bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia
Authors: Oehler Vivian G. , Gooley Ted , Snyder David S. , Johnston Laura , Lin Allen , Cummings Carrie C. , Chu Su , Bhatia Ravi , Forman Stephen J. , Negrin Robert S. , Appelbaum Frederick R. , Radich Jerald P.
Published: October 2006

The impact of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) on subsequent allogeneic transplantation is uncertain. To better understand this relationship, we retrospectively compared 145 patients with CML receiving IM for a minimum of 3 months before allogeneic hematopoietic cell transplantation (HCT) to 231 patients with CML who did not. IM treatment was associated with no increase in early hepatotoxicity or engraftment delay after HCT compared with the historical cohort. In addition, there was no statistically significant difference in the IM-treated cohort compared with the historical cohort with regard to overall survival, disease-free survival, relapse, and nonrelapse mortality. For chronic-phase (CP) patients, IM response prior to HCT was associated with post-HCT outcome. Patients who underwent transplantation in CP with a suboptimal response or a loss of response on IM had a statistically significant higher hazard of mortality when compared with CP patients who achieved a complete cytogenetic response (CCR) or major cytogenetic response (MCR) on IM (HR = 5.31, 95% confidence interval [CI] 1.13-25.05, P = .03). These data indicate that pre-HCT IM is not associated with increased transplant-related morbidity (TRM) or poorer outcomes. However, patients with a suboptimal or loss of IM response before HCT do worse, suggesting a more aggressive disease course for these patients.
Modulation of glutaredoxin in the lung and sputum of cigarette smokers and chronic obstructive pulmonary disease
Authors: Peltoniemi Mirva J , Rytilä Paula H , Harju Terttu H , Soini Ylermi M , Salmenkivi Kaisa M , Ruddock Lloyd W , Kinnula Vuokko L
Published: October 2006

Background

One typical feature in chronic obstructive pulmonary disease (COPD) is the disturbance of the oxidant/antioxidant balance. Glutaredoxins (Grx) are thiol disulfide oxido-reductases with antioxidant capacity and catalytic functions closely associated with glutathione, the major small molecular weight antioxidant of human lung. However, the role of Grxs in smoking related diseases is unclear.

Methods

Immunohistochemical and Western blot analyses were conducted with lung specimens (n = 45 and n = 32, respectively) and induced sputum (n = 50) of healthy non-smokers and smokers without COPD and at different stages of COPD.

Results

Grx1 was expressed mainly in alveolar macrophages. The percentage of Grx1 positive macrophages was significantly lower in GOLD stage IV COPD than in healthy smokers (p = 0.021) and the level of Grx1 in total lung homogenate decreased both in stage I–II (p = 0.045) and stage IV COPD (p = 0.022). The percentage of Grx1 positive macrophages correlated with the lung function parameters (FEV1, r = 0.45, p = 0.008; FEV1%, r = 0.46, p = 0.007, FEV/FVC%, r = 0.55, p = 0.001). Grx1 could also be detected in sputum supernatants, the levels being increased in the supernatants from acute exacerbations of COPD compared to non-smokers (p = 0.013) and smokers (p = 0.051).

Conclusion

The present cross-sectional study showed that Grx1 was expressed mainly in alveolar macrophages, the levels being decreased in COPD patients. In addition, the results also demonstrated the presence of Grx1 in extracellular fluids including sputum supernatants. Overall, the present study suggests that Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung.
Nuclear envelope transmembrane proteins (NETs) that are up-regulated during myogenesis
Authors: Chen I-Hsiung Brandon , Huber Michael , Guan Tinglu , Bubeck Anja , Gerace Larry
Published: October 2006

Background

The nuclear lamina is a protein meshwork lining the inner nuclear membrane, which contains a polymer of nuclear lamins associated with transmembrane proteins of the inner nuclear membrane. The lamina is involved in nuclear structure, gene expression, and association of the cytoplasmic cytoskeleton with the nucleus. We previously identified a group of 67 novel putative nuclear envelope transmembrane proteins (NETs) in a large-scale proteomics analysis. Because mutations in lamina proteins have been linked to several human diseases affecting skeletal muscle, we examined NET expression during differentiation of C2C12 myoblasts. Our goal was to identify new nuclear envelope and lamina components whose expression is coordinated with muscle differentiation.

Results

Using transcriptional microarray analysis, we found that expression of 6 of the NETs significantly increases during myoblast differentiation. We confirmed these results using quantitative RT-PCR, and furthermore, found that all 6 NETs are expressed at high levels in adult mouse skeletal muscle relative to 9 other tissues examined. Using epitope-tagged cDNAs, we determined that the 5 NETs we could analyze (NETs 9, 25, 32, 37 and 39) all target to the nuclear envelope in C2C12 cells. Furthermore, the 3 NETs that we could analyze by immunoblotting were highly enriched in nuclear envelopes relative to microsomal membranes purified from mouse liver. Database searches showed that 4 of the 6 up-regulated NETs contain regions of homology to proteins previously linked to signaling.

Conclusion

This work identified 6 NETs that are predicted to have important functions in muscle development and/or maintenance from their expression patterns during myoblast differentiation and in mouse tissues. We confirmed that 5 of these NETs are authentic nuclear envelope proteins. Four members of this group have potential signaling functions at the NE, based on their sequence homologies.
Functional role of aspartic proteinase cathepsin D in insect metamorphosis
Authors: Gui Zhong Zheng , Lee Kwang Sik , Kim Bo Yeon , Choi Yong Soo , Wei Ya Dong , Choo Young Moo , Kang Pil Don , Yoon Hyung Joo , Kim Iksoo , Je Yeon Ho , Seo Sook Jae , Lee Sang Mong , Guo Xijie , Sohn Hung Dae , Jin Byung Rae
Published: October 2006

Background

Metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. Here we show a novel functional role for the aspartic proteinase cathepsin D during insect metamorphosis.

Results

Cathepsin D of the silkworm Bombyx mori (BmCatD) was ecdysone-induced, differentially and spatially expressed in the larval fat body of the final instar and in the larval gut of pupal stage, and its expression led to programmed cell death. Furthermore, BmCatD was highly induced in the fat body of baculovirus-infected B. mori larvae, suggesting that this gene is involved in the induction of metamorphosis of host insects infected with baculovirus. RNA interference (RNAi)-mediated BmCatD knock-down inhibited programmed cell death of the larval fat body, resulting in the arrest of larval-pupal transformation. BmCatD RNAi also inhibited the programmed cell death of larval gut during pupal stage.

Conclusion

Based on these results, we concluded that BmCatD is critically involved in the programmed cell death of the larval fat body and larval gut in silkworm metamorphosis.
SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers
Authors: Chia June A , Simms Lisa A , Cozzi Sarah-Jane , Young Joanne , Jass Jeremy R , Walsh Michael D , Spring Kevin J , Leggett Barbara A , Whitehall Vicki LJ
Published: October 2006

Background

SnoN is an important regulator of the transforming growth factor beta (TGFβ) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity.

Methods

To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis.

Results

Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P ≤ 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFβRII gene (P ≤ 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFβ signalling.

Conclusion

Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions.
Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma
Authors: Lázcoz Paula , Muñoz Jorge , Nistal Manuel , Pestaña Ángel , Encío Ignacio , Castresana Javier S
Published: October 2006

Background

Epigenetic alterations and loss of heterozygosity are mechanisms of tumor suppressor gene inactivation. A new carcinogenic pathway, targeting the RAS effectors has recently been documented. RASSF1A, on 3p21.3, and NORE1A, on 1q32.1, are among the most important, representative RAS effectors.

Methods

We screened the 3p21 locus for the loss of heterozygosity and the hypermethylation status of RASSF1A, NORE1A and BLU (the latter located at 3p21.3) in 41 neuroblastic tumors. The statistical relationship of these data was correlated with CASP8 hypermethylation. The expression levels of these genes, in cell lines, were analyzed by RT-PCR.

Results

Loss of heterozygosity and microsatellite instability at 3p21 were detected in 14% of the analyzed tumors. Methylation was different for tumors and cell lines (tumors: 83% in RASSF1A, 3% in NORE1A, 8% in BLU and 60% in CASP8; cell lines: 100% in RASSF1A, 50% in NORE1A, 66% in BLU and 92% in CASP8). In cell lines, a correlation with lack of expression was evident for RASSF1A, but less clear for NORE1A, BLU and CASP8. We could only demonstrate a statistically significant association between hypermethylation of RASSF1A and hypermethylation of CASP8, while no association with MYCN amplification, 1p deletion, and/or aggressive histological pattern of the tumor was demonstrated.

Conclusion

1) LOH at 3p21 appears in a small percentage of neuroblastomas, indicating that a candidate tumor suppressor gene of neuroblastic tumors is not located in this region.

2) Promoter hypermethylation of RASSF1A and CASP8 occurs at a high frequency in neuroblastomas.
Structure of vaccinia virus thymidine kinase in complex with dTTP: insights for drug design
Authors: El Omari Kamel , Solaroli Nicola , Karlsson Anna , Balzarini Jan , Stammers David K
Published: October 2006

Background

Development of countermeasures to bioterrorist threats such as those posed by the smallpox virus (variola), include vaccination and drug development. Selective activation of nucleoside analogues by virus-encoded thymidine (dThd) kinases (TK) represents one of the most successful strategies for antiviral chemotherapy as demonstrated for anti-herpes drugs. Vaccinia virus TK is a close orthologue of variola TK but also shares a relatively high sequence identity to human type 2 TK (hTK), thus achieving drug selectivity relative to the host enzyme is challenging.

Results

In order to identify any differences compared to hTK that may be exploitable in drug design, we have determined the crystal structure of VVTK, in complex with thymidine 5'-triphosphate (dTTP). Although most of the active site residues are conserved between hTK and VVTK, we observe a difference in conformation of residues Asp-43 and Arg-45. The equivalent residues in hTK hydrogen bond to dTTP, whereas in subunit D of VVTK, Asp-43 and Arg-45 adopt a different conformation preventing interaction with this nucleotide. Asp-43 and Arg-45 are present in a flexible loop, which is disordered in subunits A, B and C. The observed difference in conformation and flexibility may also explain the ability of VVTK to phosphorylate (South)-methanocarbathymine whereas, in contrast, no substrate activity with hTK is reported for this compound.

Conclusion

The difference in conformation for Asp-43 and Arg-45 could thus be used in drug design to generate VVTK/Variola TK-selective nucleoside analogue substrates and/or inhibitors that have lower affinity for hTK.
Too much data, but little inter-changeability: a lesson learned from mining public data on tissue specificity of gene expression
Authors: Li Shuyu , Li Yiqun Helen , Wei Tao , Su Eric Wen , Duffin Kevin , Liao Birong
Published: October 2006

Background

The tissue expression pattern of a gene often provides an important clue to its potential role in a biological process. A vast amount of gene expression data have been and are being accumulated in public repository through different technology platforms. However, exploitations of these rich data sources remain limited in part due to issues of technology standardization. Our objective is to test the data comparability between SAGE and microarray technologies, through examining the expression pattern of genes under normal physiological states across variety of tissues.

Results

There are 42–54% of genes showing significant correlations in tissue expression patterns between SAGE and GeneChip, with 30–40% of genes whose expression patterns are positively correlated and 10–15% of genes whose expression patterns are negatively correlated at a statistically significant level (p = 0.05). Our analysis suggests that the discrepancy on the expression patterns derived from technology platforms is not likely from the heterogeneity of tissues used in these technologies, or other spurious correlations resulting from microarray probe design, abundance of genes, or gene function. The discrepancy can be partially explained by errors in the original assignment of SAGE tags to genes due to the evolution of sequence databases. In addition, sequence analysis has indicated that many SAGE tags and Affymetrix array probe sets are mapped to different splice variants or different sequence regions although they represent the same gene, which also contributes to the observed discrepancies between SAGE and array expression data.

Conclusion

To our knowledge, this is the first report attempting to mine gene expression patterns across tissues using public data from different technology platforms. Unlike previous similar studies that only demonstrated the discrepancies between the two gene expression platforms, we carried out in-depth analysis to further investigate the cause for such discrepancies. Our study shows that the exploitation of rich public expression resource requires extensive knowledge about the technologies, and experiment. Informatic methodologies for better interoperability among platforms still remain a gap. One of the areas that can be improved practically is the accurate sequence mapping of SAGE tags and array probes to full-length genes.

Reviewers

This article was reviewed by Dr. I. King Jordan, Dr. Joel Bader, and Dr. Arcady Mushegian.
An enhanced RNA alignment benchmark for sequence alignment programs
Authors: Wilm Andreas , Mainz Indra , Steger Gerhard
Published: October 2006

Background

The performance of alignment programs is traditionally tested on sets of protein sequences, of which a reference alignment is known. Conclusions drawn from such protein benchmarks do not necessarily hold for the RNA alignment problem, as was demonstrated in the first RNA alignment benchmark published so far. For example, the twilight zone – the similarity range where alignment quality drops drastically – starts at 60 % for RNAs in comparison to 20 % for proteins. In this study we enhance the previous benchmark.

Results

The RNA sequence sets in the benchmark database are taken from an increased number of RNA families to avoid unintended impact by using only a few families. The size of sets varies from 2 to 15 sequences to assess the influence of the number of sequences on program performance. Alignment quality is scored by two measures: one takes into account only nucleotide matches, the other measures structural conservation. The performance order of parameters – like nucleotide substitution matrices and gap-costs – as well as of programs is rated by rank tests.

Conclusion

Most sequence alignment programs perform equally well on RNA sequence sets with high sequence identity, that is with an average pairwise sequence identity (APSI) above 75 %. Parameters for gap-open and gap-extension have a large influence on alignment quality lower than APSI ≤ 75 %; optimal parameter combinations are shown for several programs. The use of different 4 × 4 substitution matrices improved program performance only in some cases. The performance of iterative programs drastically increases with increasing sequence numbers and/or decreasing sequence identity, which makes them clearly superior to programs using a purely non-iterative, progressive approach. The best sequence alignment programs produce alignments of high quality down to APSI > 55 %; at lower APSI the use of sequence+structure alignment programs is recommended.
The generation and function of soluble apoE receptors in the CNS
Authors: Rebeck G William , LaDu Mary Jo , Estus Steven , Bu Guojun , Weeber Edwin J
Published: October 2006

More than a decade has passed since apolipoprotein E4 (APOE-ε4) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein system integrates into the puzzle of AD etiology. The specific pathological actions of apoE4, methods of modulating apolipoprotein E4-associated risk, and possible roles of apoE in normal synaptic function are still being debated. These critical questions will never be fully answered without a complete understanding of the life cycle of the apolipoprotein receptors that mediate the uptake, signaling, and degradation of apoE. The present review will focus on apoE receptors as modulators of apoE actions and, in particular, explore the functions of soluble apoE receptors, a field almost entirely overlooked until now.
Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population
Authors: Lee Sang-Hoon , Lee Yeon-Ah , Woo Doo-Hyun , Song Ran , Park Eun-Kyung , Ryu Mi-Hyun , Kim Young-Hoon , Kim Kyoung-Soo , Hong Seung-Jae , Yoo Myung Chul , Yang Hyung-In
Published: October 2006

The PD-1 (programmed death 1) molecule is a negative regulator of T cells.PDCD1(programmed cell death 1) has been reported to have a genetic association in systemic lupus erythematosus and rheumatoid arthritis in Caucasians. However, there are no reports on the association between this gene and ankylosing spondylitis (AS). The present study investigated the association of the PD-1 polymorphisms and the haplotypes with AS in a Korean population sample. In a case-control association study, two single-nucleotide polymorphisms, PD-1.5 C/T and PD-1.9 T/C, were genotyped in 95 AS patients and 130 healthy controls. The T allele of the PD-1.9 polymorphism was more frequent in the Korean male population with AS than in the Korean male controls (21.0% versus 6.9%, odds ratio 1.89, 95% confidence interval 1.483 to 2.408). The frequency of the CT haplotype (PD-1.5 C/T and PD-1.9 T/C) was higher in the AS patients (19%) than the controls (5.4%) (odds ratio 1.83, 95% confidence interval 1.559 to 2.521). The PD-1 polymorphism was demonstrated in Korean AS patients. The results suggest a genetic association between the PD-1 polymorphism and susceptibility to AS.
Prognostic Parameters of Metastatic Adrenocortical Carcinoma
Authors: Assié Guillaume , Antoni Guillemette , Tissier Frédérique , Caillou Bernard , Abiven Gwenaelle , Gicquel Christine , Leboulleux Sophie , Travagli Jean-Paul , Dromain Clarisse , Bertagna Xavier , Bertherat Jérôme , Schlumberger Martin , Baudin Eric
Published: October 2006

Context: Prognostic parameters of metastatic adrenocortical carcinoma (ACC) are poorly characterized.

Objective: The objective of the study was to describe the clinical presentation of metastatic ACC and determine prognostic factors for survival.

Design: This was a retrospective cohort study (1988–2004).

Setting: The study was conducted in an institutional practice.

Patients: Participants included 124 consecutive patients with metastatic ACC, 70 from Gustave-Roussy Institute (main cohort) and 54 patients from the Cochin Hospital (validation cohort). Clinical data concerning all patients, histopathologic slides of primary tumors (44 in the main cohort and 40 in the validation cohort), and molecular biology data on 15 primary tumors (main cohort) were analyzed.

Intervention: There was no intervention.

Main Outcome: The main outcome was the specific survival after discovery of the first metastasis (Kaplan-Meier method). This included univariate analysis on the main cohort, confirmed on the validation cohort and then analyzed in a multivariate analysis.

Results: In the main cohort, overall median survival was 20 months. In univariate analysis, the presence of hepatic and bone metastases, the number of metastatic lesions and the number of tumoral organs at the time of the first metastasis, a high mitotic rate (>20 per 50 high-power field), and atypical mitoses in the primary tumor predicted survival (P = 0.05, 0.003, 0.046, 0.001, 0.01, and < 0.001, respectively). The number of tumoral organs and a high mitotic rate were confirmed on the validation cohort (P = 0.009 and 0.03, respectively). These two parameters were confirmed in multivariate analysis (P = 0.0058 and 0.049).

Conclusion: Metastatic ACC is a heterogeneous disease with poor outcome. The combination of the number of tumoral organs at the time of the first metastasis and the mitotic rate can predict different outcomes.
Atherogenic Lipoprotein Phenotype and Low-Density Lipoproteins Size and Subclasses in Women with Polycystic Ovary Syndrome
Authors: Berneis Kaspar , Rizzo Manfredi , Lazzaroni Veronica , Fruzzetti Franca , Carmina Enrico
Published: October 2006

Context: An altered lipid profile is common in polycystic ovary syndrome (PCOS) and is usually characterized by increased triglycerides and low high-density lipoprotein (HDL)-cholesterol levels. In the general population, these alterations are often associated with the increase of small low-density lipoproteins (LDLs) in the so-called “atherogenic lipoprotein phenotype” (ALP) that determines a further increase of cardiovascular risk. In this study, we evaluated the presence of ALP in the plasma of women with PCOS.

Setting: Measurements and analysis of LDL size were performed at the Clinic of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital, Zurich. PCOS patients were recruited at the Department of Clinical Medicine, University of Palermo, and the Department of Obstetrics and Gynecology, University of Pisa.

Patients: Thirty patients with PCOS (hyperandrogenism and chronic anovulation) and 24 matched controls were studied. Anthropometric data, blood glucose, serum insulin lipid profile, and LDL size and subclasses were evaluated.

Results: Compared with controls, patients with PCOS had higher plasma concentrations of insulin and triglycerides and lower HDL-cholesterol concentrations but no differences in LDL-cholesterol and total cholesterol. Patients with PCOS had smaller LDL size due to a reduction in LDL subclass I, with a concomitant increase in LDL subclasses III and IV. Fourteen PCOS patients had an increase of smaller LDL particles, and it represented the second most common lipid alteration after decrease in HDL-cholesterol. However, because in this PCOS population hypertriglyceridemia was only present in two patients, complete ALP was relatively uncommon.

Conclusions: Increase of type III or type IV LDL subclasses is a common finding in PCOS and represents the second most common lipid alteration after HDL-cholesterol decrease. However, in our PCOS patients, because of relatively low triglyceride levels, complete ALP is uncommon.
Methylation of histone H3 at Lys4 differs between paternal and maternal chromosomes inSciara ocellarisgermline development
Authors: Greciano Patricia G. , Goday Clara
Published: October 2006

An outstanding example of programmed chromosome elimination and genomic imprinting is found in sciarid flies (Diptera, Sciaridae), where whole chromosomes of paternal origin are selectively discarded from the genome during development. In early germ cells a single paternal X chromosome is eliminated in embryos of both sexes and in male meiotic cells the whole paternal complement is discarded. In sciarids, differential acetylation of histones H3 and H4 occurs between chromosomes of different parental origin, both in early germ nuclei and in male meiotic cells (Goday and Ruiz, 2002). We here investigated histone methylation modifications between chromosomes in germline cells of Sciara ocellaris. In early germ nuclei, maternal chromosomes show high levels of di- and trimethylated histone H3 at Lys4, whereas this histone modification is not detected in paternal chromosomes. In male meiosis, only the eliminated paternal chromosomes exhibit high levels of di- and trimethylated histones H3 at Lys4 and dimethylated H4 at Lys20. In early germ nuclei, RNA polymerase II associates to maternally-derived chromosomes but lacks phosphorylation of the C-terminal domain on Ser2. We found that histone H3 methylation at Lys4 does not correlate with transcriptional activity in early Sciara germline nuclei. The results support the conclusion that specific covalent chromatin modifications are involved in the imprinted behaviour of germline chromosomes in Sciara.
Heat transfer modelling of rail thermite welding
Authors: Chen Y , Lawrence F V , Barkan C P L , Dantzig J A
Published: October 2006

Rail thermite (or Thermit®) welding is a valuable welding technology for the railway industry because of its simplicity, portability, and economy. Using the finite-element method, a heat transfer analysis is conducted in this study. Only the heat transfer by conduction was simulated explicitly in the model, the other thermally significant phenomena were included through the boundary and initial conditions. Despite these simplifications, the model can be used to analyse the thermal conditions during thermite welding with sufficient accuracy. The predicted temperature history, weld deposit, and HAZ profiles were in good agreement with the experimental measurements in laboratory welds. It is found that the weld gap is the most influential welding parameter for rail thermite welding. A wider-gap weld appears to be less sensitive to chance variations in the other welding parameters, and therefore fairly consistent thermal conditions can be obtained.
Simulated comparisons of wagon coupler systems in heavy haul trains
Authors: Cole C , Sun Y Q
Published: October 2006

Three types of wagon connection coupling systems are evaluated in a train simulation model consisting of 107 vehicles. The three wagon connection coupling systems are auto-couplers with standard draft gears, auto-couplers with draft gears with wedge unlocking features, and the traditional drawhook buffer system. The train is made up of 103 wagons and 4 locomotives. The locomotives are placed in groups of two at the head and mid-train positions. Dynamic response and fatigue damage is compared for a control disturbance on a crest and on a flat track section. The effect of coupling-free travel (slack) is also investigated.
Use of a reduced scale model for the study of wheel/rail interaction
Authors: Armstrong T D , Thompson D J
Published: October 2006

The high frequency dynamic interaction of the wheels rolling on the track is a major contributor to the noise generated by railways. By making use of measurements on a reduced scale laboratory facility, it is possible to study the interaction in a more controllable and accessible way than is possible on an operational railway. A one-fifth scale facility is described along with measurement results. Particular problems of measuring at reduced scale are addressed. Particular attention is given to the influence of the contact patch filtering effects on the wheel and rail surface roughness, the wheel and track dynamics, and the decay of vibration along the length of the rail. Comparisons with the results from a simple prediction model show good agreement.
Rail weld geometry and assessment concepts
Authors: Steenbergen M J M M , Esveld C
Published: October 2006

Worldwide, metallurgical rail welds are being geometrically assessed by the principle of vertical deviations satisfying given tolerances, measured with steel straightedges or occasionally with digital/electronic straightedges. In this approach, the geometrical shape of the weld in longitudinal direction has no real influence, although it has a direct relation with the dynamic wheel-rail interaction forces, which are responsible for track deterioration. In this article, different new assessment methods for rail welds are proposed and evaluated in practice, after which a choice is made for the best method. This is done in line with the situation in the Netherlands, where the chosen new method was recently introduced and standardized (2005). The proposed method is based on a limitation of the gradient of the discrete measurement signal, implying a limitation of the wheel-rail dynamic contact force.
Tribological properties of extremely thin protective carbon nitride films deposited on magnetic discs by complex treatment
Authors: Miyake S , Saito T , Wang M , Watanabe S
Published: October 2006

Extremely thin nitrogen-containing carbon (C-N) films with thicknesses of 3, 6, and 9 nm were prepared as a protective overcoat on CoCrTa magnetic discs by complex treatment, including plasma irradiation and C-N reactive sputtering in an atmosphere of nitrogen (N2) and nitrogen and helium (N2 + He) gaseous mixture. Films of various thicknesses were obtained by controlling deposition time. The bonding structure and composition of the film were studied by X-ray photoelectron spectroscopy. A radio frequency power of 25 W was experimentally confirmed to be the optimum plasma irradiation power at which a ratio of magnetic loss is <5 per cent. Nanohardness and elastic modulus of the films were measured by nanoindentation. Wear and oscillation scratch tests were carried out to investigate the wear-resistance property of the films. The improved performance of C-N films is attributed to the high indentation hardness, good wear-resistant property, and corrosion resistance of the coatings due to complex treatment and He addition.
Investigation of gas flow in the rolling element bearing assembly of a centrifugal compressor
Authors: Cui M. M.
Published: October 2006

Combined with the geometric features, the pressure differential and bearing motion define the gas flow through the rolling-element-bearing assembly of a centrifugal compressor. The gas flowfield then affects the oil distribution and heat transfer characteristics of the assembly accordingly. Investigations of the refrigerant gas flow through the rolling element bearing assembly of a centrifugal compressor are presented. A series of cases are studied for different operating conditions. The analyses include the geometric details of the assembly, such as the shaft, races, cages, balls, oil feeding system, and surrounding components. Refrigerant R123 is used as the working fluid. Both detailed three-dimensional flowfield features and integrated parameters are calculated. The interactions between bearing motion and the surrounding structures are characterized. The flow patterns inside the bearings are defined. These results help in gaining an insight into the basic physics that governs the bearing internal mass and heat transfer. The data and techniques developed can be used to design and optimize bearing and oil supply systems for the improvement of lubrication and cooling efficiency.
Effect of water temperature on the adhesion between rail and wheel
Authors: Chen H , Ban T , Ishida M , Nakahara T
Published: October 2006

The effects of factors such as rolling speed, contact load, water temperature, and surface roughness on the adhesion coefficient between wheel and rail under wet conditions were investigated theoretically by adopting elasto-hydrodynamic lubrication theory and rough surfaces contact theory [1]. It was found that the water temperature and the surface roughness greatly affect the adhesion performance comparing the other factors. This paper describes an experimental investigation on the effect of water temperature on the adhesion coefficient to verify the significant effect of the water temperature on the adhesion coefficient. The experimental results indicated that a rise in water temperature causes an increase in the adhesion coefficient, which was qualitatively consistent to the numerically calculated results in the previous paper [1].
Development of a novel metastable composite material
Authors: Bradley G R , MacKenzie P M
Published: October 2006

The development of a new family of mouldable metastable composite materials has been demonstrated. Their special quality is derived from the ability to maintain the matrix as a supercooled liquid or gel whose solidification can be triggered mechanically, as desired, by a user. This article describes some aspects of the development work. In particular, the following are explained: the choice of matrix material; the use of additives to enhance the properties of the matrix; and the selection of reinforcement fibre. As part of the work, some mechanical testing was performed on several variations of a matrix-fibre pair and, to demonstrate the potential of such materials, some comparisons were made with a possible competitor material, a glass-reinforced urethane. It was shown that the metastable material could be formulated to provide mechanical properties that would make it suitable for applications such as orthopaedic casting, splinting and body armour, and in items of sports equipment, these being areas where its mouldability could be particularly desirable.
Genetic and biochemical characterization ofDrosophilaSnipper: A promiscuous member of the metazoan 3′hExo/ERI-1 family of 3′ to 5′ exonucleases
Authors: Kupsco Jeremy M. , Wu Ming-Jing , Marzluff William F. , Thapar Roopa , Duronio Robert J.
Published: October 2006

The DnaQ-H family exonuclease Snipper (Snp) is a 33-kDaDrosophila melanogasterhomolog of 3′hExo and ERI-1, exoribonucleases implicated in the degradation of histone mRNA in mammals and in the negative regulation of RNA interference (RNAi) inCaenorhabditis elegans, respectively. In metazoans, Snp, Exod1, 3′hExo, ERI-1, and the prpip nucleases define a new subclass of structure-specific 3′-5′ exonucleases that bind and degrade double-stranded RNA and/or DNA substrates with 3′ overhangs of 2–5 nucleotides (nt) in the presence of Mg2+with no apparent sequence specificity. These nucleases are also capable of degrading linear substrates. Snp efficiently degrades structured RNA and DNA substrates as long as there exists a minimum 3′ overhang of 2 nt to initiate degradation. We identified aSnpmutant and used it to test whether Snp plays a role in regulating histone mRNA degradation or RNAi in vivo.Snpmutant flies are viable, and display no obvious developmental abnormalities. The expression pattern and level of histone H3 mRNA inSnpmutant embryos and third instar imaginal eye discs was indistinguishable from wild type, suggesting that Snp does not play a significant role in the turnover of histone mRNA at the end of the S phase. The loss ofSnpwas also unable to enhance the silencing capability of two different RNAi transgenes targeting thewhiteandyellowgenes, suggesting that Snp does not negatively modulate RNAi. Therefore, Snp is a nonessential exonuclease that is not a functional ortholog of either 3′hExo or ERI-1.
Brain radiation necrosis following treatment of an esthesioneuroblastoma (olfactory neurocytoma)
Authors: Baron Shirley Harold
Published: October 2006

Esthesioneuroblastoma is an uncommon malignant nasal tumor which may be difficult to diagnose. Once diagnosed, selection of treatment may be a dilemma. Some advocate preoperative radiation and surgery; others, surgery and postoperative radiation if needed. A case that developed brain necrosis from postoperative radiation is presented. It is felt that the possibility exists that the patient might still be living with tumor had irradiation not been given. This is a plea for the conservative approach to treatment. The author agrees with John S. Lewis that it is unwise to use all modalities at once as there is no definite evidence that any one method of treatment or a combination of surgery and irradiation will alter the prognosis. The paper stresses the brain hazards of irradiation.
Prevention of major and minor fistulae after laryngectomy
Authors: Horgan Edwin C. , Dedo Herbert H.
Published: October 2006

Every Head and Neck surgeon has special techniques which he uses to get maximum rates of five‐year survival and minimum fistula formation, especially major fistula and carotid rupture. The literature reflects a wide variation in the rate of fistula formation. We reviewed the senior author's prior 78 total laryngectomies and noted a fistula rate of 10.3% (6.4% minor fistulae and 3.9% major fistulae). We also reviewed contributing factors and discuss surgical techniques designed to minimize fistula formation.
Stability of Vancomycin in Icodextrin Peritoneal Dialysis Solution
Authors: Nornoo Adwoa O , Elwell Rowland J
Published: October 2006

Background:

Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. There are few data regarding the long-term stability of vancomycin in icodextrin PD solution.

Objective:

To determine the chemical stability of vancomycin in icodextrin PD solution in polyvinyl chloride containers over a 7 day period at 4, 24, and 37 °C.

Methods:

Study samples were prepared by adding 2000 mg vancomycin HCl to commercially available 2.0 L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (5 °C), 3 at room temperature (24 °C), and 3 at body temperature (37 °C). Samples were withdrawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of vancomycin in dialysate fluid was determined by high performance liquid chromatography.

Results:

Under refrigeration, a mean ± SD of 99.7% ± 0.5% of the initial vancomycin concentration remained at 168 hours (7 days). At room temperature, 97.5% ± 3.4% remained at 168 hours. At body temperature, 94.3% ± 3.9% remained at 24 hours. Stability was not assessed beyond these time points.

Conclusions:

Premixed vancomycin-icodextrin PD solutions, whether stored refrigerated or at room temperature, were found to be stable for up to 7 days. However, we recommend that these solutions be kept refrigerated whenever possible. Solutions stored at body temperature were stable for up to 24 hours, permitting the practice of prewarming solutions prior to administration.
Formulary Forum Doxercalciferol Treatment of Secondary Hyperparathyroidism
Authors: Dennis Vincent C , Albertson Guy L
Published: October 2006

Objective:

To review the pharmacology, pharmacokinetics, effectiveness, safety, and therapeutic considerations related to the use of doxercalciferol in the treatment of secondary hyperparathyroidism.

Data Sources:

A MEDLINE search (1966–June 2006) was conducted using the key words vitamin D, ergocalciferols, and secondary hyperparathyroidism. Text word searches were also performed for the terms 1-ά-hydroxy-vitamin D2,1-ά-hydroxyergocalciferol, Hectorol, and doxercalciferol. Searches were limited to studies published in English and conducted in human subjects.

Study Selection and Data Extraction:

All published clinical studies evaluating the safety and effectiveness of doxercalciferol in secondary hyperparathyroidism were reviewed, and anecdotal patient reports were also evaluated. Selected clinical studies involving the use of calcitriol and/or paricalcitol in the treatment of secondary hyperparathyroidism were also included.

Data Synthesis:

Doxercalciferol effectively reduces parathyroid hormone levels in patients with chronic kidney disease (CKD). Both oral and intravenous administration can significantly increase serum calcium and/or phosphorus levels as evidenced by placebo-controlled clinical trials. This agent has not been studied comparatively with calcitriol or paricalcitol to assess relative safety.

Conclusions:

Doxercalciferol is approved for and effective in the treatment of secondary hyperparathyroidism related to CKD, both before and during dialysis, but has not demonstrated a lower incidence of hypercalcemia and/or hyperphosphatemia in relation to other vitamin D therapies. The drug is available in both oral and intravenous dosage forms. Doxercalciferol should be maintained as a formulary alternative for patients unresponsive to or intolerant of other vitamin D therapies, but comparative randomized studies are needed to differentiate its place in therapy.
Erlotinib-Induced Breast Cancer Regression
Authors: Catania Chiara , Martino De Pas Tommaso , Pelosi Giuseppe , Manzotti Michela , Adamoli Laura , Nolè Franco , Goldhirsch Aran
Published: October 2006

Objective:

To report a case of erlotinib-induced breast cancer regression.

Case Summary:

A 38-year-old woman developed bilateral locoregional malignant cutaneous lymphangitis following a right subcutaneous mastectomy and 3 months of adjuvant chemotherapy. After several systemic chemotherapy regimens, the lymphangitis worsened rapidly, with progressive skin ulceration. Morphine and dexamethasone were given, with suboptimal pain control. A chemotherapy regimen of gemcitabine and vinorelbine was started. After 2 full-dose administrations, while lymphangitis continued to worsen, erlotinib 150 mg/day was added to the regimen. After 10 weeks of treatment, pain subsided and analgesics were discontinued. Physical examination revealed a partial regression of malignant cutaneous lymphangitis and pulmonary metastases, with resolution of ulceration.

Discussion:

There has been increased interest in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the treatment of breast cancer. Gefitinib has shown a low level of efficacy, while preliminary clinical data on erlotinib were not conclusive and suggested lack of clinical activity. Molecular analysis of the tumor in our patient revealed a profile predictive of response to EGFR selective inhibitors in some patients with lung cancer.

Conclusions:

The addition of erlotinib to our patient's chemotherapy regimen resulted in antitumor activity in breast cancer in which an activated EGFR pathway was demonstrated. This finding is consistent with available preclinical and clinical data on EGFR tyrosine kinase inhibitors across tumor types and supports the efforts to optimize EGFR selective inhibitors in treating breast cancer and other malignancies.
Treatment of Burkitt's Lymphoma During Pregnancy
Authors: Lam Masha SH
Published: October 2006

Objective:

To report a case of both successful maternal treatment outcome and normal fetal outcome in a patient who was diagnosed with Burkitt's lymphoma (BL) and aggressively treated with 6 different chemotherapy agents during the second and third trimesters of pregnancy.

Case Summary:

A 21-year-old white woman was diagnosed with stage II BL of the head and neck at 26 weeks' gestation. She was treated with 2 cycles of systemic intensive polychemotherapy, including cyclophosphamide, vincristine, doxorubicin, cytarabine, etoposide, ifosfamide, mesna, and intrathecal cytarabine with growth factor support during the second and third trimesters. She delivered a healthy, premature boy 6 weeks after diagnosis. At a follow-up 1 year after diagnosis, the patient remained disease-free and the baby remained healthy.

Discussion:

The prognosis of BL depends on the stage at diagnosis, as well as treatment aggressiveness. Previous reports indicate that most patients diagnosed with BL during pregnancy received either no treatment or only one chemotherapy agent, and the majority ultimately died of rapidly progressive diseases. The fetal outcomes seem to depend primarily on the time of exposure to chemotherapy and/or radiation, doses, specific chemotherapy agent given, and frequency of treatment during pregnancy. Limited retrospective data suggest that chemotherapy given after the first trimester is relatively safe and does not adversely affect the short-and long-term fetal outcomes.

Conclusions:

Treatment of BL during pregnancy can be very challenging because an aggressive approach is the main key to maximize the patient's long-term disease-free survival. However, the health of the unborn child should also be a concern when choosing treatment. This case demonstrates that combination chemotherapy given after the first trimester did not result in any congenital malformations or acute adverse effects in the fetus. Long-term follow-up of the child remains necessary to evaluate possible long-term complications.
Narrative research in psychotherapy: A critical review
Authors: Avdi Evrinomy , Georgaca Eugenie
Published: October 2006

Purpose. This paper is a review of studies which utilise the notion of narrative to analyse psychotherapy. Its purpose is to systematically present this diverse field of research, to highlight common themes and divergences between different strands and to further the development and integration of narrative research in psychotherapy.

Methods. The paper reviews studies which employ an applied textual analysis of narratives produced in the context of psychotherapy. Criteria for inclusion of studies are, firstly, the analysis of therapeutic and therapy‐related texts and, secondly, the adoption of a narrative psychological perspective. The studies were examined on the basis of the notion of narrative they employ and the aspects of client narratives they focus on, and were grouped accordingly in the review.

Results. The majority of the studies reviewed assume a constructivist approach to narrative, adopt a representational view of language, focus primarily on client micro‐narratives and relate to cognitive‐constructivist and process‐experiential psychotherapeutic approaches. A smaller group of studies assume a social constructionist approach to narrative and a functional view of language, focus on micro‐narratives, highlight the interactional and wider social aspects of narrative and relate to postmodern trends in psychotherapy.

Conclusions. The range of conceptualisations of narrative in the studies reviewed, from a representational psychological view to a constructionist social view, reflects tensions within narrative psychology itself. Moreover, two trends can be discerned in the field reviewed, narrative analysis of therapy, which draws from narrative theory and utilises the analytic approaches of narrative research to study psychotherapy, and analyses of narrative in therapy, which study client narratives using non‐narrative qualitative methods. Finally, the paper highlights the need for integration of this diverse field of research and urges for the development of narrative studies of psychotherapy which employ a broader social understanding of narrative production and transformation.