bluuebunny/crossref_metadata_2025 huggingface dataset:
Joining process selection in support of a proactive design for assembly
Authors: Brown N J , Swift K G , Booker J D
Published: September 2002

There is extensive evidence to suggest that many industrial products are designed with far too many parts. Design for assembly (DFA) case studies indicate that, in many designs, large proportions of excess components are only used for joining. In many cases an excessive number of incorrect joining processes are used, possibly due to a lack of knowledge of such factors as availability, cost and functional performance of alternatives. Selection methodologies exist for some individual joining technologies. However, selecting the most appropriate technology is usually left to the designer through a non-formalized judgemental approach. This paper introduces a new methodology for identifying the most appropriate joining technology and its specific process variants, through both a paper-based methodology and software implementation, as a part of a proactive approach to DFA. The underlying strategy adopted is described and the selection process itself and its application to industrial case studies is demonstrated.
Investigations on the application of solid lubricants in grinding
Authors: Shaji S , Radhakrishnan V
Published: September 2002

The intense heat generation involved in the grinding process, due to high specific energy and high wheel-workpiece friction, is critical to the product quality. Cooling and lubrication therefore play decisive roles in grinding tribology. Conventional liquid coolants employed in flood form are ineffective due to the ‘air barrier’ and ‘film boiling’ effects. Further, grinding fluids cannot be recommended in the light of ecological and economic manufacture. Minimization or possible elimination of grinding fluids by substituting their functions by some other means is emerging as a thrust area of research in grinding. The present study explored the possibility of application of solid lubricants in grinding, as a means to reduce the heat generated due to friction, towards finding an alternative for the conventional coolants. It covers a feasibility investigation with a variety of solid lubricants and the development of grinding processes or technologies with this concept. Improved process results were obtained with solid lubricant application; if it can be applied in a proper way with means for swarf removal and wheel cleaning, this concept could emerge as an effective alternative to conventional coolants.
Global tool interference detection in five-axis machining of sculptured surfaces
Authors: Cai Y-L , Xi G
Published: September 2002

This paper presents a new method for the detection and elimination of global interference in five-axis machining of sculptured surfaces. Projecting points on the surface to the axis of cutter, the minimum distance from surface to cutter axis can be directly calculated by an iterative algorithm; the amount of interference is subsequently determined. A corrective method for generating an interferential-free cutter location is then proposed. The implementation has proved that the proposed method has a high efficiency and precision.
Feasibility study of acoustic sensing for the welding pool mode in variable-polarity plasma arc welding
Authors: Wang H , Kovacevic R
Published: September 2002

The relationships between the acoustic signal and the modes of the welding pool, such as no-keyhole (melt-in), keyhole and cutting, in variable-polarity plasma arc welding are investigated. The Welch power spectral density (PSD) estimate and short-time Fourier transformation are implemented to analyse and identify the different modes of the welding pool. The results show that the no-keyhole mode (melt-in welding process) can be clearly distinguished from the keyhole and the cutting modes. The keyhole size is inversely proportional to the Welch PSD estimate of the acoustic signal.
Forming parameters for incremental forming of aluminium alloy sheet metal
Authors: Jeswiet J , Hagan E , Szekeres A
Published: September 2002

The forming parameters for incremental forming of aluminium alloy 3003 sheet are presented. Using two shapes for testing (a conical shape and a pyramid shape) and forming the sheet to various draft angles, the following data have been assembled: tensile tests, strain measurements, strength coefficient K and strain-hardening exponent n. The method of analysis of stress-strain diagrams used by Ford in the plane strain compression test are shown to be applicable. Relationships such as the sine law for spinning have been applied to the data and are presented.
Multiple pulse heating cycles during the enclosed laser ablation of a laminated metallized polymer
Authors: Stewart R , Li L , Isherwood R
Published: September 2002

A vacuum-deposited aluminium layer (about 20nm) is sandwiched between two layers of laminated oriented polyporpylene (OPP) film whose thickness varies from 20 to 40 μm. Selected areas of this sealed system were transparentised by the rearrangement of the aluminium layer without breaking the seal or causing damage to the OPP film using a 75 W Q-swiched neodymumdoped yttrium aluminium garnet laser. This paper investigates the effecst of the laser repetition with changes in experimentally produced laser tracks.
On cutting forces in peripheral milling of curved surfaces
Authors: Zhang L , Zheng L , Zhang Z-H , Liu Y , Li Z-Z
Published: September 2002

This paper presents the development of an analytical model of cutting forces in peripheral milling of curved surfaces. The effect of the workpiece curvature is taken into account in the model construction. Based on the relationship of differential cutting forces and chip load, the total cutting forces are formulated by integration of the differential cutting forces along the cutting flutes in the feed and cross-feed directions. This formulation leads to an explicit expression for the force waveforms as algebraic functions of cutter variables, process parameters, machining configuration and workpiece geometry. Experiments are performed over a wide range of conditions to verify the model and meanwhile the effects of the process parameters on the cutting forces are revealed. The presented model facilitates force estimation and provides a basis for the analysis, prediction and improvement of surface accuracy in peripheral milling of curved surfaces.
Optimization strategy for turning operation accounting for cutting tool wear history
Authors: Axinte D A , Gindy N
Published: September 2002

The paper reports on a methodology for monitoring and evaluating the progress of cutting tool wear and an optimization strategy for turning operations in which the progress of cutting tool wear is taken into account in optimizing process parameters. The methodology evaluates tool wear history’ when a cutting tool is used under different process conditions (e.g. change in workplace material and range of cutting parameters) which a cutting tool is likely to encounter in small batch production operations. The optimization strategy proposed attempts to maximize material removal rate taking into account surface roughness, system stability and cutting tool failure as its technical constraints. One of the novel aspects of this work is that it enables a more complete tool failure avoidance strategy to be developed, taking into account tool wear progression under a variety of conditions. The machining strategy is aimed at optimizing batch production in turning where it is likely that the same cutting tool edge is used to process parts made of different workpiece materials and therefore the cutting tool reaches its limiting flank wear under variable sets of cutting conditions.
Visuo‐spatial working memory in navigation
Authors: Garden Sharin , Cornoldi Cesare , Logie Robert H.
Published: October 2002

Two experiments employed dual task techniques to explore the role of working memory in route learning and subsequent route retrieval. Experiment 1 involved contrasting performance of two groups of volunteers respectively learning a route from a series of map segments or a series of visually presented nonsense words. Both groups performed learning and recognition under articulatory suppression or concurrent spatial tapping. Both concurrent tasks had an overall disruptive effect on each learning task. However, spatial tapping disrupted route recognition rather more than did articulatory suppression, while the nonsense word recognition was impaired more by articulatory suppression than by concurrent spatial tapping. Experiment 2 again used dual task methodology, but explored route learning by asking volunteers to follow the experimenter through the winding streets of a medieval European town centre. Retrieval involved following the same route while the experimenter followed and noted errors in navigation. Overall the results partially replicated those of Experiment 1 in that both concurrent tasks interfered with route learning. However, volunteers with high spatial ability appeared more affected by the concurrent spatial tapping task, whereas low spatial subjects appeared more affected by the concurrent articulatory suppression task. Results are interpreted to suggest that different aspects of working memory are involved in learning a route from a map with a greater emphasis on visuo‐spatial resources, but in tasks set in real environments where many cues of a varied nature are available, only high spatial ability subjects appear to rely heavily upon the visuospatial component of working memory. Copyright © 2002 John Wiley & Sons, Ltd.
Retrieval‐induced forgetting in eyewitness memory: forgetting as a consequence of remembering
Authors: MacLeod Malcolm
Published: October 2002

Recent psychological research on memory has demonstrated that the act of remembering can also prompt forgetting, or more specifically, the inhibition of particular items in memory (i.e. retrieval‐induced forgetting). Extending this line of inquiry, this article reports the findings from two studies designed to establish whether retrieval‐induced forgetting can occur for meaningful stimuli that could be experienced under eyewitness situations. In Study 1, participants were asked to recall previously presented household items that had ostensibly been stolen in burglaries, while in Study 2, participants were asked to recall descriptive details about two individuals suspected of making bogus money collections. Both studies provided unequivocal evidence that retrieval‐induced forgetting can occur for such meaningful stimuli. Importantly, in each case it was demonstrated that the observed effects could not be attributed to output interference. This article considers the likely extent of the problem posed by retrieval‐induced forgetting for eyewitness reliability and some of the practical and theoretical implications of this work. Copyright © 2002 John Wiley & Sons, Ltd.
Self‐ratings of sense of direction and route reversal performance
Authors: Donald Heth C. , Cornell Edward H. , Flood Tonya L.
Published: October 2002

One of the most pervasive beliefs about human way finding is that some people have a natural ability that distinguishes them from others. In this research, we asked children and adults to rate their own sense of direction, a promising index of orientation skills despite its simplicity and reliance on self‐assessment. Ratings were obtained before and after reversal of a newly learned outdoor route. Self‐ratings by children and adults before route reversal only weakly predicted two of a variety of measures of route and bearing knowledge. However, adults' ratings after the route reversal reflected performance on almost all of these same measures. In addition, route reversal performance was easily improved by instructing children and adults during route acquisition to look back in anticipation of the return. The pattern of results suggests that way finders' beliefs about their sense of direction are based on a recollection of the outcomes of the attentive and mnemonic strategies they use. Copyright © 2002 John Wiley & Sons, Ltd.
The effect of repeated experience on children's suggestibility across two question types
Authors: Powell Martine B. , Roberts Kim P.
Published: October 2002

There is a discrepancy in the literature regarding the effect of repeated experience on children's suggestibility. Some researchers have concluded that repeated experience increases children's suggestibility for variable details whereas others have reported no detrimental effect. This study demonstrated that the type of question used to test memory (cued‐recall versus yes/no questions) could account for the different reported conclusions. Children aged 5–6 years took part in an event either once or four times. Three or 21 days later, they were given a suggestive interview about the single/final occurrence of the event during which half of the event details were inaccurately described. When later asked yes/no questions, the children with repeated experience agreed with more of the suggestions than did those in the single‐experience condition, especially at the longer delay. In relation to cued‐recall questions, however, experience did not mediate the number of times that false suggestions from the biasing interview were reported. This latter finding was revealed irrespective of the retention interval. Copyright © 2002 John Wiley & Sons, Ltd.
Guaranteed recursive non‐linear state bounding using interval analysis
Authors: Kieffer Michel , Jaulin Luc , Walter Éric
Published: October 2002

The problem considered here is state estimation in the presence of unknown but bounded state perturbations and measurement noise. In this context, most available results are for linear models, and the purpose of the present paper is to deal with the non‐linear case. Based on interval analysis and the notion of set inversion, a new state estimator is presented, which evaluates a set estimateguaranteedto contain all values of the state that are consistent with the available observations, given the perturbation and noise bounds and a set containing the initial value of the state. To the best of our knowledge, it is the first estimator for which this claim can be made. The precision of the set estimate can be improved, at the cost of more computation. Theoretical properties of the estimator are studied, and computer implementation receives special attention. A simple illustrative example is treated. Copyright © 2002 John Wiley & Sons, Ltd.
Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk
Authors: Schabath Matthew B. , Spitz Margaret R. , Delclos George L. , Gunn Gary B. , Whitehead Lawrence W. , Wu Xifeng
Published: October 2002

Background

As observed in tobacco‐associated carcinogenesis, genetic factors such as the polymorphic metabolic/oxidative enzyme myeloperoxidase (MPO) could modulate individual susceptibility to asbestos‐associated carcinogenesis.

Methods

RFLP‐PCR analysis identified the MPO genotypes in 375 Caucasian lung cancer cases and 378 matched controls. An epidemiological interview elicited detailed information regarding smoking history and occupational history and exposures.

Results

Asbestos exposure was associated with a significantly elevated risk estimate (OR = 1.45; 95% CI 1.04–2.02). On stratified analysis, we found the MPO genotypes modified the effect of asbestos exposure on lung cancer risk. Specifically, G/G carriers who were exposed to asbestos had an odds ratio (OR) of 1.72 (95% CI; 1.09–2.66), while A‐allele carriers (G/A + A/A) exposed to asbestos exhibited a reduced OR of 0.89 (95% CI; 0.56–1.44). The OR was further reduced to 0.73 (0.49–1.06) for A‐allele carriers not exposed to asbestos. A similar trend was observed for the joint effects between the MPO genotypes and pack‐years smoking. Next, all three risk factors (MPO genotypes, asbestos exposure, and smoking) were analyzed simultaneously for joint effects. Heavy smokers with the G/G genotype and a history of asbestos exposure demonstrated a statistically significant elevated risk estimate (OR = 2.19; 95% CI 1.16–4.11), while the A‐allele carriers with the same exposure profile were at a lower risk for lung cancer (OR = 1.18; 95% CI 0.58–2.38). The A‐allele genotypes demonstrated similar protective effects for the other three exposure profiles.

Conclusions

For a similar level of exposure to established carcinogens, individuals with the MPO A‐allele genotypes appear to have a reduced risk of lung cancer. Am. J. Ind. Med. 42:29–37, 2002. © 2002 Wiley‐Liss, Inc.
Multicultural genetic counseling: Then, now, and in the 21st century
Authors: Ota Wang Vivian
Published: October 2002

Scholars, educators, and practitioners have argued that racial–cultural issues are obstacles for those seeking genetic counseling. When available, cross‐cultural genetic counseling has focused on simplistic knowledge of client health beliefs and cultural customs, professional cultures, and biased theoretical models as reasons for failure to create realistic knowledge of members of racial–cultural groups in the United States. Recognizing the importance of meeting the needs for all who seek genetic counseling services, genetic counselors have been providing direction in cross‐cultural genetic counseling research, practice, training, and developing competency, ethical, and professional guidelines. However, emanating from a cultural pluralism perspective, cross‐cultural genetic counseling has often resulted in homogenized group stereotypes without attention to intragroup variation and individual differences. A transition from cross‐cultural towards multicultural genetics shifts from culture‐specific group norms to an integrated social, historical, psychological, and political perspective. By valuing the process of personal and professional racial–cultural identity development, the evolution from cross‐cultural to multicultural genetic counseling that has occurred within the past quarter century is discussed. © 2001 Wiley‐Liss, Inc.
Empowering primary care health professionals in medical genetics: How soon? How fast? How far?
Authors: Greendale Karen , Pyeritz Reed E.
Published: October 2002

Applications of genetics to the practices of medicine and public health are important today and will only become more compelling as our understanding of the human genome evolves. Because of a perceived lack of medical genetics professionals, it is generally believed that primary health care providers (PCPs) will need to assume prominent roles in delivering clinical genetics services. However, a number of studies indicate that most PCPs are neither well enough educated in genetics nor interested enough in becoming so to effectively contribute. Those who advocate empowering PCPs must be aware of potential problems with any approach thus far suggested for achieving this goal. Moreover, any analysis of this model must consider the potential ramifications for medical genetics professionals, patients, and families. In this article, we explore some of the unique features of the culture of medical genetics services and service providers. We discuss how important this culture is to clinical outcomes and the likelihood that its positive attributes would be preserved in a PCP model of medical genetics service delivery. © 2001 Wiley‐Liss, Inc.
Impact of genetic and non‐genetic factors in type 1 diabetes
Authors: Hawa Mohammed Iqbal , Beyan Huriya , Buckley Lisa Rebecca , Leslie Richard David Graham
Published: October 2002

Type 1 insulin‐dependent diabetes is due to destruction of the insulin secreting cells of the islets of Langerhans. The disease is caused by non‐genetic, probably environmental, factors operating in a genetically susceptible host to initiate a destructive immune process. These unknown environmental factors may operate over a limited period either in early or later and to a variable degree, playing a particularly substantial role in adults. The environment then induces an immune process associated with destruction of the islet β cell that can be detected in early life and persists up to disease onset. Apart from an association with the insulin gene there is no evidence that genes associated with type 1 diabetes, including HLA and CTLA4 influence the targeting of the immune response to the insulin‐secreting cells. The critical period of immune activation is probably short and the process leading to diabetes probably has a long prodrome but of variable duration that determines the age at presentation with clinical disease. The amplification both of this immune response and the destructive process is in part genetically determined, involving HLA genes. The clinical spectrum of the disease process associated with type 1 diabetes is wide, encompassing insulin‐dependence, non‐insulin dependence and even transient impaired glucose tolerance. Type 1 diabetes presenting in adults, in contrast to children, is predominantly determined by non‐genetic factors with a reduced role for protective and susceptibility HLA alleles. Thus, the evidence is that genes involved in genetic susceptibility to type 1 diabetes operate predominantly in children not adults and in both amplify the immune response and the rate of disease progression. © 2002 Wiley‐Liss, Inc.
Genetic analysis of patients with the Saethre‐Chotzen phenotype
Authors: Chun Kathy , Teebi Ahmad S. , Jung Jack H. , Kennedy Shelley , Laframboise Rachel , Meschino Wendy S. , Nakabayashi Kazuhiko , Scherer Stephen W. , Ray Peter N. , Teshima Ikuko
Published: October 2002

Saethre‐Chotzen syndrome is a common craniosynostosis syndrome characterized by craniofacial and limb anomalies. Intragenic mutations of the TWIST gene within 7p21 have been identified as a cause of this disorder. There is phenotypic overlap with other craniosynostosis syndromes, and intragenic mutations in FGFR2 (fibroblast growth factor receptor 2) and FGFR3 (fibroblast growth factor receptor 3) have been demonstrated in the other conditions. Furthermore, complete gene deletions of TWIST have also been found in a significant proportion of patients with Saethre‐Chotzen syndrome. We investigated 11 patients clinically identified as having the Saethre‐Chotzen phenotype and 4 patients with craniosynostosis but without a clear diagnosis. Of the patients with the Saethre‐Chotzen phenotype, four were found to carry the FGFR3 P250R mutation, three were found to be heterozygous for three different novel mutations in the coding region of TWIST, and two were found to have a deletion of one copy of the entire TWIST gene. Developmental delay was a distinguishing feature of the patients with deletions, compared to patients with intragenic mutations of TWIST, in agreement with the results of Johnson et al. [1998: Am J Hum Genet 63:1282–1293]. No mutations were found for the four patients with craniosynostosis without a clear diagnosis. Therefore, 9 of our 11 patients (82%) with the Saethre‐Chotzen phenotype had detectable genetic changes in FGFR3 or TWIST. We propose that initial screening for the FGFR3 P250R mutation, followed by sequencing of TWIST and then fluorescence in situ hybridization (FISH) for deletion detection of TWIST, is sufficient to detect mutations in > 80% of patients with the Saethre‐Chotzen phenotype. © 2002 Wiley‐Liss, Inc.
Effect of the APOE‐491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study
Authors: Roks G. , Cruts M. , Houwing‐Duistermaat J.J. , Dermaut B. , Serneels S. , Havekes L.M. , Hofman A. , Breteler M.M.B. , Van Broeckhoven C. , van Duijn C.M.
Published: October 2002

The apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this −491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population‐based case‐control study. We found that there was a modest but statistically significant effect of the −491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the −491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the −491A/T polymorphism has an APOE genotype‐independent effect on plasma apolipoprotein E levels but no APOE‐independent effect on AD risk. © 2002 Wiley‐Liss, Inc.
Evaluation of FOXP2 as an autism susceptibility gene
Authors: Wassink Thomas H. , Piven Joseph , Vieland Veronica J. , Pietila Jennifer , Goedken Rhinda J. , Folstein Susan E. , Sheffield Val C.
Published: October 2002

A mutation in the gene FOXP2 was recently identified as being responsible for a complicated speech and language phenotype in a single large extended pedigree. This gene is of interest to autism because it lies in one of the most consistently linked autism chromosomal regions of interest. We therefore tested this gene for its involvement in autism in a large sample of autism families. We completely sequenced the exon containing the mutation, screened the remaining coding sequence using SSCP technology, and identified and genotyped two novel intronic tetranucleotide repeat polymorphisms that were then analyzed for evidence of linkage and linkage disequilibrium (LD). We identified two families in which heterozygous deletions of a small number of glutamines in a long poly‐glutamine stretch were found in one parent and the autistic probands; no other non‐conservative coding sequence changes were identified. Linkage and LD analyses were performed in 75 affected sibling pair families and in two subgroups of this sample defined by the presence/absence of severe language impairment. One allele appeared to have an opposite pattern of transmission in the language based subgroups, but otherwise the linkage and LD analyses were negative. We conclude that FOXP2 is unlikely to contribute significantly to autism susceptibility. © 2002 Wiley‐Liss, Inc.
Mosaic r(13) resulting in large deletion of chromosome 13q in a newborn female with multiple congenital anomalies
Authors: Lorentz Cindy Pham , Jalal Syed M. , Thompson Dana M. , Babovic‐Vuksanovic Dusica
Published: October 2002

A newborn female presented with multiple congenital anomalies including facial dysmorphism, agenesis of the corpus callosum, type I laryngeal cleft, tracheal stenosis, bilaterally small kidneys, segmental vertebral anomalies, extranumerary rib, bilateral hip dislocation, digital anomalies, and growth retardation. Newborn aneuploidy detection (NAD) based on interphase fluorescence in situ hybridization (FISH) indicated monosomy 13 in 47 of 200 (23.5%) peripheral blood cells (normal cutoff 8.5% at 95% CI). The follow‐up banded metaphase‐based analysis of 20 cells revealed a karyotype of 46,XX. The analysis of 30 additional cells revealed one cell to have monosomy 13 and a small ring chromosome. In the abnormal cell line, the ring was positive for whole chromosome paint (wcp) 13 and negative for Rb1 (13q14.3). The ring was detected in 4% of 80 additional metaphases studied by FISH. Therefore, the ring was present in 4% (5/130) of metaphases from peripheral blood. Analysis of buccal cells by FISH indicated the ring was present in 36% of cells. A higher degree of mosaicism (60%) was detected in fibroblast cultures from a skin biopsy. The low‐level mosaicism of ring 13 in metaphase cells from peripheral blood would have been missed if the standard 20 GTL‐banded metaphases had been analyzed. In this case, a preliminary interphase FISH study had indicated monosomy 13 resulting from a large 13q deletion that included the Rb1 locus. This finding initiated the analysis of additional metaphases by GTL‐banding and the analysis of metaphases and interphases by FISH. The clinical presentation of our patient was consistent with reported cases of 13q deletions. In addition, our patient had airway anomalies, including a type I laryngeal cleft and tracheal stenosis, which are previously unreported. © 2002 Wiley‐Liss, Inc.
Childhood‐onset ataxia: Testing for large CAG‐repeats in SCA2 and SCA7
Authors: Mao Rong , Aylsworth Arthur S. , Potter Nicholas , Wilson William G. , Breningstall Galen , Wick Myra J. , Babovic‐Vuksanovic Dusica , Nance Martha , Patterson Marc C. , Gomez Christopher M. , Snow Karen
Published: October 2002

Infantile‐ and juvenile‐onset spinal cerebellar ataxia (SCA) is associated with expansion of 130 to more than 200 CAG‐repeats in the SCA2 and SCA7 genes. Routine clinical assays for SCA2 and SCA7, which use polymerase chain reaction (PCR) and denaturing PAGE (polyacrylamide gel electrophoresis), will not reliably detect such large expansions. An assay based on separation of PCR products on an agarose gel, blotting, and hybridization with a (CAG)6 oligonucleotide probe was used to test DNA from individuals more than 10 years of age who had a possible diagnosis of SCA. Among 25 cases, the PCR‐blot assay confirmed the presence of SCA2 expansions between 230 and 500 repeats in four unrelated individuals, but did not detect any cases of extreme expansion in the SCA7 gene. The PCR‐blot assay provides reliable detection of extreme expansion mutations. Routine incorporation of this assay in clinical laboratories may reveal that infantile–juvenile forms of SCA2 and SCA7 are more prevalent than previously recognized. © 2002 Wiley‐Liss, Inc.
Maternal isodisomy for 14q21‐q24 in a man with diabetes mellitus
Authors: Kayashima Tomohiko , Katahira Masahito , Harada Naoki , Miwa Nobutomo , Ohta Tohru , Yoshiura Koh‐ichiro , Matsumoto Naomichi , Nakane Yoshibumi , Nakamura Yusuke , Kajii Tadashi , Niikawa Norio , Kishino Tatsuya
Published: October 2002

We report a 20‐year‐old man with maternal uniparental disomy for chromosome 14 (UPD14) and maturity‐onset diabetes mellitus (DM). He had pre‐ and postnatal growth retardation, developed DM at age 20 years without any autoimmune antibodies, and had a mosaic 45,XY,der(14;14)(q10;q10)[129]/46,XY,+14,der(14;14)(q10;q10)[1] karyotype. Allelotyping using microsatellite markers covering the entire 14q indicated segmental maternal isodisomy for 14q21‐q24 and maternal heterodisomy of the remaining regions of the chromosome. It is thus tempting to speculate that the segmental isodisomy led to reduction to homozygosity for a mutant gene and thus caused his DM, although the possibility of coincidental occurrence of the two events cannot totally be ruled out. Fluorescence in situ hybridization (FISH) analysis using BAC clone probes revealed that the isodisomic segment did not overlap any known IDDM or NIDDM susceptibility loci on chromosome 14, suggesting a novel locus for a subset of DM at the isodisomic segment. © 2002 Wiley‐Liss, Inc.
Difference in disease‐free survival curve and regional distribution according to subtype of spinocerebellar ataxia: A study of 1,286 Japanese patients
Authors: Maruyama Hirofumi , Izumi Yuishin , Morino Hiroyuki , Oda Masaya , Toji Hiromasa , Nakamura Shigenobu , Kawakami Hideshi
Published: October 2002

Expansions of trinucleotide repeats have been discovered in spinocerebellar ataxia (SCA) types 1, 2, 6, 7, 12, and 17, Machado‐Joseph disease (MJD/SCA3), and dentatorubropallidoluysian atrophy (DRPLA). However, the frequency of familial SCA in Japan remains unclear. The number of trinucleotide repeats was determined for 1,286 patients. Three hundred and thirty families (523 cases) were autosomal dominant group (A), and 165 families were positive for family history but not autosomal dominant group (B), while the remaining 598 cases were the sporadic group (C). The frequency of SCA subtypes in autosomal dominant group was: 1) 5.5% for SCA1; 2) 2.4% for SCA2; 3) 27.6% for MJD/SCA3; 4) 25.5% for SCA6; 5) 0.3% for SCA17; and 6) 7.3% for DRPLA. Abnormal expansion of SCA12 was not detected. Another 31.5% of the patients in the autosomal dominant group had unknown genetic abnormalities. Within group B, SCA6 was the most prominent and within the sporadic group MJD/SCA3 and SCA6 were the most common subtypes observed. The disease‐free survival curve of SCA6 was different from that of other SCAs and the mean age at onset for SCA6 was found to be later than that of the other types. Regional differences were observed in the relative rate of SCA subtypes. MJD/SCA3 appears more common in the Kanto and Kyushu districts of Japan, whereas SCA6 is most common in the Chugoku district. In order to establish an effective social welfare system for SCA patients, clinical course and regional differences in the prevalence of SCA subtypes must be taken into consideration. © 2002 Wiley‐Liss, Inc.
Evaluation of multiple presenilin 2 SNPs for association with early‐onset sporadic Alzheimer disease
Authors: Howell W. Mathias , Brookes Anthony J.
Published: October 2002

The presenilin genes encode proteins that modify, mediate, or perform similar functions to γ‐secretase, the enzyme responsible for converting amyloid β precursor protein (APP) into beta‐amyloid. Mutations in the presenilin genes cause an increased production of Aβ42, the aberrant form of beta‐amyloid found in the neural plaques of Alzheimer disease patients. Previously reported association studies of presenilin 2 (PSEN2) polymorphisms with early‐onset Alzheimer disease (EOAD) have produced contradictory results. In an effort to resolve these differences, we tested eight single nucleotide polymorphisms in and around the 3′ region of the PSEN2 gene for association with EOAD. An initial set of Scottish EOAD cases (n = 121) and controls (n = 152) was screened using the genotyping method dynamic allele‐specific hybridization (DASH). No significant differences were seen between allele or genotype frequencies of cases and controls. However, when conditioned on the risk allele (ε4) APOE, three polymorphisms showed allelic association with a P value below 0.05. These same polymorphisms were in near 100% linkage disequilibrium with each other (P < 5 × 10−5), and in each, one of the homozygous genotypes was absent in controls but present in the cases. Replication in an independent set of Scottish EOAD cases (n = 84) and controls (n = 173) did not confirm this finding. From this study we find no evidence to suggest that variations in the PSEN2 gene pose as major risk factors for sporadic EOAD. © 2002 Wiley‐Liss, Inc.
Duplication of (2)(q11.1‐q13.2) in a boy with mental retardation and cleft lip and palate: Another clefting gene locus on proximal 2q?
Authors: Riegel Mariluce , Schinzel Albert
Published: October 2002

A 4‐year‐old boy with left cleft lip and cleft palate, multiple minor anomalies and developmental delay revealed an abnormal chromosome 2 with enlarged proximal long arm, de novo, in his karyotype. Fluorescence in situ hybridization with a chromosome 2 library and band‐specific YACs confined the duplicated segment to 2q11.1‐q13.2 and indicated a direct tandem duplication due to unbalanced crossover between chromatids. © 2002 Wiley‐Liss, Inc.
Aromatic amino acid hydroxylase genes and schizophrenia
Authors: Chao Helen M. , Richardson Mary Ann
Published: October 2002

Phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate‐limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and serotonin. Because these neurotransmitter systems have all been implicated in the pathophysiology of schizophrenia, the aromatic amino acid hydroxylases are among the likely candidates for genes associated with schizophrenia. A mutation in the functionally critical tetrahydrobiopterin cofactor binding domain of the PAH gene had been identified in African‐American patients with the diagnosis of schizophrenia, and biochemical analyses suggested that this mutation has physiological consequences related to amine neurotransmitter function. DNA sequencing of the highly conserved cofactor binding domain of the PAH, TH, and TPH genes in African‐American subjects with schizophrenia and unrelated, never mentally ill subjects from the NIMH Schizophrenia Genetics Initiative, was undertaken to assess the concordance of mutant genotype with psychiatric phenotype. The K274E mutation was observed in the PAH gene cofactor binding domain, and several polymorphisms were identified in adjacent intronic regions of the PAH, TH, and TPH genes. All of the genetic variants observed were represented in the schizophrenia group and in the never mentally ill group. Genetic evaluation of the family members of subjects with the PAH K274E mutation showed that all individuals with the K274E mutation also exhibited the PAH L321L polymorphism in the catalytic domain of the PAH enzyme. © 2002 Wiley‐Liss, Inc.
Ion channels and epilepsy
Authors: Lerche Holger , Jurkat‐Rott Karin , Lehmann‐Horn Frank
Published: October 2002

Ion channels provide the basis for the regulation of excitability in the central nervous system and in other excitable tissues such as skeletal and heart muscle. Consequently, mutations in ion channel encoding genes are found in a variety of inherited diseases associated with hyper‐ or hypoexcitability of the affected tissue, the so‐called ‘channelopathies.’ An increasing number of epileptic syndromes belongs to this group of rare disorders: Autosomal dominant nocturnal frontal lobe epilepsy is caused by mutations in a neuronal nicotinic acetylcholine receptor (affected genes: CHRNA4, CHRNB2), benign familial neonatal convulsions by mutations in potassium channels constituting the M‐current (KCNQ2, KCNQ3), generalized epilepsy with febrile seizures plus by mutations in subunits of the voltage‐gated sodium channel or the GABAA receptor (SCN1B, SCN1A, GABRG2), and episodic ataxia type 1—which is associated with epilepsy in a few patients—by mutations within another voltage‐gated potassium channel (KCNA1). These rare disorders provide interesting models to study the etiology and pathophysiology of disturbed excitability in molecular detail. On the basis of genetic and electrophysiologic studies of the channelopathies, novel therapeutic strategies can be developed, as has been shown recently for the antiepileptic drug retigabine activating neuronal KCNQ potassium channels. © 2001 Wiley‐Liss, Inc.
Aggressive and neutral interventions in conflicts in captive groups of brown lemurs (Eulemur fulvus fulvus)
Authors: Roeder J.J. , Duval L. , Gosset D.
Published: October 2002

Third‐party interventions in conflicts have revealed complexity in primate social relationships. This type of intervention has seldom been analyzed in prosimians, although many of these species exhibit complex (multimale/multifemale) social organizations. The present study on captive brown lemurs (Eulemur fulvus fulvus) shows that dominant individuals were more likely to intervene in conflicts. Both males and females intervened aggressively in conflicts. Female aggressive interventions occurred mainly on behalf of close kin, whereas males mainly intervened on behalf of juveniles. This study also provides the first record of neutral or peaceful interventions in lemurs. Although females intervened neutrally, almost all neutral interventions were by dominant males. Dominant males intervened in conflicts neutrally more often than agressively, principally in conflicts between adults and juveniles or between juveniles. Neutral interventions by males always ended the conflicts and were often followed by affiliative contacts between participants (intervenors and opponents). In lemurs, female interventions can be explained by kin selection, while the nature of dominant males' interventions suggests a control role. Interventions by males on behalf of juveniles may increase the formers' fitness. Am J Phys Anthropol 118:253–258, 2002. © 2002 Wiley‐Liss, Inc.
Role of parkin mutations in 111 community‐based patients with early‐onset parkinsonism
Authors: Kann Martin , Jacobs Helfried , Mohrmann Kathrin , Schumacher Kirsten , Hedrich Katja , Garrels Jennifer , Wiegers Karin , Schwinger Eberhard , Pramstaller Peter P. , Breakefield Xandra O. , Ozelius Laurie J. , Vieregge Peter , Klein Christine
Published: October 2002

Early‐onset parkinsonism is frequently reported in connection with mutations in the parkin gene. In this study, we present the results of extensive genetic screening for parkin mutations in 111 community‐derived early‐onset parkinsonism patients (age of onset <50 years) from Germany with an overall mutation rate of 9.0%. Gene dosage alterations represented 67% of the mutations found, underlining the importance of quantitative analyses of parkin. In summary, parkin mutations accounted for a low but significant percentage of early‐onset parkinsonism patients in a community‐derived sample.
Effects of oxcarbazepine on sodium concentration and water handling
Authors: Sachdeo Rajesh C. , Wasserstein Alan , Mesenbrink Peter J. , D'Souza Joseph
Published: October 2002

Oxcarbazepine, a keto‐analogue of carbamazepine, was recently approved in the United States for the treatment of seizures of partial onset. Some patients treated with oxcarbazepine showed the development of hyponatremia, which in most instances was asymptomatic. Understanding the mechanisms by which oxcarbazepine can lead to a reduction of serum sodium levels could have therapeutic implications for the few patients in whom symptomatic hyponatremia develops. In this study, we evaluated sodium and water handling in patients with epilepsy and in healthy subjects titrated over 3 weeks to a maximum daily oxcarbazepine dose of 2,400mg. All subjects were evaluated in a hospital setting after an overnight fast and after an acute water‐load test performed before oxcarbazepine exposure and after maintenance on the medication for 3 weeks. Before oxcarbazepine exposure, the percentage of water load excreted was normal as both groups excreted more than 80% of the administered water load. After the intake of oxcarbazepine, the water load resulted in a reduction of the serum sodium and free water clearance without a concomitant increase in the arginine vasopressin serum levels. Most subjects in both groups failed to excrete 80% or more of the water load, suggesting that the effect of oxcarbazepine is physiological. We found that, after the water load, serum sodium and free water clearance were diminished in both groups without a concomitant increase in the arginine vasopressin serum levels. These findings indicate that oxcarbazepine‐induced hyponatremia is not attributable to the syndrome of inappropriate secretion of antidiuretic hormone. Possible mechanisms include a direct effect of oxcarbazepine on the renal collecting tubules or an enhancement of their responsiveness to circulating antidiuretic hormone.
Impact of sustained deprenyl (selegiline) in levodopa‐treated Parkinson's disease: A randomized placebo‐controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial
Authors: Shoulson Ira , Oakes David , Fahn Stanley , Lang Anthony , Langston J. William , LeWitt Peter , Olanow C. Warren , Penney John B. , Tanner Caroline , Kieburtz Karl , Rudolph Alice ,   the Parkinson Study Group
Published: October 2002

Deprenyl (selegiline) delays the need for levodopa therapy in patients with early Parkinson's disease, but the long‐term benefits of this treatment remain unclear. During 1987 to 1988, 800 patients with early Parkinson's disease were randomized in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial to receive deprenyl, tocopherol, combined treatments, or a placebo and were then placed on active deprenyl (10mg/day). A second, independent randomization was carried out in early 1993 for 368 subjects who by that time had required levodopa and who had consented to continuing the deprenyl treatment (D subjects) or changing to a matching placebo (P subjects) under double‐blind conditions. The first development of wearing off, dyskinesias, or on–off motor fluctuations was the prespecified primary outcome measure. During the average 2‐year follow‐up, there were no differences between the treatment groups with respect to the primary outcome measure (hazard ratio, 0.87; 95% confidence interval, 0.63, 1.19;p= 0.38), withdrawal from the study, death, or adverse events. Although 34% of D subjects developed dyskinesias and only 19% of P subjects did (p= 0.006), only 16% of D subjects developed freezing of gait but 29% of P subjects did (p= 0.0003). Decline in motor performance was less in D subjects than P subjects. Levodopa‐treated Parkinson's disease patients who had been treated with deprenyl for up to 7 years, compared with patients who were changed to a placebo after about 5 years, experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait.
Minicolumnar pathology in dyslexia
Authors: Casanova Manuel F. , Buxhoeveden Daniel P. , Cohen Morris , Switala Andrew E. , Roy Emil L.
Published: October 2002

The minicolumn is an anatomical and functional unit of the brain whose genesis accrues from germinal cell divisions in the ventricular zone of the brain. Disturbances in the morphometry of minicolumns have been demonstrated recently for both autism and Down's syndrome. We report minicolumnar abnormalities in the brain of a dyslexic patient. The corresponding developmental disturbance (ie, large minicolumns) could account for the perceptual errors observed in dyslexia.
A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA
Authors: Taanman Jan‐Willem , Kateeb Ihab , Muntau Ania C. , Jaksch Michaela , Cohen Nadine , Mandel Hanna
Published: October 2002

Recently, a homozygous single‐nucleotide deletion in exon 2 of the deoxyguanosine kinase gene (DGUOK) was identified as the disease‐causing mutation in 3 apparently unrelated Israeli‐Druze families with depleted hepatocerebral mitochondrial DNA. We have discovered a novel homozygous nonsense mutation in exon 3 of DGUOK (313C→T) from a patient born to nonconsanguineous German parents. This finding shows that mutations in DGUOK causing mitochondrial DNA depletion are not confined to a single ethnic group.
Effect of vibration on rheology of polymer melt
Authors: Yan Zheng , Shen Kai Zhi , Zhang Jie , Chen Li Min , Zhou Chixing
Published: October 2002

In this article, under shearing vibration and pressure vibration, the rheological behavior of HDPE, ABS, and PS melts and the mechanical properties of molded parts are studied. The experimental results show that, under the vibration condition, the apparent viscosity of the polymer melt decreases with an increasing of the vibration frequency and amplitude applied. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1587–1592, 2002
Biodegradability, mechanical properties, melt flow index, and morphology of polypropylene/amylose/amylose‐ester blends
Authors: Basu Diya , Datta Chandan , Banerjee Amarnath
Published: October 2002

We blended polypropylene (PP) with amylose (AM) and/or dodecanoyl ester of amylose (DODAM) in an effort to make it biodegradable. The content of AM/DODAM was varied from 0 to 40% in the blends. The biodegradability, mechanical properties, melt flow indexes (MFIs), and morphologies of the blends were studied. Biodegradability increased with increases in AM/DODAM content. It was found to be dependent on DODAM content and was at a maximum in blends containing 40% AM + DODAM. Blends with no DODAM or 2.5% DODAM showed almost no adherence of the phases. Dispersion of AM improved in blends with 5% DODAM, and it showed satisfactory adherence to PP also. The tensile strength, elongation at break, and Izod impact strength decreased with increasing AM content. However, in blends with both AM and DODAM, all these properties, especially the elongation at break, showed improvements. The same trend was observed for MFI. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1434–1442, 2002