bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying a General Analytic Method for Assessing Bias Sensitivity to Bias-Adjusted Threat and Equitable Threat Scores
Authors: Brill Keith F. , Mesinger Fedor 
Published: June 2009

Abstract
Bias-adjusted threat and equitable threat scores were designed to account for the effects of placement errors in assessing the performance of under- or overbiased forecasts. These bias-adjusted performance measures exhibit bias sensitivity. The critical performance ratio (CPR) is the minimum fraction of added forecasts that are correct for a performance measure to indicate improvement if bias is increased. In the opposite case, the CPR is the maximum fraction of removed forecasts that are correct for a performance measure to indicate improvement if bias is decreased. The CPR is derived here for the bias-adjusted threat and equitable threat scores to quantify bias sensitivity relative to several other measures of performance including conventional threat and equitable threat scores. The CPR for a bias-adjusted equitable threat score may indicate the likelihood of preserving or increasing the conventional equitable threat score if forecasts are bias corrected based on past performance.
Evidence for a mitochondrial localization of the retinoblastoma protein
Authors: Ferecatu Ioana , Le Floch Nathalie , Bergeaud Marie , Rodríguez-Enfedaque Aida , Rincheval Vincent , Oliver Lisa , Vallette François M , Mignotte Bernard , Vayssière Jean-Luc 
Published: June 2009

Abstract

Background
The retinoblastoma protein (Rb) plays a central role in the regulation of cell cycle, differentiation and apoptosis. In cancer cells, ablation of Rb function or its pathway is a consequence of genetic inactivation, viral oncoprotein binding or deregulated hyperphosphorylation. Some recent data suggest that Rb relocation could also account for the regulation of its tumor suppressor activity, as is the case for other tumor suppressor proteins, such as p53.

Results
In this reported study, we present evidence that a fraction of the total amount of Rb protein can localize to the mitochondria in proliferative cells taken from both rodent and human cells. This result is also supported by the use of Rb siRNAs, which substantially reduced the amount of mitochondrial Rb, and by acellular assays, in which [35S]-Methionine-labeled Rb proteins bind strongly to mitochondria isolated from rat liver. Moreover, endogenous Rb is found in an internal compartment of the mitochondria, within the inner-membrane. This is consistent with the protection of Rb from alkaline treatment, which destroys any interaction of proteins that are weakly bound to mitochondria.

Conclusion
Although a few data regarding an unspecific cytosolic localization of Rb protein have been reported for some tumor cells, our results are the first evidence of a mitochondrial localization of Rb. The mitochondrial localization of Rb is observed in parallel with its classic nuclear location and paves the way for the study of potential as-yet-unknown roles of Rb at this site.
Analysis of salivary transcripts and antigens of the sand fly Phlebotomus arabicus
Authors: Hostomská Jitka , Volfová Věra , Mu Jianbing , Garfield Mark , Rohoušová Iva , Volf Petr , Valenzuela Jesus G , Jochim Ryan C 
Published: June 2009

AbstractBackgroundSand fly saliva plays an important role in blood feeding andLeishmaniatransmission as it was shown to increase parasite virulence. On the other hand, immunity to salivary components impedes the establishment of infection. Therefore, it is most desirable to gain a deeper insight into the composition of saliva in sand fly species which serve as vectors of various forms of leishmaniases. In the present work, we focused onPhlebotomus (Adlerius) arabicus, which was recently shown to transmitLeishmania tropica, the causative agent of cutaneous leishmaniasis in Israel.ResultsA cDNA library from salivary glands ofP. arabicusfemales was constructed and transcripts were sequenced and analyzed. The most abundant protein families identified were SP15-like proteins, ParSP25-like proteins, D7-related proteins, yellow-related proteins, PpSP32-like proteins, antigen 5-related proteins, and 34 kDa-like proteins. Sequences coding for apyrases, hyaluronidase and other putative secreted enzymes were also represented, including endonuclease, phospholipase, pyrophosphatase, amylase and trehalase. Mass spectrometry analysis confirmed the presence of 20 proteins predicted to be secreted in the salivary proteome. Humoral response of mice bitten byP. arabicusto salivary antigens was assessed and many salivary proteins were determined to be antigenic.ConclusionThis transcriptomic analysis ofP. arabicussalivary glands is the first description of salivary proteins of a sand fly in the subgenusAdlerius. Proteomic analysis ofP. arabicussalivary glands produced the most comprehensive account in a single sand fly species to date. Detailed information and phylogenetic relationships of the salivary proteins are provided, expanding the knowledge base of molecules that are likely important factors of sand fly-host and sand fly-Leishmaniainteractions. Enzymatic and immunological investigations further demonstrate the value of functional transcriptomics in advancing biological and epidemiological research that can impact leishmaniasis.
Breast cancer stem cells: tools and models to rely on
Authors: Charafe-Jauffret Emmanuelle , Ginestier Christophe , Birnbaum Daniel 
Published: June 2009

AbstractThere is increasing evidence for the "cancer stem cell (CSC) hypothesis", which holds that cancers are driven by a cellular component that has stem cell properties, including self-renewal, tumorigenicity and multi-lineage differentiation capacity. Researchers and oncologists see in this model an explanation as to why cancer may be so difficult to cure, as well as a promising ground for novel therapeutic strategies. Given the specific stem cell features of self-renewal and differentiation, which drive tumorigenesis and contribute to cellular heterogeneity, each marker and assay designed to isolate and characterize CSCs has to be functionally validated. In this review, we survey tools and markers available or promising to identify breast CSCs. We review the main models used to study breast CSCs and how they challenge the CSC hypothesis.
Simulation of the cost-effectiveness of malaria vaccines
Authors: Tediosi Fabrizio , Maire Nicolas , Penny Melissa , Studer Alain , Smith Thomas A 
Published: June 2009

AbstractBackgroundA wide range of possible malaria vaccines is being considered and there is a need to identify which vaccines should be prioritized for clinical development. An important element of the information needed for this prioritization is a prediction of the cost-effectiveness of potential vaccines in the transmission settings in which they are likely to be deployed. This analysis needs to consider a range of delivery modalities to ensure that clinical development plans can be aligned with the most appropriate deployment strategies.MethodsThe simulations are based on a previously published individual-based stochastic model for the natural history and epidemiology ofPlasmodium falciparummalaria. Three different vaccine types: pre-erythrocytic vaccines (PEV), blood stage vaccines (BSV), mosquito-stage transmission-blocking vaccines (MSTBV), and combinations of these, are considered each delivered via a range of delivery modalities (Expanded Programme of Immunization – EPI-, EPI with booster, and mass vaccination combined with EPI). The cost-effectiveness ratios presented are calculated for four health outcomes, for assumed vaccine prices of US$ 2 or US$ 10 per dose, projected over a 10-year period.ResultsThe simulations suggest that PEV will be more cost-effective in low transmission settings, while BSV at higher transmission settings. Combinations of BSV and PEV are more efficient than PEV, especially in moderate to high transmission settings, while compared to BSV they are more cost-effective in moderate to low transmission settings. Combinations of MSTBV and PEV or PEV and BSV improve the effectiveness and the cost-effectiveness compared to PEV and BSV alone only when applied with EPI and mass vaccinations. Adding booster doses to the EPI is unlikely to be a cost-effective alternative to delivering vaccines via the EPI for any vaccine, while mass vaccination improves effectiveness, especially in low transmission settings, and is often a more efficient alternative to the EPI. However, the costs of increasing the coverage of mass vaccination over 50% often exceed the benefits.ConclusionThe simulations indicate malaria vaccines might be efficient malaria control interventions, and that both transmission setting and vaccine delivery modality are important to their cost-effectiveness. Alternative vaccine delivery modalities to the EPI may be more efficient than the EPI. Mass vaccination is predicted to provide substantial health benefits at low additional costs, although achieving high coverage rates can lead to substantial incremental costs.
Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish
Authors: Ju Bensheng , Spitsbergen Jan , Eden Christopher J , Taylor Michael R , Chen Wenbiao 
Published: June 2009

Abstract
The zebrafish has become an important model for cancer research. Several cancer models have been established by transgenic expression of human or mouse oncogenes in zebrafish. Since it is amenable to efficient transgenesis, zebrafish have immense potential to be used for studying interaction of oncogenes and pathways at the organismal level. Using the Gal4VP16-UAS binary transgenic expression approach, we established stable transgenic lines expressing an EGFP fusion protein of an activated zebrafish Smoothened (Smoa1-EGFP). Expression of the zebrafish Smoa1-EGFP itself did not lead to tumor formation either in founder fish or subsequent generations, however, co-expressing a constitutively active human AKT1 resulted in several tumor types, including spindle cell sarcoma, rhabdomyoma, ocular melanoma, astrocytoma, and myoxma. All tumor types showed GFP expression and increased Patched 1 levels, suggesting involvement of zebrafish Smoa1 in tumorigenesis. Immunofluorescence studies showed that tumors also expressed elevated levels of phosphorylated AKT, indicating activation of the PI3K-AKT pathway. These results suggest that co-activation of the hedgehog and AKT pathways promote tumorigenesis, and that the binary transgenic approach is a useful tool for studying interaction of oncogenes and oncogenic pathways in zebrafish.
Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread
Authors: Holtz Lori R , Finkbeiner Stacy R , Zhao Guoyan , Kirkwood Carl D , Girones Rosina , Pipas James M , Wang David 
Published: June 2009

Abstract

Background
Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea.

Results
Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain.

Conclusion
Klassevirus 1 is a previously undescribed picornavirus that is globally widespread and present on at least three continents. Further investigations to determine whether klassevirus 1 is a human pathogen are needed.
A gene signature for post-infectious chronic fatigue syndrome
Authors: Gow John W , Hagan Suzanne , Herzyk Pawel , Cannon Celia , Behan Peter O , Chaudhuri Abhijit 
Published: June 2009

AbstractBackgroundAt present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition.MethodsHuman genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7).ResultsPatients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significanceConclusionDifferential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment.
Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review
Authors: Chaudhary Ajay Kumar , Singh Mamta , Sundaram Shanthy , Mehrotra Ravi 
Published: June 2009

Abstract
Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil® (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix® (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here.
Exercise therapy for the management of osteoarthritis of the hip joint: a systematic review
Authors: McNair Peter J , Simmonds Marion A , Boocock Mark G , Larmer Peter J 
Published: June 2009

Abstract
Introduction
Recent guidelines pertaining to exercise for individuals with osteoarthritis have been released. These guidelines have been based primarily on studies of knee-joint osteoarthritis. The current study was focused on the hip joint, which has different biomechanical features and risk factors for osteoarthritis and has received much less attention in the literature. The purpose was to conduct a systematic review of the literature to evaluate the exercise programs used in intervention studies focused solely on hip-joint osteoarthritis, to decide whether their exercise regimens met the new guidelines, and to determine the level of support for exercise-therapy interventions in the management of hip-joint osteoarthritis.

Methods
A systematic literature search of 14 electronic databases was undertaken to identify interventions that used exercise therapy as a treatment modality for hip osteoarthritis. The quality of each article was critically appraised and graded according to standardized methodologic approaches. A 'pattern-of-evidence' approach was used to determine the overall level of evidence in support of exercise-therapy interventions for treating hip osteoarthritis.

Results
More than 4,000 articles were identified, of which 338 were considered suitable for abstract review. Of these, only 6 intervention studies met the inclusion criteria. Few well-designed studies specifically investigated the use of exercise-therapy management on hip-joint osteoarthritis. Insufficient evidence was found to suggest that exercise therapy can be an effective short-term management approach for reducing pain levels, improving joint function and the quality of life.

Conclusions
Limited information was available on which conclusions regarding the efficacy of exercise could be clearly based. No studies met the level of exercise recommended for individuals with osteoarthritis. High-quality trials are needed, and further consideration should be given to establishing the optimal exercises and exposure levels necessary for achieving long-term gains in the management of osteoarthritis of the hip.
The effects of social desirability response bias on STAXI‐2 profiles in a clinical forensic sample
Authors: McEwan Troy E. , Davis Michael R. , MacKenzie Rachel , Mullen Paul E. 
Published: June 2009

Objectives. This study investigated the proposition that the ‘State–trait anger expression inventory’ (2nd ed.; STAXI‐2) is susceptible to impression management (IM) and Self‐Deceptive Enhancement (SDE) in clinical forensic populations. It was hypothesized that individuals engaging in IM would report significantly lower levels of trait anger, external expression of anger, and internal expression of anger on the STAXI‐2. Those reporting above average SDE were predicted to claim higher levels of anger control.Design. A between‐groups design was used, comparing STAXI‐2 scores of individuals who reported high levels of IM and SDE to those who did not.Method. One‐hundred and fifty‐nine male patients of a community forensic mental health service, referred for assessment of stalking behaviours, completed the STAXI‐2 and Paulhus Deception Scales (PDS). Individuals engaging in high levels of IM and SDE were compared to low scorers in regard to STAXI‐2 scales using Mann–Whitney U tests.Results. Individuals engaging in IM had significantly lower levels of reported trait anger, outward expression of anger, and inward expression of anger, and higher levels of anger control. Similar results were found with the SDE scale, although the magnitude of the effect was smaller and not apparent on all subscales.Conclusions. The STAXI‐2 was vulnerable to social desirability response bias in this sample of forensic clients. Where the STAXI‐2 is used as a basis for treatment recommendations and decisions, it should be administered and interpreted in conjunction with a recognized measure of such bias to improve validity.
THE CALCULATION OF COLLAPSE LOADS FOR FRAMED STRUCTURES. (INCLUDES APPENDIX).
Authors: NEAL B G , SYMONDS P S 
Published: June 2009

Synopsis The Paper presents a new method for the determination of the collapse load for structures of any degree of complexity by a simple routine analysis. The method is limited only by the time which would be taken in the analysis for a large frame. It is shown, however, that a skilled analyst may be able to reduce the labour involved to a considerable extent. The method is contrasted with the method which is used at present, in which the designer guesses the locations of the plastic hinges which form when the structure collapses, and then adjusts his guesses in a systematic manner.
THE CALCULATION OF FAILURE LOADS ON PLANE FRAMES UNDER ARBITRARY LOADING PROGRAMMES.
Authors: SYMONDS P S , NEAL B G 
Published: June 2009

Synopsis The Paper extends the plastic theory for plane frames of mild steel to cover the cases in which the detailed loading programmes of a set of independently variable loads are either wholly or partially unspecified and there is no restriction on the number of times each load may be applied. A general method for analysing framed structures of mild steel, under arbitrary loading programmes, is presented. A two-bay portal frame with rigid joints, subjected to three independent forces, is taken as the basis for discussion, and a complete numerical analysis of the “shake-down” problem for this frame is given to illustrate the general method. Once the elastic analysis has been made, the time required for the “shake-down” analysis will, in many cases, be not much longer than that which would be needed to make the analysis for plastic collapse. Limitations of the present theory are discussed, and some suggestions as to its probable applications to design problems are offered.
Calculating Continuous Time Ruin Probabilities for a Large Portfolio with Varying Premiums
Authors: Afonso Lourdes B. , dos Reis Alfredo D. Egídio , Waters Howard R. 
Published: June 2009

AbstractIn this paper we present a method for the numerical evaluation of the ruin probability in continuous and finite time for a classical risk process where the premium can change from year to year. A major consideration in the development of this methodology is that it should be easily applicable to large portfolios. Our method is based on the simulation of the annual aggregate claims and then on the calculation of the ruin probability for a given surplus at the start and at the end of each year. We calculate the within-year ruin probability assuming a translated gamma distribution approximation for aggregate claim amounts.We illustrate our method by studying the case where the premium at the start of each year is a function of the surplus level at that time or at an earlier time.
Estimating the Variance of Bootstrapped Risk Measures
Authors: Kim Joseph H.T. , Hardy Mary R. 
Published: June 2009

AbstractIn Kim and Hardy (2007) the exact bootstrap was used to estimate certain risk measures including Value at Risk and the Conditional Tail Expectation. In this paper we continue this work by deriving the influence function of the exact-bootstrapped quantile risk measure. We can use the influence function to estimate the variance of the exact-bootstrap risk measure. We then extend the result to the L-estimator class, which includes the conditional tail expectation risk measure. The resulting formula provides an alternative way to estimate the variance of the bootstrapped risk measures, or the whole L-estimator class in an analytic form. A simulation study shows that this new method is comparable to the ordinary resampling-based bootstrap method, with the advantages of an analytic approach.