachers' Perceptions of Their Technological Pedagogical and Content Knowledge in Karachi Pakistan
Authors:   Govt. Graduate College for Women, Ghaffar Rabia , Khoso Farzana Jabeen ,   Shah Abdul Latif University Khairpur, Sahito Zahid Hussain ,   Shah Abdul Latif University Khairpur
Published: April 2024

Introduction: This study evaluated District South Karachi public secondary school teachers' material, pedagogical, and technological skills. Effective teaching and learning need understanding teachers' Technological Pedagogical Content Knowledge (TPACK) as technology is increasingly integrated into teaching and learning. Methodology: Simple descriptive survey was used. We targeted all secondary school teachers in District South Karachi, Pakistan. A random sample of 100 public secondary school teachers (26 males and 74 women) was chosen. Teachers' responses to a TPACK questionnaire were scored from severely disagree to highly agree. TPACK comprehension was considered satisfactory if scores above three. Results/Findings: Analysis of the data revealed that teachers exhibited a favorable attitude toward TPACK knowledge. However, subject matter competence and classroom technology use should be improved. The findings show that secondary schools should focus on professional development to improve teachers' technology and content expertise. Future Research Direction: Future studies should examine how educational background, teaching experience, and professional development opportunities affect instructors' TPACK. Comparative research across districts or regions may reveal TPACK and educational practices differences. Longitudinal studies could examine how TPACK training affects teaching and student results over time
Big data, ethics, and social impact theory: A conceptual framework
Authors: White Gwen , Ariyachandra Thilini
Published: April 2024

Decisions made using big data, impact ethical issues like privacy, security, ownership, and decision making. In addition, those same decisions can have a positive or negative social impact. This paper proposes a framework that explains how decisions made using big data impact ethics and social impact theory. A broad literature review explored how big data and ethics can have a social impact on society. The proposed framework of big data, ethics and social impact is illustrated through three examples. Insurance companies manipulate big data to impact sales. The Center for Disease Control examines big data to determine the location of the next outbreak. Companies analyze big data in predictive analytics to increase marketing or determine a new trend. It was found that these uses of big data directly affect ethics which has a positive or negative social impact. Simple decisions can change the outcome for one or millions.
Multi-Dimensional Clustering Based on Restricted Distance-Dependent Mixture Dirichlet Process for Diffusion Tensor Imaging
Authors: Park Soyun , Yu Jihnhee , Sternberg Zohi
Published: April 2024

Brain imaging research poses challenges due to the intricate structure of the brain and the absence of clearly discernible features in the images. In this study, we propose a technique for analyzing brain image data identifying crucial regions relevant to patients’ conditions, specifically focusing on Diffusion Tensor Imaging data. Our method utilizes the Bayesian Dirichlet process prior incorporating generalized linear models, that enhances clustering performance while it benefits from the flexibility of accommodating varying numbers of clusters. Our approach improves the performance of identifying potential classes utilizing locational information by considering the proximity between locations as clustering constraints. We apply our technique to a dataset from Transforming Research and Clinical Knowledge in Traumatic Brain Injury study, aiming to identify important regions in the brain’s gray matter, white matter, and overall brain tissue that differentiate between young and old age groups. Additionally, we explore a link between our discoveries and the existing outcomes in the field of brain network research.
Technical and Economic Aspects of the Choice of Enclosing Wall Structures with a Similar Heat Flow for Low-rise Housing Construction
Authors: Shakirova Veronika Aleksandrovna , Tolochko Olga Romanovna
Published: April 2024

This article is devoted to the analysis of multilayer enclosing structures used for the construction of exterior walls of low-rise buildings based on a comparison of thermal and economic indicators. For the calculations in this article, the most relevant and popular multilayer wall designs are selected. The object of the study is the structural solutions of multilayer wall enclosing structures in low-rise housing construction, which are used in the city of Krasnoyarsk. The subject of the study is: the influence of the composition of multilayer wall enclosing structures with a similar heat flow on the estimated cost of their construction for the city of Krasnoyarsk and the estimated cost of 1 square meter of each wall structure is determined. At the moment, the construction of low-rise residential buildings is gaining popularity and is supported by state programs both at the federal level and at the levels of the subjects of the Russian Federation and municipalities. Low-rise housing construction is considered as one of the possibilities of solving the housing problem or improving housing conditions for the population. Multilayer enclosing structures with exterior facade decoration have been widely used in low-rise and multi-storey construction. As part of the study, we considered the most common types of multilayer structures and exterior wall facade finishing options, performed thermal engineering and cost estimates to determine the most profitable option for a multilayer wall structure in low-rise housing construction.
Failure distribution and reliable analysis of ferroelectric ceramics under pulsed electric field
Authors: Zhang Fu-Ping , Li Xi-Qin , Du Jin-Mei , Liu Yu-Sheng , Ye Fu-Qing ,   D&M Center of Equipment and Engineering, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang 621900, China
Published: April 2024

Dielectric breakdown at high electric field plays an important role in the application of ferroelectric ceramics. In this paper, the failure probability versus electric shock time of ferroelectric ceramics under positive pulse electric field is analyzed statistically. The failure probability distribution of ceramics after 10 electric shocks is studied. Piezoelectric constant, P-E loop of ferroelectric ceramics after 10 thousand electric shocks are measured and the breakdown mechanism is discussed. The results indicate that the relation between failure probability and electric shock number of ferroelectric ceramics is shown by a bath-tube curve and the failure probability of samples after 10 electric shocks decreases by 4 orders of magnitudes compared with that of origin sample. According to the results of piezoelectric constant and P-E loop, the samples subjected to positive pulse electric field many times do not show obvious fatigue or aging effect. So pulse electric field loading at 4.5 kV/mm is close to non-destructive condition. Considering the spread speed of cracks, it can be found that the rupture of ferroelectric ceramics under pulsed electric field roots from extension and connection of multi-cracks from multi-defects.
Top cell design and optimization of all-chalcopyrite CuGaSe2/CuInSe2 two-terminal tandem solar cells
Authors: Zhong Jian-Cheng , Zhang Xiao-Tian , Lin Chang-Qing , Xue Yang , Tang Huan , Huang Dan ,   School of Physical Science and Technology, Guangxi University, Nanning 530004, China,   Guangxi Key Laboratory of Precision Navigation Technology and Application, Guilin University of Electronic Technology, Guilin 541004, China
Published: April 2024

Solar cells have attracted much attention, for they can convert solar energy directly into electric energy, and have been widely utilized in manufacturing industry and people’s daily life. Although the power conversion efficiency (PCE) of single-junction solar cells has gradually improved in recent years, its maximum efficiency is still limited by the Shockley-Queisser (SQ) limit of single-junction solar cells. To exceed the SQ limit and further obtain high-efficiency solar cells, the concept of tandem solar cells has been proposed. In this work, the chalcopyrite CuGaSe2/CuInSe2 tandem solar cells are studied systematically in theory by combining first-principle calculations and SCAPS-1D device simulations. Firstly, the electronic structure, defect properties and corresponding macroscopic performance parameters of CuGaSe2 (CGS) are obtained by first-principles calculations, and are used as input parameters for subsequent device simulations of CGS solar cells. Then, the single-junction CGS and CuInSe2 (CIS) solar cells are simulated by using SCAPS-1D software, respectively. The simulation results for the single junction CIS solar cells are in good agreement with the experimental values. For single-junction CGS cells, the device simulations reveal that the CGS single-junction solar cells have the highest short-circuit current (Jsc) and PCE under the Cu-rich, Ga-rich and Se-poor chemical growth condition. Further optimization in the growth environment with the highest short circuit current (Jsc) shows that the open-circuit voltage (Voc) and PCE of CGS solar cells can be improved by replacing the electron transport layer (ETL) with ZnSe. Finally, after the optimized CGS and CIS solar cells are connected in series with two-terminal (2T) monolithic tandem solar cell, the device simulation results show that under the growth temperature of 700 K and the growth environment of Cu-rich, Ga-rich, and Se-poor, with ZnSe serving as the ETL, the CGS thickness of 2000 nm and the CIS thickness of 1336 nm, the PCE of 2T monolithic CGS/CIS tandem solar cell can reach 28.91%, which is higher than the ever-recorded efficiency of the current single-junction solar cells, and shows that this solar cell has a good application prospect.
A scenario for an evolutionary selection of ageing
Authors: Roget Tristan , MacMurray Claire , Jolivet Pierre , Méléard Sylvie , Rera Michael
Published: April 2024

Signs of ageing become apparent only late in life, after organismal development is finalized. Ageing, most notably, decreases an individual’s fitness. As such, it is most commonly perceived as a non-adaptive force of evolution and considered a by-product of natural selection.Building upon the evolutionarily conserved age-related Smurf phenotype, we propose a simple mathematical life-history trait model in which an organism is characterized by two core abilities: reproduction and homeostasis.Through the simulation of this model, we observe 1) the convergence of fertility’s end with the onset of senescence, 2) the relative success of ageing populations, as compared to non-ageing populations, and 3) the enhanced evolvability (i.e. the generation of genetic variability) of ageing populations. In addition, we formally demonstrate the mathematical convergence observed in 1).We thus theorize that mechanisms that link the timing of fertility and ageing have been selected and fixed over evolutionary history, which, in turn, explains why ageing populations are more evolvable and therefore more successful. Broadly speaking, our work suggests that ageing is an adaptive force of evolution.
A systematic literature review of hate speech identification on Arabic Twitter data: research challenges and future directions
Authors: Alhazmi Ali , Mahmud Rohana , Idris Norisma , Mohamed Abo Mohamed Elhag , Eke Christopher
Published: April 2024

The automatic speech identification in Arabic tweets has generated substantial attention among academics in the fields of text mining and natural language processing (NLP). The quantity of studies done on this subject has experienced significant growth. This study aims to provide an overview of this field by conducting a systematic review of literature that focuses on automatic hate speech identification, particularly in the Arabic language. The goal is to examine the research trends in Arabic hate speech identification and offer guidance to researchers by highlighting the most significant studies published between 2018 and 2023. This systematic study addresses five specific research questions concerning the types of the Arabic language used, hate speech categories, classification techniques, feature engineering techniques, performance metrics, validation methods, existing challenges faced by researchers, and potential future research directions. Through a comprehensive search across nine academic databases, 24 studies that met the predefined inclusion criteria and quality assessment were identified. The review findings revealed the existence of many Arabic linguistic varieties used in hate speech on Twitter, with modern standard Arabic (MSA) being the most prominent. In identification techniques, machine learning categories are the most used technique for Arabic hate speech identification. The result also shows different feature engineering techniques used and indicates that N-gram and CBOW are the most used techniques. F1-score, precision, recall, and accuracy were also identified as the most used performance metric. The review also shows that the most used validation method is the train/test split method. Therefore, the findings of this study can serve as valuable guidance for researchers in enhancing the efficacy of their models in future investigations. Besides, algorithm development, policy rule regulation, community management, and legal and ethical consideration are other real-world applications that can be reaped from this research.
Enhancing Resilience: Smart Grid Cybersecurity and Fault Diagnosis Strategies
Authors: Basharat Arooj , Huma Zilly
Published: April 2024

The increasing integration of advanced technologies within the power grid infrastructure has led to significant advancements in efficiency, reliability, and sustainability. However, this integration also introduces new vulnerabilities, particularly in the realm of cybersecurity. This paper presents an overview of smart grid cybersecurity challenges and proposes strategies for enhancing resilience through fault diagnosis techniques. Firstly, the paper examines the evolving threat landscape facing smart grids, encompassing cyber-attacks, insider threats, and natural disasters. It highlights the critical need for robust cybersecurity measures to safeguard grid operations and prevent potentially catastrophic disruptions. Next, the paper delves into various cybersecurity frameworks and standards tailored specifically for smart grids, emphasizing the importance of comprehensive risk assessment, intrusion detection systems, and secure communication protocols. Additionally, it discusses the role of machine learning and artificial intelligence in augmenting cyber defense capabilities, enabling proactive threat detection and rapid response. Furthermore, the paper explores fault diagnosis strategies aimed at maintaining grid resilience in the face of cyber incidents or physical faults. It discusses the integration of data analytics, predictive modeling, and real-time monitoring to identify and mitigate potential grid disturbances swiftly.
Islam, Islamic Banking and Entrepreneurship: Evidence from OIC Member Countries
Authors: Kamdjo Célestin
Published: April 2024

There is a view that Islam hinders entrepreneurship in Muslim societies in general. Unfortunately, there is little empirical work testing the negative effect of Islam as a religion on entrepreneurship. In an attempt to fill this gap, this study aims to reassess this effect in OIC member countries. Specifically, the aim is to assess whether Islam is an impediment to entrepreneurship in these countries and whether the presence of Islamic banking institutions in these countries strengthens or moderates such a relationship. Using multivariate regression analysis, the results indicate that there is indeed a negative relationship between Islam and entrepreneurship in OIC countries where Islamic banking is absent. But, this relationship does not hold where Islamic banking exists. Indeed, the presence of Islamic banks in countries where Islam is the state religion cancels out any negative effect of Islam and has a positive effect on entrepreneurship in the country concerned. The results of this study thus reopen the debate on whether Islam as a religion discourages competition, innovation, entrepreneurship and economic development compared to other religions.
Cover Picture: Fabrication of Elastomeric Wires by Selective Electroless Metallization of Poly(dimethylsiloxane) (Adv. Mater. 1/2008)
Authors: Miller M. S. , Davidson G. J. E. , Sahli B. J. , Mailloux C. M. , Carmichael T. B.
Published: December 2007

Tricia Carmichael and co‐workers employ a simple, low‐cost method for the fabrication of patterned metal films on elastomeric poly(dimethylsiloxane) (PDMS) substrates, as described on p. 59. The metal/PDMS composites are electrically conductive and mechanically flexible, making them suitable for use in the fabrication of lightweight, flexible devices such as wearable electronics, biocompatible sensors, and artificial nerves, skins, and muscles. Copper wires on PDMS remain conductive when subjected to linear strains of up to 52 %. The utility of these wires is demonstrated by using them as laminated top contacts in an organic light‐emitting device.
Inside Front Cover: Superhydrophobic Surfaces Generated from Water‐Borne Dispersions of Hierarchically Assembled Nanoparticles Coated with a Reversibly Switchable Shell (Adv. Mater. 1/2008)
Authors: Motornov M. , Sheparovych R. , Lupitskyy R. , MacWilliams E. , Minko S.
Published: December 2007

On p. 200, Sergiy Minko and co‐workers report on the fabrication of a superhydrophobic coating from aqueous dispersions of hybrid responsive nanoparticles with no application of surfactants and organic solvents. A suspension of the particles forms a textured hydrophilic coating upon casting. Heating above the glass transition temperature of polystyrene, or treatment in acidic water, resulted in backward and forward switching between the superhydrophobic and the hydrophilic material, respectively.
A green process for preparing silver nanoparticles using spinning disk reactor
Authors: Tai Clifford Y. , Wang Yao‐Hsuan , Liu Hwai‐Shen
Published: December 2007

The main theme of this research was to synthesize nanoparticles using green materials in a spinning disk reactor (SDR), which is a type of Higee equipment. The reducing agent and protecting agent were glucose and starch, respectively, either of which is an inexpensive and nontoxic material. Silver particles were prepared by continuously pumping two solutions, which were a mixture of AgNO3 aqueous solution containing protecting agent and another mixture of NaOH aqueous solution containing the reducing agent, into the chamber of the SDR, where a liquid–liquid reaction took place. The reaction time was less than 10 min, which was much shorter than the traditional methods. After washing and redispersing, silver particles of 10 nm or smaller were obtained, and the redispersed aqueous suspensions were stable for more than 40 days with or without the addition of a dispersing agent. A high‐gravity process that combines economic benefit with environmental benignancy was successfully developed to produce silver nanoparticles. © 2007 American Institute of Chemical Engineers AIChE J, 2008
Gene copy number variation in schizophrenia
Authors: Sutrala Smitha R. , Norton Nadine , Williams Nigel M. , Buckland Paul R.
Published: December 2007

Recent reports have highlighted the possibility that gene copy number variations play a role in the development of complex disorders and have suggested that some variations are very common in schizophrenic patients. We have carried out a comparative genomic hybridization screen using oligonucleotide probes of 891 candidate genes to look for very common copy number variance in schizophrenic patients. In addition we have developed a new approach for the detection and validation of putative copy number variation based upon established methods of allele quantification by DNA pooling and have used it to study 15 major candidates including dysbindin (DTNBP1), neuregulin (NRG1), RGS4 and DISC1. With the exception of positive control sequences, no copy number variations were found for any of the genes in any samples by the use of either technique. Our data for the genes studied are in line with the known existence and frequency of CNVs as reported by recent large scale studies and suggest that gene copy number variations are not more common in schizophrenics than controls, although large ethnic differences cannot be excluded. © 2007 Wiley‐Liss, Inc.
PRODH gene is associated with executive function in schizophrenic families
Authors: Li Tao , Ma Xiaohong , Hu Xun , Wang Yingcheng , Yan Chengying , Meng Huaqing , Liu Xiehe , Toulopoulou Timothea , Murray Robin M. , Collier David A.
Published: December 2007

The aim of this study was to investigate the relationship between polymorphisms in the PRODH and COMT genes and selected neurocognitive functions. Six SNPs in PRODH and two SNPs in COMT were genotyped in 167 first‐episode schizophrenic families who had been assessed by a set of 14 neuropsychological tests. Neuropsychological measures were selected as quantitative traits for association analysis. The haplotype of SNPs PRODH 1945T/C and PRODH 1852G/A was associated with impaired performance on the Tower of Hanoi, a problem‐solving task mainly reflecting planning capacity. There was no significant evidence for association with any other neuropsychological traits for other SNPs or haplotypes of paired SNPs in the two genes. This study takes previous findings of association between PRODH and schizophrenia further by associating variation within the gene with performance on a neurocognitive trait characteristic of the illness. It fails to confirm previous reports of an association between COMT and cognitive function. © 2007 Wiley‐Liss, Inc.
Parent of origin effects in attention/deficit hyperactivity disorder (ADHD): Analysis of data from the international multicenter ADHD genetics (IMAGE) program
Authors: Anney Richard J.L. , Hawi Ziarih , Sheehan Karen , Mulligan Aisling , Pinto Carlos , Brookes Keeley J. , Xu Xiaohui , Zhou Kaixin , Franke Barbara , Buitelaar Jan , Vermeulen Sita H. , Banaschewski Tobias , Sonuga‐Barke Edmund , Ebstein Richard , Manor Iris , Miranda Ana , Mulas Fernando , Oades Robert D. , Roeyers Herbert , Rommelse Nanda , Rothenberger Aribert , Sergeant Joseph , Steinhausen Hans‐Christoph , Taylor Eric , Thompson Margaret , Asherson Philip , Faraone Stephen V. , Gill Michael
Published: December 2007

There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over‐transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene‐specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi‐square. There was no overall parent of origin effect in the IMAGE sample ($\chi _1^2 = 1.82$, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co‐workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene‐specific parent of origin effect in the etiology ADHD. © 2007 Wiley‐Liss, Inc.
Evidence for a heritable unidimensional symptom factor underlying obsessionality
Authors: Mathews Carol A. , Greenwood Tiffany , Wessel Jennifer , Azzam Amin , Garrido Helena , Chavira Denise A. , Chandavarkar Uma , Bagnarello Monica , Stein Murray , Schork Nicholas J.
Published: December 2007

The division of obsessive‐compulsive symptoms (OCS) into specific factors is now widely accepted. However, the utility of these categories for genetic studies remains unclear, as studies examining their heritability have been inconsistent. Less attention has been paid to the possibility that clinically significant obsessionality is primarily determined by a “core” group of OCS that crosses the boundaries between symptom subgroups. The aim of this study is to determine whether such a core group exists, and to compare its heritability to that of the more traditionally derived symptom factors. We examined the properties and heritability of obsessive‐compulsive symptoms in college students, medical students, and obsessive‐compulsive disorder (OCD) families using the Leyton Obsessional Inventory. In each of the three samples, we identified a core group of symptoms that comprised a single unique construct and accounted for over 90% of the variation of the four more traditional symptom factors. This core construct was highly correlated with OCD in our families and had a heritability estimate of 0.19 when OCD was not included as a covariate and 0.49 when OCD was included as a covariate. In contrast, the four symptom factors were not heritable. There appears to be an underlying unidimensional component to obsessionality, both in non‐clinical and clinical samples. This component, which is heritable, accounts for the majority of the variation of the more traditionally derived symptom factors in our sample, and is composed of OCS that are not specific to any of the symptom subgroups. © 2007 Wiley‐Liss, Inc.
A linkage analysis of cigarette and alcohol consumption in an unselected Mexican American population
Authors: Viel Kevin , Charlesworth Jac , Tejero Elizabeth , Dyer Thomas , Cole Shelley , Haack Karin , MacCluer Jean , Blangero John , Almasy Laura
Published: December 2007

The use of alcohol and tobacco is highly prevalent. Studying the rate of consumption in a non‐selected population could contribute to the elucidation of pathways involved in addiction or to the development of prevention programs. The San Antonio Family Heart Study has approximately 1,400 members with longitudinal data and did not select the proband with regard to exposure status. The goal of this study was to perform genome‐wide linkage analysis of the rate of alcohol and cigarette consumption in a “normal” population. We used SOLAR to perform variance‐components based analysis of the transformed maximal rate of consumption. Despite estimated heritabilities of 0.52 (P < 0.001) for cigarette and 0.39 (P < 0.001) for alcohol consumption, univariate linkage analyses produced only suggestive LOD scores, however the second suggestive linkage peak for the alcohol phenotype was present at 148 cM on chromosome 10, in the exact vicinity of the peak for the cigarette phenotype. In a bivariate analyses, the environmental correlation between alcohol and cigarette consumption was not significantly different from zero (ρe = −0.15, P = 0.18) and the overall genetic correlation was not different from zero (ρg = 0.16, P = 0.34). The results from the bivariate linkage analysis found a maximum LOD score of 3.82 (genome‐wide P = 0.0054) at 151 cM on chromosome 10, at the location of the overlapping peaks from the univariate analyses. © 2007 Wiley‐Liss, Inc.
Variation in GABA‐A subunit gene copy number in an autistic patient with mosaic 4 p duplication (p12p16)
Authors: Kakinuma Hiroaki , Ozaki Mamoru , Sato Hitoshi , Takahashi Hiroaki
Published: December 2007

Autism has been associated with chromosomal aberrations, including duplications at chromosome 4, and the identification of genetic factors contributing to the etiology of this disease is the focus of much research. Here we report a Japanese girl with mosaic of chromosome 4p duplication, mos 46,XX,dup(4)(p12p16)[54]/46,XX[6], who was diagnosed with autism at 3 years of age. Fluorescence in situ hybridization (FISH) with probes covering the region spanning a cluster of the gamma aminobutyric acid A (GABA‐A) receptor subunit genes in the proximal short arm of chromosome 4 demonstrated total three signals for the GABRG1, GABRA4, and GABRA2 genes, but only two signals for GABRB1. This suggests that aberrant copy number of the GABA‐A receptor subunit genes may contribute to the etiology of autism in this patient. © 2007 Wiley‐Liss, Inc.
The utility of SELENBP1 gene expression as a biomarker for major psychotic disorders: Replication in schizophrenia and extension to bipolar disorder with psychosis
Authors: Kanazawa Tetsufumi , Chana Gursharan , Glatt Stephen J. , Mizuno Hideya , Masliah Eliezer , Yoneda Hiroshi , Tsuang Ming T. , Everall Ian P.
Published: December 2007

While microarray studies are generating novel insights into the etiology of major psychiatric disorders, the validation of microarray‐identified candidate genes and their role in the causality of these disorders has been less often studied. We have previously demonstrated, by microarray, up‐regulation of SELENBP1 in the brain and blood of patients with schizophrenia. The main aim of the current study was to validate this finding using quantitative real‐time PCR (QPCR) in an independent brain cohort that included patients with bipolar disorder. Our sample consisted of mRNAs from the dorsolateral prefrontal cortex (dlPFC) of 34 schizophrenic patients, 33 bipolar disorder patients (including 20 with psychotic history), and 34 normal control subjects. QPCR was employed to assess gene expression changes, with C(T) values analyzed using an ANCOVA approach. The results demonstrated that SELENBP1 mRNA was upregulated in schizophrenic brains versus controls (P = 0.046) and, in addition, that SELENBP1 gene expression was strongly positively correlated with presence of psychosis across diagnoses (P < 0.001, increased by 12%). Based on these findings, we conclude that elevated SELENBP1 is a possibly consistent feature in the schizophrenic brain and that this finding could underlie some commonalities of psychosis across the boundaries of diagnoses. Future studies should exploit DNA‐based methods and molecular investigations on the role of SELENBP1 in order to gain insights into the nature of its influence on schizophrenia and psychotic symptoms. © 2007 Wiley‐Liss, Inc.
No association with the 5,10‐methylenetetrahydrofolate reductase gene and major depressive disorder: Results of the depression case control (DeCC) study and a meta‐analysis
Authors: Gaysina D. , Cohen S. , Craddock N. , Farmer A. , Hoda F. , Korszun A. , Owen M. J. , Craig I.W. , McGuffin P.
Published: December 2007

Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10‐methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta‐analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme. The MTHFR 677TT genotype, and to a lesser extent the 677CT genotype, is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations. This may parallel a similar reduction in 5‐methyltetrahydrofolate in the CNS, leading to a potential reduction in monoamine neurotransmitter function and an elevated risk of depressive disorder. To test the hypothesis that the MTHFR C677T polymorphism is involved in the predisposition to MDD, we conducted an association study of 1,222 patients with recurrent MDD and 835 control subjects. This allows 99% power to detect an effect of the size reported in the study of Bjelland et al. 2003, however no significant differences in genotype or allele frequencies between depressive patients and controls were observed. This was the case in the sample as a whole, and when females and males were considered separately. Our findings suggest that the MTHFR C677T polymorphism is not involved in the etiology of clinically significant recurrent MDD. © 2007 Wiley‐Liss, Inc.
Do mood symptoms subdivide the schizophrenia phenotype? association of the GMP6A gene with a depression subgroup
Authors: Boks Marco P.M. , Hoogendoorn Mechteld , Jungerius Bart J. , Bakker Steven C. , Sommer Iris E. , Sinke Richard J. , Ophoff Roel A. , Kahn René S.
Published: December 2007

Genetic studies of clinically defined subgroups of schizophrenia patients may reduce the phenotypic heterogeneity of schizophrenia and thus facilitate the identification of genes that confer risk to this disorder. Several latent class analyses have provided subgroups of psychotic disorders that show considerable consistency over these studies. The presence or absence of mood symptoms was found to contribute most to the delineations of these subgroups. In this study we used six previously published subtypes of psychosis derived from latent class analysis of a large sample of psychosis patients. In 280 schizophrenia patients and 525 healthy controls we investigated the associations of these subgroups with myelin related genes. After bonferroni correction we found an association of the glycoprotein M6A gene (GPM6A) with the subgroup of schizophrenia patients with high levels of depression (P‐corrected = 0.006). Borderline association of the microtubulin associated protein tau (MAPT) with a primarily non‐affective group of schizophrenia patients (P‐corrected = 0.052) was also observed. GPM6A modulates the influence of stress on the hippocampus in animals. Thus our findings could suggest that GMP6A plays a role in the stress‐induced hippocampal alterations that are found in psychiatric disorders in general and schizophrenia in particular. Overall, these finding suggests that investigating subgroups of schizophrenia based symptoms profile and particularly mood symptoms can facilitate genetic studies of schizophrenia. © 2007 Wiley‐Liss, Inc.
Association of complement factor H Y402H gene polymorphism with Alzheimer's disease
Authors: Zetterberg Madeleine , Landgren Sara , Andersson Malin E. , Palmér Mona Seibt , Gustafson Deborah R. , Skoog Ingmar , Minthon Lennart , Thelle Dag S. , Wallin Anders , Bogdanovic Nenad , Andreasen Niels , Blennow Kaj , Zetterberg Henrik
Published: December 2007

Alzheimer's disease (AD) and age‐related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD‐associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n = 800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non‐demented controls (n = 1265) were included in this multi‐center case‐control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini‐Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total‐tau (T‐tau), phospho‐tau181 (P‐tau181), and β‐amyloid1–42 (Aβ1–42). The AMD‐associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval [CI] 1.02–1.50). When APOE ε4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08–1.65, P = 0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE ε4 allele. Positive C carrier status was also associated with lower levels of CSF Aβ1–42 selectively in the control group in an APOE ε4‐independent manner (P = 0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE ε4 alleles. The CFH 1277C allele may predispose patients for co‐morbidity in AD and AMD. © 2007 Wiley‐Liss, Inc.
Identification of pharmacogenetic markers in smoking cessation therapy
Authors: Heitjan Daniel F. , Guo Mengye , Ray Riju , Wileyto E. Paul , Epstein Leonard H. , Lerman Caryn
Published: December 2007

Pharmacogenetic clinical trials seek to identify genetic modifiers of treatment effects. When a trial has collected data on many potential genetic markers, a first step in analysis is to screen for evidence of pharmacogenetic effects by testing for treatment‐by‐marker interactions in a statistical model for the outcome of interest. This approach is potentially problematic because (i) individual significance tests can be overly sensitive, particularly when sample sizes are large; and (ii) standard significance tests fail to distinguish between markers that are likely, on biological grounds, to have an effect, and those that are not. One way to address these concerns is to perform Bayesian hypothesis tests [Berger (1985) Statistical decision theory and Bayesian analysis. New York: Springer; Kass and Raftery (1995) J Am Stat Assoc 90:773–795], which are typically more conservative than standard uncorrected frequentist tests, less conservative than multiplicity‐corrected tests, and make explicit use of relevant biological information through specification of the prior distribution. In this article we use a Bayesian testing approach to screen a panel of genetic markers recorded in a randomized clinical trial of bupropion versus placebo for smoking cessation. From a panel of 59 single‐nucleotide polymorphisms (SNPs) located on 11 candidate genes, we identify four SNPs (one each onCHRNA5andCHRNA2and two onCHAT) that appear to have pharmacogenetic relevance. Of these, the SNP onCHRNA5is most robust to specification of the prior. An unadjusted frequentist test identifies seven SNPs, including these four, none of which remains significant upon correction for multiplicity. In a panel of 43 randomly selected control SNPs, none is significant by either the Bayesian or the corrected frequentist test. © 2007 Wiley‐Liss, Inc.
Association analysis of 528 intra‐genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease
Authors: Morgan A.R. , Hamilton G. , Turic D. , Jehu L. , Harold D. , Abraham R. , Hollingworth P. , Moskvina V. , Brayne C. , Rubinsztein D.C. , Lynch A. , Lawlor B. , Gill M. , O'Donovan M. , Powell J. , Lovestone S. , Williams J. , Owen M.J.
Published: December 2007

Late‐onset Alzheimer's disease (LOAD) is a genetically complex neurodegenerative disorder. Currently, only the ε4 allele of the Apolipoprotein E gene has been identified unequivocally as a genetic susceptibility factor for LOAD. Others remain to be found. In 2002 we observed genome‐wide significant evidence of linkage to a region on chromosome 10q11.23–q21.3 [Myers et al. (2002) Am J Med Genet 114:235–244]. Our objective in this study was to test every gene within the maximum LOD‐1 linkage region, for association with LOAD. We obtained results for 528 SNPs from 67 genes, with an average density of 1 SNP every 10 kb within the genes. We demonstrated nominally significant association with LOAD for 4 SNPs: rs1881747 near DKK1 (P = 0.011, OR = 1.24), rs2279420 in ANK3 (P = 0.022, OR = 0.79), rs2306402 in CTNNA3 (P = 0.024, OR = 1.18), and rs5030882 in CXXC6 (P = 0.046, OR = 1.29) in 1,160 cases and 1,389 controls. These results would not survive correction for multiple testing but warrant attempts at confirmation in independent samples. © 2007 Wiley‐Liss, Inc.
Identification of FMRP‐associated mRNAs using yeast three‐hybrid system
Authors: Zou Ke , Liu Jian , Zhu Ning , Lin Jianhong , Liang Qi , Brown W. Ted , Shen Yan , Zhong Nanbert
Published: December 2007

Fragile X syndrome, one of the most common forms of inherited mental retardation, results from the absence of the fragile X mental retardation protein (FMRP), which is encoded by the fragile X mental retardation gene 1 (FMR1). FMRP is an RNA‐binding protein involved in translational regulation of targeted mRNAs. Identification of targeted mRNAs associated with FMRP is important to understand the function of FMRP and the pathogenic basis of the fragile X syndrome. Employing a yeast three‐hybrid system and a human fetal hippocampus cDNA library, we identified 22 candidate target mRNAs, and 18 of them were confirmed to be associated with FMRP in vitro by gel retardation. Some of these mRNAs code for structural proteins, enzymes or proteins involved in cellular processes, especially in the development and function of neural system. To further investigate the role of FMRP in regulating targeted gene expression, we analyzed the expression profile of TXNRD1, one of the candidate mRNAs, after knocking down the expression of endogenous FMRP by siRNA. The results showed that endogenous TXNRD1 translation increased along with depletion of FMRP, which suggested FMRP negatively regulates TXNRD1 translation. © 2007 Wiley‐Liss, Inc.
Regulation of a novel αN‐catenin splice variant in schizophrenic smokers
Authors: Mexal Sharon , Berger Ralph , Pearce Lucy , Barton Amanda , Logel Judy , Adams Catherine E. , Ross Randal G. , Freedman Robert , Leonard Sherry
Published: December 2007

The αN‐catenin (CTNNA2) gene represents a promising candidate gene for schizophrenia based upon previous genetic linkage, expression, and mouse knockout studies. CTNNA2 is differentially regulated by smoking in schizophrenic patients. In this report, the genomic structure of a primate‐specific αN‐catenin splice variant (αN‐catenin III) is described. A comparison of αN‐catenin III mRNA expression across postmortem hippocampi from schizophrenic and non‐mentally ill smokers and non‐smokers revealed a significant decrease in expression among patient non‐smokers compared to all other groups. The recent evolutionary divergence of this gene, as well as the differences in gene expression in postmortem brain of schizophrenic non‐smokers, supports the role of αN‐catenin III as a novel disease susceptibility gene. © 2007 Wiley‐Liss, Inc.
Association of DAO and G72(DAOA)/G30 genes with bipolar affective disorder
Authors: Prata Diana , Breen Gerome , Osborne Sarah , Munro Janet , St. Clair David , Collier David
Published: December 2007

There is growing evidence of partial aetiological overlap between schizophrenia and bipolar disorder (BP) from linkage analysis, genetic epidemiology and molecular genetics studies. In the present study we investigated whether individual polymorphisms or haplotypes of the DAO and G72(DAOA)/G30 genes, which have been previously implicated in schizophrenia, are also associated with bipolar disorder. For each gene, we genotyped 213 cases and 197 controls for SNPs previously associated with schizophrenia: rs2111902 (MDAAO‐4), rs3918346 (MDAAO‐5), rs3741775 (MDAAO‐6) and rs3918347 (MDAAO‐7) in DAO and rs746187 (M7), rs3916966 (M13), rs2391191 (M15) and rs3916972 (M25) in G72. Although none of the individual SNPs in these genes reached statistical significance, we found haplotype wise associations with bipolar disorder for both genes. These included a two‐SNP haplotype in DAO (rs2111902‐A and rs3918346‐T; global P = 0.003, individual P = 0.002, Z = 3.1) and a two‐SNP haplotype for G72(DAOA)/G30 (rs746187‐G and rs3916972‐G; global P = 0.05; individual P = 0.005, Z = 2.81). However, we found no evidence for an epistatic interaction between the SNPs and/or haplotypes of the two genes. In summary, our findings provide some support for the individual involvement of DAO and G72(DAOA)/G30 in the etiology of bipolar disorder. © 2007 Wiley‐Liss, Inc.