bluuebunny/crossref_metadata_2025 huggingface dataset:
The clathrin-binding motif and the J-domain of Drosophila Auxilin are essential for facilitating Notch ligand endocytosis
Authors: Kandachar Vasundhara , Bai Ting , Chang Henry C
Published: May 2008

Background

Ligand endocytosis plays a critical role in regulating the activity of the Notch pathway. The Drosophila homolog of auxilin (dAux), a J-domain-containing protein best known for its role in the disassembly of clathrin coats from clathrin-coated vesicles, has recently been implicated in Notch signaling, although its exact mechanism remains poorly understood.

Results

To understand the role of auxilin in Notch ligand endocytosis, we have analyzed several point mutations affecting specific domains of dAux. In agreement with previous work, analysis using these stronger dAux alleles shows that dAux is required for several Notch-dependent processes, and its function during Notch signaling is required in the signaling cells. In support of the genetic evidences, the level of Delta appears elevated in dAux deficient cells, suggesting that the endocytosis of Notch ligand is disrupted. Deletion analysis shows that the clathrin-binding motif and the J-domain, when over-expressed, are sufficient for rescuing dAux phenotypes, implying that the recruitment of Hsc70 to clathrin is a critical role for dAux. However, surface labeling experiment shows that, in dAux mutant cells, Delta accumulates at the cell surface. In dAux mutant cells, clathrin appears to form large aggregates, although Delta is not enriched in these aberrant clathrin-positive structures.

Conclusion

Our data suggest that dAux mutations inhibit Notch ligand internalization at an early step during clathrin-mediated endocytosis, before the disassembly of clathrin-coated vesicles. Further, the inhibition of ligand endocytosis in dAux mutant cells possibly occurs due to depletion of cytosolic pools of clathrin via the formation of clathrin aggregates. Together, our observations argue that ligand endocytosis is critical for Notch signaling and auxilin participates in Notch signaling by facilitating ligand internalization.
Performance of a 70-mer oligonucleotide microarray for genotyping of Campylobacter jejuni
Authors: Rodin Sandra , Andersson Anders F , Wirta Valtteri , Eriksson Lena , Ljungström Marianne , Björkholm Britta , Lindmark Hans , Engstrand Lars
Published: May 2008

Background

Campylobacter jejuni is widespread in the environment and is the major cause of bacterial gastroenteritis in humans. In the present study we use microarray-based comparative genomic hybridizations (CGH), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to analyze closely related C. jejuni isolates from chicken and human infection.

Results

With the exception of one isolate, the microarray data clusters the isolates according to the five groups determined by PFGE. In contrast, MLST defines only three genotypes among the isolates, indicating a lower resolution. All methods show that there is no inherit difference between isolates infecting humans and chicken, suggesting a common underlying population of C. jejuni. We further identify regions that frequently differ between isolates, including both previously described and novel regions. Finally, we show that genes that belong to certain functional groups differ between isolates more often than expected by chance.

Conclusion

In this study we demonstrated the utility of 70-mer oligonucleotide microarrays for genotyping of Campylobacter jejuni isolates, with resolution outperforming MLST.
Association between amebic liver abscess and Human Immunodeficiency Virus infection in Taiwanese subjects
Authors: Hsu Meng-Shuian , Hsieh Szu-Min , Chen Mao-Yuan , Hung Chien-Ching , Chang Shan-Chwen
Published: May 2008

Purpose

Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated.

Results

Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis.

Conclusion

While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.
Discontinuation rates in clinical trials in musculoskeletal pain: meta-analysis from etoricoxib clinical trial reports
Authors: Moore R Andrew , Derry Sheena , McQuay Henry J
Published: May 2008

Introduction

Patient adherence to therapy in clinical practice is often low, and the difference between efficacy measured in clinical trials and effectiveness in clinical practice is probably a function of discontinuation of therapy because of lack of efficacy or because of unmanageable or intolerable adverse events. Discontinuation is frequently measured in clinical trials but is not usually described in detail in published reports, often because of limitations in the size of publications. By contrast, company clinical trial reports include much more detail.

Methods

We examined company clinical trial reports of trials involving etoricoxib in four musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, chronic low back pain and ankylosing spondylitis. Information was available from 18 randomized trials (10,143 patients) lasting 4 to 12 weeks (one 4 weeks, three 6 weeks, one 8 weeks and seven 12 weeks) and from three trials with a mean duration of about 80 weeks (34,695 patients). These clinical trial reports contain over 73,000 pages of information.

Results

Over 12 weeks, lack of efficacy and adverse event discontinuations were similar between osteoarthritis, rheumatoid arthritis and back pain, with lack of efficacy discontinuation rates some three times higher than for adverse events. All-cause and lack of efficacy discontinuations were lower with etoricoxib (all doses combined) and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) than with placebo, although NSAIDs produced higher rates of clinical adverse events and gastrointestinal discontinuations than did placebo. Etoricoxib had fewer discontinuations than NSAIDs for lack of efficacy, clinical adverse events, and laboratory and gastrointestinal adverse events, but with more discontinuations because of hypertension and oedema. Comparison with two similar meta-analyses of other cyclo-oxygenase-2 selective inhibitors (more than 80,000 patients in total) revealed consistency between analyses.

Conclusion

Examining discontinuation data from clinical trials, even when the numbers of patients are very large, does not necessarily predict what will happen in the real world, where clinical effectiveness may differ from clinical efficacy assessed in trials. Data from these analyses appears to agree with findings from real world practice.
Severe hyperlactatemia with normal base excess: a quantitative analysis using conventional and Stewart approaches
Authors: Tuhay Graciela , Pein María Carolina , Masevicius Fabio Daniel , Kutscherauer Daniela Olmos , Dubin Arnaldo
Published: May 2008

Introduction

Critically ill patients might present complex acid–base disorders, even when the pH, PCO2, [HCO3-], and base excess ([BE]) levels are normal. Our hypothesis was that the acidifying effect of severe hyperlactatemia is frequently masked by alkalinizing processes that normalize the [BE]. The goal of the present study was therefore to quantify these disorders using both Stewart and conventional approaches.

Methods

A total of 1,592 consecutive patients were prospectively evaluated on intensive care unit admission. Patients with severe hyperlactatemia (lactate level ≥ 4.0 mmol/l) were grouped according to low or normal [BE] values (<-3 mmol/l or >-3 mmol/l).

Results

Severe hyperlactatemia was present in 168 of the patients (11%). One hundred and thirty-four (80%) patients had low [BE] levels while 34 (20%) patients did not. Shock was more frequently present in the low [BE] group (46% versus 24%, P = 0.02) and chronic obstructive pulmonary disease in the normal [BE] group (38% versus 4%, P < 0.0001). Levels of lactate were slightly higher in patients with low [BE] (6.4 ± 2.4 mmol/l versus 5.6 ± 2.1 mmol/l, P = 0.08). According to our study design, the pH, [HCO3-], and strong-ion difference values were lower in patients with low [BE]. Patients with normal [BE] had lower plasma [Cl-] (100 ± 6 mmol/l versus 107 ± 5 mmol/l, P < 0.0001) and higher differences between the changes in anion gap and [HCO3-] (5 ± 6 mmol/l versus 1 ± 4 mmol/l, P < 0.0001).

Conclusion

Critically ill patients may present severe hyperlactatemia with normal values of pH, [HCO3-], and [BE] as a result of associated hypochloremic alkalosis.
Redefining the Role of Doxorubicin for the Treatment of Children With Hepatoblastoma
Authors: Malogolowkin Marcio H. , Katzenstein Howard M. , Krailo Mark , Chen Zhengjia , Quinn John J. , Reynolds Marleta , Ortega Jorge A.
Published: May 2008

Purpose

Systemic chemotherapy has improved the survival of patients with hepatoblastoma (HB). INT-0098 Intergroup Liver Tumor Study demonstrated that patients with HB treated with either cisplatin/fluorouracil/vincristine (CFV) or cisplatin/doxorubicin (CD) had a similar survival. The Children's Oncology Group adopted the less toxic CFV as the standard regimen for treating HB. However, international cooperative groups still favor the CD combination. We therefore decided to revisit the role of doxorubicin for the treatment of HB.

Methods

Outcomes of patients with HB on the INT-0098 study were reviewed with an emphasis on the postevent survival time for both regimens to elucidate the role of doxorubicin in their retrieval.

Results

Sixty-four of the 173 randomly assigned patients had an event. Of these, 55 experienced progression or recurrence after initial treatment. Eleven (31%) of 36 patients treated with CFV were successfully retrieved with a doxorubicin-containing regimen and surgery and remain alive at last contact, whereas only one (6%) of 18 patients treated with CD was alive after retrieval therapy.

Conclusion

CFV is effective for stage I or II HB. Doxorubicin can be omitted as part of initial therapy in the majority of these patients, potentially limiting the long-term cardiac toxicities, without compromising outcome. Doxorubicin is effective in rescuing patients with recurrent disease after CFV and should be incorporated as a means of intensifying initial therapy for advanced-stage, nonmetastatic HB. Outcome of patients with metastatic disease at diagnosis is poor, and improving their survival will require new therapeutic approaches.
Bortezomib With or Without Irinotecan in Relapsed or Refractory Colorectal Cancer: Results From a Randomized Phase II Study
Authors: Kozuch Peter S. , Rocha-Lima Caio Max , Dragovich Tomislav , Hochster Howard , O'Neil Bert H. , Atiq Omar T. , Pipas J. Marc , Ryan David P. , Lenz Heinz-Josef
Published: May 2008

Purpose

To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC).

Patients and Methods

Patients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m2 (arm A) or bortezomib 1.3 mg/m2 plus irinotecan 125 mg/m2 (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability.

Results

A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade ≥ 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B.

Conclusion

Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC.
Quantitative Analysis of Methylation of Genomic Loci in Early-Stage Rectal Cancer Predicts Distant Recurrence
Authors: de Maat Michiel F.G. , van de Velde Cornelis J.H. , van der Werff Martijn P.J. , Putter Hein , Umetani Naoyuki , Klein-Kranenbarg Elma Meershoek , Turner Roderick R. , van Krieken J. Han J.M. , Bilchik Anton , Tollenaar Rob A.E.M. , Hoon Dave S.B.
Published: May 2008

Purpose

There are no accurate prognostic biomarkers specific for rectal cancer. Epigenetic aberrations, in the form of DNA methylation, accumulate early during rectal tumor formation. In a preliminary study, we investigated absolute quantitative methylation changes associated with tumor progression of rectal tissue at multiple genomic methylated-in-tumor (MINT) loci sequences. We then explored in a different clinical patient group whether these epigenetic changes could be correlated with clinical outcome.

Patients and Methods

Absolute quantitative assessment of methylated alleles was used to assay methylation changes at MINT 1, 2, 3, 12, 17, 25, and 31 in sets of normal, adenomatous, and malignant tissues from 46 patients with rectal cancer. Methylation levels of these biomarkers were then assessed in operative specimens of 251 patients who underwent total mesorectal excision (TME) without neoadjuvant radiotherapy in a multicenter clinical trial.

Results

Methylation at MINT 2, 3, and 31 increased 11-fold (P = .005), 15-fold (P < .001), and two-fold (P = .02), respectively, during adenomatous transformation in normal rectal epithelium. Unsupervised grouping analyses of quantitative MINT methylation data of TME trial patients demonstrated two prognostic subclasses. In multivariate analysis of node-negative patients, this subclassification was the only predictor for distant recurrence (hazard ratio [HR], 4.17; 95% CI, 1.72 to 10.10; P = .002), cancer-specific survival (HR, 3.74; 95% CI, 1.4 to 9.43; P = .003), and overall survival (HR, 2.68; 95% CI, 1.41 to 5.11; P = .005).

Conclusion

Methylation levels of specific MINT loci can be used as prognostic variables in patients with American Joint Committee on Cancer stage I and II rectal cancer. Quantitative epigenetic classification of rectal cancer merits evaluation as a stratification factor for adjuvant treatment in early disease.
Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial
Authors: Ravaud Alain , Hawkins Robert , Gardner Jason P. , von der Maase Hans , Zantl Niko , Harper Peter , Rolland Frédéric , Audhuy Bruno , Machiels Jean-Pascal , Pétavy Frank , Gore Martin , Schöffski Patrick , El-Hariry Iman
Published: May 2008

Purpose

Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2–positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2.

Patients and Methods

Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy—stratified by Karnofsky performance status and number of metastatic sites—were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses.

Results

Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%).

Conclusion

Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.
Use of Antidepressants and Risk of Cancer in Individuals Infected With HIV
Authors: Stebbing Justin , Powles Tom , Mandalia Sundhiya , Nelson Mark , Gazzard Brian , Bower Mark
Published: May 2008

Purpose

Preclinical and cohort studies suggest that certain antidepressants are associated with a predisposition to cancer whereas others decrease the risk. We aimed to assess whether different classes of antidepressants were associated with changes in cancer incidence in a population of HIV-1 infected individuals, based on duration of exposure.

Methods

Antidepressant exposure was measured from date of first prescription of the antidepressant until the date of last follow-up or cancer diagnosis. Univariate and multivariate analyses were performed to establish the risk of AIDS-related cancers and non–AIDS-related cancers according to whether patients were receiving selective serotonin reuptake inhibitors, tricyclic antidepressants, or other medicines for depression. We analyzed data for time exposed to antidepressants, before and during the era of highly active antiretroviral therapy (HAART).

Results

From a cohort of 10,997 patients representing 52,656 years of follow-up attending a large HIV center during the pre-HAART and HAART eras, a total of 2,004 (18%) were prescribed antidepressants representing 15,850 years exposed. A total of 1,607 (15%) individuals were diagnosed with cancer. There were no significant associations between any class of antidepressant and any type of cancer (P = .19), in either the pre-HAART or HAART era (P = .23), and use of serotonin reuptake inhibitors did not alter the risk of Burkitt lymphoma.

Conclusion

Antidepressants, irrespective of their class, do not affect cancer risk in HIV-infected individuals.
The effect of endovenous laser ablation on restless legs syndrome
Authors: Hayes C A , Kingsley J R , Hamby K R , Carlow J
Published: May 2008

Objectives

Venous disease was proposed as a cause of restless legs syndrome (RLS) by Dr Karl A Ekbom in 1944, but has since remained largely unexplored. This study examines the effect of endovenous laser ablation (ELA) in patients with concurrent RLS and duplex-proven superficial venous insufficiency (SVI).

Methods

Thirty-five patients with moderate to very severe RLS (as defined by the 2003 National Institute of Health (NIH) RLS criteria) and duplex-proven SVI completed an international RLS rating scale questionnaire (IRLS) and underwent standard duplex examination to objectively measure the baseline severity of their conditions. They were separated into non-operative and operative cohorts. The operative cohort underwent ELA of refluxing superficial axial veins using the CoolTouch CTEV 1320 nm laser and ultrasound-guided sclerotherapy of the associated varicose veins with foamed sodium tetradecyl sulphate (STS). All patients then completed a follow-up IRLS questionnaire. Baseline and follow-up IRLS scores were compared.

Results

Operative correction of the SVI decreased the mean IRLS score by 21.4 points from 26.9 to 5.5, corresponding to an average of 80% improvement in symptoms. A total of 89% of patients enjoyed a decrease in their score of ≥15 points. Fifty-three percent of patients had a follow-up score of ≤5, indicating their symptoms had been largely alleviated and 31% had a follow-up score of zero, indicating a complete relief of RLS symptoms.

Conclusions

ELA of refluxing axial veins with the CTEV 1320 nm laser and foamed STS sclerotherapy of associated varicosities alleviates RLS symptoms in patients with SVI and moderate to very severe RLS.

Recommendations

SVI should be ruled-out in all patients with RLS before initiation or continuation of drug therapy.
Molecular architecture of a miRNA-regulated 3′ UTR
Authors: Didiano Dominic , Hobert Oliver
Published: May 2008

Animal genomes contain hundreds of microRNAs (miRNAs), small regulatory RNAs that control gene expression by binding to complementary sites in target mRNAs. Some rules that govern miRNA/target interaction have been elucidated but their general applicability awaits further experimentation on a case-by-case basis. We use here an assay system in transgenic nematodes to analyze the interaction of the Caenorhabditis elegans lsy-6 miRNA with 3′ UTR sequences. In contrast to many previously described assay systems used to analyze miRNA/target interactions, our assay system operates within the cellular context in which lsy-6 normally functions, a single neuron in the nervous system of C. elegans. Through extensive mutational analysis, we define features in the known and experimentally validated target of lsy-6, the 3′ UTR of the cog-1 homeobox gene, that are required for a functional miRNA/target interaction. We describe that both in the context of the cog-1 3′ UTR and in the context of heterologous 3′ UTRs, one or more seed matches are not a reliable predictor for a functional miRNA/target interaction. We rather find that two nonsequence specific contextual features beyond miRNA target sites are critical determinants of miRNA-mediated 3′ UTR regulation. The contextual features reside 3′ of lsy-6 binding sites in the 3′ UTR and act in a combinatorial manner; mutation of each results in limited defects in 3′ UTR regulation, but a combinatorial deletion results in complete loss of 3′ UTR regulation. Together with two lsy-6 sites, these two contextual features are capable of imparting regulation on a heterologous 3′ UTR. Moreover, the contextual features need to be present in a specific configuration relative to miRNA binding sites and could either represent protein binding sites or provide an appropriate structural context. We conclude that a given target site resides in a 3′ UTR context that evolved beyond target site complementarity to support regulation by a specific miRNA. The large number of 3′ UTRs that we analyzed in this study will also be useful to computational biologists in designing the next generation of miRNA/target prediction algorithms.
A Multiobjective Branch-and-Bound Framework: Application to the Biobjective Spanning Tree Problem
Authors: Sourd Francis , Spanjaard Olivier
Published: May 2008

This paper focuses on a multiobjective derivation of branch-and-bound procedures. Such a procedure aims to provide the set of Pareto-optimal solutions of a multiobjective combinatorial optimization problem. Unlike previous works on this issue, the bounding is performed here via a set of points rather than a single ideal point. The main idea is that a node in the search tree can be discarded if one can define a separating hypersurface in the objective space between the set of feasible solutions in the subtree and the set of points corresponding to potential Pareto-optimal solutions. Numerical experiments on the biobjective spanning tree problem are provided that show the efficiency of the approach in a biobjective setting.
Practice Prize Report—The Power of CLV: Managing Customer Lifetime Value at IBM
Authors: Kumar V. , Venkatesan Rajkumar , Bohling Tim , Beckmann Denise
Published: May 2008

Customer management activities at firms involve making consistent decisions over time, about: (a) which customers to select for targeting, (b) determining the level of resources to be allocated to the selected customers, and (c) selecting customers to be nurtured to increase future profitability. Measurement of customer profitability and a deep understanding of the link between firm actions and customer profitability are critical for ensuring the success of the above decisions. We present the case study of how IBM used customer lifetime value (CLV) as an indicator of customer profitability and allocated marketing resources based on CLV. CLV was used as a criterion for determining the level of marketing contacts through direct mail, telesales, e-mail, and catalogs for each customer. In a pilot study implemented for about 35,000 customers, this approach led to reallocation of resources for about 14% of the customers as compared to the allocation rules used previously (which were based on past spending history). The CLV-based resource reallocation led to an increase in revenue of about $20 million (a tenfold increase) without any changes in the level of marketing investment. Overall, the successful implementation of the CLV-based approach resulted in increased productivity from marketing investments. We also discuss the organizational and implementation challenges that surrounded the adoption of CLV in this firm.
Logos and Initial Compliance: A Strong Case of Mindless Trust
Authors: Rafaeli Anat , Sagy Yael , Derfler-Rozin Rellie
Published: May 2008

In four studies we examine the relationship between the presence of an organizational logo and initial compliance with a request made by a stranger and document higher compliance rates in the presence than in the absence of the logo. Study 1 verified this relationship in the field, and Study 2 replicated the field findings in a lab setting. Study 2 also confirmed trust as a mediator and risk as a moderator of this relationship, showing that trust and greater compliance are produced by the presence of a logo in high-risk but not in low-risk situations. Study 3 confirmed the moderating effects of risk on these findings in a field setting. Study 4 then used a lab set-up to confirm generalization of the findings to different logos. The findings hold important implications for research and management of symbols, trust, and compliance in organizations and for organization theory on initial trust and compliance.
Institutional Ownership and Monitoring Effectiveness: It's Not Just How Much but What Else You Own
Authors: Dharwadkar Ravi , Goranova Maria , Brandes Pamela , Khan Raihan
Published: May 2008

Corporate governance research indicates that large owners provide effective monitoring. In this article, we expand firm-level notions of monitoring to include large institutional owners' investment portfolios and suggest that portfolio characteristics affect owners' motivation and capacity to monitor, which compromises the positive effects of monitoring at the firm level. Specifically, using data from 533 large firms over a 10-year period, we find that increases in the size of portfolio holdings, number of portfolio blockholdings, portfolio turnover, and the importance of a particular holding reduce monitoring effectiveness in the context of executive compensation. Overall, we provide preliminary evidence that the portfolio characteristics of the largest institutional owners contradict firm-level monitoring effects; therefore, we strongly recommend that future studies consider both firm- and portfolio-level effects simultaneously to understand monitoring effectiveness.
New Directions in Corporate Governance Research
Authors: Hambrick Donald C. , Werder Axel v. , Zajac Edward J.
Published: May 2008

In this essay, we seek to identify the contributions that strategy and organizational researchers have made, and continue to make, in enhancing our understanding of a wide variety of important corporate governance questions. We begin by discussing how these research contributions stem from a willingness to draw from and contribute to different streams of intellectual thought, and we provide an orienting framework to situate this work.
Direct Determination of the Experimentally Observed Penetration Depth of the Evanescent Field via Near-Infrared Absorptions Enhanced by the Off-Resonance of Surface Plasmons
Authors: Ikehata Akifumi , Ohara Kazuaki , Ozaki Yukihiro
Published: May 2008

Recently, absorption-sensitive surface plasmon resonance (SPR) techniques have attracted much attention. SPR near-infrared spectroscopy (SPR-NIRS) based on the Kretschmann configuration is one of the techniques for absorption enhancement. The enhanced spectrum obtained by SPR-NIRS basically corresponds to the measurement of an NIR absorption spectrum with a very short path length. However, the path length cannot be applied for Lambert's law due to the enhanced evanescent field. A direct determination of the penetration depth of the evanescent field is carried out via NIR absorptions enhanced by the off-resonance of surface plasmons, which is a principle of SPR-NIRS. The signal intensities of the enhanced NIR spectra of micrometer-thick polymer films having various thicknesses are compared with the classic theory of penetration depth. It is confirmed that the effective depth of the SPR-NIRS measurement can be expressed by the classic theory of penetration depth of the evanescent field proposed by Harrick.
Lipid Compositions and French Registered Designations of Origins of Virgin Olive Oils Predicted by Chemometric Analysis of Mid-Infrared Spectra
Authors: Galtier O. , Dréau Y. LE , Ollivier D. , Kister J. , Artaud J. , Dupuy N.
Published: May 2008

The combination of mid-infrared (MIR) spectroscopy with multivariate analysis provides an original approach to study the profile of virgin olive oils (VOOs) in relation to composition and geographical origin. Chemometric treatment of mid-infrared spectra ( n = 402) is assessed for quantification of fatty acids (14 components) and triacylglycerols (19 components) in VOO samples and for classification into six very geographically closed registered designations of origin (RDOs) of French VOO (“Aix-en-Provence”, “Haute-Provence”, “Vallée des Baux de Provence”, “Nice”, “Nîmes”, and “Nyons”). Spectroscopic interpretation of regression vectors has shown that each RDO is correlated to one specific component of VOO according to their cultivar compositions. The results are satisfactory, in spite of the similarity of cultivar compositions between two denominations of origin (“Aix-en-Provence” and “Vallée des Baux de Provence”). Chemometric treatment of MIR spectra makes it possible to obtain similar results to those obtained by time-consuming analytical techniques such as gas chromatography (GC) and high-performance liquid chromatography (HPLC) and constitutes a fast and robust tool for authentication of these French VOOs.
Attenuated Total Reflection Fourier Transform Infrared Spectroscopy Analysis of Human Hair Fiber Structure
Authors: Lyman Donald J. , Schofield Paula
Published: May 2008

The structure of human hair was studied by attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy. The use of Ge, ZnSe, and Si internal reflection elements, various incident light angles, and difference spectra allowed detailed analysis of the cuticle, cortex, and cuticle–cortex intercellular regions without physically or mechanically removing the cuticle of the hair fiber. The ATR-FT-IR data showed the cuticle to be composed of protein having predominately beta-sheet and disorder and beta-turn configurations. In contrast, the cortex spectra showed alpha-helical structures due to the presence of intermediate filaments of alpha keratin plus beta-sheet, beta-turn and disorder structures. In the cuticle–cortex interface region the protein structures were primarily disorder and beta-turn with small amounts of beta-sheet configurations. The spectral analyses are consistent with the general information on hair fiber structure proposed in the literature.
Welcome to Dreamland: The realist impulse in Pawel Pawlikowski's Last Resort
Authors: Bardan Alice
Published: May 2008

After first exploring Pawel Pawlikowski's status as an outsider in British cinema through a brief comparison to German director Fatih Akin, I focus on Pawlikowski's film Last Resort (UK, 2000) to assess and problematize its portrayal of refugees. I argue that rather than relying
on open didacticism, Pawlikowski's representation of asylum seekers defies the established conventions of the genre, highlighting the fragility of hospitable conventions. Neither portraying them as despairing victims lacking agency nor commending them as virtuous heroes (as if by default),
Last Resort does not allow its spectators an easy access to the spectacle of the Others' suffering. Instead, it points to the discrepancy between the projected image of Britain as a welcoming country and the exclusions through which it operates. Moreover, the focus on a Russian woman's
narrative provides the opportunity to open up a discussion on how whiteness is negotiated in a European context. Given that a majority of films portray Britain as a utopian land strongly desired by migrants, Pawlikowski's significant intervention is that he ultimately presents it as a counter-utopia,
a space from which one wishes to escape. Since Pawlikowski's poetic realism has been aligned with that of Michael Winterbottom's, in the last part of the article I discuss Last Resort in conjunction with Winterbottom's Wonderland (UK, 1999).
Corrosion of Phosphoric Irons in Acidic Environments
Authors: Sahoo Gadadhar , Balasubramaniam R.
Published: May 2008

The corrosion behavior of phosphoric irons (i.e., Fe-P alloys containing low phosphorus in the range 0.1 to 0.5 wt. %), prepared by ingot metallurgy route, was evaluated in acidic and chloride environments, e.g., 0.25 M H2SO4 of pH 0.6, 0.5 M Na2SO4 of pH 3 and 3.5 % NaCl of pH 6.8. A plain carbon steel and a low alloy (Cu-Cr) steel were also studied for comparison purpose. The effect of Cu and Cr additions was beneficial in a highly acidic condition. While similar corrosion rates observed for plain carbon steel and low alloy steel in 0.5 M Na2SO4 of pH 3, a slightly higher corrosion rate was observed for phosphoric irons. All alloys exhibited lowest and similar corrosion rates in neutral 3.5 % NaCl corrosive media. The linearity of Tafel slopes in the cathodic region varied with the pH of the solution. Corrosion rates were higher at lower pH due to the major contribution of hydrogen evolution reaction to the cathodic current.
Macedonian discourse markers in the Balkan Sprachbund
Authors: Fielder Grace E.
Published: May 2008

This paper examines the adversative discourse markers ама and ами in Macedonian in order to shed light on the interdependence of typology and convergence. Macedonian is typically located in the center of the Balkan Sprachbund. At the same time, a comparison of these two particular discourse markers in Macedonian and Bulgarian, both Balkan Slavic languages, demonstrates that a simplistic application of the criterion of Turkish borrowings would suggest that Bulgarian be considered the more central member of the Balkan Sprachbund. What the following discussion will reveal, however, is that the source of borrowing (i.e. Turkish versus Greek) is not as important as the actual fact of borrowing, i.e. the intensity of multilingual contact, for the determination of centrality.
Advantages and disadvantages of late standardization
Authors: Topolińska Zuzanna
Published: May 2008

The author analyzes the linguistic and extralinguistic factors which have influenced processes of standardization of the Macedonian language and processes of implementation of the standard norm. She compares the Macedonian situation with the situation in other Slavic linguistic communities.
Chrissy Caviar
Authors: stark jim
Published: May 2008

CHRISSY CAVIAR©© ("the world's most expensive luxury consumable item") is the creation of New York artist Chrissy Conant. Using IVF methods to increase egg production, she harvested some of her eggs and placed them in specially designed and labeled jars. She has displayed the results in a refrigerated deli case (along with blown up photos of the label featuring her picture) and registered a trademark to protect what she calls CHRISSY CAVIAR. Her piece raises interesting questions about what we eat, why we eat it and even wryly suggests the possibility of cannibalism. Documentation of her project can be found at www.chrissycaviar.com.
Curiously Chocolate: April Banks
Authors: caruth nicole j.
Published: May 2008

In 2004, Bay Area conceptual artist April Banks traveled to West Africa, which produces seventy percent of the world's cocoa, to learn firsthand about the cocoa farms of the region and their relationship to the modern-day chocolate industry. Her related research has been wide, including travel to cocoa farms in Cuba and a visit to the New York Board of Trade. Free Chocolate, Banks's resulting body of work, follows cocoa's global exchange from forest to palate, farmer to consumer, illustrating the mingled effects of desire, greed, and manipulation. This article examines two photographic works in the Free Chocolate series, placing them in their broader cultural and economic contexts.
"A Different Kind of Beauty": Scientific and Architectural Style in I. M. Pei's Mesa Laboratory and Louis Kahn's Salk Institute
Authors: Leslie Stuart W.
Published: May 2008

I. M. Pei's Mesa Laboratory for the National Center for Atmospheric Research in Boulder, Colorado, and Louis Kahn's Salk Institute in La Jolla, California, are rare examples of laboratories as celebrated for their architecture as for their scientific contributions. Completed in the mid-1960s, these signature buildings still express the scientific style of their founding directors, Walter Roberts and Jonas Salk. Yet in commissioning their laboratories, Roberts and Salk had to work with architects as strongwilled as themselves. A close reading of the two laboratories reveals the ongoing negotiations and tensions in collaborations between visionary scientist and visionary architect. Moreover, Roberts and Salk also had to become architects of atmospheric and biomedical sciences. For laboratory architecture, however flexible in theory, necessarily stabilizes scientific practice, since a philosophy of research is embedded in the very structure of the building and persists far longer than the initial vision and mission that gave it life. Roberts and Salk's experiences suggest that even the most carefully designed laboratories must successfully adapt to new disciplinary configurations, funding opportunities, and research priorities, or risk becoming mere architectural icons.
Legitimating a Nuclear Critic: John Gofman, Radiation Safety, and Cancer Risks
Authors: Semendeferi Ioanna
Published: May 2008

Whether low-level ionizing radiation has an effect on humans has been a polarizing issue for the last fifty years. The epicenter of this controversy has been the validity of the linear non-threshold dose-response model, according to which any amount of radiation, however small, causes damage to human genes and health. In the late 1960s and early 1970s, the nuclear scientist and medical researcher John Gofman (1918–2007) played a pivotal role in the debate. Historical accounts have treated Gofman as a radical antinuclear scientist whose unscientific arguments put enormous political pressure on the nuclear power industry and regulatory agencies. Gofman's bitter struggle with the Atomic Energy Commission, which funded his research at Lawrence Livermore National Laboratory, partly accounts for this view. However, my analysis of Gofman's involvement in the low-level radiation debate shows how he also helped shift the focus in radiation safety from the risks of genetic damage or leukemia to somatic or cancer risks. His arguments led to the introduction of the linear nonthreshold radiation model as a means of numerically estimating cancer risks. This was a watershed event in radiation-safety science and politics. Gofman's case sheds light on the process by which a scientist could secure legitimation even when his technical arguments threatened the government's interests. I conclude that it also points to an open issue in the history of antinuclear scientists, or of other politically active scientists or technology critics: treating them as critics should not preclude historians from treating them as scientists.
Disability and “Late Style” in Music
Authors: STRAUS JOSEPH N.
Published: May 2008

“Late style” is a longstanding aesthetic category in all the arts. Late-style music is presumed to have certain internal qualities (such as fragmentation, intimacy, nostalgia, or concision) and to be associated with certain external factors (such as the age of the composer, his or her proximity to and foreknowledge of death, lateness within a historical period, or a sense of authorial belatedness with respect to significant predecessors). Upon closer inspection, it appears that many of these external factors are unreliably correlated with a musical style that might be described as late. Late style is often better correlated with the bodily or mental condition of the composer: most composers who write in what is recognized as a late style have shared experiences of non-normative bodily or mental function, that is, of impairment and disability. Composers inscribe their disabilities in their music, and the result is often correlated with what is generally called late style. Close readings of four modernist works serve to illuminate the concept: Stravinsky, Requiem Canticles; Schoenberg, String Trio; Bartók, Third Piano Concerto; and Copland, Night Thoughts. In each case, I contend that the features of these works generally understood as markers of lateness are better understood in relation to the disabled bodies of their composers.
Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?
Authors: Tanriverdi Fatih , De Bellis Annamaria , Bizzarro Antonio , Sinisi Antonio Agostino , Bellastella Giuseppe , Pane Elena , Bellastella Antonio , Unluhizarci Kursad , Selcuklu Ahmet , Casanueva Felipe F , Kelestimur Fahrettin
Published: May 2008

Objective

Traumatic brain injury (TBI) is a devastating public health problem that may result in hypopituitarism. However, the mechanisms responsible for hypothalamic–pituitary dysfunction due to TBI are still unclear. Although the antibodies against neurons have been demonstrated in injured animal studies, investigations regarding the occurrence of antipituitary antibodies (APAs) in patients with TBI are lacking in the literature. In order to investigate whether autoimmune mechanisms could play a role in the pituitary dysfunction after TBI, we have planned this study aimed at investigating the presence of APA at the third year of TBI and association between the TBI-induced hypopituitarism and APA.

Patients and design

Twenty-nine (25 males and 4 females; age 36.5±2.3 years) patients who had completed a 3-year follow-up after TBI were included in the present study. APA and pituitary function were evaluated in all the patients 3 years after TBI; moreover, APAs were tested also in sera of 60 age-/sex-matched normal controls. The APAs were investigated by an indirect immunofluorescence method.

Results

APAs were detected in 13 out of the 29 TBI patients (44.8%), but in none of the normal controls. Pituitary dysfunction development ratio was significantly higher in APA-positive patients (46.2%) when compared with APA-negative ones (12.5%;P=0.04). There was a significant association between APA positivity and hypopituitarism due to TBI (odds ratio: 2.25, 95% confidence intervals 1.1–4.6). Moreover, there was a significant positive correlation (r=0.74,P=0.004) between APA titer ratio and peak GH response to GHRH+GH related peptide (GHRP)-6 test, suggesting that high APA titers were associated with low GH response to GHRH+GHRP-6 test.

Conclusions

This study shows for the first time the presence of the APA in TBI patients 3 years after head trauma. Moreover, present investigation indicates preliminary evidence that APA may be associated with the development of TBI-induced pituitary dysfunction, thus suggesting that autoimmunity may contribute in the development of TBI-induced hypopituitarism. The presence of the association between APA and TBI-induced hypopituitarism may provide a new point of view in this field and promote further clinical and experimental studies.
Homozygous and heterozygous expression of a novel mutation of the acid-labile subunit
Authors: van Duyvenvoorde H A , Kempers M J E , Twickler Th B , van Doorn J , Gerver W J , Noordam C , Losekoot M , Karperien M , Wit J M , Hermus A R M M
Published: May 2008

Context

Acid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown.

Objective

To investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers.

Subjects

Three short Kurdish brothers and their relatives.

Results

The index cases presented with short stature, microcephaly, and low circulating IGF-I and IGF-binding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives.

Conclusions

The clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect.