bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo‐FISH, and allelotyping
Authors: Adamovic Tatjana , Trossö Fredrik , Roshani Leyla , Andersson Lars , Petersen Greta , Rajaei Saide , Helou Khalil , Levan Göran
Published: June 2005

The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11–q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer‐related genes in the region. The analysis revealed that seven tumors contained large RNO6‐derived homogeneously staining regions (HSRs) in addition to several normal or near‐normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11–q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone‐dependent tumor. © 2005 Wiley‐Liss, Inc.
Familial occurrence of thymoma and autoimmune diseases with the constitutional translocation t(14;20)(q24.1;p12.3)
Authors: Nicodème Frédéric , Geffroy Sandrine , Conti Massimo , Delobel Bruno , Soenen Valérie , Grardel Nathalie , Porte Henri , Copin Marie‐Christine , Laï Jean‐Luc , Andrieux Joris
Published: June 2005

Thymomas are low‐grade epithelial cancers of the thymus whose prevalence varies between 0.1/100,000 and 0.4/100,000. Familial occurrence of thymoma is very rare. We studied a family bearing the constitutional chromosome translocation t(14;20)(q24;p12), 3 of whose members had a thymoma. In this family, among 27 patients, 11 had the translocation: 3 had thymoma and 4 others had 5 different autoimmune diseases: type 1 diabetes mellitus, Graves' disease, pernicious anemia, primitive Sjögren disease, and autoimmune pancytopenia. FISH studies allowed us to be more specific about the translocation breakpoints. The 14q24 breakpoint was in intron 5 of RAD51L1, and the 20p12 breakpoint was 100 kb telomeric to BMP2. RAD51L1 is a tumor‐suppressor gene belonging to the RAD51 family, already implicated in many tumors (uterine leiomyomas, pseudo‐Meigs syndromes, pulmonary chondroid hamartomas) and involved in recombinational repair of DNA double‐strand breaks. BMP2 belongs to the TGFβ superfamily, and the BMP2–BMP4 genes are involved in thymocyte differentiation by blocking progression from CD4−CD8− to CD4+CD8+ while maintaining a sufficient pool of immature precursors. Dysregulation of RAD51L1 and/or BMP2 may explain this familial occurrence of thymomas and autoimmune diseases. Using QRT‐PCR, we studied the expression of BMP2 in 20 sporadic thymomas and found various levels of expression that may be associated with autoimmune diseases. © 2005 Wiley‐Liss, Inc.
Nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone‐induced pulmonary adenocarcinomas in Syrian golden hamsters contain beta 2‐adrenergic receptor single‐nucleotide polymorphisms
Authors: Masi Thomas , Cekanova Maria , Walker Kindra , Bernert Heike , Majidi Mourad , Becker Jeffrey M. , Schuller Hildegard M.
Published: June 2005

Cigarette smoking contributes to the development of lung cancer throughout the world, with cases of pulmonary adenocarcinoma (PAC) the most numerous. Nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), which is formed from nicotine, has been demonstrated to cause mutations in genes that affect cell regulation and proliferation. Moreover, NNK has been shown to interact directly with and stimulate beta adrenergic receptor (ADRB) signal transduction pathways. Our goal was to determine whether single‐nucleotide polymorphisms (SNPs) in the Adrb2 from PAC tumors were induced in golden hamsters by the injection of NNK. Here we report the cloning and sequencing of Adrb2 clones from either dissected lung tumors from NNK‐injected animals or whole‐lung tissue from water‐injected controls. Both sets of animals contained SNPs; however, we found significantly more SNPs in the Adrb2 from NNK‐injected animals than in the controls. The majority of these SNPs were novel, nonsynonymous mutations found in regions of the Adrb2 known to be involved in ligand binding, G‐protein coupling, and desensitization/down‐regulation. Our data verified the mutagenic effects of NNK as well as demonstrated that this animal model provides an outstanding way of identifying mutations not only in the Adrb2, but also in other genes that may play essential roles in the regulation and growth of pulmonary adenocarcinomas. © 2005 Wiley‐Liss, Inc.
Location and spatial profile of category‐specific regions in human extrastriate cortex
Authors: Spiridon Mona , Fischl Bruce , Kanwisher Nancy
Published: June 2005

Subjects were scanned in a single functional MRI (fMRI) experiment that enabled us to localize cortical regions in each subject in the occipital and temporal lobes that responded significantly in a variety of contrasts: faces > objects, body parts > objects, scenes > objects, objects > scrambled objects, and moving > stationary stimuli. The resulting activation maps were coregistered across subjects using spherical surface coordinates [Fischl et al., Hum Brain Mapp 1999;8:272–284] to produce a “percentage overlap map” indicating the percentage of subjects who showed a significant response for each contrast at each point on the surface. Prominent among the overlapping activations in these contrasts were the fusiform face area (FFA), extrastriate body area (EBA), parahippocampal place area (PPA), lateral occipital complex (LOC), and MT+/V5; only a few other areas responded consistently across subjects in these contrasts. Another analysis showed that the spatial profile of the selective response drops off quite sharply outside the standard borders of the FFA and PPA (less so for the EBA and MT+/V5), indicating that these regions are not simply peaks of very broad selectivities spanning centimeters of cortex, but fairly discrete regions of cortex with distinctive functional profiles. The data also yielded a surprise that challenges our understanding of the function of area MT+: a higher response to body parts than to objects. The anatomical consistency of each of our functionally defined regions across subjects and the spatial sharpness of their activation profiles within subjects highlight the fact that these regions constitute replicable and distinctive landmarks in the functional organization of the human brain. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Solving the Poisson–Boltzmann equation with the specialized computer chip MD‐GRAPE‐2
Authors: Höfinger Siegfried
Published: June 2005

The accurate description of solvation effects is highly desirable in numerous computational chemistry applications. One widely used methodology treats the solvent as a uniform continuum (“implicit solvation”), and describes its net interaction with the solute by solving the Poisson–Boltzmann (PB) equation using the Boundary Element Method (BEM). These calculations are very time consuming using conventional computers. A new, efficient way of solving the PB equation on the special‐purpose hardware chip MDGRAPE‐2 is presented. The MDGRAPE‐2 chip was originally developed to speed up the calculation of pairwise van der Waals and electrostatic interactions. By recasting the BEM equations and applying an iterative solution procedure, a hardware‐accelerated PB solver on MDGRAPE‐2 could be implemented. The performance and reliability of the method is demonstrated on three examples ranging from small peptides to large proteins, whereby the obtained acceleration factors range from 15‐fold to up to 40‐fold with no loss of accuracy compared to the conventional approach. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1148–1154, 2005
The end of clinical psychology as we know it? A response to Snyder and Elliott's four level matrix model
Authors: Desrochers Stephan , Halpern Diane F. , Tan Sherylle J. , Riggio Heidi R.
Published: June 2005

C.R. Snyder and T.R. Elliott's proposed model (this issue) represents a good effort toward reexamining the premises of clinical psychology education. However, there are several concepts left underdeveloped and inadequately defined. Furthermore, their ideas for improving clinical training seem largely divorced from the model proposed. Before making propositions toward a “new clinical psychology,” clarification of the constructs and model is needed to understand how it can better educate and prepare future clinical psychologists for the demands of tomorrow's marketplaces. © 2005 Wiley Periodicals, Inc. J Clin Psychol.
Behavioural linking of stranger rapes
Authors: Santtila Pekka , Junkkila Jenny , Sandnabba N. Kenneth
Published: June 2005

A sample of serial stranger rape cases ( n = 43) that had occurred in Finland during the years 1983–2001 were studied with the objectives being to: (a) describe the characteristics of the offenders; (b) explore the structure of serial rape; and (c) demonstrate behavioural linkage through an analysis of the offenders' crime scene behaviour using both multidimensional scaling (MDS) and discriminant function analysis (DFA). The material was content analysed with regard to the occurrence of a number of dichotomous variables. The inter‐relationships of the variables was studied using MDS. The analysis revealed two previously identified major modes of interaction with the victim: involvement and hostility. Employing MDS and DFA, it was shown that the offences of different offenders were distinguishable in terms of variation between the offences of different offenders and consistency within the offences of a single offender. Using DFA, the classification accuracy clearly exceeds that expected by chance, and 25.6% of the cases were classified without any error. The results are discussed in relation to their practical utility and previous studies. Copyright © 2005 John Wiley & Sons, Ltd.
Serial homicide: an investigation of behavioural consistency
Authors: Salfati C. Gabrielle , Bateman Alicia L.
Published: June 2005

To examine if serial homicide offenders are consistent across their crimes, a model was developed empirically that could be used to distinguish between crimes that were instrumental and those that were expressive. The first known three offences in each series of 69 US serial homicides committed by 23 offenders, were examined and the instrumental and expressive themes determined. Three models were then explored that test for consistency across these themes. The most liberal model was found to classify all of the offences effectively and to reveal complete consistency across the three crimes for all offenders. The implications of these results for offender profiling and further study of serial homicide are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Life story accounts of left wing terrorists in India
Authors: Sarangi Sudhanshu , Alison Laurence
Published: June 2005

This paper explores the life story accounts of 12 left wing terrorists in India. Narrative interviews revealed that the accounts were broadly coherent and contained similar rhetorical structures with regard to: i) images of the self (imagoes); ii) significant others (interpersonal figures); and iii) visions of the future (generativity script). Specifically, it appeared that individuals developed imagoes of poverty and oppression, identified the state structure as corrupt, and terrorist leaders as heroes of the oppressed. Further, the accounts revealed a commitment to an exploitation‐free society (generativity script) and an ideological devotion to a rhetoric that justifies extreme violence. The paper considers the possibility that such coherence is formulated around propaganda and indoctrination that is more sympathetic and harmonious with these individuals' worldview and hence has a powerful shaping process on their development. Finally, we discuss the practical implications of the findings and suggest major policy shifts in dealing with the left wing terrorist groups in India. Copyright © 2005 John Wiley & Sons, Ltd.
A classification of computer security incidents based on reported attack data
Authors: Kjaerland Maria
Published: June 2005

Previous studies of computer criminals have attempted to differentiate between offenders, but have not used data from the actual attacks. Drawing on theories from investigative psychology as well as information security, the current study differentiates 2755 computer security incidents using information about Method of Operation (MO), Impact, and Source Sector from reported attacks. Multivariate statistical analyses were applied on the data‐matrix of 22 variables and showed the co‐occurrences of various aspects of computer security incidents. A radex structure emerged where the high frequency variables were positioned in the centre of the data‐plot. Based on a previously developed taxonomy of cyber intrusions, the results of the analysis showed that it was possible to draw inferences about the less informative category of Objective, from information about Attacker, Tools, Access, and Results. By applying the division‐lines indicating the Objectives of Challenge/Status, Destruction, Political Gain and Financial Gain on the SSA‐plot, it was shown how the taxonomies could be further developed by taking into account the relationships between the categories. Copyright © 2005 John Wiley & Sons, Ltd.
Kit with technetium‐99m labelled antimicrobial peptide UBI 29‐41 for specific infection detection
Authors: Welling Mick M. , Korsak Agnieszka , Gorska Barbara , Oliver Patricia , Mikolajczak Renata , Balter Henia S. , Feitsma Hans I. J. , Pauwels Ernest K. J.
Published: June 2005

The purpose of this study was to investigate radiochemical and biological characteristics of an instant kit for the preparation of 99mTc‐labelled UBI 29‐41 for specific detection of infections. The kit is based on 99mTc‐labelling via HYNIC conjugated to the terminal amine of the peptide, producing a well‐understood labelled compound.

One hour after the addition of fresh 99mTcO to the kit ITLC and HPLC reverse‐phase analysis was performed. Stability of the labelled complex was challenged and the binding to bacterial pellets was assessed. Finally, the biodistribution and accumulation in MRSA‐infected tissues were studied using scintigraphy and ex vivo countings. Data were compared to a non‐kit control method.

Radiochemical analysis indicated >96% labelling, stability for 24 h and the preparation was used without purification. In vitro studies showed 41% of radioactivity was bound to bacteria. After injection into mice with a bacterial infection the site of infection was visualized within 30 min. Kit prepared 99mTc‐HYNIC‐UBI 29‐41 was rapidly (half‐life 113 min) cleared via the kidneys and urinary bladder, essentially slower than control peptide (half‐life 74 min). This slower clearance results in higher activities in blood and other tissues. Nevertheless, 99mTc‐HYNIC‐UBI 29‐41 shows favourable radiochemical characteristics and deserves further evaluation in a clinical setting. Copyright © 2005 John Wiley & Sons, Ltd.
The generation of monthly gridded datasets for a range of climatic variables over the UK
Authors: Perry Matthew , Hollis Daniel
Published: June 2005

Monthly or annual 5 km × 5 km gridded datasets covering the UK are generated for the 1961–2000 period, for 36 climatic parameters. As well as the usual elements of temperature, rainfall, sunshine, cloud, wind speed, and pressure, derived temperature variables (such as growing‐season length, heating degree days, and heat and cold wave durations) and further precipitation variables (such as rainfall intensity, maximum consecutive dry days, and days of snow, hail and thunder) are analysed.

The analysis process uses geographical information system capabilities to combine multiple regression with inverse‐distance‐weighted interpolation. Geographic and topographic factors, such as easting and northing, terrain height and shape, and urban and coastal effects, are incorporated either through normalization with regard to the 1961–90 average climate, or as independent variables in the regression. Local variations are then incorporated through the spatial interpolation of regression residuals.

For each of the climatic parameters, the choice of model is based on verification statistics produced by excluding a random set of stations from the analysis for a selection of months, and comparing the observed values with the estimated values at each point. This gives some insight into the significance, direction, and seasonality of factors affecting different climate elements. It also gives a measure of the accuracy of the method at predicting values between station locations.

The datasets are being used for the verification of climate modelling scenarios and are available via the Internet. © Crown Copyright 2005. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Mathematical Model and Parameter Estimation for Gas‐Phase Ethylene/Hexene Copolymerization With Metallocene Catalyst
Authors: Kou Bo , McAuley Kim B. , Hsu James C. C. , Bacon David W.
Published: June 2005

Summary: Models were developed to simulate gas‐phase ethylene/hexene copolymerization using a silica‐supported (BuCp)2ZrCl2 catalyst in a semi‐batch laboratory reactor. The models are able to predict ethylene consumption rate, gas composition drift during the experimental runs, as well as number‐and weight‐average molecular weight, and short‐chain branching levels, and triad sequence distributions of copolymer removed from the reactor at the end of each run. A single‐site model was first developed, but it failed to accurately predict the molecular weight data and its distribution. Sequentially, a two‐site model was built to improve model predictions. Parameter estimability analysis was performed to guide model simplification and to ensure that the parameter estimation problem would be well conditioned. After model simplification, which reduced the number of unknown parameters from 55 to 37, the parameters were estimated and good fitting of most experimental data was obtained. The simplified two‐site model was validated using the data from four extra experimental runs, which were not employed in the parameter estimation process. Most of the model predictions fall within the 95% confidence intervals of the experimental data.

Model validation of hexene concentration. (The lines are model predictions and the solid diamonds with error bars are experimental data.)

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Model validation of hexene concentration. (The lines are model predictions and the solid diamonds with error bars are experimental data.)
Ethylene Polymerization Kinetics with a Heterogeneous Metallocene Catalyst – Comparison of Gas and Slurry Phases
Authors: Bergstra Michiel F. , Weickert Günter
Published: June 2005

Summary: Ethylene homopolymerizations were executed with a supported Ind2ZrCl2/MAO catalyst using the so‐called Reactive Bed Preparation method. This RBP method combined a slurry polymerization with a gas phase polymerization with the same polymerizing particles, i.e., a reactive bed. Polymerization kinetics were measured with high accuracy and reproducibility. Slurry and gas phase polymerization rates showed the same dependency on monomer bulk concentration. A complexation model has been proposed to describe the non‐first order polymerization rate‐monomer concentration dependence observed. This model also explains the non‐Arrhenius temperature dependence and the observed pressure dependence of the activation energy of the commonly used polymerization rate model: Rp = kp · C* · M.

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Gas assisted injection molding of a handle: Three‐dimensional simulation and experimental verification
Authors: Polynkin A. , Pittman J.F.T. , Sienz J.
Published: June 2005

Methods implemented in a three‐dimensional finite element code for the simulation of gas assisted injection molding are described, and predictions compared with the results of molding trials. The emphasis is on prediction of primary gas penetration and plastic wall thickness, including the effects of cooling during a delay before gas injection. For the latter, time dependent heat transfer coefficients at the cavity surface are used, determined in a separate analysis of transient heat conduction through the plastic and the mold tool to the circulating coolant. This shows how the initial value of 25,000 W/m2K falls by about an order of magnitude during the first few seconds of cooling, and also how values vary from cycle to cycle as steady periodic conditions are approached. For a tubular handle molded in polystyrene, with melt flow modeled by a Cross WLF model, comparisons of simulations with sectioned parts show excellent prediction of wall thickness and its variation circumferentially and in bends. The increase in wall thickness due to cooling during a gas delay is accurately modeled, as is the occurrence of a blow out. POLYM. ENG. SCI. 45:1049–1058, 2005. © 2005 Society of Plastics Engineers
Influence of interactions on the mechanical, morphological and thermal properties of in situ ternary composites based on fluorocarbon elastomer, acrylic elastomer and liquid crystalline polymer blends
Authors: Shivakumar E , Pandey KN , Alam S , Das CK
Published: June 2005

The mechanical, morphological and thermal properties of the binary and ternary blends of a fluorocarbon elastomer (FKM), an acrylic elastomer (ACM) and a liquid crystalline polymer (LCP) were investigated. The ternary blends were prepared by varying the amount of the LCP but fixing the ratio of the FKM and ACM. Addition of a third component, a polyacrylic rubber which interacted with the LCP, facilitated the structural development of the LCP phase by acting at the interface. The mechanical properties of the ternary blends were substantially improved because of both the fibril generation and adhesion of rubber particles on the LCP fibrils, which were attributed to the ACM interaction. Morphological investigations suggest that the fine fibrillation of the LCP domains is more apparent in the ternary blends than in the binary blends of FKM and LCP prepared under the same processing conditions. Thermogravimetric analysis (TGA) revealed an improved thermal stability of the FKM in the presence of the LCP for the binary blends, but a lower thermal stability for the ternary blends. Copyright © 2005 Society of Chemical Industry
Influence of molecular weight on liquid crystalline behavior of linear and star mesogen‐jacketed liquid crystal polymers
Authors: Wang Xingzhu , Zhang Hailiang , Chen Erqiang , Wang Xiayu , Zhou Qifeng
Published: June 2005

A series of novel multi‐armed (di‐, tri‐ and tetra‐armed) mesogen‐jacketed liquid crystal polymers (MJLCPs) were synthesized by atom transfer radical polymerization (ATRP) of {2,5‐bis[(4‐methoxyphenyl)oxycarbonyl]styrene}(MPCS) using di‐, tri‐ and tetrafunctional initiator, respectively. The results show that the number average molecular weight (Mn,GPC) was increased versus monomer conversion, and the polydispersities were quite narrow (<1.19), which is the characteristic of controlled polymerization. The chemical structures of these multi‐armed mesogen‐jacketed liquid crystal polymers were confirmed by 1H NMR. The liquid crystalline behavior of these multi‐armed MJLCPs with arms ranging from two to four was studied by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and wide‐angle X‐ray diffraction (WAXD). It was found that liquid crystalline phases appeared simply when the number molecular weights (Mn,GPC) of these multi‐armed MJLCPs was higher than a certain critical values, that is, Mn,GPC > 1.87 × 104 g/mol, 1.84 × 104 g/mol, 2.69 × 104 and 3.68 × 104 g/mol, which were initiated by coil difunctional initiator, hard difunctional initiator, trifunctional initiator and tetrafunctional initiator, respectively. All the liquid crystalline phase was found to be stable up to the decomposition temperature of these multi‐armed MJLCPs. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3232–3244, 2005
Effect of aniline formaldehyde resin on the conjugation length and structure of doped polyaniline: Spectral studies
Authors: Ho Ko‐Shan , Hsieh Tar‐Hwa , Kuo Chung‐Wen , Lee Swu‐Wen , Lin Jong‐Jing , Huang Ying‐Jie
Published: June 2005

A DBSA (n‐dodecylbenzene sulfate)‐complexed aniline formaldehyde [AF(DBSA)1.0] was successfully synthesized with excess aniline (compared with formaldehyde) in the presence of n‐dodecylbenzene sulfonic acid (HDBSA), which was complexed with aniline monomer before polymerization. The resin was carefully characterized with 1H and 13C NMR, electron spectroscopy for chemical analysis, and Fourier transform infrared and was demonstrated to be a polymer in which anilines were all complexed with HDBSA and became anilinium salts. A drastic decrease of the maximum absorption wavelength (ultraviolet–visible spectra) of DBSA‐doped polyaniline [PANI(DBSA)0.5] was found when AF(DBSA)1.0 was mixed, and this resulted from the reduced conjugation length. A similar effect on PANI(DBSA)0.5 was found when free HDBSAs were mixed with PANI(DBSA)0.5. Visual inspection with an optical microscope revealed that PANI(DBSA)0.5/AF(DBSA)1.0 gave uniform morphologies in various compositions, showing possible miscibility for this system. X‐ray diffraction patterns of PANI(DBSA)0.5/AF(DBSA)1.0 showed that the layered structure of PANI(DBSA)0.5 was still present but became shorter in the polyblend because of the presence of AF(DBSA)1.0. Solid‐state 13C NMR spectra revealed that the reduced conjugation length was derived from the interaction of alkyl groups between HDBSA, complexed DBSA, and dopant DBSAs. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3116–3125, 2005
Complementary medicine use by Australian women with gynaecological cancer
Authors: Markovic Milica , Manderson Lenore , Wray Natalie , Quinn Michael
Published: June 2005

Aims and objectives: Social and cultural factors are identified that impact on complementary therapy use among Australia‐born and immigrant women diagnosed with gynaecological cancer.

Methods: A qualitative study design including in‐depth interviews with women diagnosed with gynaecological cancer (N=53) and participant observation was conducted.

Results: Approximately one‐third of women utilized complementary and alternative medicine, with this being determined by current health concerns and health beliefs related to the efficacy of different modalities. Four types of complementary therapy users emerged: consequential, therapeutic, informed and exploratory.

Conclusion: There was a relatively low uptake of complementary treatments. Choice was influenced by women's socio‐demographic background, clinical and personal history, lack of personal experiences of gynaecological cancer among study participants' kin and friends, and lack of popular alternative literature on such cancer. Copyright © 2005 John Wiley & Sons, Ltd.
Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia
Authors: Deterding Robin R. , Pye Catherine , Fan Leland L. , Langston Claire
Published: June 2005

We sought to determine the clinical course and histologic findings in lung biopsies from a group of children who presented with signs and symptoms of interstitial lung disease (ILD) without identified etiology. Patients were identified from the pathology files at the Texas Children's Hospital who presented below age 2 years with persistent tachypnea, hypoxia, retractions, or respiratory crackles, and with nonspecific and nondiagnostic lung biopsy findings. Age‐matched lung biopsy controls were also identified. Their clinical courses were retrospectively reviewed. Biopsies were reviewed, and immunostaining with antibodies to neuroendocrine cells was done. Fifteen pediatric ILD patients and four control patients were identified for inclusion in the study. Clinically, the mean onset of symptoms was 3.8 months (range, 0–11 months). Radiographs demonstrated hyperinflation, interstitial markings, and ground‐glass densities. Oxygen was initially required for prolonged periods, and medication trials did not eliminate symptoms. After a mean of 5 years, no deaths had occurred, and patients had improved. On review of the lung biopsies, all had a similar appearance, with few abnormalities noted. Immunostaining with antibodies to neuroendocrine cell products showed consistently increased bombesin staining. Subsequent morphometric analysis showed that immunoreactivity for bombesin and serotonin was significantly increased over age‐matched controls. In conclusion, we believe this may represent a distinct group of pediatric patients defined by the absence of known lung diseases, clinical signs and symptoms of ILD, and idiopathic neuroendocrine cell hyperplasia of infancy. These findings may be important for the evaluation of ILD in young children. Pediatr Pulmonol. 2005; 40:157–165. © 2005 Wiley‐Liss, Inc.
Self‐assembly of GaAs holed nanostructures by droplet epitaxy
Authors: Wang Zhiming M. , Holmes Kyland , Shultz John L. , Salamo Gregory J.
Published: June 2005

The cover picture refers to the Rapid Research Letter by Zhiming M. Wang et al. [1] and displays the nanostructure evolution during GaAs growth by droplet epitaxy. The two colored AFM images of 2 µm × 2 µm show the formation of GaAs nano‐crystals shaped like lighted candles and square‐holed round coins.

The first author, Zhiming M. Wang, is a research professor at the University of Arkansas, USA, and a member of the Molecular‐Beam Epitaxial group of Distinguished Professor Gregory J. Salamo. His current research interests include low‐dimensional semiconductor nanostructures, ferroelectronic and ferromagnetic nanostructures, and manipulation of single molecules.

This issue of physica status solidi (a) also contains contributions from the 4th International Conference “Porous Semiconductors – Science and Technology”, held 14–19 March 2004 in Cullera (Valencia), Spain. Further papers from PSST‐2004 are published in phys. stat. sol. (c) 2, No. 9 (2005).
The Saccharomyces cerevisiae Sub2 protein suppresses heterochromatic silencing at telomeres and subtelomeric genes
Authors: Lahue Elaine , Heckathorn John , Meyer Zachary , Smith Jennie , Wolfe Christopher
Published: June 2005

We show that overexpression of Sub2p, a multifunctional Saccharomyces cerevisiae helicase family member that is involved in mRNA elongation and transport, also suppresses heterochromatic silencing at telomeres. Genetic assays show cells that overexpress SUB2 from a high copy plasmid exhibit increased survival rates when selecting for a telomere‐silenced URA3 reporter. Two temperature‐sensitive sub2 mutations that affect different helicase domains were also examined at the permissive temperature; these mutants also overcome silencing of the URA3 reporter. The degree to which silencing is suppressed correlates with SUB2 RNA and protein levels. Additionally, we find that Sub2p localizes to the telomeres, as determined by chromatin immunoprecipitation assays, suggesting that Sub2p has a direct effect at telomeres. Genome‐wide analysis of transcripts was used to assess whether Sub2p overproduction affects only the silenced URA3 reporter gene, or whether other subtelomeric genes are also affected. Of the 70 RNA transcripts elevated in the Sub2p overexpressing cells, 28% are encoded by subtelomeric genes that are located within 5 Kbp of a core X or Y′ repeat. The remainder of the transcripts clustered into several functional groups, including the iron homeostasis pathway, purine nucleotide metabolism, and miscellaneous transport genes, among others. These results suggest a targeted effect of Sub2p on transcription. Our results also confirm that Sub2p affects heterochromatic gene expression, similar to that observed with the Drosophila Hel25E homologue. The above observations imply that Sub2p affects chromatin structure in addition to, or in parallel with, its functions in transcription elongation, splicing and mRNA transport. Copyright © 2005 John Wiley & Sons, Ltd.
The ubiquitin ligase SCFGrr1 is necessary for pheromone sensitivity in Saccharomyces cerevisiae
Authors: Schweitzer Kelly , Cocklin Ross , Garrett Lisa , Desai Falguni , Goebl Mark
Published: June 2005

The presence of the appropriate pheromone induces α and a cells of the yeast Saccharomyces cerevisiae to activate both changes in transcriptional expression and cell polarity that eventually lead to the mating of α and a cells to form a/α diploid cells. A third response after exposure to mating pheromone is a transient cell cycle arrest, allowing synchronization of the two cell types in G1 prior to cell fusion. At least in part, this cell cycle arrest requires the inactivation of Cln‐kinase activity through transcriptional inactivation of the CLN1 and CLN2 genes, degradation of the Cln proteins and direct inhibition of Cln‐kinase complexes. Here we report that GRR1, which encodes a substrate recognition subunit of SCF complexes, is critical for pheromone sensitivity and likely for this arrest. Loss of SCFGrr1 function by deletion of the GRR1 gene causes pheromone resistance. However, deletion of CLN1 and CLN2 restores pheromone sensitivity to grr1Δ cells. Thus, rapid loss of Cln‐kinase activity during mating may require coordinated inactivation of the Cln‐kinase complexes, inactivation of CLN transcription and SCFGrr1‐dependent Cln degradation. Copyright © 2005 John Wiley & Sons, Ltd.
Riparian vegetation loss, stream channelization, and web‐weaving spiders in northern Japan
Authors: Laeser Scott R. , Baxter Colden V. , Fausch Kurt D.
Published: June 2005

Removal of riparian vegetation and straightening of stream channels (channelization) are the most prevalent forms of habitat degradation in streams and their riparian zones. Both have direct effects on organisms in the habitats where they occur, but also have potential to cause indirect effects by interrupting the flux of invertebrate prey between the two adjacent ecosystems. We measured abundance of web‐building riparian spiders along four types of streams in Hokkaido, Japan: relatively undisturbed streams, streams where riparian vegetation had been removed, previously channelized streams where the banks had revegetated, and streams that had been both channelized and had the vegetation removed. Spider abundance was reduced by 70% or more by either habitat disturbance alone, or both combined, and the number of spider families was also reduced. Spiders of the family Tetragnathidae, which specialize in capturing adult insects emerging from streams, were strongly reduced by either form of habitat degradation alone, or in combination. In contrast, abundance of spiders in other families that capture prey from both terrestrial and aquatic sources was reduced more strongly by vegetation loss than channelization. These results indicate that riparian vegetation loss has strong direct effects on spiders by reducing habitat for web sites. They also suggest that channelization can have strong indirect effects on riparian‐specialist tetragnathid spiders, probably by reducing the flux of adult aquatic insects from the stream to the riparian zone.
Patterns of Hand Fractures and Dislocations in A District General Hospital
Authors: PACKER G. J. , SHAHEEN M. A.
Published: June 2005

In a retrospective survey of patients with fractures and dislocations attending the Accident department of a District General hospital, comparison was made between patients with fractures and dislocations in the hand and fractures and dislocations of other sites.

Patients with hand injuries accounted for 28% of the total patients seen. They were more likely than other fracture patients to be male and between the ages of 10 and 40 years. Almost a quarter of hand injuries attended on Monday.

Leisure activities outside the home formed the commonest aetiological factor. Only 66% of patients with hand injuries attended the Accident department within 24 hours of injury. The little finger was the commonest site of injury.

This survey emphasizes the differences between hand injuries and injuries of other sites, identifies the risk factors for hand injuries and has implications for the management of hand injuries in a District General Hospital.
JAK—STAT signaling pathway in pulmonary arterial smooth muscle cells is activated by hypoxia
Authors: Wang Guan‐Song , Qian Gui‐Sheng , Zhou De‐Shan , Zhao Ji‐Qing
Published: June 2005

Pulmonary arterial smooth muscle cells (PASMC) were divided into a normoxic group (N), 2, 8 and 12 h hypoxic groups (H2, H8 and H12) and an AG490 plus 8 h hypoxic group (AG490). The expression of JAK1, JAK2, JAK3 and TYK2 mRNA was analyzed by reverse transcription‐polymerase chain reaction (RT‐PCR). STAT1 and STAT3 protein expressions were determined by Western blotting. The results showed that the levels of JAK1, JAK2 and JAK3 mRNA did not change significantly in the N group but were increased after 2 h exposure to hypoxia. JAK1, JAK2 and JAK3 mRNA expressions peaked at 8 h. It decreased at 12 h but remained above those in the N group. TYK2 mRNA was not found in either hypoxic or normal PASMC. The phospho‐STAT1 and ‐STAT3 protein levels increased after 2 h exposure to hypoxia. They were about 2.8 and 4.1 times the N group, respectively, after 8 h. They decreased at 12 h but remained above those in the N group. AG490 inhibited phospho‐STAT3 protein expression by about 25.5% at 8 h but did not block the expression of phospho‐STAT1 protein. These findings suggest that hypoxia induces the expression of JAK1, JAK2, JAK3 and phospho‐STAT1 and ‐STAT3 in PASMC. Hypoxia activates the JAKs—STATs signaling pathway, which may participate in the pathogenesis of hypoxic PASMC injury.
Pathways to caspase activation
Authors: Wang Zi‐Bing , Liu Yu‐Qing , Cui Yu‐Fang
Published: June 2005

Apoptosis or programmed cell death is an active form of cell death which is essential for tissue homeostasis. Many proteins are involved in the molecular signal transduction of apoptosis. The caspase enzymes, a family of specific cysteine proteases, play a central role in cell death machinery. In this review, we mainly discuss the current understanding of several pathways to activate caspases and some key proteins related to these pathways.
A crevice adjoining the ribosome tunnel: Hints for cotranslational folding
Authors: Amit Maya , Berisio Rita , Baram David , Harms Joerg , Bashan Anat , Yonath Ada
Published: June 2005

RNA protection experiments and the crystal structure of a complex of the large ribosomal subunit from the eubacterium Deinococcus radiodurans with rapamycin, a polyketide compound resembling macrolides and ketolides, showed that rapamycin binds to a crevice located at the boundaries of the nascent protein exit tunnel, near its entrance. At this location rapamycin cannot occlude the ribosome exit tunnel, consistent with its failure to act as a ribosomal antibiotic drug. In accord with recent biochemical data, this crevice may play a role in facilitating local cotranslational folding of nascent chains, in particular for transmembrane proteins.
Second nature: Biological functions of the Raf‐1 “kinase”
Authors: Baccarini Manuela
Published: June 2005

More than 20 years ago, Raf was discovered as a cellular oncogene transduced by transforming retroviruses. Since then, the three Raf isoforms have been intensively studied, mainly as the kinases linking Ras to the MEK/ERK signaling module. As this pathway is activated in human cancer, the Raf kinases are considered promising therapeutic targets, and we have learned a lot about their regulation, targets, and functions. Do they still hold surprises? Recent gene targeting studies indicate that they do. This review focuses on the regulation and biology of the best‐studied Raf isoform, Raf‐1, in the context of its kinase‐independent functions.
At the pulse of time: protein interactions determine the pace of circadian clocks
Authors: Schöning Jan C. , Staiger Dorothee
Published: June 2005

Circadian clocks, internal timekeepers that generate a daily rhythmicity, help organisms to be prepared for periodic environmental changes of light and temperature. These molecular clocks are transcriptional feedback loops that generate 24‐h oscillations in the abundance of clock proteins. For the maintenance of this rhythm inside the core clockwork and for its transmission to downstream genes the clock proteins additionally rely on post‐transcriptional and post‐translational mechanisms. Thus clock proteins engage in a variety of interactions with DNA, RNA and other proteins. Based on the model organisms Drosophila melanogaster and Arabidopsis thaliana molecular principles of circadian clocks are discussed in this review.
Oncogenic breakdowns in endocytic adaptor proteins
Authors: Crosetto Nicola , Tikkanen Ritva , Dikic Ivan
Published: June 2005

Endocytosis is a versatile tool to regulate the intensity, localization, half‐life and function of signaling complexes (signalosomes) that form in cells upon binding of growth factors, cytokines and morphogens to their cognate receptors. Endocytic adaptors are non‐catalytic proteins that assemble effectors and structural components of the endocytic machinery around the trafficking cargo and serve as scaffolds for signalosomes, which in turn modify their location and activity by various post‐translational modifications. We discuss how breakdowns in the function of endocytic adaptors might facilitate impairment of tissue homeostasis and consequent tumor development.
MafA transcription factor is phosphorylated by p38 MAP kinase
Authors: Sii-Felice Karine , Pouponnot Celio , Gillet Sylvie , Lecoin Laure , Girault Jean-Antoine , Eychène Alain , Felder-Schmittbuhl Marie-Paule
Published: June 2005

Basic‐leucine zipper transcription factors of the Maf family are key regulators of various developmental and differentiation processes. We previously reported that the phosphorylation status of MafA is a critical determinant of its biological functions. Using Western blot and mass spectrometry analysis, we now show that MafA is phosphorylated by p38 MAP kinase and identify three phosphoacceptor sites: threonine 113 and threonine 57, evolutionarily conserved residues located in the transcription activating domain, and serine 272. Mutation of these residues severely impaired MafA biological activity. Furthermore, we show that p38 also phosphorylates MafB and c‐Maf. Together, these findings suggest that the p38 MAP kinase pathway is a novel regulator of large Maf transcription factors.
Tubulin cofactor A gene silencing in mammalian cells induces changes in microtubule cytoskeleton, cell cycle arrest and cell death
Authors: Nolasco Sofia , Bellido Javier , Gonçalves João , Zabala Juan Carlos , Soares Helena
Published: June 2005

Microtubules are polymers of α/β‐tubulin participating in essential cell functions. A multistep process involving distinct molecular chaperones and cofactors produces new tubulin heterodimers competent to polymerise. In vitro cofactor A (TBCA) interacts with β‐tubulin in a quasi‐native state behaving as a molecular chaperone. We have used siRNA to silence TBCA expression in HeLa and MCF‐7 mammalian cell lines. TBCA is essential for cell viability and its knockdown produces a decrease in the amount of soluble tubulin, modifications in microtubules and G1 cell cycle arrest. In MCF‐7 cells, cell death was preceded by a change in cell shape resembling differentiation.
An archaeal SET domain protein exhibits distinct lysine methyltransferase activity towards DNA‐associated protein MC1‐α
Authors: Manzur Karishma L. , Zhou Ming-Ming
Published: June 2005

The evolutionarily conserved SET domain proteins in eukaryotes have been shown to function as site‐specific histone lysine methyltransferases, and play an important role in regulating chromatin‐mediated gene transcriptional activation and silencing. Structure‐based sequence analysis has revealed that SET domains are also encoded by viruses and bacteria, as well as Archaea. However, their cellular functions remain elusive. In this study, we have characterized a SET domain protein from Methanosarcina mazei strain Gö1 that we refer to as Gö1‐SET. We show that Gö1‐SET exists as a homodimer in solution, and functions as a lysine methyltransferase with high substrate specificity that is dependent on the amino acid sequence flanking the lysine methylation site. Particularly, Gö1‐SET exhibits selective methyltransferase activity towards one of the major archaeal DNA interacting protein MC1‐α at lysine 37. Our findings suggest that SET domain proteins such as Gö1‐SET may restructure archaeal chromatin that is composed of MC1–DNA complexes, and that modulation of chromatin structure by lysine methylation may have arisen before the divergence of the archaeal and eukaryotic lineages.
Involvement of circadian clock gene Clock in diabetes‐induced circadian augmentation of plasminogen activator inhibitor‐1 (PAI‐1) expression in the mouse heart
Authors: Oishi Katsutaka , Ohkura Naoki , Amagai Noriko , Ishida Norio
Published: June 2005

Diabetes is associated with an excess risk of cardiac events, and one of the risk factors for infarction is the elevated‐levels of plasminogen activator inhibitor‐1 (PAI‐1). To evaluate how the molecular clock mechanism is involved in the diabetes‐induced circadian augmentation of PAI‐1 gene expression, we examined the expression profiles of PAI‐1 mRNA in the hearts of Clock mutant mice with streptozotocin‐induced diabetes. Circadian expression of PAI‐1 mRNA was blunted to low levels under both normal and diabetic conditions in Clock mutant mice, although the expression rhythm was augmented in diabetic wild‐type (WT) mice. Furthermore, plasma PAI‐1 levels became significantly higher in WT mice than in Clock mutant mice after STZ administration. Our results suggested that the circadian clock component, CLOCK, is involved in the diabetes‐induced circadian augmentation of PAI‐1 expression in the mouse heart.
Impaired nuclear translocation of CAR in hepatic preneoplastic lesions: Association with an attenuated CYP2B induction by phenobarbital
Authors: Numazawa Satoshi , Shindo Sawako , Maruyama Keiji , Chibana Fumika , Kawahara Yosuke , Ashino Takashi , Tanaka Sachiko , Yoshida Takemi
Published: June 2005

Phenobarbital (PB) induction of CYP2B, a representative target gene of constitutive androstane receptor (CAR), has been observed to be attenuated in preneoplastic lesions of rat liver; however, molecular basis for this attenuation is poorly understood. In this report, we provide evidence indicating that the CAR expressed in the hepatic preneoplastic lesions of rats and mice was resistant to nuclear translocation and transactivation of the PB‐responsive enhancer module upon PB treatment. These observations suggest that the attenuation of the induction of CYP2B by PB in hepatic preneoplastic lesions is evidently a consequence of impaired nuclear translocation of CAR.