bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of novel oligodendroglioma‐associated candidate tumor suppressor genes in 1p36 and 19q13 using microarray‐based expression profiling
Authors: Tews Bjoern , Felsberg Joerg , Hartmann Christian , Kunitz Annegret , Hahn Meinhard , Toedt Grischa , Neben Kai , Hummerich Lars , von Deimling Andreas , Reifenberger Guido , Lichter Peter
Published: March 2006

Loss of heterozygosity (LOH) on chromosomal arms 1p and 19q is the most common genetic alteration in oligodendroglial tumors and associated with response to radio‐ and chemotherapy as well as favorable prognosis. Using microsatellite analysis, we previously identified the chromosomal regions 1p36.22‐p36.31 and 19q13.3, as candidate tumor suppressor gene regions being commonly deleted in these tumors. To identify genes within these regions that are downregulated in oligodendroglial tumors with LOH 1p/19q, we performed cDNA microarray‐based RNA expression profiling of 35 gliomas with known allelic status on 1p and 19q, including 7 oligodendrogliomas and 8 diffuse astrocytomas of World Health Organization (WHO) grade II, as well as 14 anaplastic oligodendrogliomas and 6 anaplastic oligoastrocytomas of WHO grade III. The microarrays used for expression profiling carried ∼7,000 gene‐specific cDNAs, with complete coverage of the genes located in 1p36.13‐p36.31 and 19q13.2‐q13.33. Microarray analysis identified 8 genes from these regions (MGC4399, SRM, ICMT, RPL18, FTL, ZIN, FLJ10781 and DBP), which all showed significantly lower expression in 1p/19q‐deleted gliomas when compared to gliomas without 1p/19q losses. Quantitative real‐time reverse transcription‐PCR analyses were performed for the MGC4399, ICMT and RPL18 genes and confirmed the microarray findings. In addition, we found that the cytosolic phospholipase A2 (PLA2G4C) gene at 19q13.3 demonstrated significantly lower expression in anaplastic oligodendrogliomas (WHO grade III) when compared to well‐differentiated oligodendrogliomas (WHO grade II). Taken together, our study provides a set of interesting novel candidate genes that may play important roles in the pathogenesis of oligodendroglial tumors. © 2006 Wiley‐Liss, Inc.
Increasing cyclooxygenase‐2 (cox‐2) gene expression in the progression of Barrett's esophagus to adenocarcinoma correlates with that of Bcl‐2
Authors: Shimizu Daisuke , Vallböhmer Daniel , Kuramochi Hidekazu , Uchida Kazumi , Schneider Sylke , Chandrasoma Parakrama T. , Shimada Hiroshi , DeMeester Tom R. , Danenberg Kathleen D. , Peters Jeffrey H. , DeMeester Steven R , Danenberg Peter V.
Published: March 2006

Previous studies from our laboratory and others have suggested that increased expression of cox‐2 is important in the genesis of esophageal adenocarcinoma. In vitro studies suggest that cox‐2 regulates expression of the anti‐apoptotic protein bcl‐2, thus possibly accounting for reduced apoptosis in carcinogenesis. The aim of this study was to investigate the relationship of these 2 genes in the development of Barrett's‐associated adenocarcinoma. Histologic sections from endoscopic biopsies or esophagectomy specimens were classified as non‐dysplastic Barrett's (n = 30), intraepithelial neoplasia (n = 12) and adenocarcinoma (n = 48). The desired tissue was isolated by laser capture microdissection and expression levels of cox‐2 and bcl‐2 were measured by quantitative real‐time PCR (Taqman®). Gene expression levels were compared to samples of the distal esophageal squamous epithelium (n = 55) and reflux‐esophagitis (n = 25), without Barrett's or cancer. Expression of both bcl‐2 and cox‐2 were increased in non‐dysplastic Barrett's (p = 0.0077, p = 0.0037), intraepithelial neoplasia (p = 0.0053, p = 0.0220) and adenocarcinoma (p < 0.0001, p < 0.0001) compared to squamous epithelium or reflux‐esophagitis. Furthermore, there is a significant correlation between these two genes, especially in carcinoma (p < 0.0001). © 2006 Wiley‐Liss, Inc.
Tc‐99m depreotide imaging of I‐131‐negative recurrent metastatic papillary thyroid carcinoma
Authors: Valsamaki Pipitsa , Gotzamani‐Psarrakou Anna , Tsiouris Spyridon , Molyvda‐Athanasopoulou Elissavet , Psarrakos Kyriakos , Papantoniou Vassilios , Gerali Sophia , Zerva Cherry
Published: March 2006

The detection of radioiodine (I‐131)‐negative metastases of differentiated thyroid carcinoma (DTC) has been hitherto successfully tried by the well‐known synthetic somatostatin analogue indium‐111‐labeled DTPA‐octreotide (In‐111 pentetreotide). The objective of this study was to evaluate the usefulness of scintiscan with the newer synthetic somatostatin analogue Tc‐99m depreotide, in the restaging of papillary thyroid carcinoma (PTC) with detectable serum thyroglobulin (Tg) levels and negative I‐131 whole‐body scan (WBS). Whole‐body planar and cervico‐thoracic tomographic scintigraphy (single‐photon emission tomography—SPET) with Tc‐99m depreotide was performed in a 68‐year‐old male patient suffering from PTC stage III, with a mild increase in serum Tg levels coupled with a recent negative I‐131 WBS. The findings were compared with those of neck ultrasonography (US) and computerized tomography (CT). Nodal neck dissection and histopathology provided the definitive diagnosis. Tc‐99m depreotide scanning revealed foci of cervical lymph node metastases, which did not accumulate I‐131. The findings were in accordance with neck US and CT. Histopathology established the diagnosis of metastatic cervical lymph node PTC. Lymph node immunoreactivity was positive for the somatostatin receptor subtypes 2, 5 and 3. Scintigraphy with Tc‐99m depreotide could prove a useful adjunct to the armamentarium for the follow‐up of PTC, especially in the setting of detectable serum Tg and negative I‐131 WBS. © 2006 Wiley‐Liss, Inc.
Evaluation of xeroderma pigmentosum XPA, XPC, XPD, XPF, XPB, XPG and DDB2 genes in familial early‐onset lung cancer predisposition
Authors: Matakidou Athena , Eisen Tim , Fleischmann Christina , Bridle Helen , Houlston Richard S. ,   Members of the GELCAPS Consortium
Published: March 2006

Epidemiological data has implicated heterozygosity for xeroderma pigmentosum (XP) as a risk factor for lung cancer. XP has 8 known complementation groups, 7 of which are caused by mutations in genes encoding components of the nucleotide excision repair (NER) pathway. To formally investigate the role of XP‐related NER genes in lung cancer susceptibility, we screened germline DNA from 92 familial early‐onset lung cancer patients for mutations in all coding regions and intron–exon boundaries of XPA, XPC, XPD, XPF, XPB, XPG and DDB2. Forty‐one exonic variants were identified. Twenty‐four were nonsynonymous, of which 14 were previously documented polymorphisms. Ten missense variants had not been previously described; none of which were detected in germline DNA from 278 cancer‐free controls. Two of the novel missense changes are predicted to be functionally deleterious. Our findings are compatible with XP heterozygosity being a risk factor for lung cancer susceptibility. © 2006 Wiley‐Liss, Inc.
Curcumin inhibits the mammalian target of rapamycin‐mediated signaling pathways in cancer cells
Authors: Beevers Christopher S. , Li Fengjun , Liu Lei , Huang Shile
Published: March 2006

Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Here we show that curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2–5 μM) and arrested cells in G1 phase of the cell cycle. Curcumin also induced apoptosis and inhibited the basal or type I insulin‐like growth factor‐induced motility of the cells. At physiological concentrations (˜2.5 μM), curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream effector molecules, p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E‐BP1), in a panel of cell lines (Rh1, Rh30, DU145, MCF‐7 and Hela). Curcumin also inhibited phosphorylation of Akt in the cells, but only at high concentrations (>40 μM). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR‐mediated signaling pathways in the tumor cells. © 2006 Wiley‐Liss, Inc.
A recombinant endogenous retrovirus amplified in a mouse neuroblastoma is involved in tumor growth in vivo
Authors: Pothlichet Julien , Heidmann Thierry , Mangeney Marianne
Published: March 2006

The theory of immunoediting postulates that tumor cells exhibit a reduced immunogenicity to escape eradication by the host immune system. It has been proposed that endogenous retroviruses—provided that they are active—could play a role in this process, via the immunosuppressive domain carried by their envelope protein. Here, we demonstrate that the Neuro‐2a tumor cell line—originating from a spontaneous A/J mouse neuroblastoma—produces an infectious retrovirus that most probably results from a recombination event between 2 mouse endogenous retroviral elements. This Neuro‐2a‐associated recombinant retrovirus derives from the unique ecotropic provirus located at the Emv‐1 locus, but with a gag sequence conferring B‐tropism, thus allowing its high‐level amplification in Neuro‐2a cells. We show that knocking down ‐by RNA interference‐ this endogenous retrovirus in Neuro‐2a cells has no effect on the transformed phenotype of the cells, but results in delayed tumor growth and prolonged animal survival, following engraftment of the cells into immunocompetent mice. Recombination between endogenous retroviruses, amplification of the resulting element and high‐level expression of its immunosuppressive activity are therefore likely steps of an immunoediting process, leading to an invading tumor. © 2006 Wiley‐Liss, Inc.
Heat shock transcription factor (Hsf)‐4b recruits Brg1 during the G1 phase of the cell cycle and regulates the expression of heat shock proteins
Authors: Tu Naxin , Hu Yanzhong , Mivechi Nahid F.
Published: March 2006

Human brahma‐related gene 1(Brg1) is a subunit of the switching/sucrose non‐fermenting (SWI/SNF) chromatin‐remodeling complex and regulates transcription during cell growth and differentiation and has been found to be mutated in many types of human cancers. Mammalian heat shock factor 1 (Hsf1), which binds conserved sequences on the promoter of the hsp70 gene when cells are exposed to various stress stimuli, utilizes Brg1–SWI/SNF complexes and stimulates transcription in vitro at the level of initiation and elongation. In contrast to the stress‐inducibility of Hsf1, in vitro transcribed/translated Hsf4b binds to the heat shock element (HSE) constitutively and loses its ability to bind HSEs following stress. The regulation of Hsf4b transcriptional activity in vivo remains unclear. Here, we present evidence that Hsf4b recruits Brg1 complexes to the promoters of heat shock proteins (HSPs) under physiological growth conditions. Furthermore, in an asynchronous cell population, the association of Hsf4b with Brg1 complexes is regulated in response to activation/inactivation of the extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathway. Since Brg1 is also the target of mitogen‐activated protein (MAP) kinases and other protein kinases and it is hyperphosphorylated and inactivated during the G2/M phase of the cell cycle, we tested whether the association of Hsf4b with Brg1 complexes is altered during the cell cycle. The results indicate that association of Hsf4b with Brg1 complexes is undetectable during G2/M; however, an Hsf4b interaction with Brg1 complexes is evident at 1–3 h after progression of cells into G1, where chromatin structure is presumed to be more accessible to transcriptional regulatory proteins. At this time, Hsf4b exhibits increased DNA‐binding activity and is detectable on promoters of multiple Hsps. To determine the unique role of Hsf4b in stimulating the expression of Hsps during the cell cycle, experiments were conducted with mouse embryo fibroblasts (MEFs) deficient in individual Hsfs. The results indicate that in the absence of Hsf1 and Hsf2, Hsf4b expression in cells leads to increased ability of Hsf4b to bind HSE during G1, leading to enhanced synthesis of inducible Hsp70. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Carbenoxolone inhibits junctional transfer and upregulates connexin43 expression by a protein kinase A‐dependent pathway
Authors: Sagar G.D. Vivek , Larson D.M.
Published: March 2006

We have been investigating the function and gene expression of connexins by vascular wall cells, especially Connexin43 (Cx43) in bovine aortic endothelial cells (BAEC). In this study, we tested the effects of carbenoxolone (CBN), a gap junction communication (GJC) blocker on the junctional transfer of Lucifer yellow in BAEC. CBN is a water‐soluble derivative of the liquorice‐root extract 18‐α‐glycyrrhetinic acid. CBN rapidly abolished dye‐transfer in the scrape‐load transfer assay (a measure of GJC) in a reversible and dose‐dependent fashion. We then asked whether the BAEC might somehow compensate for the loss of junctional communication by altering the expression of connexins. Thus, we treated BAEC with 100 µM CBN in serum free medium and determined the total Cx43 cellular distribution (immunostaining) and protein content (immunoblotting). Besides changes in distribution, by 6 h, Cx43 content levels increased to 166% ± 22% (P < 0.0001) of controls. RNA blot data showed two‐three fold increases in Cx43 message in BAEC after 6 h of CBN treatment, suggesting transcriptional control. Since CBN has structural similarities to corticosteroids, we tested both aldosterone and prednisolone but neither drug increased Cx43 levels, suggesting that the CBN response was not due to a generalized steroid effect. Staurosporine inhibited the CBN‐induced increase in Cx43 content, suggesting a role for kinases in the signaling pathway. Further studies with inhibitors indicated that PKA but not PKC was implicated. In summary, CBN blocks junctional communication and modulates Cx43 expression in BAEC. These results suggest a feedback mechanism for control of connexin expression based on junctional patency. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Consensus between GCM climate change projections with empirical downscaling: precipitation downscaling over South Africa
Authors: Hewitson B. C. , Crane R. G.
Published: March 2006

This paper discusses issues that surround the development of empirical downscaling techniques as context for presenting a new approach based on self‐organizing maps (SOMs). The technique is applied to the downscaling of daily precipitation over South Africa. SOMs are used to characterize the state of the atmosphere on a localized domain surrounding each target location on the basis of NCEP 6‐hourly reanalysis data from 1979 to 2002, and using surface and 700‐hPa u and v wind vectors, specific and relative humidities, and surface temperature. Each unique atmospheric state is associated with an observed precipitation probability density function (PDF). Future climate states are derived from three global climate models (GCMs): HadAM3, ECHAM4.5, CSIRO Mk2. In each case, the GCM data are mapped to the NCEP SOMs for each target location and a precipitation value is drawn at random from the associated precipitation PDF. The downscaling approach combines the advantages of a direct transfer function and a stochastic weather generator, and provides an indication of the strength of the regional versus stochastic forcing, as well as a measure of stationarity in the atmosphere–precipitation relationship.

The methodology is applied to South Africa. The downscaling reveals a similarity in the projected climate change between the models. Each GCM projects similar changes in atmospheric state and they converge on a downscaled solution that points to increased summer rainfall in the interior and the eastern part of the country, and a decrease in winter rainfall in the Western Cape. The actual GCM precipitation projections from the three models show large areas of intermodel disagreement, suggesting that the model differences may be due to their precipitation parameterization schemes, rather than to basic disagreements in their projections of the changing atmospheric state over South Africa. Copyright © 2006 Royal Meteorological Society.
Daily cycle of the surface energy balance in Antarctica and the influence of clouds
Authors: Van Den Broeke Michiel , Reijmer Carleen , Van As Dirk , Boot Wim
Published: March 2006

We present the summertime daily cycle of the Antarctic surface energy balance (SEB) and its sensitivity to cloud cover. We use data of automatic weather stations (AWS) located in four major Antarctic climate zones: the coastal ice shelf, the coastal and interior katabatic wind zone and the interior plateau. Absorbed short wave radiation drives the daily cycle of the SEB, in spite of the high surface albedo (0.84–0.88). The dominant heat sink is the cooling by long wave radiation, but this flux is distributed more evenly throughout the day so that a pronounced daily cycle in net all‐wave radiation remains with all‐sky night‐time heat losses of 20–30 W m−2 and noontime heat gains of 30–40 W m−2. During the night, heat is re‐supplied to the snow surface by the sensible heat flux, especially in the katabatic wind zone, and the sub‐surface heat flux. Daytime radiative energy excess is removed from the surface by sublimation (except at the high plateau) and sub‐surface heat transport. Daytime convection occurs at all sites around solar noon but is generally weak. Spatial differences in the SEB are largely controlled by differences in cloud cover. Clouds are associated with higher surface temperatures and near‐surface wind speeds. This especially limits nocturnal cooling, so that the strongest daytime convection is found during overcast conditions on the interior plateau. Copyright © 2006 Royal Meteorological Society.
Applications of silica supports in affinity chromatography
Authors: Schiel John E. , Mallik Rangan , Soman Sony , Joseph Krina S. , Hage David S.
Published: March 2006

The combined use of silica‐based chromatographic supports with immobilized affinity ligands can be used in many preparative and analytical applications. One example is the use of silica‐based affinity columns in HPLC, giving rise to a method known as high‐performance affinity chromatography (HPAC). This review discusses the role that silica has played in the development of affinity chromatography and HPAC and the applications of silica in these methods. This includes a discussion of the types of ligands that have been employed with silica and the methods by which these ligands have been immobilized. Various formats have also been presented for the use of silica in affinity chromatographic methods, including assays involving direct or indirect analyte detection, on‐line or off‐line affinity extraction, and chiral separations. The use of silica‐based affinity columns in studies of biological systems based on zonal elution and frontal analysis methods will also be considered.
Kinetic characterization of a transient reaction by degeneration of the precursor mechanism: Application to the synthesis of 3,4‐diazabicyclo[4.3.0]‐ non‐2‐ene
Authors: Delalu H. , Berthet J. , Metz R. , Elkhatib M.
Published: March 2006

The rate of the oxidation of N‐amino‐3‐azabicyclo[3.3.0]octane by chloramine has been studied by GC and HPLC between pH 10.5 and 13.5. The second‐order reaction exhibits specific acid catalysis. The formation of N,N′‐azo‐3‐azabicyclo[3.3.0]octane or 3,4‐diazabicyclo[4.3.0]non‐2‐ene is pH, concentration, and temperature dependent. In alkaline media, the exclusive formation of 3,4‐diazabicyclo[4.3.0]non‐2‐ene is observed. Kinetic studies show that the oxidation of N‐amino‐3‐azabicyclo[3.3.0]octane by chloramine is a multistep process with the initial formation of a diazene‐type intermediate, which is converted by hydroxide ions into 3,4‐diazabicyclo[4.3.0]non‐2‐ene. Because it was not possible to follow the rate of change of the intermediate concentration, to determine the kinetics of 3,4‐diazabicyclo[4.3.0]non‐2‐ene formation, a procedure based on the degeneration of the precursor process was adopted. An appropriate mathematical treatment allowed a quantitative interpretation of all the phenomena observed over the given pH interval. The activation parameters were determined. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 327–338, 2006
Reactions of hydroxymethyl derivatives of uric acid with oxiranes: Recognition of mechanism based on kinetic studies
Authors: Lubczak Jacek
Published: March 2006

Kinetic and mechanistic studies on the reaction between 1 equivalent of 1,3,7,9‐tetrakis(hydroxymethyl) ureate with 1 equivalent of oxirane (ethylene oxide or propylene oxide) are presented. This study led to recognition of the mechanism of reaction. It has been found that during the reaction the release of formaldehyde from hydroxymethyl groups blocked with oxirane occurs. The formaldehyde is consequently bound to the end of etherol chain. Owing to this rearrangement, the amount of formaldehyde remains constant during the process. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 345–350, 2006
Protein phosphatase 1α activity prevents oncogenic transformation
Authors: Liu Cathy W.Y. , Wang Rui‐Hong , Berndt Norbert
Published: March 2006

Cyclin‐dependent kinase 2 (Cdk2) phosphorylates Thr320 of protein phosphatase 1α (PP1α) in late G1, thereby inhibiting its activity. Phosphorylation‐resistant PP1αT320A, acting as a constitutively active (CA) mutant, causes a late G1 arrest by preventing the phosphorylation and inactivation of the retinoblastoma protein (pRb). Both PP1α‐mediated G1 arrest and PP1α phosphorylation in late G1 require the presence of pRb, indicating that PP1α is a crucial regulator of the pRb pathway, which is almost invariably mutated in human cancer. These findings prompted us to investigate whether PP1α interferes with oncogenic transformation. The ability of NIH 3T3 cells to form foci after transformation with ras/cyclin D1 was significantly inhibited by co‐transfection with PP1αT320A, but not PP1α. Likewise, cells expressing PP1αT320A or PP1αT320A fused to green fluorescent protein (GFP) were unable to form colonies in soft agar, regardless of whether PP1α constructs were co‐transfected with ras/cyclin D1 or transfected into stably transformed cells. Overexpressed wild‐type (Wt) PP1α and GFP‐PP1α were phosphorylated in Thr320, most likely explaining its lack of effect. Expression of GFP‐PP1αT320A was associated with caspase‐cleaved pRb in Western blots (WB) and morphological signs of cell death. These findings demonstrate that PP1α activity can override oncogenic signaling by causing cell‐cycle arrest and/or apoptosis rather than restoring contact inhibition or anchorage dependence. © 2006 Wiley‐Liss, Inc.
Creutzfeldt–Jakob disease presenting with alien limb sign
Authors: Fogel Brent , Wu Mark , Kremen Sarah , Murthy Kolar , Jackson George , Vanek Zeba
Published: March 2006

Creutzfeldt–Jakob disease is a fatal spongiform encephalopathy, which typically presents with a rapidly progressing dementia and additional neurological findings that can be quite variable and diverse. Here we report the unusual case of a patient who presented with left alien limb sign without overt cognitive impairment and was ultimately diagnosed with pathologically confirmed Creutzfeldt–Jakob disease. © 2006 Movement Disorder Society
Effect of substrate temperature on the physical properties of dc magnetron sputtered Cu2O films
Authors: Sivasankar Reddy A. , Sreedhara Reddy P. , Uthanna S. , Venkata Rao G. , Klein A.
Published: March 2006

Cuprous oxide (Cu2O) films were formed by dc reactive magnetron sputtering onto glass substrates held at various temperatures in the range 303–648 K. The substrate temperature was found to be an important parameter in controlling the physical properties of the deposited films. The variation of cathode potential and deposition rate with the substrate temperature was studied. The dependence of crystallographic structure, electrical properties and optical absorption of the films on the substrate temperature was systematically investigated. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Restoration and colonization of freshwater mussels and fish in a southeastern United States tailwater
Authors: Layzer James B. , Scott Edwin M.
Published: March 2006

The French Broad River originates in North Carolina, flows west into Tennessee and at its confluence with the Holston River forms the Tennessee River. Douglas Dam, located on the French Broad River 52 km above its mouth, is operated primarily for peaking hydroelectric power and flood control. Prior to completion of the dam in 1943, the lower French Broad River contained about 53 species of freshwater mussels and 100 species of fish. By 1977, the fauna in the 52‐km‐long tailwater was reduced to 12 species of mussels and 42 native species of fish. Improvements in tailwater conditions occurred following initiation of minimum flows in 1987, and consistent reaeration of discharge in 1993. From 1988 to 2002, we sampled three sites (4, 28, and 39 km downstream of the dam) to monitor the fish assemblage. Each year since 1988, we have collected one or more additional species, indicating continued immigration. We collected 82 native and 9 exotic species of fish overall, but the maximum of 67 species in 1 year suggests that some species reside in the tailwater at low densities or all immigrants may not successfully colonize the tailwater. There is limited potential for most extirpated species of mussels to naturally recolonize the tailwater because source populations are isolated. Consequently, 19 754 adult mussels of 19 species were introduced between 1997 and 2000. Survival of translocated mussels has been high, and successful reproduction of at least one translocated species has occurred. Additionally, four mussel species are naturally colonizing the tailwater. Colonization and recruitment of additional mussel species is expected as populations of their host fishes increase. We believe that the improved conditions of the tailwater may allow for the re‐establishment of sustaining populations of 30 mussel species of historic occurrence, but the continued operation of Douglas Dam as a peaking hydroelectric project will reduce the probability of successfully reintroducing some species. Published in 2006 by John Wiley & Sons, Ltd.
Suitability of requirements prioritization methods for market‐driven software product development
Authors: Lehtola Laura , Kauppinen Marjo
Published: March 2006

In a company producing off‐the‐shelf software for mass markets, the future development steps of the products cannot be negotiated with one or few customers. The decisions concerning the priorities of the requirements must be made within the company, the developer bearing all the financial risks included. This means that finding the right priorities for the requirements is important. However, requirements prioritization is recognized as a difficult activity in software product development. The literature offers methods for requirements prioritization, but many authors report that practices in companies are mostly informal. In this study, we evaluated two requirements prioritization methods in industrial product development projects. In the first case, the users of the system evaluated thepair‐wise comparison techniquefor prioritizing user needs. In the second case, practitioners evaluatedWiegers' methodfor change requests. In addition, we interviewed 11 practitioners from 6 companies about their current requirements prioritization practices and the models that they use as a basis of their prioritization decisions. Our findings indicate that prioritization methods may have limited ability to support decision‐making in a complex area like requirements prioritization in market‐driven product development. In addition, there are practical difficulties in the usage of methods, and therefore, prioritization results should be taken more as being indicative than as an ultimate truth. Copyright © 2006 John Wiley & Sons, Ltd.
Global software development projects in one of the biggest companies in Latvia: is geographical distribution a problem?
Authors: Šmite Darja
Published: March 2006

Global software development appears to be the latest trend in software engineering, bringing new opportunities as reaching mobility in resources, speeding time‐to‐market, obtaining extra knowledge, and increasing operational efficiency. Despite the popularity of the topic, there is a lack of research answering all the questions about how to perform in a distributed environment. This article describes research that aims to develop a framework for global project management and performance. In particular, the research shares information about the variety of collaboration models and project characteristics, and highlights areas of concern and specific risks examined in an observation of 19 distributed projects in a software development company in Latvia. The case study gives an overview of distributed projects emphasizing the specific risks such as organizational and cultural differences, language and time zone differences, lack of personal contact, and troubled communication over geographical distances. The preliminary research concludes that there is a necessity of specific methods and practices for effective project performance in a distributed environment. Copyright © 2006 John Wiley & Sons, Ltd.
A study on optimal scheduling for software projects
Authors: Padberg Frank
Published: March 2006

Software projects often suffer from unexpected rework and delays. Therefore, project scheduling remains a difficult task for the managers. In this article, we compute optimal scheduling strategies for a set of sample software projects and simulate their behavior. The computations are based on a stochastic Markov decision model for software projects, which focuses on capturing the feedback between concurrent development activities. Since the underlying process model is stochastic, the strategies are stochastically optimal, that is, they minimize the expected project duration. The ultimate goal of this research is to develop guidelines for managers to schedule their software projects under uncertainty in the best possible way.

The sample projects are similar, but differ in certain characteristics of the project or product, such as the strength of the coupling between the components or the degree of specialization of the teams on the tasks. By using a set of related projects, we can study how the project characteristics influence the optimal scheduling decisions in a project. After computing the optimal scheduling policies for the sample projects, we use extensive discrete‐event simulations to study the behavior of the optimal policy for each given setting and compare the performance of the optimal policy against the possible list policies. List policies are a simple and commonly used class of scheduling policies. For our sample projects, the simulations show that the best list policy in general is not optimal. The higher the degree of specialization of the teams, the larger the performance gap is. On the other hand, the stronger the coupling between the components, the smaller is the improvement that the optimal policy achieves over the best list policy. Copyright © 2006 John Wiley & Sons, Ltd.
The business of engineering
Authors: Strand Donald R.
Published: March 2006

The members comprising the Los Angeles Tall Buildings Structural Design Council are very active in activities relating to the design of tall buildings. The firms evolved from designing buildings of more moderate height during the 1960s to modern, tall, high‐rise buildings, which are now more easily designed with advanced computer systems and procedures. In these present procedures there is now more ‘paper’ developed in analysis and in construction administration, and requires a more hands‐on approach in a project. The authors in this special issue therefore are presenting information as to how they started, how they handle day‐to‐day projects and responsibilities, and where they think structural engineering design is headed. Copyright © 2005 John Wiley & Sons, Ltd.
1,25‐Dihydroxyvitamin D3 inhibits tumor necrosis factor‐α‐induced adhesion molecule expression in endothelial cells
Authors: Martinesi Maria , Bruni Sara , Stio Maria , Treves Cristina
Published: March 2006

This study tested the hypothesis that 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] plays a role in human umbilical vein endothelial cells (HUVEC) cultures. HUVEC were incubated with 10 or 100 nM 1,25(OH)2D3 for 24 h, in the absence or presence of 40 ng/ml tumor necrosis factor‐α (TNF‐α) or 2 ng/ml interleukin‐1α (IL‐1α). 1,25(OH)2D3 did not affect HUVEC viability and proliferation, while TNF‐α, alone or in combination with the hormone, significantly inhibited HUVEC viability. [3H]thymidine incorporation in HUVEC treated with TNF‐α or IL‐1α significantly decreased, in the absence or in the presence of the hormone, while the levels of vitamin D receptor markedly increased in the presence of 1,25(OH)2D3 alone or associated with TNF‐α or IL‐1α, in comparison to the control. The noteworthy increase in protein levels of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) induced by TNF‐α was significantly decreased after incubation of the cells with 1,25(OH)2D3, this effect not being seen on E‐selectin expression. Neither apoptosis nor nuclear translocation of NF‐κB, induced in HUVEC by TNF‐α was influenced by 1,25(OH)2D3 treatment.
An evaluation of the measurement of pain catastrophizing by the coping strategies questionnaire
Authors: Hirsh Adam T. , George Steven Z. , Riley Joseph L. , Robinson Michael E.
Published: March 2006

Measurement and conceptual issues of pain catastrophizing have been raised in the literature. The issues of construct redundancy and measurement overlap have received particular attention, with suggestions that measures of pain catastrophizing are confounded with measures of negative mood, namely depression. The current study sought to investigate these issues in the coping strategies questionnaire‐catastrophizing subscale (CSQ‐CAT), a widely used measure of pain catastrophizing. Chronic pain patients (n = 152) were recruited from the University of Florida pain clinics and completed a battery of psychological measures. Regression analyses indicated that measures of depression, anxiety, and anger accounted for 69% and 19% of the variance in measures of pain catastrophizing and pain, respectively. Trait anger and the cognitive and fearful dimensions of depression and anxiety were uniquely associated with pain catastrophizing. After controlling for measures of negative mood, pain catastrophizing contributed minimally to the prediction of pain. This study suggests that the CSQ‐CAT is highly related to measures of negative mood and raises doubts about its measurement of the construct of pain catastrophizing. Results also provide support for theoretical accounts of the relationships between pain catastrophizing, negative mood, and pain. Clinical implications, future research directions, and alternative measures of pain catastrophizing are discussed.
Increased seroprevalence of parvovirus B 19 IgG in complex regional pain syndrome is not associated with antiendothelial autoimmunity
Authors: Gross Oliver , Tschernatsch Marlene , Bräu Michael E. , Hempelmann Gunter , Birklein Frank , Kaps Manfred , Madlener Katharina , Blaes Franz
Published: March 2006

The etiology of complex regional pain syndrome (CRPS) is unclear yet. Recently autoantibodies and antecedent viral infections have been discussed to be involved in the pathogenesis of CRPS. We investigated sera from 39 CRPS patients and healthy controls for parvovirus B19 IgG and the occurrence of antiendothelial autoantibodies (AECA). CRPS patients showed a higher seroprevalence of parvovirus B19 IgG than controls (p<0.01). All CRPS 2 patients were positive. 10.2% of the CRPS patients and 10.0% of the controls had AECA (n.s.) and AECA were not associated with parvovirus B19 seropositivity. Our findings suggest the involvement of parvovirus B19, but not autoantibody‐mediated endothelial cell damage, in the pathogenesis of CRPS.
The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome
Authors: Geisser Michael E. , Gracely Richard H. , Giesecke Thorsten , Petzke Frank W. , Williams David A. , Clauw Daniel J.
Published: March 2006

Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little data regarding the relationship between the two. In addition, there are few data regarding the types of stimuli and stimulus intensities that are most closely related to clinical pain.

In this study, 36 subjects with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent experimental pain testing utilizing heat and pressure stimulation. Stimulation levels evoking low, moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for both types of stimuli using random staircase methods. Clinical pain was assessed using visual analogue ratings and the short form of the McGill Pain Questionnaire (MPQ).

Ratings of heat pain sensation were not significantly associated with clinical pain ratings, with the exception of unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by dolorimetry were significantly associated with average measures of clinical pain. Both intensity and unpleasantness ratings of pressure delivered using random staircase methods were significantly associated with clinical pain at low, moderate and high levels, and the strength of the association was greater at increasingly noxious stimulus intensities.

These findings suggest that random pressure stimulation as an experimental pain model in these populations more closely reflects the clinical pain for these conditions. These findings merit consideration when designing experimental studies of clinical pain associated with FM and CFS.
Role of spinal microglia in rat models of peripheral nerve injury and inflammation
Authors: Clark Anna K. , Gentry Clive , Bradbury Elizabeth J. , McMahon Stephen B. , Malcangio Marzia
Published: March 2006

Mounting evidence supports the hypothesis that spinal microglia modulate the development and maintenance of some chronic pain states. Here we examined the role of spinal microglia following both peripheral inflammatory insult and peripheral nerve injury. We observed significant ipsilateral dorsal horn microglia activation 2 weeks after injury and bilateral activation 50 days following nerve injury as well as 24 h following intraplantar zymosan but not intraplantar complete Freund's adjuvant (CFA). Ipsilateral but not contralateral microglia activation was associated with hind paw mechanical hyperalgesia. Spinal injection of the glial metabolic inactivator fluorocitrate attenuated ipsilateral hyperalgesia and bilateral spinal microglia activation after peripheral nerve injury. Intrathecal fluorocitrate reversed hyperalgesia after intraplantar zymosan and produced no reversal of CFA‐induced hyperalgesia. These data suggest a role for spinal glia in the persistence of mechanical hyperalgesia following peripheral nerve injury. However, activation of spinal microglia contralaterally did not correlate to nociception. Furthermore, it would appear that the time course of microglia activation and their contribution to inflammatory pain is dependent on the inflammatory stimulus administered.
Prevalence and co‐occurrence of self‐rated pain and perceived health in school‐children: Age and gender differences
Authors: Sundblad Gunilla M. Brun , Saartok Tönu , Engström Lars‐Magnus T. ,   In collaboration with University College of Physical Education and Sports, Stockholm, Sweden
Published: March 2006

In this nationwide study, 1975 students from grades 3, 6, and 9 (ages 9, 12, and 15 at the onset of the year), were recruited from randomly selected schools, which represented different geographical areas throughout Sweden.

The main aim of the study was to assess the prevalence of self‐reported pain (headache, abdominal, and musculoskeletal pain) and perceived health (problems sleeping and/or if they often felt tired, lonely and sad). A second aim was to study the co‐occurrence among different pain and health variables. The students, (n=1908 distributed by grade 3: 255 girls and 305 boys, grade 6: 347 girls and 352 boys, grade 9: 329 girls and 320 boys) answered retrospectively (three months) a specially designed questionnaire.

Fifty percent (50%) of the students reported that they had experienced pain, either as headache, abdominal pain or musculoskeletal pain, within the recall period. Gender differences were especially noticeable for headaches, where twice as many girls (17%, n=159) than boys (8%, n=80) reported that they suffered such pain at least once a week or more often. Co‐occurrence among the variables was moderate (0.3–0.5).

For the total of the seven variables, the perception of pain and health complaints decreased with age for boys from grades 3 to 9, while multiple complaints increased for girls.
Evaluation of a modified interview version and of a self-rating version of the Suicide Assessment Scale
Authors: Niméus A. , Hjalmarsson Ståhlfors F. , Sunnqvist C. , Stanley B. , Träskman-Bendz L.
Published: March 2006

The Suicide Assessment Scale (SUAS) was constructed to be sensitive to change of suicidality. It was recently found to be predictive of suicide in a group of suicide attempters. The aim of the present study was to evaluate the reliability and validity of a modified interview version of SUAS with defined scores and also a new self-rating version (SUAS-S). The subjects consisted of former inpatients, 42 persons who had been admitted because of a suicide attempt about 12 years ago and 22 control patients. The subjects were rated according to the SUAS, the SUAS-S, as well as the Montgomery Asberg Depression Rating Scale (MADRS). The interrater reliability was found to be high. The SUAS correlated significantly with the MADRS, but the concordance was not consistent, which indicates that the SUAS measures something different from depression. The SUAS-S correlated significantly with the interview-rated SUAS, thus exhibiting good concurrent validity. In summary, both the modified interview version of SUAS and the SUAS-S seem to be valid, reliable and easily used suicide assessment instruments.
Meningocele and ankyloblepharon following in utero exposure to olanzapine
Authors: Arora M. , Praharaj S.K.
Published: March 2006

Although atypical antipsychotics are widely used during pregnancy, their safety is not well established. This case highlights the possible teratogenic effect of olanzapine, in which the baby was born with meningocele and ankyloblepharon. It is suggested that olanzapine may interfere with embryonic development at different stages of pregnancy.
An Arabidopsis SBP‐domain fragment with a disrupted C‐terminal zinc‐binding site retains its tertiary structure
Authors: Yamasaki Kazuhiko , Kigawa Takanori , Inoue Makoto , Yamasaki Tomoko , Yabuki Takashi , Aoki Masaaki , Seki Eiko , Matsuda Takayoshi , Tomo Yasuko , Terada Takaho , Shirouzu Mikako , Tanaka Akiko , Seki Motoaki , Shinozaki Kazuo , Yokoyama Shigeyuki
Published: March 2006

SQUAMOSA promoter‐binding proteins (SBPs) form a major family of plant‐specific transcription factors, mainly related to flower development. SBPs share a highly conserved DNA‐binding domain of ∼80 amino acids (SBP domain), which contains two non‐interleaved zinc‐binding sites formed by eight conserved Cys or His residues. In the present study, an Arabidopsis SPL12 SBP‐domain fragment that lacks a Cys residue involved in the C‐terminal zinc‐binding pocket was found to retain a folded structure, even though only a single Zn2+ ion binds to the fragment. Solution structure of this fragment determined by NMR is very similar to the previously determined structures of the full SBP domains of Arabidopsis SPL4 and SPL7. Considering the previous observations that chelating all the Zn2+ ions of SBPs resulted in the complete unfolding of the structure and that a mutation of the Cys residue equivalent to that described above impaired the DNA‐binding activity, we propose that the Zn2+ ion at the N‐terminal site is necessary to maintain the overall tertiary structure, while the Zn2+ ion at the C‐terminal site is necessary for the DNA binding, mainly by guiding the basic C‐terminal loop to correctly fit into the DNA groove.
Identification of new central nervous system specific mouse microRNAs
Authors: Wheeler Guy , Ntounia-Fousara Sofia , Granda Begona , Rathjen Tina , Dalmay Tamas
Published: March 2006

MicroRNAs (miRNAs) are small regulatory molecules suppressing mRNA activity in metazoans. Here we describe two new miRNAs cloned from brain tissue of mouse embryos. These miRNAs are expressed mainly during embryogenesis and specifically in the central nervous system. We also established the expression patterns of three recently identified miRNAs that were found in our short RNA library. All of them were expressed in the brain and spinal chord but while miR‐410 and miR‐431 were central nervous system specific, miR‐500 was also expressed in limb buds. In addition, the expression of miR‐500 in limb buds showed very strong asymmetry in favour of the left hand side.
A short motif in the C‐terminus of mouse bestrophin 4 inhibits its activation as a Cl channel
Authors: Qu Zhiqiang , Cui Yuanyuan , Hartzell Criss
Published: March 2006

Bestrophins are a new family of anion channels. Here, we examined the Cl channel activity of mBest4. Surprisingly, wild type mouse bestrophin‐4 (mBest4) did not induce functional Cl channels when over‐expressed in HEK293 cells. However, deletion of part of the C‐terminus (residues 353–669) produced large Cl currents, suggesting the presence of a C‐terminal motif that inhibited Cl channel function. Deletion of a short motif (356–364) or substitution of certain residues in this motif with alanines also resulted in expression of robust Cl currents. The channel activity of the mBest4 protein lacking the C‐terminus (residues 353–669) was specifically inhibited by co‐expression of C‐terminal fragments of mBest4 having the inhibitory motif, suggesting that the C‐terminal motif blocked mBest4 channel activity probably by interacting with the channel pore.
Expression of pannexin family of proteins in the retina
Authors: Dvoriantchikova Galina , Ivanov Dmitry , Panchin Yuri , Shestopalov Valery I.
Published: March 2006

Expression of the Panx1 and Panx2 members of the pannexin family of gap junction proteins was studied in the retina by in situ hybridization and qRT‐PCR. Both pannexins showed robust expression across the retina with predominant accumulation in the retinal ganglion cells (RGCs). In concordance, immunohistochemical analysis showed accumulation of the Panx1 protein in RGCs, amacrine, horizontal cells and their processes. Two Panx1 isoforms were detected: a ubiquitously expressed 58 kDa protein, and a 43 kDa isoform that specifically accumulated in the retina and brain. Our results indicated that Panx1 and Panx2 are abundantly expressed in the retina, and may therefore contribute to the electrical and metabolic coupling, or to signaling between retinal neurons via the secondary messengers.