bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma
Authors: Jenner Matthew W. , Leone Paola E. , Walker Brian A. , Ross Fiona M. , Johnson David C. , Gonzalez David , Chiecchio Laura , Dachs Cabanas Elisabet , Paolo Dagrada Gian , Nightingale Mathew , Protheroe Rebecca K. M. , Stockley David , Else Monica , Dickens Nicholas J. , Cross Nicholas C. P. , Davies Faith E. , Morgan Gareth J. 
Published: July 2007

Abstract
We performed fluorescent in situ hybridization (FISH) for 16q23 abnormalities in 861 patients with newly diagnosed multiple myeloma and identified deletion of 16q [del(16q)] in 19.5%. In 467 cases in which demographic and survival data were available, del(16q) was associated with a worse overall survival (OS). It was an independent prognostic marker and conferred additional adverse survival impact in cases with the known poor-risk cytogenetic factors t(4;14) and del(17p). Gene expression profiling and gene mapping using 500K single-nucleotide polymorphism (SNP) mapping arrays revealed loss of heterozygosity (LOH) involving 3 regions: the whole of 16q, a region centered on 16q12 (the location of CYLD), and a region centered on 16q23 (the location of the WW domain-containing oxidoreductase gene WWOX). CYLD is a negative regulator of the NF-κB pathway, and cases with low expression of CYLD were used to define a “low-CYLD signature.” Cases with 16q LOH or t(14;16) had significantly reduced WWOX expression. WWOX, the site of the translocation breakpoint in t(14;16) cases, is a known tumor suppressor gene involved in apoptosis, and we were able to generate a “low-WWOX signature” defined by WWOX expression. These 2 genes and their corresponding pathways provide an important insight into the potential mechanisms by which 16q LOH confers poor prognosis.
Improved classification accuracy in 1- and 2-dimensional NMR metabolomics data using the variance stabilising generalised logarithm transformation
Authors: Parsons Helen M , Ludwig Christian , Günther Ulrich L , Viant Mark R 
Published: July 2007

Abstract

Background
Classifying nuclear magnetic resonance (NMR) spectra is a crucial step in many metabolomics experiments. Since several multivariate classification techniques depend upon the variance of the data, it is important to first minimise any contribution from unwanted technical variance arising from sample preparation and analytical measurements, and thereby maximise any contribution from wanted biological variance between different classes. The generalised logarithm (glog) transform was developed to stabilise the variance in DNA microarray datasets, but has rarely been applied to metabolomics data. In particular, it has not been rigorously evaluated against other scaling techniques used in metabolomics, nor tested on all forms of NMR spectra including 1-dimensional (1D) 1H, projections of 2D 1H, 1H J-resolved (pJRES), and intact 2D J-resolved (JRES).

Results
Here, the effects of the glog transform are compared against two commonly used variance stabilising techniques, autoscaling and Pareto scaling, as well as unscaled data. The four methods are evaluated in terms of the effects on the variance of NMR metabolomics data and on the classification accuracy following multivariate analysis, the latter achieved using principal component analysis followed by linear discriminant analysis. For two of three datasets analysed, classification accuracies were highest following glog transformation: 100% accuracy for discriminating 1D NMR spectra of hypoxic and normoxic invertebrate muscle, and 100% accuracy for discriminating 2D JRES spectra of fish livers sampled from two rivers. For the third dataset, pJRES spectra of urine from two breeds of dog, the glog transform and autoscaling achieved equal highest accuracies. Additionally we extended the glog algorithm to effectively suppress noise, which proved critical for the analysis of 2D JRES spectra.

Conclusion
We have demonstrated that the glog and extended glog transforms stabilise the technical variance in NMR metabolomics datasets. This significantly improves the discrimination between sample classes and has resulted in higher classification accuracies compared to unscaled, autoscaled or Pareto scaled data. Additionally we have confirmed the broad applicability of the glog approach using three disparate datasets from different biological samples using 1D NMR spectra, 1D projections of 2D JRES spectra, and intact 2D JRES spectra.
Analysis of septins across kingdoms reveals orthology and new motifs
Authors: Pan Fangfang , Malmberg Russell L , Momany Michelle 
Published: July 2007

Abstract

Background
Septins are cytoskeletal GTPase proteins first discovered in the fungus Saccharomyces cerevisiae where they organize the septum and link nuclear division with cell division. More recently septins have been found in animals where they are important in processes ranging from actin and microtubule organization to embryonic patterning and where defects in septins have been implicated in human disease. Previous studies suggested that many animal septins fell into independent evolutionary groups, confounding cross-kingdom comparison.

Results
In the current work, we identified 162 septins from fungi, microsporidia and animals and analyzed their phylogenetic relationships. There was support for five groups of septins with orthology between kingdoms. Group 1 (which includes S. cerevisiae Cdc10p and human Sept9) and Group 2 (which includes S. cerevisiae Cdc3p and human Sept7) contain sequences from fungi and animals. Group 3 (which includes S. cerevisiae Cdc11p) and Group 4 (which includes S. cerevisiae Cdc12p) contain sequences from fungi and microsporidia. Group 5 (which includes Aspergillus nidulans AspE) contains sequences from filamentous fungi. We suggest a modified nomenclature based on these phylogenetic relationships. Comparative sequence alignments revealed septin derivatives of already known G1, G3 and G4 GTPase motifs, four new motifs from two to twelve amino acids long and six conserved single amino acid positions. One of these new motifs is septin-specific and several are group specific.

Conclusion
Our studies provide an evolutionary history for this important family of proteins and a framework and consistent nomenclature for comparison of septin orthologs across kingdoms.
A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition
Authors: Harris Sarah E , Fox Helen , Wright Alan F , Hayward Caroline , Starr John M , Whalley Lawrence J , Deary Ian J 
Published: July 2007

Abstract

Background
Non-pathological cognitive ageing is a distressing condition affecting an increasing number of people in our 'ageing society'. Oxidative stress is hypothesised to have a major role in cellular ageing, including brain ageing.

Results
Associations between cognitive ageing and 325 single nucleotide polymorphisms (SNPs), located in 109 genes implicated in oxidative stress and/or cognition, were examined in a unique cohort of relatively healthy older people, on whom we have cognitive ability scores at ages 11 and 79 years (LBC1921). SNPs showing a significant positive association were then genotyped in a second cohort for whom we have cognitive ability scores at the ages of 11 and 64 years (ABC1936). An intronic SNP in the APP gene (rs2830102) was significantly associated with cognitive ageing in both LBC1921 and a combined LBC1921/ABC1936 analysis (p < 0.01), but not in ABC1936 alone.

Conclusion
This study suggests a possible role for APP in normal cognitive ageing, in addition to its role in Alzheimer's disease.
Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses
Authors: Turcotte Eric , Wiens Linda W , Grierson John R , Peterson Lanell M , Wener Mark H , Vesselle Hubert 
Published: July 2007

Abstract

Background

18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT.

Methods
Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12).

Results
No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 ± 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial.

Conclusion
This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.
Association of diminished expression of RASSF1A with promoter methylation in primary gastric cancer from patients of central China
Authors: Ye Mei , Xia Bing , Guo Qiusha , Zhou Feng , Zhang Xiaolian 
Published: July 2007

AbstractBackgroundAlthough methylation-mediated inactivation of expression of RASSF1A, a candidate tumor suppressor gene, has been observed in several human cancers, the data concerning alteration of RASSF1A expression and methylation in Chinese primary gastric cancer are scarce. Moreover, direct evidence showing the association between protein expression of RASSF1A and primary human cancers is lacking. The aim of this study was to investigate RASSF1A expression in tissue of primary gastric cancer (GC) at mRNA and protein levels, and to establish the possible relationship between DNA methylation status and protein expression of RASSF1A in Chinese.MethodsFifty-four patients with primary gastric cancers were included in the study of RASSF1A mRNA expression and methylation status between the cancer tissue and the corresponding adjacent normal tissue. 20 out of 54 patients were included for study of RASSF1A protein expression. The expression of RASSF1A at mRNA and protein levels was determined by RT-PCR and Western-blotting, respectively. The RASSF1A promoter methylation was detected by methylation-specific PCR.ResultsRASSF1A mRNA and protein expressions in GC were reduced significantly with comparison to the corresponding normal tissues (OD value: 0.2589 ± 0.2407 vs 0.5448 ± 0.2971,P< 0.0001; 0.1874 ± 0.0737 vs 0.6654 ± 0.2201,P< 0.0001, respectively). Methylation frequency of RASSF1A in primary GC is higher than that in the corresponding normal tissues (66.7% vs. 14.8%,P< 0.0001). Furthermore, RASSF1A mRNA expression in methylation group of GC was further reduced when compared to the unmethylation group of GC (0.1384 ± 0.1142 vs. 0.5018 ± 0.2463,P< 0.0001).ConclusionExpression of RASSF1A was reduced in tissue of GC at mRNA and protein levels. Diminished expression of RASSF1A was associated with the promoter methylation.
Reincentivizing – a new theory of work and work absence
Authors: Thulesius Hans O , Grahn Birgitta E 
Published: July 2007

Abstract
Background
Work capacity correlates weakly to disease concepts, which in turn are insufficient to explain sick leave behavior. With data mainly from Sweden, a welfare state with high sickness absence rates, our aim was to develop an explanatory theory of how to understand and deal with work absence and sick leave.

Methods
We used classic grounded theory for analyzing data from >130 interviews with people working or on sick leave, physicians, social security officers, and literature. Several hundreds of typed and handwritten memos were the basis for writing up the theory.

Results
In this paper we present a theory of work incentives and how to deal with work absence. We suggest that work disability can be seen as hurt work drivers or people caught in mode traps. Work drivers are specified as work capacities + work incentives, monetary and non-monetary. Also, people can get trapped in certain modes of behavior through changed capacities or incentives, or by inertia. Different modes have different drivers and these can trap the individual from reincentivizing, ie from going back to work or go on working. Hurt drivers and mode traps are recognized by driver assessments done on several different levels. Mode driver calculations are done by the worker. Then follows employer, physician, and social insurance officer assessments. Also, driver assessments are done on the macro level by legislators and other stakeholders. Reincentivizing is done by different repair strategies for hurt work drivers such as body repair, self repair, work-place repair, rehumanizing, controlling sick leave insurance, and strengthening monetary work incentives. Combinations of these driver repair strategies also do release people from mode traps.

Conclusion
Reincentivizing is about recognizing hurt work drivers and mode traps followed by repairing and releasing the same drivers and traps. Reincentivizing aims at explaining what is going on when work absence is dealt with and the theory may add to social psychological research on work and work absence, and possibly inform sick leave policies.
4D treatment planning for scanned ion beams
Authors: Bert Christoph , Rietzel Eike 
Published: July 2007

AbstractAt Gesellschaft für Schwerionenforschung (GSI) more than 330 patients have been treated with scanned carbon ion beams in a pilot project. To date, only stationary tumors have been treated. In the presence of motion, scanned ion beam therapy is not yet possible because of interplay effects between scanned beam and target motion which can cause severe mis-dosage. We have started a project to treat tumors that are subject to respiratory motion. A prototype beam application system for target tracking with the scanned pencil beam has been developed and commissioned.To facilitate treatment planning for tumors that are subject to organ motion, we have extended our standard treatment planning system TRiP to full 4D functionality. The 4D version of TRiP allows to calculate dose distributions in the presence of motion. Furthermore, for motion mitigation techniques tracking, gating, rescanning, and internal margins optimization of treatment parameters has been implemented. 4D calculations are based on 4D computed tomography data, deformable registration maps, organ motion traces, and beam scanning parameters.We describe the methods of our 4D treatment planning approach and demonstrate functionality of the system for phantom as well as patient data.
Finite-element analysis of axi-symmetric rotors
Authors: Stordahl H , Christensen H 
Published: July 2007

The finite-element method (1) (2)∗ is increasingly used in the stress analysis of mechanical-engineering problems. It is the purpose of this paper to described how the finite-element method can be used as an effective tool in the design of rotors. Up to the present time this method has mainly been used in the analysis of two-dimensional problems. However, a special class of three-dimensional problems, namely axi-symmetric rotors, can be treated as a nearly two-dimensional problem. This paper summarizes the development of the finite-element method as applied to the analysis of the axi-symmetric rotor. A computer programme is then briefly described, and the application of the method to the solution of three examples taken from practical engineering experience are presented.
Residual stresses in rolling contact
Authors: Pomeroy R J , Johnson K L 
Published: July 2007

The paper reports an experimental investigation into the residual strsses induced into cylndrical discs by the action of rolling-contact loads sufficiently high to cause some plastic deformation in the near-surface layers. A general method is first described for finding both circumferential and axial components of residual stress in cylindrical bodies in circumstances where the stresses vary with the radial co-ordinate only. This method is believed to be an improvement on previous methods for separating the two components of residual stress, particularly where only specimens of restricted length are available. For example, the method could be applied to thick-walled tubes. Measurements have been made of the residual stresses due to rolling contact, in pure rolling and in combined rolling and sliding. In all cases both components of residual stress were compressive and reached a maximum value below the surface at about the depth of the maximum Hertz shear stress. The measured residual stresses in the sub-surface region were roughly in agreement with the theoretical predictions of Merwin, Johnson, and Jefferis. A subsidiary peak of compressive stress was found at the surface itself. Neither the surface nor the subsurface stresses were found to be greatly influenced by the presence of friction forces when sliding accompanied rolling.
Book reviews
Authors: Jaffe Ira , Herbert Daniel , Kramer Gary M 
Published: July 2007

Jason Wood, Scott McGehee, David Siegal 100 American Independent Films London: BFI Film Guides, 2004
Erica Sheen and Annette Davison, Editors The Cinema of David Lynch: American Dreams, Nightmare Visions London: Wallflower Press, 2004
Lucia Nagib, Editor The New
Brazilian Cinema London: I.B.Tauris, 2003
Contrasting cellular and humoral autoimmunity associated with latent autoimmune diabetes in adults
Authors: Mayer A , Fabien N , Gutowski M C , Dubois V , Gebuhrer L , Bienvenu J , Orgiazzi J , Madec A M 
Published: July 2007

Objective: Diabetes is clinically classified into two types: type 1 (T1D) and type 2 diabetes (T2D). Nevertheless, intermediate forms of diabetes are frequent and difficult to recognize and manage appropriately. In this study, we investigated whether patients with intermediate form of diabetes, here called unclassified diabetes (UD), have β-cell autoimmune markers.
Research design and methods: β-cell autoimmune markers (β-cell autoantibodies (aAb), peripheral blood mononuclear cells (PBMC) responsive to five islet proteins, cytokine secretion, and human leukocyte antigen (HLA)-DQB1 genotypes) were analyzed in 50 UD patients, 23 age- and HLA-matched normal control subjects, and 23 classic T2D patients.
Results: We observed that 16 out of 50 (32%) UD patients demonstrated responsive PBMCs, as opposed to 1 out of 23 (5%) age- and HLA-matched normal control subjects, and 0 out of 23 classic T2D patients. Overall, 29 (58%) UD patients had at least one marker of β-cell autoimmunity (β-cell aAb and/or PBMC autoreactivity), in association with high-risk HLA genotypes DQB1*0201 and/or DQB1*0302. Moreover, the 13 (26%) UD patients who had β-cell aAb were not the same as those with PBMC autoreactivity, except for one patient. Patients with PBMC autoreactivity were older at the onset of the disease and had a better residual β-cell function than those with β-cell aAb.
Conclusions: Our data confirm that T-cell autoimmunity can be detected in latent autoimmune diabetes in adults patients. We show an inverse correlation between humoral and cellular β-cell autoimmunities. Possible protective cellular responses in the patients with β-cell PBMC autoreactivity could have potential therapeutic implications.
Trajectories of Socioeconomic Status Across Children's Lifetime Predict Health
Authors: Chen Edith , Martin Andrew D. , Matthews Karen A. 
Published: July 2007

OBJECTIVE. Socioeconomic status is one of the most robust social factors associated with health, but the dynamics of how socioeconomic status over time affects children's health remains unclear. This study tested how various models of childhood socioeconomic status (accumulation, change, variability, and critical periods of family income) would predict health outcomes at a final time point in childhood.
METHODS. This was a prospective, longitudinal study of 6306 children who were aged 10 to 11 years and whose families were interviewed every other year from birth onward. The sample came from the US National Longitudinal Survey of Youth–Children. In the same data set, a replication sample of 4305 14- to 15-year-old children was also examined. Primary outcomes included parent report of asthma and conditions that limited activity and school and required physician treatment.
RESULTS. Lower cumulative family income was associated with higher odds for having a condition that limited childhood activities, as well as a condition that required treatment by a physician at ages 10 to 11. Cumulative family income was a stronger predictor than change in income or variability in income. Lower family income early in life (ages 0–5 years) was associated with higher odds for having a condition that limited activities and a condition that required treatment by a physician at ages 10 to 11, independent of current socioeconomic status. Findings were replicated in the 14- to 15-year-old sample.
CONCLUSIONS. These findings suggest that the accumulation of socioeconomic status in terms of family income across childhood is more important than social mobility or variability in socioeconomic status, although there may be certain periods of time (early life) that have stronger effects on health. These findings suggest the importance of childhood interventions for reducing health disparities.
A study of high capacity busways in developing cities
Authors: Gardner G. 
Published: July 2007

Many of the world's major cities face the ever-increasing problem of traffic congestion. Buses are forced to compete for road space with all other road users and hence frequently fail to deliver an acceptable public transport service. Numerous cities throughout the world are now planning rail-based metro systems to provide public transport. Because of the extremely high capital costs, however, metros will rarely be appropriate, particularly in developing countries. Modern bus systems, including busways, could provide a viable mass transit option. This Paper presents the main findings of a TRRL (now TRL) research project on the performance of busways in developing cities. From a case study of eight such systems, capacity figures are presented which show that passenger flows of over 20000 per hour per direction are possible and that even higher flows might be achievable given the right combination of design and operational features A busway transit network with a dedicated track, trffic signal priority and similar stop-spacing to that of a metro is potentially able to provide a suitable alternative to a rail-based system, at a fraction of the cost. With high-quality buses and a good corporate image, such a system could be attractive to city authorities in many UK and European cities Bus stop spacing and design are found to be the critical component of a high capacity busway transit system, although the provision of overtaking bays, together with efficient ticketing arrangements, can greatly improve throughput. The advantages of busways for a developing country include their relatively low costs, with minimal foreign-exchange requirement, and much greater flexibility and adaptability when compared to a fixed-route system.