bluuebunny/crossref_metadata_2025 huggingface dataset:
Program Achievements in the Formerly Utilized Sites Remedial Action Program
Authors: Huston Kip R. , McDaniel Tomiann
Published: August 2002

The Atomic Energy Commission (AEC) initiated a survey program in 1974 that led to the creation of
the Formerly Utilized Sites Remedial Action Program (FUSRAP) under authorities granted by the Atomic
Energy Act of 1954, as amended. The U.S. Department of Energy (DOE) managed FUSRAP from 1981 to 1997,
after assuming the responsibilities of the Atomic Energy Commission. On October 13, 1997, Congress transferred
FUSRAP management to the U.S. Army Corps of Engineers (Corps) under the Energy and Water Development
Appropriations Act of 1998. Congress tasked the Corps to review and assess the program and complete it quickly
and efficiently. The Corps executes about $1.3 billion annually in environmental remediation work. In
addition to FUSRAP, the Corps' environmental remediation program consists of the Formerly Used Defense
Sites Program as well as work for a number of federal clients, including the Army, Air Force, U.S.
Environmental Protection Agency (EPA), National Aeronautics and Space Administration
(NASA), and others. FUSRAP makes up approximately 11 percent of the Corps' environmental
remediation program. The Corps has encountered many challenges and achieved many successes since the program
was transferred. © 2002 Wiley Periodicals, Inc.*
Hype or Hope: The Potential of Phytoremediation as an Emerging Green Technology
Authors: Schwitzguébel Jean‐Paul
Published: August 2002

Phytoremediation is defined as the use of green plants and their associated microorganisms, soil amendments,
and agronomic techniques to remove, contain, or render harmless environmental pollutants. At the present time,
phytoremediation is an emerging technology and there is still a significant need to pursue both fundamental and
applied research to fully exploit the metabolic and growth habits of higher plants. It is precisely the purpose of
the European COST Action 837 to stimulate the development and evaluate the potential of plant biotechnology for
the removal of organic pollutants and toxic metals from wastewater and contaminated sites. However, green plants
grow under nonsterile conditions and thus strongly interact with many microorganisms, like bacteria and
mycorrhizal fungi. In this context, an Inter‐COST Workshop on bioremediation was recently organized to
address the significance of soil microorganisms for plants, and the importance of their interactions, with regard
to their potential for phytoremediation. Based on the outcomes of this workshop, the potential use of
phytoremediation is presented in this article. © 2002 Wiley Periodicals, Inc. Reprinted from
Remediation Volume 11, Number 4.
Composition of the essential oil from the leaves of Eruca sativa
Authors: Miyazawa Mitsuo , Maehara Takako , Kurose Kohsuke
Published: August 2002

The components of the essential oil from the leaves of Eruca sativa were analysed by capillary GC and GC–MS. The essential oil from the leaves of Eruca sativa was found to contain 67 volatile components, representing 96.52% of the oil, which were characterized. The main constituents were 4‐methylthiobutylisothiocyanate (60.13%) and 5‐methylthiopentanonitrile (11.25%). The essential oil from the leaves of E. sativa was characterized by a high content of sulfur‐ and nitrogen‐containing compounds. Copyright © 2002 John Wiley & Sons, Ltd.
Spectral analysis of flux vector splitting finite volume methods
Authors: Sengupta Tapan K. , Sridar D. , Sarkar S. , De S.
Published: August 2002

New results are presented here for finite volume (FV) methods that use flux vector splitting (FVS) along with higher‐order reconstruction schemes. Apart from spectral accuracy of the resultant methods, the numerical stability is investigated which restricts the allowable time step or the Courant–Friedrich–Lewy (CFL) number. Also the dispersion relation preservation (DRP) property of various spatial and temporal discretization schemes is investigated. The DRP property simultaneously fixes space and time steps. This aspect of numerical schemes is important for simulation of high‐Reynolds number flows, compressible flows with shock(s) and computational aero‐acoustics. It is shown here that for direct numerical simulation applications, the DRP property is more restrictive than stability criteria. Copyright © 2001 John Wiley & Sons, Ltd.
Unsteady RANS method for surface ship boundary layer and wake and wave field
Authors: Rhee Shin Hyung , Stern Fred
Published: August 2002

Results are reported of an unsteady Reynolds‐averaged Navier–Stokes (RANS) method for simulation of the boundary layer and wake and wave field for a surface ship advancing in regular head waves, but restrained from body motions. Second‐order finite differences are used for both spatial and temporal discretization and a Poisson equation projection method is used for velocity–pressure coupling. The exact kinematic free‐surface boundary condition is solved for the free‐surface elevation using a body‐fitted/free‐surface conforming grid updated in each time step. The simulations are for the model problem of a Wigley hull advancing in calm water and in regular head waves. Verification and validation procedures are followed, which include careful consideration of both simulation and experimental uncertainties. The steady flow results are comparable to other steady RANS methods in predicting resistance, boundary layer and wake, and free‐surface effects. The unsteady flow results cover a wide range of Froude number, wavelength, and amplitude for which first harmonic amplitude and phase force and moment experimental data are available for validation along with frequency domain, linear potential flow results for comparisons. The present results, which include the effects of turbulent flow and non‐linear interactions, are in good agreement with the data and overall show better capability than the potential flow results. The physics of the unsteady boundary layer and wake and wave field response are explained with regard to frequency of encounter and seakeeping theory. The results of the present study suggest applicability for additional complexities such as practical ship geometry, ship motion, and maneuvering in arbitrary ambient waves. Copyright © 2001 John Wiley & Sons, Ltd.
A method for analysing nesting techniques for the linearized shallow water equations
Authors: Heggelund Yngve , Berntsen Jarle
Published: August 2002

A method for analysing different nesting techniques for the linearized shallow water equations is presented. The problem is formulated as an eigenvector–eigenvalue problem. A necessary condition for stability is that the spectral radius of the propagation matrix is less than or equal to one. Two test cases are presented. The first test case is analysed, and effects of enforcing volume conservation and nudging in time are studied. A nesting technique is found that causes no growth of any eigenvectors for reasonable time steps. This nesting technique is then used on both test cases, and results are compared to an everywhere refined model and a coarse grid model. Copyright © 2002 John Wiley & Sons, Ltd.
The direct simulation Monte Carlo method using unstructured adaptive mesh and its application
Authors: Wu J.‐S. , Tseng K.‐C. , Kuo C.‐H.
Published: August 2002

The implementation of an adaptive mesh‐embedding (h‐refinement) scheme using unstructured grid in two‐dimensional direct simulation Monte Carlo (DSMC) method is reported. In this technique, local isotropic refinement is used to introduce new mesh where the local cell Knudsen number is less than some preset value. This simple scheme, however, has several severe consequences affecting the performance of the DSMC method. Thus, we have applied a technique to remove the hanging node, by introducing the an‐isotropic refinement in the interfacial cells between refined and non‐refined cells. Not only does this remedy increase a negligible amount of work, but it also removes all the difficulties presented in the originals scheme. We have tested the proposed scheme for argon gas in a high‐speed driven cavity flow. The results show an improved flow resolution as compared with that of un‐adaptive mesh. Finally, we have used triangular adaptive mesh to compute a near‐continuum gas flow, a hypersonic flow over a cylinder. The results show fairly good agreement with previous studies. In summary, the proposed simple mesh adaptation is very useful in computing rarefied gas flows, which involve both complicated geometry and highly non‐uniform density variations throughout the flow field. Copyright © 2002 John Wiley & Sons, Ltd.
Transition and heat transfer predictions in a turbine cascade at various free‐stream turbulence intensities through a one‐equation turbulence model
Authors: Tsourakis G. I. , Koubogiannis D. G. , Giannakoglou K. C.
Published: August 2002

The one‐equation Spalart–Allmaras turbulence model, coupled with criteria for the prediction of the transition onset, is employed for the numerical prediction of the heat transfer along the nozzle guide vanes of a high‐pressure turbine, at various operating conditions. Emphasis is put on how to overcome a known shortcoming of the Spalart–Allmaras model, i.e. its insensitivity to free‐stream turbulence. For this purpose, an extra viscosity coefficient is defined and used in the mean flow equations. This extra viscosity is proportional to the free‐stream turbulence with a damping in the boundary layer. Its use is adequate to circumvent the aforementioned weakness of the Spalart–Allmaras model, without any other intervention in the model itself. For the prediction of the onset of transition, the Abu‐Ghannam and Shaw and the Mayle criteria are used, depending on the level of free‐stream turbulence. Both yield very satisfactory predictions in a wide range of Reynolds numbers and/or turbulence intensities. From a numerical point of view, this paper proposes techniques for the implementation of the solution method on unstructured grids with triangular elements and reconfirms findings of previous works, like the suitability of the containment‐circle tessellation in highly stretched grids. Copyright © 2002 John Wiley & Sons, Ltd.
The accuracy and efficiency of alternative option pricing approaches relative to a log‐transformed trinomial model
Authors: Chen Hsuan‐Chi , Chen David M. , Chung San‐Lin
Published: August 2002

This article presents a log‐transformed trinomial approach to option pricing and finds that various
numerical procedures in the option pricing literature are embedded in this approach with choices of different
parameters. The unified view also facilitates comparisons of computational efficiency among numerous lattice
approaches and explicit finite difference methods. We use the root‐mean‐squared relative error and
the minimum convergence step to evaluate the accuracy and efficiency for alternative option pricing approaches.
The numerical results show that the equal‐probability trinomial specification of He (12) and Tian (25) and the sharpened trinomial
specification of Omberg (21) outperform other lattice approaches and explicit
finite difference methods. © 2002 Wiley Periodicals, Inc. Jrl Fut Mark 22:557–577, 2002
21q22 balanced chromosome aberrations in therapy‐related hematopoietic disorders: Report from an International Workshop†
Authors: Slovak Marilyn L. , Bedell Victoria , Popplewell Leslie , Arber Daniel A. , Schoch Claudia , Slater Rosalyn
Published: August 2002

The International Workshop on the relationship between prior therapy and balanced chromosome aberrations in therapy‐related myelodysplastic syndromes (t‐MDS) and therapy‐related acute leukemia (t‐AL) identified 79 of 511 (15.5%) patients with balanced 21q22 translocations. Patients were treated for their primary disease, including solid tumors (56%), hematologic malignancy (43%), and juvenile rheumatoid arthritis (single case), by radiation therapy (5 patients), chemotherapy (36 patients), or combined‐modality therapy (38 patients). 21q translocations involved common partner chromosomes in 81% of cases: t(8;21) (n = 44; 56%), t(3;21) (n = 16; 20%), and t(16;21) (n = 4; 5%). Translocations involving 15 other partner chromosomes were also documented with involvement of AML1(CBFA2/RUNX1), identifying a total of 23 different 21q22/AML1 translocations. The data analysis was carried out on the basis of five subsets of 21q22 cases, that is, t(8;21) with and without additional aberrations, t(3;21), t(16;21), and other 21q22 translocations. Dysplastic features were present in all 21q22 cases. Therapy‐related acute myeloid leukemia (t‐AML) at presentation was highest in t(8;21) (82%) and lowest in t(3;21) (37.5%) patients. Cumulative drug dose exposure scores for alkylating agents (AAs) and topoisomerase II inhibitors indicated that t(3;21) patients received the most intensive therapy among the five 21q22 subsets, and the median AA score for patients with secondary chromosome 7 aberrations was double the AA score for the entire 21q22 group. All five patients who received only radiation therapy had t(8;21) t‐AML. The median latency and overall survival (OS) for 21q22 patients were 39 and 14 months (mo), compared to 26 and 8 mo for 11q23 patients, 22 and 28 mo for inv(16), 69 and 7 mo for Rare recurring aberrations, and 59 and 7 mo for Unique (nonrecurring) balanced aberration (latency P ≤ 0.016 for all pairwise comparisons; OS, P ≤ 0.018 for all pairwise comparisons). The percentages of 21q22 patients surviving 1 year, 2 years, and 5 years were 58%, 33%, and 18%, respectively. Noticeable differences were observed in median OS between 21q22 patients (n = 7) receiving transplant (BMT) (31 mo) compared to 21q22 patients who received intensive non‐BMT therapy (n = 46) (17 mo); however, this was nonsignificant because of the small sample size (log‐rank, P = 0.33). t‐MDS/t‐AML with balanced 21q22 aberrations was associated with prior exposure to radiation, epipodophyllotoxins, and anthracyclines, dysplastic morphologic features, multiple partner chromosomes, and longer latency periods when compared to 11q23 and inv(16) t‐MDS/AML Workshop subgroups. In general, patients could be divided into two prognostic risk groups, those with t(8;21) (median OS, 19 mo) and those without t(8;21) (median OS, 7 mo) leukemia (log‐rank, P = 0.0007). © 2002 Wiley‐Liss, Inc.
Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: Relationship to clinicopathological parameters
Authors: Kondo Keiichi , Yao Masahiro , Yoshida Minoru , Kishida Takeshi , Shuin Taro , Miura Takeshi , Moriyama Masatoshi , Kobayashi Kazuki , Sakai Naoki , Kaneko Shigeki , Kawakami Satoshi , Baba Masaya , Nakaigawa Noboru , Nagashima Yoji , Nakatani Yukio , Hosaka Masahiko
Published: August 2002

To delineate more precisely the somatic von Hippel‐Lindau disease (VHL) gene alteration as well as to elucidate its etiologic role in renal tumorigenesis, we examined a total of 240 sporadic renal cell carcinomas (RCCs) for somatic VHL gene alterations by DNA‐SSCP followed by sequencing, methylation‐specific PCR assay, microsatellite LOH study, and Southern blot analysis. Intragenic mutation of the VHL gene was found exclusively in clear‐cell or variant‐type RCCs at a frequency of 51% (104/202). Hypermethylation of the VHL promoter region was detected in an additional 11 clear‐cell RCCs. Microsatellite analysis demonstrated that LOH of the VHL locus was found in 140/155 (90%) informative clear‐cell RCCs. The VHL gene therefore seems to be inactivated in a two‐hit manner by intragenic mutation or hypermethylation plus allelic loss in clear‐cell RCC. Genomic rearrangement of the VHL gene detected by Southern analysis was not found (0/216 cases); this is in contrast to germ lines in which Southern aberrations consisted of 7–19% of the mutations. Clinicopathologic data demonstrated that VHL mutation/LOH did not vary according to tumor progression in clear‐cell RCC, including tumor diameter, stage, grading, distant metastasis, and lymph node metastasis. Interestingly, VHL mutation was significantly less frequent in RCCs occurring in younger (≦ 55 years) than that in older (≧ 56 years) patients. These data suggested that the inactivation of the VHL tumor‐suppressor gene is a specific genetic change in clear‐cell RCC, and that it may occur at an early or first step in the clear‐cell tumorigenic pathway rather than as a late event. © 2002 Wiley‐Liss, Inc.
Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis
Authors: Inoue Hiroko , Furukawa Toru , Sunamura Makoto , Takeda Kazunori , Matsuno Seiki , Horii Akira
Published: August 2002

Pancreatic ductal carcinoma is one of the malignant diseases with the poorest prognosis. To develop effective methods for better treatment of pancreatic cancer patients, we tried to analyze the course of multistep carcinogenesis of the pancreatic ductal cells. IPMT (intraductal papillary‐mucinous tumor) is thought to be one of the premalignant lesions of the pancreas, which would transform into carcinomas. Loss of 18q at the SMAD4 locus is known to be an early genetic change in pancreatic ductal carcinomas. It is not clear, however, whether or not the target gene for inactivation is SMAD4. Using 18 IPMTs, we analyzed LOH at the SMAD4 locus and observed frequent LOH (7/14, 50%). No mutations were observed in any of the tumors. Moreover, the expression level of the SMAD4 protein did not show a reduction in IPMTs. These results suggested that (i) inactivating mutation of the SMAD4 gene is a rather late genetic change in pancreatic carcinogenesis, and (ii) there may be an unknown tumor suppressor gene in 18q, other than SMAD4, that is involved in pancreatic ductal carcinogenesis. © 2001 Wiley‐Liss, Inc.
Identification of tumor metastasis suppressor region on the short arm of human chromosome 20
Authors: Goodarzi Goodarz , Mashimo Tomoyuki , Watabe Misako , Cuthbert Andrew P. , Newbold Robert F. , Pai Sudha K. , Hirota Shigeru , Hosobe Sadahiro , Miura Kunio , Bandyopadhyay Sucharita , Gross Steven C. , Balaji Kethandapatti C. , Watabe Kounosuke
Published: August 2002

Acquisition of metastatic ability by prostate cancer cells is the hallmark of their lethal trait and outcome. However, the genetic alterations underlying the clinical progression and pathogenesis of prostate cancer are not well understood. Several studies involving loss of heterozygosity (LOH) and comparative genomic hybridization analysis have identified distinctively altered regions on various human chromosomes, and genomic imbalance of chromosome 20 was implicated in progression and recurrence of prostate tumors. To examine the role of chromosome 20 in prostate neoplasms, we introduced this chromosome into highly metastatic rat prostate cancer cells using the microcell‐mediated chromosome transfer technique. Introduction of the chromosome resulted in significant suppression of the metastatic ability of the hybrid cells, by as much as 98%, without any interference with the in vivo growth rate or tumorigenicity of primary tumor in SCID mice. Our STS‐PCR analysis on 10 hybrid clones indicates that the suppressor activity of chromosome 20 is located in the p11.23‐12 region. Further examination of the hybrid clones by experimental metastasis assay and histologic analysis as well as Matrigel invasion assay suggests the involvement of the suppressor region at an early stage of invasion and extravasation. We also investigated the status of the chromosome 20 suppressor region in pathology specimens from human prostate cancer patients and detected the frequent loss of this region in high‐grade tumors. These results suggest the presence of a putative suppressor gene on human chromosome 20 that is functionally involved in development of prostate cancer metastases. © 2001 Wiley‐Liss, Inc.
Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma
Authors: Máximo Valdemar , Soares Paula , Seruca Raquel , Rocha Ana Sofia , Castro Patrícia , Sobrinho‐Simões Manuel
Published: August 2002

Mitochondrial DNA (mtDNA) large deletions and mtDNA mutations have been demonstrated in various types of human cancer. The relationship between the occurrence of such alterations and the nuclear microsatellite instability (MSI) status of the neoplastic cells remains controversial. In an attempt to clarify the situation in gastric carcinoma, we studied, by PCR/SSCP and sequencing, five mitochondrial genes and two D‐loop regions in 32 gastric carcinomas that had been previously screened for MSI and mitochondrial common deletion. MtDNA alterations were detected in 26 carcinomas (81%). All the mtDNA mutations, which occurred mainly in the D‐loop and ND1 and ND5 genes, were transitions. D‐loop alterations (insertions and/or deletions) were not significantly associated with mutations in the coding regions. There was a trend towards an inverse relationship between the occurrence of mitochondrial common deletion and mtDNA mutations. No significant relationship was observed between MSI status and mtDNA mutations, whereas the mitochondrial common deletion appeared to be almost exclusively restricted to MSI‐negative tumors. The latter finding—almost no gastric carcinoma with MSI‐positive phenotype has large deletions of mtDNA—needs to be confirmed in a larger series and in tumors from other organs. © 2001 Wiley‐Liss, Inc.
Cre‐mediated transgene activation in the developing and adult mouse brain
Authors: Cinato Elisa , Mirotsou Maria , Sablitzky Fred
Published: August 2002

Summary: The neuron‐specific rat enolase (NSE) promoter was employed to establish transgenic mice expressing Cre recombinase in the central nervous system. Founders were crossed with dormant lacZ indicator mice and specificity as well as efficiency of Cre‐mediated transgene activation was determined by PCR and/or X‐gal staining. Whereas most transgenic lines exhibited Cre activity in early development resulting in widespread Cre activity, one line (NSE‐Cre26) expressed high levels of Cre in the developing and adult brain. With the exception of kidney, which showed occasionally low level of Cre activity, Cre recombination in double transgenics was restricted to the nervous system. Whole‐mount X‐gal staining of 9.5 dpc embryos indicated Cre‐mediated lacZ expression in forebrain, hindbrain, and along the midbrain flexure. A similar expression pattern was observed during later stages of embryogenesis (11.5–13.5 dpc). In adult mice, Cre recombinase was expressed in cerebral cortex and cerebellum and high levels of Cre‐mediated lacZ expression were observed in hippocampus, cortex, and septum. The NSE‐Cre26 transgenic mouse line thus provides a useful tool to specifically overexpress and/or inactivate genes in the developing and adult brain. genesis 31:118–125, 2001. © 2001 Wiley‐Liss, Inc.
DNA methylation variation in cloned mice
Authors: Ohgane Jun , Wakayama Teruhiko , Kogo Yasushi , Senda Sho , Hattori Naka , Tanaka Satoshi , Yanagimachi Ryuzo , Shiota Kunio
Published: August 2002

Summary: Mammalian cloning has been accomplished in several mammalian species by nuclear transfer. However, the production rate of cloned animals is quite low, and many cloned offspring die or show abnormal symptoms. A possible cause of the low success rate of cloning and abnormal symptoms in many cloned animals is the incomplete reestablishment of DNA methylation after nuclear transfer. We first analyzed tissue‐specific methylation patterns in the placenta, skin, and kidney of normal B6D2F1 mice. There were seven spots/CpG islands (0.5% of the total CpG islands detected) methylated differently in the three different tissues examined. In the placenta and skin of two cloned fetuses, a total of four CpG islands were aberrantly methylated or unmethylated. Interestingly, three of these four loci corresponded to the tissue‐specific loci in the normal control fetuses. The extent of aberrant methylation of genomic DNA varied between the cloned animals. In cloned animals, aberrant methylation occurred mainly at tissue‐specific methylated loci. Individual cloned animals have different methylation aberrations. In other words, cloned animals are by no means perfect copies of the original animals as far as the methylation status of genomic DNA is concerned. genesis 30:45–50, 2001. © 2001 Wiley‐Liss, Inc.
A morpholino phenocopy of the mouse MOS mutation
Authors: Coonrod Scott A. , Bolling Laura C. , Wright Paul W. , Visconti Pablo E. , Herr John C.
Published: August 2002

genesis 30:198–200, 2001. © 2001 Wiley‐Liss, Inc.
Cloning and sequence analysis of a zebrafish cDNA encoding DNA (cytosine‐5)‐methyltransferase‐1
Authors: Mhanni Aizeddin A. , Yoder Jeffrey A. , Dubesky Christa , McGowan Ross A.
Published: August 2002

Summary: The zebrafish has become a well‐established animal model for the analysis of development and of several disease phenotypes. Several of the favorable traits that make it a popular model organism would also be beneficial for the study of normal and abnormal vertebrate development in which DNA methylation may play a role. We report the determination of the full‐length cDNA sequence corresponding to the zebrafish DNA (cytosine‐5‐) methyltransferase gene, Dnmt1. It is 4,907 bases long and has an open reading frame predicted to encode a 1,499 amino acid protein that is similar in size and sequence to a number of other methyltransferases identified in other organisms. genesis 30:213–219, 2001. © 2001 Wiley‐Liss, Inc.
Interactions between genetic and reproductive factors in breast cancer risk in a population‐based sample of African‐American families
Authors: Chaudru Valérie , Laing Amelia , Dunston Georgia M. , Adams‐Campbell Lucile L. , Williams Rosemary , Lynch John J. , Leffall Lasalle D. , Dewitty Robert L. , Gause Barry L. , Bonney George E. , Demenais Florence
Published: August 2002

Incidence of breast cancer (BC) varies among ethnic groups, with higher rates in white than in African‐American women. Until now, most epidemiological and genetic studies have been carried out in white women. To investigate whether interactions between genetic and reproductive risk factors may explain part of the ethnic disparity in BC incidence, a genetic epidemiology study was conducted, between 1989 and 1994, at the Howard University Cancer Center (Washington, DC), which led to the recruitment of 245 African‐American families. Segregation analysis of BC was performed by use of the class D regressive logistic model that allows for censored data to account for a variable age of onset of disease, as implemented in the REGRESS program. Segregation analysis of BC was consistent with a putative dominant gene effect (P < 0.000001) and residual sister‐dependence (P < 0.0001). This putative gene was found to interact significantly with age at menarche (P = 0.048), and an interaction with a history of spontaneous abortions was suggested (P = 0.08). A late age at menarche increased BC risk in gene carriers but had a protective effect in non‐gene carriers. A history of spontaneous abortions had a protective effect in gene carriers and increased BC risk in non‐gene carriers. Our findings agree partially with a similar analysis of French families showing a significant gene × parity interaction and a suggestive gene × age at menarche interaction. Investigating gene × risk factor interactions in different populations may have important implications for further biological investigations and for BC risk assessment. Genet. Epidemiol. 22:285–297, 2002. © 2002 Wiley‐Liss, Inc.
Power and robustness of a score test for linkage analysis of quantitative traits using identity by descent data on sib pairs
Authors: Goldstein Darlene R. , Dudoit Sandrine , Speed Terence P.
Published: August 2002

Identification of genes involved in complex traits by traditional (lod score) linkage analysis is difficult due to many complicating factors. An unfortunate drawback of non‐parametric procedures in general, though, is their low power to detect genetic effects. Recently, Dudoit and Speed [2000] proposed using a (likelihood‐based) score test for detecting linkage with IBD data on sib pairs. This method uses the likelihood for θ, the recombination fraction between a trait locus and a marker locus, conditional on the phenotypes of the two sibs to test the null hypothesis of no linkage (θ = ½). Although a genetic model must be specified, the approach offers several advantages. This paper presents results of simulation studies characterizing the power and robustness properties of this score test for linkage, and compares the power of the test to the Haseman‐Elston and modified Haseman‐Elston tests. The score test is seen to have impressively high power across a broad range of true and assumed models, particularly under multiple ascertainment. Assuming an additive model with a moderate allele frequency, in the range of p = 0.2 to 0.5, along with heritability H = 0.3 and a moderate residual correlation ρ = 0.2 resulted in a very good overall performance across a wide range of trait‐generating models. Generally, our results indicate that this score test for linkage offers a high degree of protection against wrong assumptions due to its strong robustness when used with the recommended additive model. Genet. Epidemiol. 20:415–431, 2001. © 2001 Wiley‐Liss, Inc.
Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population‐based study
Authors: Antoniou Antonis C. , Pharoah Paul D.P. , McMullan Greg , Day Nickolas E. , Ponder Bruce A.J. , Easton Douglas
Published: August 2002

We used data from a population based series of breast cancer patients to investigate the genetic models that can best explain familial breast cancer not due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed with breast cancer under age 55 registered in the East Anglia Cancer registry between 1991–1996. Blood samples taken from the patients were analysed for mutations in BRCA1 and BRCA2. The genetic models were constructed using information on breast and ovarian cancer history in first‐degree relatives and on the mutation status of the index patients. We estimated the simultaneous effects of BRCA1, BRCA2, a third hypothetical gene BRCA3, and a polygenic effect. The models were assessed by likelihood comparisons and by comparison of the observed numbers of mutations and affected relatives with the predicted numbers. BRCA1 and BRCA2 could not explain all the familial clustering of breast cancer. The best‐fitting single gene model for BRCA3 was a recessive model with a disease allele frequency 24% and penetrance 42% by age 70. However, a polygenic model gave a similarly good fit. The estimated population frequencies for BRCA1 and BRCA2 mutations were similar under both recessive and polygenic models, 0.024 and 0.041%, respectively. A dominant model for BRCA3 gave a somewhat worse fit, although the difference was not significant. The mixed recessive model was identical to the recessive model and the mixed dominant very similar to the polygenic model. The BRCA3 genetic models were robust to the BRCA1 and BRCA2 penetrance assumptions. The overall fit of all models was improved when the known effects of parity on breast and ovarian cancer risks were included in the model—in this case a polygenic model fits best. These findings suggest that a number of common, low‐penetrance genes with additive effects may account for the residual non‐BRCA1/2 familial aggregation of breast cancer, but Mendelian inheritance of an autosomal recessive allele cannot be ruled out. Genet. Epidemiol. 21:1–18, 2001. © 2001 Wiley‐Liss, Inc.
Efficiency of DNA pooling to estimate joint allele frequencies and measure linkage disequilibrium
Authors: Pfeiffer Ruth M. , Rutter Joni L. , Gail Mitchell H. , Struewing Jeffery , Gastwirth Joseph L.
Published: August 2002

Pooling DNA samples can yield efficient estimates of the prevalence of genetic variants. We extend methods of analyzing pooled DNA samples to estimate the joint prevalence of variants at two or more loci. If one has a sample from the general population, one can adapt the method for joint prevalence estimation to estimate allele frequencies and D, the measure of linkage disequilibrium. The parameter D is fundamental in population genetics and in determining the power of association studies. In addition, joint allelic prevalences can be used in case‐control studies to estimate the relative risks of disease from joint exposures to the genetic variants. Our methods allow for imperfect assay sensitivity and specificity. The expected savings in numbers of assays required when pooling is utilized compared to individual testing are quantified. Genet. Epidemiol. 22:94–102, 2002. © 2002 Wiley‐Liss, Inc.
Modifications of retinal afferent activity induce changes in astroglial plasticity in the hamster circadian clock
Authors: Lavialle Monique , Begue Anne , Papillon Catherine , Vilaplana Jordi
Published: August 2002

The circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, exhibits astroglial plasticity indicated by GFAP expression over the 24‐h period. In this study, we evaluated the role of neuronal retinal input in the observed changes. Modifications of retinal input, either by rearing animals under darkness (DD) or under constant light (LL), or by suppressing afferent input (bilateral enucleation), induced drastic changes in astroglial plasticity. In enucleated animals, a dramatic decrease in GFAP expression was evident in the area of the SCN deprived of retinal projections, whereas persistence of a rhythmic variation was in those areas still exhibiting GFAP expression. By contrast, no changes in astrocytic plasticity were detected in hamsters maintained under LL. These data suggest two fundamental roles for astrocytes within the SCN: (1) to regulate and mediate glutamate released by retinal terminals throughout the neuronal network to facilitate photic signal transmission; (2) to contribute to synchronization between suprachiasmatic neurons. GLIA 34:88–100, 2001. © 2001 Wiley‐Liss, Inc.
Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons
Authors: Sasaki Masanori , Honmou Osamu , Akiyama Yukinori , Uede Teiji , Hashi Kazuo , Kocsis Jeffery D.
Published: August 2002

The potential of bone marrow cells to differentiate into myelin‐forming cells and to repair the demyelinated rat spinal cord in vivo was studied using cell transplantation techniques. The dorsal funiculus of the spinal cord was demyelinated by x‐irradiation treatment, followed by microinjection of ethidium bromide. Suspensions of a bone marrow cell fraction acutely isolated from femoral bones in LacZ transgenic mice were prepared by centrifugation on a density gradient (Ficoll‐Paque) to remove erythrocytes, platelets, and debris. The isolated cell fraction contained hematopoietic and nonhematopoietic stem and precursor cells and lymphocytes. The cells were transplanted into the demyelinated dorsal column lesions of immunosuppressed rats. An intense blue β‐galactosidase reaction was observed in the transplantation zone. The genetically labeled bone marrow cells remyelinated the spinal cord with predominately a peripheral pattern of myelination reminiscent of Schwann cell myelination. Transplantation of CD34+ hematopoietic stem cells survived in the lesion, but did not form myelin. These results indicate that bone marrow cells can differentiate in vivo into myelin‐forming cells and repair demyelinated CNS. GLIA 35:26–34, 2001. © 2001 Wiley‐Liss, Inc.
Role of the extracellular matrix in myelination of peripheral nerve
Authors: Podratz Jewel L. , Rodriguez Esther , Windebank Anthony J.
Published: August 2002

Assembly of the extracellular matrix (ECM) has been tightly linked to compact myelin formation in the peripheral nervous system. We recently demonstrated that myelination of dorsal root ganglion (DRG) axons by Schwann cells may occur in the absence of basal lamina. We have now determined whether laminin deposition occurs around myelinating SC, even though basal lamina has not been assembled. DRG/SC co‐cultures were prepared from E15 rat embryos and incubated in fully defined medium (B27) with and without ascorbic acid for 21–24 days. Cultures were stained with a rabbit anti‐laminin antibody and examined by laser confocal fluorescence microscopy. Myelination occurred in both groups. In the presence of ascorbic acid, there was dense even laminin staining around myelinating SC. In the absence of ascorbic acid, laminin staining was also present but was irregular and less dense. DRG and SC were co‐cultured without ascorbic acid in the presence or absence of a function blocking anti‐β1 integrin receptor antibody. The antibody completely inhibited myelination. Finally, DRG/SC co‐cultures were prepared both with and without ascorbic acid and incubated under control conditions or in the presence of continual, gentle motion. Movement in the absence of ECM significantly inhibited myelination. This demonstrates that laminin deposition on the surface of SC but not ECM assembly is required for formation of compact myelin. ECM is required to provide mechanical stability during the process of myelination. GLIA 35:35–40, 2001. © 2001 Wiley‐Liss, Inc.
Activation of murine cytomegalovirus immediate‐early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice
Authors: Li Ren‐Yong , Baba Satoshi , Kosugi Isao , Arai Yoshifumi , Kawasaki Hideya , Shinmura Yuichiro , Sakakibara Shin‐Ichi , Okano Hideyuki , Tsutsui Yoshihiro
Published: August 2002

Cytomegalovirus (CMV) is the most common infectious cause of congenital anomalies of the CNS in humans. We recently reported that the murine cytomegalovirus (MCMV) immediate‐early (IE) gene promoter directs astrocyte‐specific expression in adult transgenic mice. In the present study, we analyzed the activation of the MCMV IE promoter in developing transgenic mouse brains and compared the activation with that of the Musashi 1 (Msi1) gene, which is expressed in neural progenitor cells, including neural stem cells. During the early phase of neurogenesis, the transgene was expressed predominantly in endothelial cells of the vessels, but not in neuroepithelial cells in which Msi1 was expressed. During later stages of gestation, expression of the transgene was largely restricted to the ventricular zone (VZ) in the CNS, similar to the expression of Msi1. In neurosphere cultures from transgenic embryos in the late phase of neurogenesis, the transgene was expressed in some cells of neurospheres expressing Msi1 and nestin. In neural precursor cells induced to differentiate from stem cells, expression of the transgene was detected in glial progenitor cells, expressing GFAP, nestin, and Msi1, but not in cells expressing MAP2 or MAG. In postnatal development, persistent expression of the transgene was observed in astrocyte lineage cells as was Msi1. These spatiotemporal changes of the MCMV IE promoter activity during development of transgenic mice correlated with susceptible sites in congenital HCMV infection. Moreover, this transgenic mouse model may provide useful model for analysis of the regulation of the switching of neuronal and astrocyte differentiation, and the maintenance of the astrocyte lineage. GLIA 35:41–52, 2001. © 2001 Wiley‐Liss, Inc.
Inflammation in the nervous system: The human perspective
Authors: Bauer Jan , Rauschka Helmut , Lassmann Hans
Published: August 2002

Many basic aspects of brain inflammation, recently disclosed in experimental models, are reflected in the pathology of human inflammatory brain diseases. Examples include the key role of T lymphocytes in immune surveillance and in the regulation of the inflammatory response, the essential contributions of adhesion molecules, proinflammatory cytokines, chemokines, and proteases in the recruitment of inflammatory cells into the nervous tissue, the modulating effect of glia cells on the inflammatory process and the termination of T‐cell‐mediated inflammation by apoptotic cell death. Despite this progress in our understanding of the pathogenesis of brain inflammation, there are still major unresolved questions. Because of technical constraints, most of our knowledge on central nervous system inflammation so far relates to the role of a specific T‐cell subset, the so‐called T‐helper‐1 cells. Other T‐cell subsets, in particular cytotoxic class I MHC‐restricted T lymphocytes, however, appear to be of major importance in human disease. Furthermore, the detailed mechanisms, which are responsible for the profound differences in the patterns of tissue damage in different human inflammatory brain diseases, such as multiple sclerosis or various forms of virus encephalitis, are largely unresolved. We discuss the open questions to be addressed in the future, which, when answered, may help to design novel therapeutic strategies. GLIA 36:235–243, 2001. © 2001 Wiley‐Liss, Inc.
Hyponatraemia and selective serotonin re‐uptake inhibitors in elderly patients
Authors: Kirby Dianne , Ames David
Published: August 2002

Hyponatraemia (serum sodium arbitrarily defined as less than 135 mmol/L) is an increasingly recognised adverse effect of selective serotonin re‐uptake inhibitors (SSRIs). Its precise prevalence and incidence in the elderly are hard to determine because of confounding factors including other prescribed medications and medical conditions. Although hyponatraemia has been reported with all SSRIs and venlafaxine, most studies are small, restrospective, limited by confounding variables or are individual case reports. The risk of developing hyponatraemia while on an SSRI seems to increase with age, female, sex, previous history of hyponatraemia and the concomitant use of other medications known to include hyponatraemia. The sodium concentrations of most patients with SSRI associated hyponatraemia return to normal within days to weeks of SSRI withdrawal. A few cases of SSRI rechallenge indicate that hyponatraemia may sometimes be a transient effect with tolerance developing over time. There is an urgent need for controlled, rigorous studies to confirm the extent of the association between SSRIs and hyponatraemia. Older drugs such as tricyclic antidepressants also need systematic study. It remains quite unclear whether any specific SSRI or venlafaxine has a stronger association with hyponatraemia than any other antidepressant drug. Copyright © 2001 John Wiley & Sons, Ltd
Depression, depressive symptoms and mortality in persons aged 65 and over living in the community: a systematic review of the literature
Authors: Saz Pedro , Dewey Michael E.
Published: August 2002

Background

No recent attempt has been made to synthesize information on mortality and depression despite the theoretical and practical interest in the topic. Our objective was to estimate in the older population the influence on mortality of depression and depressive symptoms.

Methods

Data sources were: Medline, Embase, personal files and colleagues' records. Studies were considered if they included a majority of persons aged ≥ 65 years at baseline either drawn from a total community sample or drawn from a random sample from the community. Samples from healthcare facilities were excluded. Effect sizes were extracted from the papers; if they were not included in the published papers, effect sizes were calculated if possible. No attempt was made to contact authors for missing data.

Results

We found 21 reports on 23 cohorts using depression diagnosis. For 15 of these, odds ratios were pooled using the Greenland method based on confidence intervals (CIs), giving an estimated odds ratio for mortality with depression of 1.73 (95% CI 1.53 to 1.95). A fixed effects meta‐regression of these studies suggested that longer follow‐up predicted smaller effect sizes (log odds ratios −0.096 per year (95% CI −0.179 to −0.014)). There is a weak suggestion of a reduced effect of depression on mortality for women. We were unable to pool effect sizes from the 17 studies using symptom totals and scales, or from eight studies of specific symptoms.

Conclusions

The studies show that diagnosed depression in community‐resident older people is associated with increased mortality. The picture for sex differences is still unclear. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis of novel N1‐(2‐furanidyl)‐5‐fluorouracil derivatives of α‐hydroxy(thio)phosphonates
Authors: Chi Guochen , Wang Xiaodong , Chen Ruyu
Published: August 2002

Several N1‐(2‐furanidyl)‐5‐fluorouracil derivatives of α‐hydroxythiophosphonates were synthesized via oxidation by Moffatt's method of N1‐(2‐furanidyl)‐N3‐(hydroxyalkyl)‐5‐fluorouracil, followed by the addition of diethyl thiophosphite. The phosphonate products were obtained by the oxidation of the corresponding thiophosphonates with m‐chloroperoxybenzoic acid. The crystal structure of compound 6a was determined by X‐ray diffraction. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:211–215, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10021
Reactions of cyclic sulfur ylides with some carbonyl compounds
Authors: Akiyama Hitoshi , Ohshima Katsuyoshi , Fujimoto Tetsuya , Yamamoto Iwao , Iriye Ryozo
Published: August 2002

The reaction of a six‐membered sulfonium ylide 5 with aldehydes or ketones afforded the oxirane derivatives 6a–d as a mixture of cis and trans isomers in excellent yields. In addition, the same reactions, using five‐ or six‐membered cyclic oxosulfonium ylides 7 and 11, gave the corresponding oxirane derivatives in good yields. Moreover, the reaction of 11 with two equimolar amounts of base and 4‐hexen‐3‐one afforded the cyclooctene oxide derivative 16 with high stereoselectivity in 59% yield via a sequential Michael–Michael‐type addition of the ylide and the resulting enolate ion followed by an intramolecular Corey–Chaykovsky reaction. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:216–222, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10022
Conversion of bis(o‐nitrophenyl)diselenides to heterocycles containing selenium and nitrogen with the aid of samarium diiodide
Authors: Chen Xiaoyuan , Zhong Weihui , Zhang Yongmin
Published: August 2002

Treatment of bis(o‐nitrophenyl)diselenides with SmI2 led to simultaneous reduction of nitro groups and reductive cleavage of SeSe bonds as well as to the formation of the intermediates 2. The intermediates 2 were “living” double‐anions formed in situ, and reacted readily with ω‐bromoketones and α‐bromocarboxylic acid derivatives to afford the desired 2H‐1,4‐benzoselenazines and 2H‐1,4‐benzoselenazin‐3(4H)‐ones, respectively, in moderate to high yields and under mild conditions. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:302–306, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10034
Three‐component 1,3‐dipolar cycloaddition reactions in synthesis of spiro[pyrrolidine‐2,3′‐oxindoline] derivatives
Authors: El‐Ahl Abdel‐Aziz S.
Published: August 2002

Regio‐ and stereospecific syntheses of several spiro[pyrrolidine2,3′‐oxindole] derivatives by cycloaddition trapping of azomethine ylides generated in situ, via decarboxylative condensation of isatin with α‐amino acids or by reaction of secondary amines with isatin, are reported. 2,6‐Dibenzylidenecyclohexanone, 2‐arylidene‐1‐tetralone, and arylidenemalononitrile derivatives have been efficiently used as trapping dipolarophiles. The regio‐ and stereochemistry of the additions are controlled by both frontier orbital and steric interactions. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:324–329, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10038