bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation into differential braking strategies for vehicle stability control
Authors: Yi Kyongsu , Chung Taeyoung , Kim Jeontae , Yi Seungjong
Published: December 2003

This paper presents a differential braking strategy for vehicle stability control. The controller has been designed using a three-degree-of-freedom (3DOF) yaw plane vehicle model, and a simulation study has been performed using a full non-linear three-dimensional vehicle model. The brake control inputs have been directly derived from the sliding control law based on a 3DOF yaw plane vehicle model with differential braking. The performance of the sliding controller has been compared with that of the direct yaw moment controller (DYC). Simulation results have shown that the proposed controller can provide a vehicle with superior performance with respect to brake actuation and system smoothness and can minimize the acceleration and jerk without compromising stability at high speed and large steering angle input.
Reaction of the electrically-heated catalyst of a four-stroke motorcycle engine under cold-start conditions with additional enrichment of the intake mixture
Authors: Horng Rong-Fang , Chou Huann-Ming , Hsu Tien-Chiu
Published: December 2003

By using additional fuel enrichment, the influence of an electrical heater and the oxidation of unburnt exhaust gases on the reaction of an electrically-heated catalyst under cold-start condition of a four-stroke motorcycle engine was investigated. The effects of different cold-start enriching times, heating temperatures, exhaust settings of the CO level and heating positions were studied. The heating temperatures were 60, 80, 100 and 120°C, and the CO levels were 1.0 and 1.8 per cent. The two heating positions were at the inlet and the mid-section of the catalyst. The results showed that additional enrichment of the intake mixture can reduce the heating temperature for self-reaction of the catalyst as well as improve the conversion effciency of the catalyst on the exhaust emissions. High conversion effciency has been achieved for a heating temperature as high as 100°C for the 1.8%CO setting level. It has also been revealed that self-reaction of the catalyst was not possible for a heating temperature of up to 140°C in the case of a 1.0%CO setting level.
Visualization of the homogeneous charge compression ignition/controlled autoignition combustion process using two-dimensional planar laser-induced fluorescence imaging of formaldehyde
Authors: Peng Z , Zhao H , Ladommatos N
Published: December 2003

The paper reports an investigation into the homogeneous charge compression ignition/ controlled autoignition (HCCI/CAI) combustion process using the two-dimensional planar laser- induced fluorescence (PLIF) technique. The PLIF of formaldehyde formed during the low-temperature reactions of HCCI/CAI combustion was excited by a tunable dye laser at 355 nm wavelength and detected by a gated intensified charge-coupled device (ICCD) camera. Times and locations of the two-stage autoignition of HCCI/CAI combustion were observed in a single-cylinder optical engine for several fuel blends mixed with n-heptane and iso-octane. The results show, when pure n-heptane was used, that the initial formation of formaldehyde and its subsequent burning were closely related to the start of the low-temperature heat-release stage and the start of the main heat-release stage of HCCI combustion respectively. Meanwhile, it was found that the formation of formaldehyde was more affected by the charge temperature than by the fuel concentration. However, its subsequent burning or the start of main heat-release combustion took place at those areas where both the fuel concentration and the charge temperature were suffciently high. As a result, it was found that the presence of stratified residual gases affected both the spatial location and the temporal site of autoignition in an HCCI/CAI combustion engine. All studied fuels were found having similar formaldehyde formation timings with n-heptane. This means that the presence of iso-octane apparently did not affect the start of low-temperature reactions. However, the heat release during the low-temperature reaction was significantly reduced with the presence of iso-octane in the studied fuels. In addition, the presence of iso-octane retarded the start of the main combustion stage.
Dimethyl ether (DME) spray characteristics in a common-rail fuel injection system
Authors: Yu J , Bae C
Published: December 2003

The fundamental spray characteristics of dimethyl ether (DME) and conventional diesel were investigated in a constant-volume vessel pressurized by nitrogen gas. A common-rail fuel injection system was adopted with a sac-type injector. DME and diesel were injected into the chamber at two different chamber pressures (atmospheric and 3 MPa) and three different injection pressures (25, 40 and 55 MPa) under room temperature condition. A charge coupled device (CCD) camera was employed to capture time series of spray images, so that spray cone angles and penetrations of the DME spray were characterized and compared with those of diesel. For evaluation of the evaporation characteristics, shadowgraphy of the DME spray using an Ar ion laser and an intensified charge coupled device (ICCD) camera was adopted, in conjunction with the Mie scattering imaging technique for single-hole spray. Intermittent hesitating DME spray was observed, depending on the injection conditions, and might be due to the unstable force balance inside the common-rail nozzle during the injection period. The macroscopic spray characteristics of the DME in the atmospheric chamber conditions proved to be intrinsic physical properties of the DME, and they became diesel-like under 3 MPa ambient pressure. A higher injection pressure produced a wider vapour phase area while it decreased with higher chamber pressure conditions.
Are UN Peacekeepers at Risk for Suicide?
Authors: Wong Albert , Escobar Michael , Lesage Alain , Loyer Michel , Vanier Claude , Sakinofsky Isaac
Published: December 2003

Media reports connecting UN peacekeeping duties by Canadian soldiers to their subsequent suicide prompted this study of peacekeeping as suicide risk. In a case‐control design we retrospectively compared 66 suicides in the Canadian military between 1990 and 1995 with two control groups: (a) 2,601 controls randomly selected from the electronic military database and (b) 66 matched controls with complete personnel and medical data. We found no increased risk of suicide in peacekeepers except among a subgroup of air force personnel. Here confounding individual factors, isolation from supports, and possibly inadequate preparation for deployment elucidated their suicides. Theater of deployment (e.g., Bosnia) did not affect the suicide rate. Military suicides experienced psychosocial stresses and psychiatric illness more often than their matched controls. We conclude that although peacekeeping per se does not increase overall suicide risk, military lifestyles may strain interpersonal relationships, encourage alcohol abuse, and contribute to psychiatric illness and suicide in a minority of vulnerable individuals irrespective of peacekeeping assignment. Careful selection, and preparatory military training that encourages intragroup bonding and mutual support, may protect against suicide risk.
Loneliness in Relation to Suicide Ideation and Parasuicide: A Population‐Wide Study
Authors: Stravynski Ariel , Boyer Richard
Published: December 2003

Some links between loneliness and different manifestations of suicidal conduct have been reported in variety of subgroups (e.g., college students, the elderly, psychiatric patients). We tested this hypothesis by using the results of a population‐wide survey. Strong associations among suicide ideation, parasuicide and different ways of being lonely and alone, defined either subjectively (i.e., the feeling), or objectively (i.e., living alone or being without friends), were observed. Moreover, prevalence of suicide ideation and parasuicide increased with the degree of loneliness. Only minimal differences between men and women were found.
Immediate Post Intervention Effects of Two Brief Youth Suicide Prevention Interventions
Authors: Randell Brooke P. , Eggert Leona L. , Pike Kenneth C.
Published: December 2003

This study evaluated the immediate postintervention effects of two brief suicide prevention protocols: a brief interview—Counselors CARE (C‐CARE)—and C‐CARE plus a 12‐session Coping and Support Training (CAST) peer‐group intervention. Subjects were students “at risk” of high school dropout and suicide potential in Grades 9–12 from seven high schools (N = 341). Students were assigned randomly to C‐CARE plus CAST, C‐CARE only, or “intervention as usual.” The predicted patterns of change were assessed using trend analyses on data available from three repeated measures. C‐CARE and CAST led to increases in personal control, problem‐solving coping, and perceived family support. Both C‐CARE plus CAST and C‐CARE only led to decreases in depression, and to enhanced self‐esteem and family goals met. All three groups showed equivalent decreases in suicide risk behaviors, anger control problems, and family distress.
An Epidemiological Profile of Suicides in Beijing, China
Authors: Yip Paul S. F.
Published: December 2003

Suicide rates in the Beijing region increase with age. The rural suicide rate is about two to five times of the urban in various age‐sex groups. The elderly suicide rate is very serious, especially in the rural area. The average suicide rate for the Beijing region for the period 1987–1996 was 9.8 per 100,000 (6.0 and 17.3 for urban and rural areas, respectively). A low male‐to‐female ratio was also observed. The female suicide rate for the 15–34 age group was higher than that of its male counterparts, which is unique in other areas of the world. These phenomena can be explained by some of the distinct cultural and economic traits of China. Also, suicides rates in the Beijing region were shown to be on a decreasing trend among the teenaged and the old‐age groups. Our findings suggest that the suicide rate in China should not be as high as the estimated rate (31.0 per 100,000), suggested in the Global Health Statistics by Murray and Lopez (1996b, p. 824).
Violent Death Among Intimate Partners: A Comparison of Homicide and Homicide Followed by Suicide in California
Authors: Lund Laura E. , Smorodinsky Svetlana
Published: December 2003

This study examines all intimate partner homicides in California during 1996 (N = 186), and differences between intimate partner homicides with and without perpetrator suicide are compared. The study found that 40 percent of perpetrators committed suicide subsequent to the homicide. Variables examined in the analysis include type of weapon used, race, age, sex of perpetrators and victims, and location of the homicide. Significant differences were found between homicides with perpetrator suicide and those without. The results lend support to previous research suggesting that intimate partner homicide and homicide followed by suicide have different characteristics and possibly distinct etiologies.
A Case Control Study of Suicide and Attempted Suicide in Older Adults
Authors: Beautrais Annette L.
Published: December 2003

Risk factors for serious suicidal behavior among older adults were examined in a case control study of 53 adults aged 55 and older who died by suicide or made medically serious suicide attempts and who were compared with 269 randomly selected comparison subjects. Multivariate analyses suggested that risk of serious suicidal behavior was elevated among those with current mood disorders (OR = 179, CI = 52.8–607.6), psychiatric hospital admission within the previous year (OR = 24.4, CI = 1.9–318.7), limited social network (OR = 4.5, CI = 1.4–14.6). The predominant role of mood disorders was confirmed by population attributable risk (PAR) estimates (73.6%), suggesting that the improved detection, treatment and management of mood disorders should be the primary focus of suicide prevention strategies for older adults.
Can Temperament Identify Affectively Ill Patients Who Engage in Lethal or Near‐Lethal Suicidal Behavior? A 14‐Year Prospective Study
Authors: Maser Jack D. , Akiskal Hagop S. , Schettler Pamela , Scheftner William , Mueller Timothy , Endicott Jean , Solomon David , Clayton Paula
Published: December 2003

Among affectively ill patients followed naturalistically for up to 14 years, 36 committed suicide, 120 attempted suicide, and 373 had no recorded suicide attempt. Comparing these three groups on clinical and intake personality revealed that suicide completed within 12 months was predicted by clinical but not personality variables, and suicide beyond 12 months was predicted by newly derived temperament factors, not clinical variables. Attempters and completers shared core characteristics: previous attempts, impulsivity, substance abuse, and psychic turmoil within a cycling/mixed bipolar disorder. Such temperament attributes as impulsivity and assertiveness were the best prospective predictors of completed suicides beyond 12 months with a sensitivity level of 74% and specificity level of 82%.
Alcohol and Suicide Death Among American Indians of New Mexico: 1980–1998
Authors: May Philip A. , Van Winkle Nancy W. , Williams Mary B. , McFeeley Patricia J. , DeBruyn Lemyra M. , Serna Patricia
Published: December 2003

The relationship between alcohol use prior to suicide was explored among American Indian decedents in New Mexico for the years 1980 through 1998. The suicide data were collected from New Mexico Vital Statistics and toxicology reports from the New Mexico Office of the Medical Investigator and matched on a case‐by‐case basis. Detailed analyses were undertaken for all cases of resident New Mexico Indians from the Navajo, Pueblo, and Apache cultures. Alcohol was detected in 69% of all suicides of American Indians with some variance by major tribal cultural groups (range = 62.1% to 84.4%). This is higher than in suicides among the overall New Mexico population (44.3%). The mean blood alcohol concentration (BAC) of the drinking Indian decedents at suicide was 0.198 (± SD of .088). Mean BACs were high for both males (0.199) and females (0.180) who had been drinking. Over 90% of the Indian decedents who had been drinking had BACs greater than the legal intoxication level of 0.08. The Navajo had the lowest percentage of cases that were alcohol involved, and their mean BAC was lower than the other two cultural groups. Alcohol use for completed suicides also varied somewhat by age, sex, method of suicide, and place of occurrence, but very little by whether the decedent was an on or off reservation resident. Analyses indicated that alcohol use prior to suicide was significantly more associated with male suicides than for females, and it was negatively correlated for those who died by overdose and also those using other drugs at suicide. Otherwise, alcohol use did not significantly differentiate American Indian suicides by age, use of firearms, hanging, use of other methods, or residence, for the presence of alcohol was a factor very commonly associated with all of these variables. Heavy alcohol consumption is, therefore, an important factor in over two thirds of all completed suicides among the Indians of New Mexico.
Lesbian, Gay, and Bisexual Suicidal Behavior: Testing a Constructivist Model
Authors: McBee‐Strayer Sandra M. , Rogers James R.
Published: December 2003

The present investigation surveyed 162 self‐identified lesbian, gay, and bisexual individuals recruited from LGB‐related social organizations or contacted through networking procedures with regard to suicidal behaviors, suicide risk factors, and reasons for living. Approximately 41% of the respondents indicated a serious consideration of suicide including the identification of a specific suicide plan (23%) or a past suicide attempt (36%) with significant intent to die (13%). Forty‐six percent of the sample indicated at least some degree of chance of attempting suicide in the future. Grounded in the existential‐constructivist theory of suicide (Rogers, 2001), empirically and theoretically identified suicide risk factors were found as a group to predict suicidal ideation (R2 = .16) and attempts (R2 = .17), with abuse‐related items independently predicting both suicidal ideation (R2 = .03) and attempts (R2 = .08). Items related to self‐identity issues and social acceptance were predictive of suicidal ideation (R2 = .04), while substance abuse was predictive of suicidal ideation (R2 = .05) and attempts (R2 = .13) for males only. The established factor structure of the Reasons for Living Inventory (Linehan et al., 1983) was not supported in the current data, suggesting that it may not be an appropriate measure of reasons for living with LGB individuals.
Self‐Destructive Behavior in Patients with Dissociative Disorders
Authors: Saxe Glenn N. , Chawla Neharika , Van der Kolk Bessel
Published: December 2003

Highrates of self‐injury have been reported in patients with dissociative disorders, yet no prior study has directly compared these patients with other psychiatric patients. The present study assesses self‐destructive behavior in a group of inpatients who have dissociative disorders compared to those who report few dissociative symptoms. These patients more frequently engage in self‐destructive behaviors, use more methods of self‐injury, and begin to injure themselves at an earlier age then patients who do not dissociate. Results have important implications for understanding the relationship between dissociation, childhood trauma, and self‐injury and for assessment and treatment of patients with dissociative disorders.
Exposure to Suicide: Incidence and Association with Suicidal Ideation and Behavior: United States, 1994
Authors: Crosby Alex E. , Sacks Jeffrey J.
Published: December 2003

Exposure to the suicide of another is common, but the magnitude and effects of such exposure are not well quantified. From a national random telephone survey of U.S. adults, we estimated the 12‐month incidence of exposure to suicide and its association with suicidal ideation, planning, and behavior. Of 5,238 respondents, 342 (a weighted 7.0% representing 13.2 million persons) reported knowing a suicide decedent from the previous year. Univariate analysis showed persons reporting such exposure were significantly more likely to describe suicidal ideation and behavior than those unexposed; multivariate analysis showed no association. Though the risk related to suicide exposure may be small, given the magnitude of exposure, it may warrant intervention efforts because of its potential societal impact.
Microbial Degradation of Tar Oil Compounds under Different Redox Conditions
Authors: Mundt Matthias , Althoff Katrin , Dott Wolfgang , Hollender Juliane
Published: December 2003

The microbial transformation of typical tar oil compounds such as acridine, benzo(b)thiophene, dibenzofuran, indane, and indene under different redox conditions was investigated in microcosm studies. Under aerobic conditions the inherent contamination in polluted soil as well as the added N‐, S‐, O‐ heterocyclic and homocyclic compounds were transformed predominantly apart from thiophene. 1‐Indanone was detected by RP‐HPLC‐DAD and GC‐MS as an intermediate metabolite from indane and indene. Under nitrate and sulfate reducing conditions indane, benzo(b)thiophene, and dibenzofuran were transformed in assays with the polluted soil samples from well B 65 and B 66 within 426 days, whereas they were persistent in assays with the highly polluted soil B 67. All heterocyclic and homocyclic compounds added to the non‐contaminated soil from well B 85 were not degraded under nitrate and sulfate reducing conditions, too. The results indicate that for the decision, wether natural attenuation can be implemented in the remediation of contaminated site, in addition to BTEX and PAHs especially the fate of further tar oil compounds in anoxic aquifers has to be considered.
A severe autosomal‐dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: An unusual familial Mediterranean fever phenotype or another MEFV‐associated periodic inflammatory disorder?
Authors: Aldea Anna , Campistol Josep M. , Arostegui Juan I. , Rius Josefa , Maso Montserrat , Vives Jordi , Yagüe Jordi
Published: December 2003

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three‐generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel‐Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV‐associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full‐length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non‐ancestral populations. © 2003 Wiley‐Liss, Inc.
DEB test for Fanconi anemia detection in patients with atypical phenotypes
Authors: Esmer Carmen , Sánchez Silvia , Ramos Sandra , Molina Bertha , Frias Sara , Carnevale Alessandra
Published: December 2003

Pancytopenia, hyperpigmentation, small stature, congenital abnormalities, and predisposition to neoplasia characterize Fanconi anemia (FA). The clinical phenotype is extremely variable, therefore the diagnosis is frequently delayed until the pancytopenia appears, making diagnosis difficult on the basis of clinical manifestations alone. Hypersensitivity of FA cells to the clastogenic effect of diepoxybutane (DEB) provides a unique marker for the diagnosis before the beginning of hematological manifestations. Our aim in this study was to detect FA in children with atypical manifestations to define which conditions should be routinely included in the DEB test screening. We performed the chromosomal breakage test in 34 patients with probable FA and 83 patients with clinical conditions that could suggest FA, but are not usually screened by the DEB test: 20 patients with aplastic anemia, 20 patients with VACTERL association, 20 with radial ray abnormalities, 7 with tracheo‐esophageal fistulae, 12 with anal atresia, and 4 with myelodysplastic syndrome. We found 18 DEB‐positive patients: 12 were in the group of probable FA and 6 in the other groups. Among the last ones: three were included because of aplastic anemia, without any other sign of FA, however when re‐examined, other anomalies were detected. The third patient had anal atresia, renal hypoplasia, pre‐axial polydactyly, and normal blood cell counts and was diagnosed as having VACTERL association. The other two patients lacking physical or hematological signs were identified among the group of radial ray abnormalities. Thus, our results highlight the need to increase the number of abnormalities indicating need for a DEB test. Delay in the diagnosis of FA may have serious consequences for the patients and their family members. © 2003 Wiley‐Liss, Inc.
Different phenotypic expression in monozygotic twins with Huntington disease
Authors: Anca M.H. , Gazit E. , Loewenthal R. , Ostrovsky O. , Frydman M. , Giladi N.
Published: December 2003

Monozygotic (MZ), 46‐year‐old, male twins, carrying the same Huntington disease (HD) mutation, presented with a different clinical course. In one of the twins, the disease process started at the age of 32 years with chorea, dysarthria, and a depressed mood. Over 14 years, the disease progressed to total functional dependence. The second twin presented at age 35 with gait disturbances. His behavior became aggressive with an obsessive pattern, whereas the motor features included hypokinesia, rigidity, gait unsteadiness, and dysarthria. This is the first report of genetic identity associated with different age of disease onset as well as a different motor and behavioral phenotype. Postzygotic events are a likely explanation for the observed differences of phenotype in these genetically identical twins. © 2003 Wiley‐Liss, Inc.
A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependence
Authors: Bierut Laura Jean , Rice John P. , Goate Alison , Hinrichs Anthony L. , Saccone Nancy L. , Foroud Tatiana , Edenberg Howard J. , Cloninger C. Robert , Begleiter Henri , Conneally P. Michael , Crowe Raymond R. , Hesselbrock Victor , Li Ting‐Kai , Nurnberger John I. , Porjesz Bernice , Schuckit Marc A. , Reich Theodore
Published: December 2003

Smoking is a highly heritable, addictive disorder that commonly co‐occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi‐generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi‐generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas (chromosomes 1 and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the development of habitual smoking and not alcohol dependence. Conversely, genetic regions that influence the development of alcohol dependence do not appear to contribute to the development of habitual smoking. Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence. © 2003 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: Delineation of 7q21.11 breakpoints
Authors: Vermeulen Stefan , Menten Björn , Van Roy Nadine , Van Limbergen Heidi , De Paepe Anne , Mortier Geert , Speleman Frank
Published: December 2003

Constitutional de novo complex chromosomal rearrangements (CCRs) are a rare finding in patients with mild to severe mental retardation. CCRs pose a challenge to the clinical cytogeneticist: generally CCRs are assumed to be the cause of the observed phenotypic abnormalities, but the complex nature of these chromosomal changes often hamper the accurate delineation of the chromosomal breakpoints and the identification of possible imbalances. In a first step towards a more detailed molecular cytogenetic characterization of CCRs, we studied four de novo CCRs using multicolor fluorescent in situ hybridization (M‐FISH), comparative genomic hybridization (CGH), and FISH with region specific probes. These methods allowed a more refined characterization of the breakpoints in three of the four CCRs. The occurrence of 7q breakpoints in three out of these four CCRs and in 30% of reported CCRs suggested preferential involvement of this chromosomal region in the formation of CCRs. Further analysis of these 7q breakpoints revealed a 2 Mb deletion at 7q21.11 in one patient and involvement of the same region in a cryptic insertion in a second patient. This particular region contains at least 5 candidate genes for mental retardation. The other patient had a breakpoint more proximal to this region. The present data together with these from the literature provide evidence that a region within 7q21.11 may be prone to breakage and formation of CCRs. © 2003 Wiley‐Liss, Inc.
Brothers with Chudley–McCullough syndrome: Sensorineural deafness, agenesis of the corpus callosum, and other structural brain abnormalities
Authors: Østergaard Elsebet , Faurholt Pedersen Vibeke , Skriver Elisabeth B. , Brøndum‐Nielsen Karen
Published: December 2003

We describe two brothers with Chudley–McCullough syndrome who are 5 and 17 years old. They were born to healthy consanguineous parents of Pakistani descent. They had severe sensorineural deafness and neuroimaging showed corpus callosum agenesis and other structural brain abnormalities. The Chudley–McCullough syndrome is an autosomal recessive disorder, first described by Chudley et al. [1997: Am J Med Genet 68:350–356]. The original description of the syndrome includes hydrocephalus due to obstruction of the foramen of Monro and early‐onset severe to profound sensorineural deafness. We review the findings in the two patients we describe, four children reported in the literature and two patients reported by Hendriks et al. [1999: Am J Med Genet 86:183–186] with sensorineural deafness, corpus callosum agenesis, and interhemispheric cysts, who may well have Chudley–McCullough syndrome. All patients had sensorineural deafness. The neuroimagings of all eight patients showed colpocephaly, which is most likely caused by corpus callosum agenesis. Three patients had other structural brain abnormalities: cortical dysplasia and gray matter heterotopia. We suggest a revision of the clinical description since the most likely basic developmental defect is corpus callosum agenesis and not foramen of Monro obstruction. © 2003 Wiley‐Liss, Inc.
Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans
Authors: Klootwijk Riko , Groenen Pascal , Schijvenaars Mascha , Hol Frans , Hamel Ben , Straatman Huub , Steegers‐Theunissen Régine , Mariman Edwin , Franke Barbara
Published: December 2003

Neural tube defects (NTD) are congenital malformations arising from incomplete neural tube closure during early embryogenesis. Most NTD in humans show complex inheritance patterns, with both genetic and environmental factors involved in the etiology of this malformation. More than 120 mouse models for human NTD exist. NTD have been observed in mice deficient for the Zic family genes, Zic1, Zic2, and Zic3. We performed mutation analysis in the human orthologs of these genes using DNA material from a large panel of NTD patients. In ZIC2 we identified a deletion of one codon that encodes an alanine residue located in the amino terminal alanine stretch of the protein. The deletion was present in one patient, but not in 364 controls. That may suggest a role—albeit small—of this variant in the etiology of NTD in humans. Transmission disequilibrium testing of a frequent polymorphism in the ZIC2 gene (1059C > T, H353H) in parent‐spina bifida aperta child triads showed no association with NTD. One silent polymorphism (858G > A, V286V) of unknown significance was identified in ZIC3. Neither mutations nor polymorphisms were found in the coding region or flanking sequences of ZIC1. Our data indicate that ZIC1, ZIC2, and ZIC3 are not major risk factors for NTD in humans. © 2003 Wiley‐Liss, Inc.
Metaphyseal chondrodysplasia with cone‐shaped epiphyses: A specific form involving the lower limbs
Authors: Dieux‐Coëslier Anne , Moerman Alexandre , Holder Muriel , Boute Odile , Maroteaux Pierre , Manouvrier Sylvie , Le Merrer Martine
Published: December 2003

Three unrelated patients affected by a characteristic metaphyseal chondrodysplasia with cup‐shaped metaphyses of the knees are described. Lower femoral and upper tibial cone‐shaped epiphyses were embedded in the metaphyses. Main clinical features are short stature, shortening of the lower limbs, limitation of knee extension, and normal hands length. Radiographs of skull, spine, and hands showed no abnormality. This particular appearance of the knees has been seldom described in acquired disease such as repeated injuries, meningoccocemia, scurvy, and hypervitaminosis A. Metaphyseal dysplasias with these distinctive radiological findings of the knees are uncommon. Differential diagnosis includes trichoscyphodysplasia and acroscyphodysplasia among others. Two other cases reported by Kozlowski showed the most similarities to our three cases and defined a new form of metaphyseal dysplasia with specific lower limbs involvement and cup‐shaped metaphyses. © 2003 Wiley‐Liss, Inc.
Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits
Authors: Subramony S. H. , Schott Kelly , Raike Robert S. , Callahan Joel , Langford Leigh R. , Christova Peka S. , Anderson John H. , Gomez Christopher M.
Published: December 2003

Episodic ataxia type 2 (EA2) is a dominantly inherited disorder, characterized by spells of ataxia, dysarthria, vertigo, and migraines, associated with mutations in the neuronal calcium‐channel gene CACNA1A. Ataxic spells lasting minutes to hours are provoked by stress, exercise, or alcohol. Some patients exhibit nystagmus between spells and some develop progressive ataxia later in life. At least 21 distinct CACNA1A mutations have been identified in EA2. The clinical and genetic complexities of EA2 have offered few insights into the underlying pathogenic mechanisms for this disorder. We identified a novel EA2 kindred in which members had ataxic spells induced by fevers or high environmental temperature. We identified a novel CACNA1A mutation (nucleotides 1253+1 G→A) that was present in all subjects with febrile spells or ataxia. Moreover, we found that, regardless of age or interictal clinical status, all affected subjects had objective evidence of abnormal saccades, ocular fixation, and postural stability. These findings suggest that early cerebellar dysfunction in EA2 results from the intrinsically abnormal properties of the CACNA1A channel rather than a degenerative process.
Hereditary spastic paraparesis: Disrupted intracellular transport associated with spastin mutation
Authors: McDermott Christopher J. , Grierson Andrew J. , Wood Jonathan D. , Bingley Megan , Wharton Stephen B. , Bushby Katharine M. D. , Shaw Pamela J.
Published: December 2003

The commonest cause of hereditary spastic paraplegia (HSP) is mutation in the spastin gene. Both the normal function of spastin in the central nervous system and the mechanism by which mutation in spastin causes axonal degeneration are unknown. One hypothesis is that mutant spastin disrupts microtubule dynamics, causing an impairment of organelle transport on the microtubule network, which leads to degeneration in the distal parts of long axons. To study this neuronal and non‐neuronal cells were transfected with either wild type or mutant spastin proteins. We demonstrated evidence of a transient interaction of wild‐type spastin with microtubules, with resulting disassembly of microtubules, supporting a role for wild‐type spastin as a microtubule‐severing protein. Mutant spastin demonstrated an abnormal interaction with microtubules, colocalizing with but no longer severing microtubules. The abnormal interaction of mutant spastin with microtubules was demonstrated to be associated with an abnormal perinuclear clustering of mitochondria and peroxisomes, suggestive of an impairment of kinesin‐mediated intracellular transport. Our findings indicate that an abnormal interaction of mutant spastin with microtubules, which disrupts organelle transport on the microtubule cytoskeleton, is likely to be the primary disease mechanism in HSP caused by missense mutations in the spastin gene.
Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions
Authors: Swartz Barbara E. , Li Sheng , Bespalova Irina , Burmeister Margit , Dulaney Eugene , Robinson Farrel R. , Leigh R. John
Published: December 2003

We describe a family of Slovenian descent with progressive ataxia, corticospinal signs, axonal sensorimotor neuropathy, and disruption of visual fixation by saccadic intrusions. Chromosome mapping indicated a mutation on 1p36, and this recessive disorder has been designated spinocerebellar ataxia with saccadic intrusions. Affected patients showed overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades; other eye movements were normal. Slowed conduction in axons that are selectively vulnerable to the molecular defect could explain both the sensorimotor neuropathy and the saccadic disorder, which would be caused by delayed feedback control because of slow conduction in cerebellar parallel fibers.

Supplementary material to this article can be viewed online at www.interscience.wiley.com/jpages/0364‐5134/suppmat/54_6.
Atypical dementia associated with a novel presenilin‐2 mutation
Authors: Binetti Giuliano , Signorini Simona , Squitti Rosanna , Alberici Antonella , Benussi Luisa , Cassetta Emanuele , Battista Frisoni Giovanni , Barbiero Laura , Feudatari Enrica , Nicosia Francesca , Testa Cristina , Zanetti Orazio , Gennarelli Massimo , Perani Daniela , Anchisi Davide , Ghidoni Roberta , Rossini Paolo Maria
Published: December 2003

We describe an Italian pedigree with hereditary dementia associated with a novel T122R mutation in the presenilin‐2 gene (PSEN2). The clinical history, symptom presentation, and structural neuroimaging were consistent with an atypical form of dementia. Disease expression varied within family members. One in a pair of mutated monozygotic twins had evident signs of disease, whereas the other did not, even if her functional neuroimaging investigations, cerebrospinal fluid levels of Aβ1‐42, and Tau protein were able to provide markers for future disease development. These observations suggest the importance of still unknown biological and perhaps environmental factors in the disease determination.
Amyloid β protein toxicity mediated by the formation of amyloid‐β protein precursor complexes
Authors: Lu Daniel C. , Shaked Gideon M. , Masliah Eliezer , Bredesen Dale E. , Koo Edward H.
Published: December 2003

The amyloid‐β protein precursor, a type 1 transmembrane protein, gives rise to the amyloid β‐protein, a neurotoxic peptide postulated to be involved in the pathogenesis of Alzheimer's disease. Here, we show that soluble amyloid β protein accelerates amyloid precursor protein complex formation, a process that contributes to neuronal cell death. The mechanism of cell death involves the recruitment of caspase‐8 to the complex, followed by intracytoplasmic caspase cleavage of amyloid precursor protein. In vivo, the levels of soluble amyloid β protein correlated with caspase‐cleaved fragments of the amyloid precursor protein in brains of Alzheimer's disease subjects. These findings suggest that soluble amyloid β protein–induced multimerization of the amyloid precursor protein may be another mechanism by which amyloid β protein contributes to synapse loss and neuronal cell death seen in Alzheimer's disease. Ann Neurol 2003;54:781–789
The release of tumor necrosis factor–α is associated with ischemic tolerance in human stroke
Authors: Castillo José , Moro María Ángeles , Blanco Miguel , Leira Rogelio , Serena Joaquín , Lizasoain Ignacio , Dávalos Antonio
Published: December 2003

Tumor necrosis factor (TNF)–α overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF‐α and interleukin (IL)–6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF‐α were higher (42.5 ± 9.9 vs 13.1 ± 6.4pg/ml, p < 0.0001) and IL‐6 levels were lower (10.1 ± 6.2 vs 28.3 ± 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF‐α/IL‐6 index was considered positive when TNF‐α was greater than 30pg/ml and IL‐6 was less than 30pg/ml. Positive TNF‐α/IL‐6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF‐α/IL‐6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF‐α in the presence of reduced concentrations of IL‐6. Ann Neurol 2003;54:811–819
A locus for complicated hereditary spastic paraplegia maps to chromosome 1q24‐q32
Authors: Blumen Sergiu C. , Bevan Simon , Abu‐Mouch Saif , Negus David , Kahana Michael , Inzelberg Rifka , Mazarib Aziz , Mahamid Ahmad , Carasso Ralph L. , Slor Hanoch , Withers David , Nisipeanu Puiu , Navon Ruth , Reid Evan
Published: December 2003

We updated the clinical features of a consanguineous Arab Israeli family, in which four of seven children were affected by spastic paraplegia complicated by skin pigmentary abnormalities. A genomewide linkage screen performed for the family identified a new locus (SPG23) for this form of hereditary spastic paraplegia, in an approximately 25cM region of chromosome 1q24‐q32, with a peak logarithm of odds score of 3.05. Ann Neurol 2003;54:796–803
Diagnostic value of electromyography and muscle biopsy in arthrogryposis multiplex congenita
Authors: Kang Peter B. , Lidov Hart G. W. , David William S. , Torres Alcy , Anthony Douglas C. , Jones H. Royden , Darras Basil T.
Published: December 2003

Arthrogryposis multiplex congenita (AMC), a clinical syndrome characterized by multiple congenital joint contractures, frequently is caused by lesions in the peripheral nervous system. Two standard tests for the evaluation of the motor unit are nerve conduction studies/electromyography (NCS/EMG) and muscle biopsy. We reviewed the diagnostic value of these two studies in the evaluation of AMC over a 23‐year period, analyzing 38 patients with AMC who had NCS/EMG, muscle biopsy, or both. Final diagnoses were classified as neurogenic (8 patients), myopathic (10 patients), “other” (12 patients), or unknown (8 patients). Neither test alone had consistently high sensitivities, positive predictive values, or specificities. However, when NCS/EMG and muscle biopsy were concordant for neurogenic or myopathic findings, they were more accurate than either test alone, especially for neurogenic diseases. Test results were most commonly discordant in patients with “other” or unknown diagnoses. These findings suggest that when the clinical evaluation indicates a specific syndromic, developmental, or exogenous cause, NCS/EMG and muscle biopsy are not helpful and may not need to be performed. When the history, examination, and genetic evaluation are unrevealing, NCS/EMG and muscle biopsy together provide valuable diagnostic information.
Vascular parkinsonism in moyamoya: Microvascular biopsy and imaging correlates
Authors: Tan Eng‐King , Chan Ling‐Ling , Yu Gui Xia , Rumpel Helmut , Wilder‐Smith Einar , Wong Meng‐Cheng
Published: December 2003

We highlight the first case to our knowledge of vascular parkinsonism with angiographic moyamoya and functional imaging correlates. In addition, transmission electron microscopy of the cutaneous vasculature revealed the mean smooth muscle cell layer of the terminal arterioles to be significantly higher compared with ischemic stroke patients classified by vascular risk factors. Smooth muscle cell thickness was also greater in those with small vessel and large vessel strokes compared with cardioembolic strokes. The marked cutaneous arteriolar smooth muscle cell hypertrophy may be a useful surrogate marker for those at risk of developing angiographic moyamoya.
Die Rolle von Radikalen bei metallvermittelten Oxygenierungen
Authors: Limberg Christian
Published: December 2003

Metallvermittelte Oxofunktionalisierungen organischer Substrate sind von fundamentaler Bedeutung – in der Natur genauso wie in Hochschul‐ und Industrielaboratorien. Ungeachtet dessen sind die Mechanismen dieser Reaktionen rätselhaft geblieben, und nur wenige Prozesse werden im Detail verstanden. Dank intensiver Forschung konnte der Wissensstand in den letzten Jahren aber erheblich verbessert werden: So wurde gezeigt, dass viele Oxygenierungen über Radikalintermediate verlaufen – mitunter auch dann, wenn eine vergleichsweise hohe Selektivität Gegenteiliges vermuten lässt. Das zeigen Beispiele aus den unterschiedlichsten Bereichen: von molekularen Metalloxokomplexen, gasförmigen und matrixisolierten Spezies über das Reaktionsverhalten von Metalloenzymen bis hin zu Prozessen an Festkörperoberflächen. Der vorliegende Aufsatz beleuchtet die Vielfalt dieser Systeme und vermittelt einen Überblick über allgemein gültige Reaktionsmuster und Prinzipien sowie einige noch ungelöste Probleme.
Titelbild: DNA Topoisomerase Inhibitor Acutissimin A and Other Flavano‐Ellagitannins in Red Wine (Angew. Chem. 48/2003)
Authors: Quideau Stéphane , Jourdes Michael , Saucier Cédric , Glories Yves , Pardon Patrick , Baudry Christian
Published: December 2003

Humane DNA‐Topoisomerase II wird in vitro durch das flavanoide Ellagitannin Acutissimin A mit einer höheren Aktivität als durch das klinische Krebstherapeutikum Etoposid inhibiert. Acutissimin A entsteht durch eine nichtenzymatische, diastereoselektive Kondensation beim Ausbau von Rotwein in Eichenfässern. Die in hohen Ausbeuten verlaufende Semisynthese beschreiben S. Quideau et al. in ihrer Zuschrift auf S. 6194 ff.
The Role of Radicals in Metal‐Assisted Oxygenation Reactions
Authors: Limberg Christian
Published: December 2003

The oxo‐functionalization of organic substrates with the aid of metal oxo moieties is of fundamental importance not only in nature but also in academic and industrial research. Nevertheless the corresponding reaction mechanisms remain among the most enigmatic in chemistry and few of them are understood in detail. Recent research efforts have resulted in significantly improved information: In the cases of many oxygenation reactions evidence has been provided for the occurrence radical intermediates, even though the high selectivity observed suggests to a different mechanism. Examples stem from various areas of chemistry and include processes involving molecular metal oxo complexes, gas‐phase and matrix‐isolated species, metalloenzymes, and solid‐state oxide surfaces. This Review treats this seemingly wide variety of systems with the aim of providing an overview of common reactivity patterns and principles, as well as open problems.