bluuebunny/crossref_metadata_2025 huggingface dataset:
Researching “Back Home”
Authors: Karra Neri , Phillips Nelson
Published: July 2007

The challenges facing international management researchers conducting research in foreign contexts are increasingly well understood. However, for a growing group of researchers, the problem is very different: Rather than being foreign researchers researching in an unfamiliar context, they are insiders conducting research in their own cultural context for publication in international journals. In this article, the authors draw on their own experiences and on the literature on autoethnography to illustrate the strengths and challenges of researching “back home.” In particular, they argue that autoethnographic approaches have four important strengths— ease of access, reduced resource requirements, ease of establishing trust and rapport, and reduced problems with translation—but at the same time pose three important challenges— lack of critical distance, role conflict, and the limits of serendipity.
Testing Equivalence in the Structure, Means, and Variances of Higher-Order Constructs With Structural Equation Modeling
Authors: Cheung Gordon W.
Published: July 2007

Recent developments in the literature provide us with a better understanding of the importance of and procedures for testing measurement equivalence in organizational research. However, whereas many constructs in organizational research are multidimensional and multifaceted, procedures for testing the measurement equivalence of higher-order constructs are not commonly known. This study first discusses the importance of examining the measurement equivalence of higher-order constructs from a theoretical perspective, and then demonstrates that importance with a small-scale simulation. Finally, the procedures for testing various forms of measurement equivalence with structural equation modeling for both firstand second-order constructs are clarified and illustrated with a numerical example.
Using Spatial Methods in Strategy Research
Authors: Doh Jonathan P. , Hahn Eugene D.
Published: July 2007

Spatial and geographic constructs have been incorporated into strategy research since its inception. Yet, strategy researchers have been slow to take advantage of methods designed specifically for these variables. This is despite the fact that spatial methods can be used to identify and remediate spatial autocorrelation—eliminating a potentially important source of bias in empirical results—and more broadly, to test hypotheses about spatial phenomena in novel ways. This article reviews the use of spatial constructs and variables in strategy research, summarizes spatial methods relevant to the strategy field, and shows how these approaches can enhance strategy research. The authors demonstrate the utility of these methods for a wide range of empirical inquiries into the role of geographic space in firm location, competition, and other phenomena, and offer three specific illustrations of their usefulness in the context of international strategy research.
Tests of the Three-Path Mediated Effect
Authors: Taylor Aaron B. , MacKinnon David P. , Tein Jenn-Yun
Published: July 2007

In a three-path mediational model, two mediators intervene in a series between an independent and a dependent variable. Methods of testing for mediation in such a model are generalized from the more often used single-mediator model. Six such methods are introduced and compared in a Monte Carlo study in terms of their Type I error, power, and coverage. Based on its results, the joint significance test is preferred when only a hypothesis test is of interest. The percentile bootstrap and bias-corrected bootstrap are preferred when a confidence interval on the mediated effect is desired, with the latter having more power but also slightly inflated Type I error in some conditions.
Designing Experiments That Generalize
Authors: Highhouse Scott
Published: July 2007

Organizational research has relied too heavily on methods characterized by passive observation, likely because there is a widespread belief that experimental research has limited generalizability. However, this is often because researchers (and reviewers or editors) misunderstand the nature of generalizability and what it requires. This article reiterates the importance of experimental research for understanding organizational phenomena and separates the legitimate concerns about experimental generalizability from the irrelevant ones. Whereas most criticisms of experiments focus on sample characteristics and mundane realism (i.e., superficial resemblance to the real world), more attention needs to be paid to the degree to which the treatment manipulation is valid, representative, and strong.
Psychometric Accuracy and (the Continuing Need for) Quality Thinking in Meta-Analysis
Authors: Bobko Philip , Roth Philip L.
Published: July 2007

The four feature-topic articles advance the accuracy of meta-analytic techniques. As might be expected, most articles focus on more precise ways to aggregate all available relationships in a given topic domain. Such aggregation results in overall estimates of relationships and estimates conditional on particular moderators. However, scholars and practitioners can expect more than empirical aggregation from meta-analysis. Careful attention to underlying theory, application, and important methodological issues will result in clearer understanding and explanation. Using the situational judgment testing literature as an example, the current analysis suggests the need for much more upfront, reflective thinking about each meta-analytic study's purpose and how this thinking relates to the inclusion or choice of primary studies, analytic method, coding, and so on. For example, when the focus is on prediction, frequent use of concurrent designs may bias aggregated parameter estimates. Also, it is noted that methods and constructs continue to be confounded in the research literatures.
Fitting Oval Pegs Into Round Holes
Authors: Pratt Michael G.
Published: July 2007

A study of qualitative researchers who have submitted and/or published their research in top-tier North American organizational and management journals reveals the evaluative criteria-in-use at these journals. Specifically, when asked to take the perspective of an (a) author, (b) evaluator (reviewer or editor), and (c) judge of the comparisons between qualitative and quantitative research, three publication tensions were evident. The author offers the metaphor of ``fitting a round peg into an oval hole'' as a means of capturing these tensions and as a vehicle for organizing the various ways these tensions can be managed.
The Application of DICTION to Content Analysis Research in Strategic Management
Authors: Short Jeremy C. , Palmer Timothy B.
Published: July 2007

DICTION is a computer-aided content analysis program grounded in a number of theoretical bases in linguistic research. DICTION has a number of attractive features that could be used to analyze unique elements of language in narrative texts germane to strategic management research. The authors apply the DICTION software to a sample of mission statements from 408 Association to Advance Collegiate Schools of Business colleges of business with a focus on gaining insights concerning how DICTION can be used in strategic management research utilizing content analysis. They find significant differences in word usage in mission statements based on organizational characteristics, including business school performance. They conclude with suggestions for future research.
Sexual Functioning as a Moderator of the Relationship Between Masculinity and Men's Adjustment Following Treatment for Prostate Cancer
Authors: Burns Shaun Michael , Mahalik James R.
Published: July 2007

Men's enactment of traditional masculine norms may contribute to their adjustment to changes in sexual functioning following treatment for prostate cancer. In the present investigation, the authors test this hypothesis by examining the moderating role of sexual functioning on the relationship between men's adherence to masculine norms and their social, role, and mental health functioning. Results of regression analyses indicate that men with poor sexual functioning evince poor social, role, and mental health functioning when they more strongly adhere to traditional masculine norms. Participants with good sexual functioning, in contrast, exhibit positive social, role, and mental health functioning when they more strongly adhere to traditional norms of masculinity. Directions for future clinical research and treatment interventions are provided.
Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems
Authors: Lundberg Anna M. , Drexler Stefan K. , Monaco Claudia , Williams Lynn M. , Sacre Sandra M. , Feldmann Marc , Foxwell Brian M.
Published: July 2007

TLR3 recognizes double-stranded RNA, a product associated with viral infections. Many details of TLR3-induced mechanisms have emerged from gene-targeted mice or inhibition studies in transformed cell lines. However, the pathways activated in human immune cells or cells from disease tissue are less well understood. We have investigated TLR3-induced mechanisms of human primary cells of the innate immune system, including dendritic cells (DCs), macrophages (MØs), endothelial cells (ECs), and synovial fibroblasts isolated from rheumatoid arthritis joint tissue (RA-SFs). Here, we report that while these cells all express TLR3, they differ substantially in their response to TLR3 stimulation. The key antiviral response chemokine IP-10 was produced by all cell types, while DCs and MØs failed to produce the proinflammatory cytokines TNFα and IL-6. Unexpectedly, TNFα was found secreted by TLR3-stimulated RA-SF. Furthermore, TLR3 stimulation did not activate NFκB, MAPKs, or IRF-3 in DCs and MØs, but was able to do so in ECs and RA-SF. These findings were specific for human cells, thereby revealing a complexity not previously expected. This is the first report of such cell type– and species-specific response for any TLR stimulation and helps to explain important difficulties in correlating murine models of inflammatory diseases and human inflammation.
Selecting highly affine and well-expressed TCRs for gene therapy of melanoma
Authors: Jorritsma Annelies , Gomez-Eerland Raquel , Dokter Maarten , van de Kasteele Willeke , Zoet Yvonne M. , Doxiadis Ilias I. N. , Rufer Nathalie , Romero Pedro , Morgan Richard A. , Schumacher Ton N. M. , Haanen John B. A. G.
Published: July 2007

A recent phase 1 trial has demonstrated that the generation of tumor-reactive T lymphocytes by transfer of specific T-cell receptor (TCR) genes into autologous lymphocytes is feasible. However, compared with results obtained by infusion of tumor-infiltrating lymphocytes, the response rate observed in this first TCR gene therapy trial is low. One strategy that is likely to enhance the success rate of TCR gene therapy is the use of tumor-reactive TCRs with a higher capacity for tumor cell recognition. We therefore sought to develop standardized procedures for the selection of well-expressed, high-affinity, and safe human TCRs. Here we show that TCR surface expression can be improved by modification of TCR alpha and beta sequences and that such improvement has a marked effect on the in vivo function of TCR gene-modified T cells. From a panel of human, melanoma-reactive TCRs we subsequently selected the TCR with the highest affinity. Furthermore, a generally applicable assay was used to assess the lack of alloreactivity of this TCR against a large series of common human leukocyte antigen alleles. The procedures described in this study should be of general value for the selection of well- and stably expressed, high-affinity, and safe human TCRs for subsequent clinical testing.
Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one
Authors: Ghafari Fataneh , Gutierrez Carlos G , Hartshorne Geraldine M
Published: July 2007

Background

The vast majority of oocytes formed in the fetal ovary do not survive beyond birth. Possible reasons for their loss include the elimination of non-viable genetic constitutions arising through meiosis, however, the precise relationship between meiotic stages and prenatal apoptosis of oocytes remains elusive. We studied oocytes in mouse fetal and neonatal ovaries, 14.5–21 days post coitum, to examine the relationship between oocyte development and programmed cell death during meiotic prophase I.

Results

Microspreads of fetal and neonatal ovarian cells underwent immunocytochemistry for meiosis- and apoptosis-related markers. COR-1 (meiosis-specific) highlighted axial elements of the synaptonemal complex and allowed definitive identification of the stages of meiotic prophase I. Labelling for cleaved poly-(ADP-ribose) polymerase (PARP-1), an inactivated DNA repair protein, indicated apoptosis. The same oocytes were then labelled for DNA double strand breaks (DSBs) using TUNEL. 1960 oocytes produced analysable results.

Oocytes at all stages of meiotic prophase I stained for cleaved PARP-1 and/or TUNEL, or neither. Oocytes with fragmented (19.8%) or compressed (21.2%) axial elements showed slight but significant differences in staining for cleaved PARP-1 and TUNEL to those with intact elements. However, fragmentation of axial elements alone was not a good indicator of cell demise. Cleaved PARP-1 and TUNEL staining were not necessarily coincident, showing that TUNEL is not a reliable marker of apoptosis in oocytes.

Conclusion

Our data indicate that apoptosis can occur throughout meiotic prophase I in mouse fetal and early postnatal oocytes, with greatest incidence at the diplotene stage. Careful selection of appropriate markers for oocyte apoptosis is essential.
Involvement of the YneS/YgiH and PlsX proteins in phospholipid biosynthesis in both Bacillus subtilis and Escherichia coli
Authors: Yoshimura Mika , Oshima Taku , Ogasawara Naotake
Published: July 2007

Background

Phospholipid biosynthesis commences with the acylation of glycerol-3-phosphate (G3P) to form 1-acyl-G3P. This step is catalyzed by the PlsB protein in Escherichia coli. The gene encoding this protein has not been identified, however, in the majority of bacterial genome sequences, including that of Bacillus subtilis. Recently, a new two-step pathway catalyzed by PlsX and PlsY proteins for the initiation of phospholipid formation in Streptococcus pneumoniae has been reported.

Results

In B. subtilis, 271 genes have been reported to be indispensable, when inactivated singly, for growth in LB medium. Among these, 11 genes encode proteins with unknown functions. As part of a genetic study to identify the functions of these genes, we show here that the B. subtilis ortholog of S. pneumoniae PlsY, YneS, is required for G3P acyltransferase activity, together with PlsX. The B. subtilis genome lacks plsB, and we show in vivo that the PlsX/Y pathway is indeed essential for the growth of bacteria lacking plsB. Interestingly, in addition to plsB, E. coli possesses plsX and the plsY ortholog, ygiH. We therefore explored the functional relationship between PlsB, PlsX and YgiH in E. coli, and found that plsB is essential for E. coli growth, indicating that PlsB plays an important role in 1-acyl-G3P synthesis in E. coli. We also found, however, that the simultaneous inactivation of plsX and ygiH was impossible, revealing important roles for PlsX and YgiH in E. coli growth.

Conclusion

Both plsX and yneS are essential for 1-acyl-G3P synthesis in B. subtilis, in agreement with recent reports on their biochemical functions. In E. coli, PlsB plays a principal role in 1-acyl-G3P synthesis and is also essential for bacterial growth. PlsX and YgiH also, however, play important roles in E. coli growth, possibly by regulating the intracellular concentration of acyl-ACP. These proteins are therefore important targets for development of new antibacterial agents.
Region- or state-related differences in expression and activation of extracellular signal-regulated kinases (ERKs) in naïve and pain-experiencing rats
Authors: Guo She-Wei , Liu Ming-Gang , Long Ya-Li , Ren Li-Ying , Lu Zhuo-Min , Yu Hou-You , Hou Jun-Feng , Li Hua , Gao Cui-Ying , Cui Xiu-Yu , An Yang-Yuan , Li Junfa , Zhao Lan-Feng , Chen Jun
Published: July 2007

Background

Extracellular signal-regulated kinase (ERK), one member of the mitogen-activated protein kinase (MAPK) family, has been suggested to regulate a diverse array of cellular functions, including cell growth, differentiation, survival, as well as neuronal plasticity. Recent evidence indicates a role for ERKs in nociceptive processing in both dorsal root ganglion and spinal cord. However, little literature has been reported to examine the differential distribution and activation of ERK isoforms, ERK1 and ERK2, at different levels of pain-related pathways under both normal and pain states. In the present study, quantitative blot immunolabeling technique was used to determine the spatial and temporal expression of ERK1 and ERK2, as well as their activated forms, in the spinal cord, primary somatosensory cortex (SI area of cortex), and hippocampus under normal, transient pain and persistent pain states.

Results

In naïve rats, we detected regional differences in total expression of ERK1 and ERK2 across different areas. In the spinal cord, ERK1 was expressed more abundantly than ERK2, while in the SI area of cortex and hippocampus, there was a larger amount of ERK2 than ERK1. Moreover, phosphorylated ERK2 (pERK2), not phosphorylated ERK1 (pERK1), was normally expressed with a high level in the SI area and hippocampus, but both pERK1 and pERK2 were barely detectable in normal spinal cord. Intraplantar saline or bee venom injection, mimicking transient or persistent pain respectively, can equally initiate an intense and long-lasting activation of ERKs in all three areas examined. However, isoform-dependent differences existed among these areas, that is, pERK2 exhibited stronger response than pERK1 in the spinal cord, whereas ERK1 was more remarkably activated than ERK2 in the S1 area and hippocampus.

Conclusion

Taken these results together, we conclude that: (1) under normal state, while ERK immunoreactivity is broadly distributed in the rat central nervous system in general, the relative abundance of ERK1 and ERK2 differs greatly among specific regions; (2) under pain state, either ERK1 or ERK2 can be effectively phosphorylated with a long-term duration by both transient and persistent pain, but their response patterns differ from each other across distinct regions; (3) The long-lasting ERKs activation induced by bee venom injection is highly correlated with our previous behavioral, electrophysiological, morphological and pharmacological observations, lending further support to the functional importance of ERKs-mediated signaling pathways in the processing of negative consequences of pain associated with sensory, emotional and cognitive dimensions.
Arabidopsis Gene Family Profiler (aGFP) – user-oriented transcriptomic database with easy-to-use graphic interface
Authors: Dupl'áková Nikoleta , Reňák David , Hovanec Patrik , Honysová Barbora , Twell David , Honys David
Published: July 2007

Background

Microarray technologies now belong to the standard functional genomics toolbox and have undergone massive development leading to increased genome coverage, accuracy and reliability. The number of experiments exploiting microarray technology has markedly increased in recent years. In parallel with the rapid accumulation of transcriptomic data, on-line analysis tools are being introduced to simplify their use. Global statistical data analysis methods contribute to the development of overall concepts about gene expression patterns and to query and compose working hypotheses. More recently, these applications are being supplemented with more specialized products offering visualization and specific data mining tools. We present a curated gene family-oriented gene expression database, Arabidopsis Gene Family Profiler (aGFP; http://agfp.ueb.cas.cz), which gives the user access to a large collection of normalised Affymetrix ATH1 microarray datasets. The database currently contains NASC Array and AtGenExpress transcriptomic datasets for various tissues at different developmental stages of wild type plants gathered from nearly 350 gene chips.

Results

The Arabidopsis GFP database has been designed as an easy-to-use tool for users needing an easily accessible resource for expression data of single genes, pre-defined gene families or custom gene sets, with the further possibility of keyword search. Arabidopsis Gene Family Profiler presents a user-friendly web interface using both graphic and text output. Data are stored at the MySQL server and individual queries are created in PHP script. The most distinguishable features of Arabidopsis Gene Family Profiler database are: 1) the presentation of normalized datasets (Affymetrix MAS algorithm and calculation of model-based gene-expression values based on the Perfect Match-only model); 2) the choice between two different normalization algorithms (Affymetrix MAS4 or MAS5 algorithms); 3) an intuitive interface; 4) an interactive "virtual plant" visualizing the spatial and developmental expression profiles of both gene families and individual genes.

Conclusion

Arabidopsis GFP gives users the possibility to analyze current Arabidopsis developmental transcriptomic data starting with simple global queries that can be expanded and further refined to visualize comparative and highly selective gene expression profiles.
A comparative map viewer integrating genetic maps for Brassica and Arabidopsis
Authors: Lim Geraldine AC , Jewell Erica G , Li Xi , Erwin Timothy A , Love Christopher , Batley Jacqueline , Spangenberg German , Edwards David
Published: July 2007

Background

Molecular genetic maps provide a means to link heritable traits with underlying genome sequence variation. Several genetic maps have been constructed for Brassica species, yet to date, there has been no simple means to compare this information or to associate mapped traits with the genome sequence of the related model plant, Arabidopsis.

Description

We have developed a comparative genetic map database for the viewing, comparison and analysis of Brassica and Arabidopsis genetic, physical and trait map information. This web-based tool allows users to view and compare genetic and physical maps, search for traits and markers, and compare genetic linkage groups within and between the amphidiploid and diploid Brassica genomes. The inclusion of Arabidopsis data enables comparison between Brassica maps that share no common markers. Analysis of conserved syntenic blocks between Arabidopsis and collated Brassica genetic maps validates the application of this system. This tool is freely available over the internet on http://bioinformatics.pbcbasc.latrobe.edu.au/cmap.

Conclusion

This database enables users to interrogate the relationship between Brassica genetic maps and the sequenced genome of A. thaliana, permitting the comparison of genetic linkage groups and mapped traits and the rapid identification of candidate genes.
In vivo MRI volumetric measurement of prostate regression and growth in mice
Authors: Nastiuk Kent L , Liu Hui , Hamamura Mark , Muftuler L Tugan , Nalcioglu Orhan , Krolewski John J
Published: July 2007

Background

Mouse models for treatment of late-stage prostate cancer are valuable tools, but assessing the extent of growth of the prostate and particularly its regression due to therapeutic intervention or castration is difficult due to the location, small size and interdigitated anatomy of the prostate gland in situ. Temporal monitoring of mouse prostate regression requires multiple animals and examination of histological sections.

Methods

Initially, T2-weighted magnetic resonance imaging (MRI) was performed on normal year-old C57/BL6 mice. Individual mice were repeatedly imaged using inhalation anesthesia to establish the reproducibility of the method and to follow hormone manipulation of the prostate volume. Subsequently, MRI fat signal was suppressed using a chemical shift-selective (CHESS) pulse to avoid signal contamination and enhance discrimination of the prostate.

Results

High field (7T) MRI provides high resolution (117 × 117 μm in plane), highly reproducible images of the normal mouse prostate. Despite long imaging times, animals can be imaged repeatedly to establish reliability of volume measurements. Prostate volume declines following castration and subsequently returns to normal with androgen administration in the same animal. CHESS imaging allowed discrimination of both the margins of the prostate and the dorsal-lateral lobes of the prostate (DLP) from the ventral lobes (VP). Castration results in a 40% reduction in the volume of the DLP and a 75% reduction in the volume of the VP.

Conclusion

MRI assessment of the volume of the mouse prostate is precise and reproducible. MRI improves volumetric determination of the extent of regression and monitoring of the same mouse over time during the course of treatment is possible. Since assessing groups of animals at each time point is avoided, this improves the accuracy of the measurement of any manipulation effect and reduces the number of animals required.
Magnetic resonance imaging of the knee in Norway 2002–2004 (national survey): rapid increase, older patients, large geographic differences
Authors: Espeland Ansgar , Natvig Nils L , Løge Ingard , Engebretsen Lars , Ellingsen Jostein
Published: July 2007

Background

Magnetic resonance imaging (MRI) of the knee is the second most common MRI examination in Norway after head/brain MRI. Little has been published internationally on trends in the use of knee MRI after 1999. This study aimed to describe levels and trends in ambulant knee MRI utilisation in Norway 2002–2004 in relation to type of radiology service, geographic regions, number of MRI-scanners, patient age and gender, and type of referring health care provider.

Methods

We analysed administrative data on all claims for reimbursement of ambulant knee MRI performed in Norway in 2002, 2003 and 2004 and noted nominal reimbursement. We also recorded the referring health care provider from clinical requests of ambulant knee MRI done consecutively during two months in 2004 at one private institute and three hospitals. Number of MRI-scanners was given by manufacturers and radiology services.

Results

In Norway, the rate of knee MRI claims for 2004 was 15.6 per 1000 persons. This rate was 74% higher in East than in North region (18.4 vs. 10.6), slightly higher for men than women (16.4 vs. 14.7) and highest for ages 50–59 years (29.0) and 60–69 years (21.2). Most claims (76% for 2004) came from private radiology services. In 2004, the referring health care provider was a general practitioner in 63% of claims (unspecified in 24%) and in 83.5% (394/472) of clinical requests. From 2002 to 2004, the rate of knee MRI claims increased 64%. In the age group 50 years or above the increase was 86%. Rate of MRI-scanners increased 43% to 21 scanners per million persons in 2004. Reimbursement for knee MRI claims (nominal value) increased 80% to 70 million Norwegian kroner in 2004.

Conclusion

Ambulant knee MRI utilisation in Norway increases rapidly especially for patients over 50, and shows large geographic differences. Evaluation of clinical outcomes of this activity is needed together with clinical guidelines for use of knee MRI.
Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep
Authors: Merimi Makram , Klener Pavel , Szynal Maud , Cleuter Yvette , Bagnis Claude , Kerkhofs Pierre , Burny Arsène , Martiat Philippe , Van den Broeke Anne
Published: July 2007

Background

During malignant progression, tumor cells need to acquire novel characteristics that lead to uncontrolled growth and reduced immunogenicity. In the Bovine Leukemia Virus-induced ovine leukemia model, silencing of viral gene expression has been proposed as a mechanism leading to immune evasion. However, whether proviral expression in tumors is completely suppressed in vivo was not conclusively demonstrated. Therefore, we studied viral expression in two selected experimentally-infected sheep, the virus or the disease of which had features that made it possible to distinguish tumor cells from their nontransformed counterparts.

Results

In the first animal, we observed the emergence of a genetically modified provirus simultaneously with leukemia onset. We found a Tax-mutated (TaxK303) replication-deficient provirus in the malignant B-cell clone while functional provirus (TaxE303) had been consistently monitored over the 17-month aleukemic period. In the second case, both non-transformed and transformed BLV-infected cells were present at the same time, but at distinct sites. While there was potentially-active provirus in the non-leukemic blood B-cell population, as demonstrated by ex-vivo culture and injection into naïve sheep, virus expression was completely suppressed in the malignant B-cells isolated from the lymphoid tumors despite the absence of genetic alterations in the proviral genome. These observations suggest that silencing of viral genes, including the oncoprotein Tax, is associated with tumor onset.

Conclusion

Our findings suggest that silencing is critical for tumor progression and identify two distinct mechanisms-genetic and epigenetic-involved in the complete suppression of virus and Tax expression. We demonstrate that, in contrast to systems that require sustained oncogene expression, the major viral transforming protein Tax can be turned-off without reversing the transformed phenotype. We propose that suppression of viral gene expression is a contributory factor in the impairment of immune surveillance and the uncontrolled proliferation of the BLV-infected tumor cell.
Celastrus aculeatusMerr. suppresses the induction and progression of autoimmune arthritis by modulating immune response to heat-shock protein 65
Authors: Tong Li , Moudgil Kamal D
Published: July 2007

Complementary and alternative medicine products are increasingly being used for the treatment of autoimmune diseases. However, the mechanisms of action of these agents are not fully defined. Using the rat adjuvant arthritis (AA) model of human rheumatoid arthritis, we determined whether the ethanol extract of Celastrus aculeatus Merr. (Celastrus), a Chinese herb, can down-modulate the severity of AA, and also examined the Celastrus-induced changes in immune responses to the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65). AA was induced in the Lewis (LEW; RT.1l) rat by immunization subcutaneously with heat-killed M. tuberculosis H37Ra (Mtb). Celastrus was fed to LEW rats by gavage daily, beginning either before Mtb challenge (preventive regimen) or after the onset of AA (therapeutic regimen). An additional group of rats was given methotrexate for comparison. All rats were graded regularly for the signs of arthritis. In parallel, the draining lymph node cells of Celastrus-treated rats were tested for proliferative and cytokine responses, whereas their sera were tested for the inflammatory mediator nitric oxide. Celastrus feeding suppressed both the induction as well as the progression of AA, and the latter effect was comparable to that of methotrexate. Celastrus treatment induced relative deviation of the cytokine response to anti-inflammatory type and enhanced the production of anti-Bhsp65 antibodies, which are known to be protective against AA. Celastrus feeding also reduced the levels of nitric oxide. On the basis of our results, we suggest further systematic exploration of Celastrus as an adjunct therapeutic modality for rheumatoid arthritis.
Breast cancer is a promising target for vaccination using cancer-testis antigens known to elicit immune responses
Authors: Taylor Mark , Bolton Louise M , Johnson Peter , Elliott Tim , Murray Nick
Published: July 2007

Introduction

Cancer-testis antigens (CTAGs) are expressed solely in germ cells and in malignant tissues. They are targets of immune responses mediated by cytotoxic T cells in some cancers, and there is much interest in developing vaccines that induce these responses. The purpose of the present study was to ascertain the frequency of expression of CTAGs in breast cancer.

Methods

Breast tumours were collected sequentially in the Southampton Tumour Bank from donors who had given written informed consent. Stored samples where there was sufficient material were sampled in sequence. An initial series of 42 tumours was screened for expression of 17 different CTAGs. A second panel of 40 tumours was screened for the expression of those antigens present in the first panel.

Results

Ninety-three per cent of tumours in the first series expressed at least one CTAG, and 62% expressed the single antigen CTAG1. Eighty per cent of tumours in the second series expressed at least one CTAG, 50% expressing CTAG1. Tumours exhibiting higher risk features tended to express more CTAGs.

Conclusion

More than two-thirds of breast cancers would be covered by a vaccine directed against just three CTAGs – CTAG1, BAGE1, and MAGEA10 – all of which are known to be targets of cytotoxic-T-lymphocyte responses.
Meta-analysis of primary target genes of peroxisome proliferator-activated receptors
Authors: Heinäniemi Merja , Uski J Oskari , Degenhardt Tatjana , Carlberg Carsten
Published: July 2007

Background

Peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the development of diseases, such as obesity, cardiovascular disease, type 2 diabetes and cancer. Here, an in silico screening method is presented, which incorporates experiment- and informatics-derived evidence, such as DNA-binding data of PPAR subtypes to a panel of PPAR response elements (PPREs), PPRE location relative to the transcription start site (TSS) and PPRE conservation across multiple species, for more reliable prediction of PPREs.

Results

In vitro binding and in vivo functionality evidence agrees with in silico predictions, validating the approach. The experimental analysis of 30 putative PPREs in eight validated PPAR target genes indicates that each gene contains at least one functional, strong PPRE that occurs without positional bias relative to the TSS. An extended analysis of the cross-species conservation of PPREs reveals limited conservation of PPRE patterns, although PPAR target genes typically contain strong or multiple medium strength PPREs. Human chromosome 19 was screened using this method, with validation of six novel PPAR target genes.

Conclusion

An in silico screening approach is presented, which allows increased sensitivity of PPAR binding site and target gene detection.
Fertility and Risk Factors for Elevated Infertility Concern in 10-Year Hematopoietic Cell Transplant Survivors and Case-Matched Controls
Authors: Hammond Camille , Abrams Janet R. , Syrjala Karen L.
Published: July 2007

Purpose

To describe fertility status and the prevalence of and risk factors for elevated infertility concern in 10-year adult cancer survivors who underwent myeloablative stem cell transplant (SCT).

Patients and Methods

Perceived fertility status, conception efforts, and infertility concern were reported before transplant and after 10 years by 120 cancer survivors who received myeloablative SCT and their case-matched controls.

Results

Respondents (including cases and controls) were predominantly white and married. Sex, age, race, ethnicity and education level were case matched. Four survivors (all males) conceived after completing cancer treatment, one with unassisted conception. Twenty-two percent of survivors compared with 9% of controls reported that they had looked into family-building options because of infertility (P = .009). Fourteen survivors (12%) compared with eight controls (7%) indicated that they had tried unsuccessfully to have children in the previous 10 years (P = not significant). One quarter of survivors had moderate to high levels of concern about infertility, compared with 7% of controls. A majority of survivors younger than age 40 years (n = 20; 54%) expressed elevated infertility concern. Survivors without children before transplant had greater risk of elevated concern after 10 years (odds ratio, 3.41; 95% CI, 1.93 to 11.30; P = .05). Although female controls were more likely to express elevated infertility concern (P = .007), sex did not discriminate concern among survivors.

Conclusion

The prevalence of infertility and related concerns is higher among long-term SCT survivors than among age-, sex-, and education-matched controls. Younger SCT recipients and those without children have persistent fertility-related needs even 10 years after treatment.
Low ERG and BAALC Expression Identifies a New Subgroup of Adult Acute T-Lymphoblastic Leukemia With a Highly Favorable Outcome
Authors: Baldus Claudia D. , Martus Peter , Burmeister Thomas , Schwartz Stefan , Gökbuget Nicola , Bloomfield Clara D. , Hoelzer Dieter , Thiel Eckhard , Hofmann Wolf K.
Published: July 2007

Purpose

Expression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia. We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile.

Patients and Methods

ERG and BAALC mRNA expression were determined by real-time reverse transcriptase polymerase chain reaction in 153 adults with T-ALL. Patients were designated low or high ERG expressers and low or high BAALC expressers.

Results

High BAALC expression correlated with a higher frequency of early T-ALL (P < .0001), CD34 positivity (P < .0001), coexpression of myeloid markers (P = .0001), and high ERG expression (P = .03). High BAALC compared with low BAALC patients had an inferior relapse-free survival (RFS; P = .0008) and overall survival (OS; P = .0001). In contrast, patients with low expression of both ERG and BAALC (representing 41% of all T-ALL patients) had the most favorable outcome (P < .0001; 4-year RFS: low ERG/low BAALC 81%; P < .0001; 4-year OS: low ERG/low BAALC 69%). On multivariable analysis, low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, P = .001; OS, P = .003).

Conclusion

Low expression of both ERG and BAALC identifies T-ALL patients with a distinctly favorable long-term outcome.
Early Interim 2-[18F]Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Is Prognostically Superior to International Prognostic Score in Advanced-Stage Hodgkin's Lymphoma: A Report From a Joint Italian-Danish Study
Authors: Gallamini Andrea , Hutchings Martin , Rigacci Luigi , Specht Lena , Merli Francesco , Hansen Mads , Patti Caterina , Loft Annika , Di Raimondo Francesco , D'Amore Francesco , Biggi Alberto , Vitolo Umberto , Stelitano Caterina , Sancetta Rosario , Trentin Livio , Luminari Stefano , Iannitto Emilio , Viviani Simonetta , Pierri Ivana , Levis Alessandro
Published: July 2007

Purpose

Starting from November 2001, 260 newly diagnosed patients with Hodgkin's lymphoma (HL) were consecutively enrolled in parallel Italian and Danish prospective trials to evaluate the prognostic role of an early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan and the International Prognostic Score (IPS) in advanced HL, treated with conventional ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy.

Patients and Methods

Most patients (n = 190) presented with advanced disease (stages IIB through IVB), whereas 70 presented in stage IIA with adverse prognostic factors. All but 11 patients were treated with standard ABVD therapy followed by consolidation radiotherapy in case of bulky presentation or residual tumor mass. Conventional radiologic staging was performed at baseline. FDG-PET scan was performed at baseline and after two courses of ABVD (PET-2). No treatment change was allowed on the basis of the PET-2 results.

Results

After a median follow-up of 2.19 years (range, 0.32 to 5.18 years), 205 patients were in continued complete remission and two patients were in partial remission. Forty-three patients progressed during therapy or immediately after, whereas 10 patients relapsed. The 2-year progression-free survival for patients with positive PET-2 results was 12.8% and for patients with negative PET-2 results was 95.0% (P < .0001). In univariate analysis, the treatment outcome was significantly associated with PET-2 (P < .0001), stage IV (P < .0001), WBC more than 15,000 (P < .0001), lymphopenia (P < .001), IPS as a continuous variable (P < .0001), extranodal involvement (P < .0001), and bulky disease (P = .012). In multivariate analyses, only PET-2 turned out to be significant (P < .0001).

Conclusion

PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL.
Inventory, Speculation, and Sourcing Strategies in the Presence of Online Exchanges
Authors: Milner Joseph M. , Kouvelis Panos
Published: July 2007

We study how online business-to-business (B2B) exchanges affect buyer-supplier relationships where an exchange takes the role of a secondary market in which buyers (of the initial product) can trade excess inventory to address supply and demand imbalances. Over the last several years, B2B exchanges have attempted to provide supply for storable industrial goods with some degree of design specification (as opposed to undifferentiated commodities). Through this research, we elucidate some aspects of how speculative online exchanges with a small number of participants might behave and the impact they will have on the use of long-term contracts for supply. By endogenizing the evolution of spot prices in response to buyers’ and their supplier’s actions, we produce price fluctuations that exhibit significant autocorrelation in such markets. We show that participating buyers accrue network benefits as the number of participating firms increases through the inventory-pooling effects, resulting in reduced costs for them. However, a supplier acting strategically will counteract such benefits by restricting availability of goods to the spot market, sacrificing short-term spot-market revenue for long-term contract volume.
Optimal Due Date Assignment and Resource Allocation to Minimize the Weighted Number of Tardy Jobs on a Single Machine
Authors: Shabtay Dvir , Steiner George
Published: July 2007

With the increased emphasis on the effective management of operational issues in supply chains, the timely delivery of products has become even more important. Companies have to quote attainable delivery dates and then meet these, or face large tardiness penalties. We study systems that can be modeled by single-machine scheduling problems with due date assignment and controllable job-processing times, which are either linear or convex functions of the amount of a continuously divisible and nonrenewable resource that is allocated to the task. The due date assignment methods studied include the common due date, the slack due date, which reflects equal waiting time allowance for the jobs, and the most general method of unrestricted due dates, when each job may be assigned a different due date. For each combination of due date assignment method and processing-time function, we provide a polynomial-time algorithm to find the optimal job sequence, due date values, and resource allocations that minimize an integrated objective function, which includes the weighted number of tardy jobs, and due date assignment, makespan, and total resource consumption costs.
Implementation of the Newsvendor Model with Clearance Pricing: How to (and How Not to) Estimate a Salvage Value
Authors: Cachon Gérard P. , Kök A. Gürhan
Published: July 2007

The newsvendor model is designed to decide how much of a product to order when the product is to be sold over a short selling season with stochastic demand and there are no additional opportunities to replenish inventory. There are many practical situations that reasonably conform to those assumptions, but the traditional newsvendor model also assumes a fixed salvage value: all inventory left over at the end of the season is sold off at a fixed per-unit price. The fixed salvage value assumption is questionable when a clearance price is rationally chosen in response to the events observed during the selling season: a deep discount should be taken if there is plenty of inventory remaining at the end of the season, whereas a shallow discount is appropriate for a product with higher than expected demand. This paper solves for the optimal order quantity in the newsvendor model, assuming rational clearance pricing. We then study the performance of the traditional newsvendor model. The key to effective implementation of the traditional newsvendor model is choosing an appropriate fixed salvage value. (We show that an optimal order quantity cannot be generally achieved by merely enhancing the traditional newsvendor model to include a nonlinear salvage value function.) We demonstrate that several intuitive methods for estimating the salvage value can lead to an excessively large order quantity and a substantial profit loss. Even though the traditional model can result in poor performance, the model seems as if it is working correctly: the order quantity chosen is optimal given the salvage value inputted to the model, and the observed salvage value given the chosen order quantity equals the inputted one. We discuss how to estimate a salvage value that leads the traditional newsvendor model to the optimal or near-optimal order quantity. Our results highlight the importance of understanding how a model can interact with its own inputs: when inputs to a model are influenced by the decisions of the model, care is needed to appreciate how that interaction influences the decisions recommended by the model and how the model’s inputs should be estimated.
Minimizing culpability increases commission errors in a mock crime paradigm
Authors: van Oorsouw K. , Giesbrecht T.
Published: July 2007

Purpose. Empirical studies have demonstrated that feigning amnesia undermines memory for a mock crime. Not much is known about the effects of other culpability‐reducing strategies on memory. The present study investigated what strategies participants use when they are instructed to minimize culpability and if these strategies undermine memory to a similar extent as claiming amnesia.

Methods. Participants performed a mock crime. Next, they were either instructed to minimize culpability for this mock crime in a simulated interrogation or asked to respond honestly. One week later, memory for the mock crime was tested.

Results. None of the participants claimed amnesia when trying to minimize culpability. Conversely, all participants fabricated an alternative account of their role in the crime. Compared with responding honestly on both tests, fabricating an alternative story on the first test undermined memory for the mock crime in terms of commission errors. Correct recall was unaffected. It appeared that this effect was related to story length: the longer the fabricated story, the more the commission errors when telling the truth 1 week later.

Conclusions. Fabricating an alternative story (i.e. lying) did not compromise correct recall, but induced more commission errors. The findings are discussed in terms of possible underlying mechanisms.