bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis
Authors: Richardson Denise , Pearson Richard G , Kurian Nisha , Latif M Liaque , Garle Michael J , Barrett David A , Kendall David A , Scammell Brigitte E , Reeve Alison J , Chapman Victoria
Published: May 2008

Introduction

Cannabis-based medicines have a number of therapeutic indications, including anti-inflammatory and analgesic effects. The endocannabinoid receptor system, including the cannabinoid receptor 1 (CB1) and receptor 2 (CB2) and the endocannabinoids, are implicated in a wide range of physiological and pathophysiological processes. Pre-clinical and clinical studies have demonstrated that cannabis-based drugs have therapeutic potential in inflammatory diseases, including rheumatoid arthritis (RA) and multiple sclerosis. The aim of this study was to determine whether the key elements of the endocannabinoid signalling system, which produces immunosuppression and analgesia, are expressed in the synovia of patients with osteoarthritis (OA) or RA.

Methods

Thirty-two OA and 13 RA patients undergoing total knee arthroplasty were included in this study. Clinical staging was conducted from x-rays scored according to Kellgren-Lawrence and Larsen scales, and synovitis of synovial biopsies was graded. Endocannabinoid levels were quantified in synovial fluid by liquid chromatography-mass spectrometry. The expression of CB1 and CB2 protein and RNA in synovial biopsies was investigated. Functional activity of these receptors was determined with mitogen-activated protein kinase assays. To assess the impact of OA and RA on this receptor system, levels of endocannabinoids in the synovial fluid of patients and non-inflamed healthy volunteers were compared. The activity of fatty acid amide hydrolase (FAAH), the predominant catabolic endocannabinoid enzyme, was measured in synovium.

Results

CB1 and CB2 protein and RNA were present in the synovia of OA and RA patients. Cannabinoid receptor stimulation of fibroblast-like cells from OA and RA patients produced a time-dependent phosphorylation of extracellular signal-regulated kinase (ERK)-1 and ERK-2 which was significantly blocked by the CB1 antagonist SR141716A. The endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) were identified in the synovial fluid of OA and RA patients. However, neither AEA nor 2-AG was detected in synovial fluid from normal volunteers. FAAH was active in the synovia of OA and RA patients and was sensitive to inhibition by URB597 (3'-(aminocarbonyl) [1,1'-biphenyl]-3-yl)-cyclohexylcarbamate).

Conclusion

Our data predict that the cannabinoid receptor system present in the synovium may be an important therapeutic target for the treatment of pain and inflammation associated with OA and RA.
Breast cancer tumor growth estimated through mammography screening data
Authors: Weedon-Fekjær Harald , Lindqvist Bo H , Vatten Lars J , Aalen Odd O , Tretli Steinar
Published: May 2008

Introduction

Knowledge of tumor growth is important in the planning and evaluation of screening programs, clinical trials, and epidemiological studies. Studies of tumor growth rates in humans are usually based on small and selected samples. In the present study based on the Norwegian Breast Cancer Screening Program, tumor growth was estimated from a large population using a new estimating procedure/model.

Methods

A likelihood-based estimating procedure was used, where both tumor growth and the screen test sensitivity were modeled as continuously increasing functions of tumor size. The method was applied to cancer incidence and tumor measurement data from 395,188 women aged 50 to 69 years.

Results

Tumor growth varied considerably between subjects, with 5% of tumors taking less than 1.2 months to grow from 10 mm to 20 mm in diameter, and another 5% taking more than 6.3 years. The mean time a tumor needed to grow from 10 mm to 20 mm in diameter was estimated as 1.7 years, increasing with age. The screen test sensitivity was estimated to increase sharply with tumor size, rising from 26% at 5 mm to 91% at 10 mm. Compared with previously used Markov models for tumor progression, the applied model gave considerably higher model fit (85% increased predictive power) and provided estimates directly linked to tumor size.

Conclusion

Screening data with tumor measurements can provide population-based estimates of tumor growth and screen test sensitivity directly linked to tumor size. There is a large variation in breast cancer tumor growth, with faster growth among younger women.
ModuleMiner - improved computational detection of cis-regulatory modules: are there different modes of gene regulation in embryonic development and adult tissues?
Authors: Van Loo Peter , Aerts Stein , Thienpont Bernard , De Moor Bart , Moreau Yves , Marynen Peter
Published: May 2008

We present ModuleMiner, a novel algorithm for computationally detecting cis-regulatory modules (CRMs) in a set of co-expressed genes. ModuleMiner outperforms other methods for CRM detection on benchmark data, and successfully detects CRMs in tissue-specific microarray clusters and in embryonic development gene sets. Interestingly, CRM predictions for differentiated tissues exhibit strong enrichment close to the transcription start site, whereas CRM predictions for embryonic development gene sets are depleted in this region.
Molecular signature of hypersaline adaptation: insights from genome and proteome composition of halophilic prokaryotes
Authors: Paul Sandip , Bag Sumit K , Das Sabyasachi , Harvill Eric T , Dutta Chitra
Published: May 2008

Background

Halophilic prokaryotes are adapted to thrive in extreme conditions of salinity. Identification and analysis of distinct macromolecular characteristics of halophiles provide insight into the factors responsible for their adaptation to high-salt environments. The current report presents an extensive and systematic comparative analysis of genome and proteome composition of halophilic and non-halophilic microorganisms, with a view to identify such macromolecular signatures of haloadaptation.

Results

Comparative analysis of the genomes and proteomes of halophiles and non-halophiles reveals some common trends in halophiles that transcend the boundary of phylogenetic relationship and the genomic GC-content of the species. At the protein level, halophilic species are characterized by low hydrophobicity, over-representation of acidic residues, especially Asp, under-representation of Cys, lower propensities for helix formation and higher propensities for coil structure. At the DNA level, the dinucleotide abundance profiles of halophilic genomes bear some common characteristics, which are quite distinct from those of non-halophiles, and hence may be regarded as specific genomic signatures for salt-adaptation. The synonymous codon usage in halophiles also exhibits similar patterns regardless of their long-term evolutionary history.

Conclusion

The generality of molecular signatures for environmental adaptation of extreme salt-loving organisms, demonstrated in the present study, advocates the convergent evolution of halophilic species towards specific genome and amino acid composition, irrespective of their varying GC-bias and widely disparate taxonomic positions. The adapted features of halophiles seem to be related to physical principles governing DNA and protein stability, in response to the extreme environmental conditions under which they thrive.
Application of time-lapse ERT imaging to watershed characterization
Authors: Miller Carlyle R. , Routh Partha S. , Brosten Troy R. , McNamara James P.
Published: May 2008

Time-lapse electrical resistivity tomography (ERT) has many practical applications to the study of subsurface properties and processes. When inverting time-lapse ERT data, it is useful to proceed beyond straightforward inversion of data differences and take advantage of the time-lapse nature of the data. We assess various approaches for inverting and interpreting time-lapse ERT data and determine that two approaches work well. The first approach is model subtraction after separate inversion of the data from two time periods, and the second approach is to use the inverted model from a base data set as the reference model or prior information for subsequent time periods. We prefer this second approach. Data inversion methodology should be consideredwhen designing data acquisition; i.e., to utilize the second approach, it is important to collect one or more data sets for which the bulk of the subsurface is in a background or relatively unperturbed state. A third and commonly used approach to time-lapse inversion, inverting the difference between two data sets, localizes the regions of the model in which change has occurred; however, varying noise levels between the two data sets can be problematic. To further assess the various time-lapse inversion approaches, we acquired field data from a catchment within the Dry Creek Experimental Watershed near Boise, Idaho, U.S.A. We combined the complimentary information from individual static ERT inversions, time-lapse ERT images, and available hydrologic data in a robust interpretation scheme to aid in quantifying seasonal variations in subsurface moisture content.
Decision Making Regarding Prophylactic Mastectomy: Stability of Preferences and the Impact of Anticipated Feelings of Regret
Authors: van Dijk Sandra , van Roosmalen Mariëlle S. , Otten Wilma , Stalmeier Peep F.M.
Published: May 2008

Purpose

Women who test positive for a BRCA1/2 mutation face difficult choices to manage their breast cancer risk; one of these choices is whether to opt for prophylactic mastectomy. Few data are available about this decision-making process. The current study provides data regarding the stability of risk-management preferences over time and the factors that are associated with these preferences.

Patients and Methods

We analyzed data from 338 women who opted for breast cancer antigen (BRCA) testing. First, we prospectively assessed preferences of 80 BRCA mutation carriers at five different points in time ranging from 1 week after blood sampling up to 9 months after BRCA-test disclosure. Second, we applied univariate and multivariate regression analyses to examine which medical, sociodemographic, and psychological factors are related to a preference for prophylactic mastectomy.

Results

Ninety percent of the women already indicated a preference regarding risk management at baseline. Moreover, most women had stable preferences over time. Furthermore, anticipated feelings of regret in case of a hypothetical breast cancer diagnosis in the near future were strongly related to risk-management preference (odds ratio = 8.93; P < .0001).

Conclusion

Women seem to decide at a relatively early stage about their risk-management preferences. Many of them may be sensitive to the possibility of regret in case of a bad outcome. We discuss whether possible regret in the future is a rational reason for opting for prophylactic mastectomy, or whether it signifies an emotional coping process or strategy in which the future costs are no longer fully considered.
Safety and Efficacy of Gemtuzumab Ozogamicin in Combination With Chemotherapy for Pediatric Acute Myeloid Leukemia: A Report From The Children's Oncology Group
Authors: Aplenc Richard , Alonzo Todd A. , Gerbing Robert B. , Lange Beverly J. , Hurwitz Craig A. , Wells Robert J. , Bernstein Irwin , Buckley Patrick , Krimmel Kathleen , Smith Franklin O. , Sievers Eric L. , Arceci Robert J.
Published: May 2008

Purpose

While gemtuzumab ozogamicin (GTMZ) is commonly used in the treatment of acute myeloid leukemia (AML) in combination with standard chemotherapy agents, the pediatric maximum-tolerated dose (MTD) of GMTZ in combination with chemotherapy has not been determined.

Patients and Methods

The Children's Oncology Group AAML00P2 trial sought to define the MTD of GMTZ in combination with cytarabine and mitoxantrone and cytarabine and l-asparaginase chemotherapy regimens.

Results

The MTD for GMTZ in combination with cytarabine and mitoxantrone was 3 mg/m2 while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m2. Toxicities observed in both treatment regimens were typical of those seen in the relapsed AML setting and consisted primarily of infectious complications. The overall remission response rate (mean ± SE) was 45% ± 15% and the 1 year event-free survival and overall survival estimates were 38% ± 14% and 53% ± 15%, respectively.

Conclusion

This trial determined the pediatric MTD for GMTZ with two commonly used AML chemotherapy combinations. Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML therapy.
Three Phase II Cytokine Working Group Trials of gp100 (210M) Peptide Plus High-Dose Interleukin-2 in Patients With HLA-A2–Positive Advanced Melanoma
Authors: Sosman Jeffrey A. , Carrillo Carole , Urba Walter J. , Flaherty Lawrence , Atkins Michael B. , Clark Joseph I. , Dutcher Janet , Margolin Kim A. , Mier James , Gollob Jarod , Kirkwood John M. , Panka David J. , Crosby Nancy A. , O'Boyle Kevin , LaFleur Bonnie , Ernstoff Marc S.
Published: May 2008

Purpose

High-dose interleukin-2 (IL-2) induces responses in 15% to 20% of patients with advanced melanoma; 5% to 8% are durable complete responses (CRs). The HLA-A2–restricted, modified gp100 peptide (210M) induces T-cell immunity in vivo and has little antitumor activity but, combined with high-dose IL-2, reportedly has a 42% (13 of 31 patients) response rate (RR). We evaluated 210M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial.

Patients and Methods

In three separate phase II trials, patients with melanoma received 210M subcutaneously during weeks 1, 4, 7, and 10 and standard high-dose IL-2 during weeks 1 and 3 (trial 1), weeks 7 and 9 (trial 2), or weeks 1, 4, 7, and 10 (trial 3). Immune assays were performed on peripheral-blood mononuclear cells collected before and after treatment.

Results

From 1998 to 2003, 131 patients with HLA-A2–positive were enrolled. With 60-month median follow-up time, the overall RR for 121 assessable patients was 16.5% (95% CI, 10% to 26%); the RRs were 23.8% in trial 1 (42 patients), 12.5% in trial 2 (40 patients), and 12.8% in trial 3 (39 patients). There were 11 CRs (9%) and nine partial responses (7%), with 11 patients (9%) progression free at ≥ 30 months. Immune studies including assays of CD3-ζ expression and numbers of CD4+/CD25+/FoxP3+regulatory T cells, CD15+/CD11b+/CD14–immature myeloid-derived cells, and CD8+gp100 tetramer-positive cells in the blood did not correlate with clinical benefit.

Conclusion

The results again demonstrate efficacy of high-dose IL-2 in advanced melanoma but did not demonstrate the promising clinical activity reported with vaccine and high-dose IL-2 in any of three phase II trials.
Phase II Study of Extended-Dose Temozolomide in Patients With Melanoma
Authors: Rietschel Petra , Wolchok Jedd D. , Krown Susan , Gerst Scott , Jungbluth Achim A. , Busam Klaus , Smith Katherine , Orlow Irene , Panageas Katherine , Chapman Paul B.
Published: May 2008

Purpose

We conducted a phase II trial of extended-dose temozolomide (TMZ) in patients with melanoma to test the hypothesis that the approximately 30% response rate observed in patients treated with extended-dose TMZ with antiangiogenic agents was caused by TMZ alone. We hypothesized that expression of methylguanine methyltransferase (MGMT) in the tumor would correlate with drug resistance to TMZ.

Patients and Methods

Patients with stage IV or unresectable stage III melanoma were treated with TMZ 75 mg/m2/d for 6 weeks followed by a 2-week rest period. Cycles were repeated until progression. Patients were stratified by M1c disease or not. The primary end point was objective response proportion. MGMT expression was assessed by methylation-specific pyrosequencing of the promoter and by immunohistochemistry.

Results

Forty-nine patients (25 with M1c disease) were assessable. Three patients (12.5%) in each cohort experienced partial responses; there were no complete responses. Ten patients (21%) had stable disease lasting more than 24 weeks. Median time to progression was 3.3 months. Median survival was 10.1 months; survival was similar in the two cohorts. The estimated 18-month survival was 27%. There was no correlation between response and either immunohistochemistry staining for MGMT or for MGMT promoter methylation. Seventy-five percent of patients developed CD4+ lymphopenia after three cycles.

Conclusion

Extended-dose TMZ therapy did not result in a 30% responses rate, which has been observed using extended-dose TMZ with antiangiogenic agents. Response did not correlate with MGMT expression or promoter methylation as a continuous variable, suggesting that other resistance mechanisms are important.
Prognostic Factors in Metastatic Rhabdomyosarcomas: Results of a Pooled Analysis From United States and European Cooperative Groups
Authors: Oberlin Odile , Rey Annie , Lyden Elizabeth , Bisogno Gianni , Stevens Michael C.G. , Meyer William H. , Carli Modesto , Anderson James R.
Published: May 2008

Purpose

To identify risk factors associated with outcome in children with metastatic rhabdomyosarcoma in a large cohort of patients

Patients and Methods

Pooled data were obtained from 788 patients treated in nine studies performed by European and American cooperative groups. Clinical factors, including age, histology, site of primary, and site(s) and number of sites of metastatic disease, were correlated with event-free survival (EFS) and overall survival (OS).

Results

Seven hundred eighty-eight patients were eligible for analysis. The 3-year OS and EFS were 34% (SE, 1.7) and 27% (SE, 1.6), respectively. By univariate analysis, 3-year EFS was significantly and adversely influenced by age, alveolar histology, location of primary tumor in unfavorable site (defined as extremity and “other” sites), presence of three or more sites of metastatic disease, and the presence of bone or bone marrow involvement. By multivariate analysis, EFS was strongly correlated to all factors except histology. Relative risks were 1.6 for age younger than 1 year or at least 10 years, 1.4 for unfavorable site of primary tumor, 1.4 for bone or bone marrow involvement, 1.4 for three or more metastatic sites. EFS was 50% for patients without any of these four adverse factors and was respectively 42%, 18%, 12%, and 5% in patients with one, two, three, or four factors (P < .0001).

Conclusion

This analysis identified subsets of patients with metastatic rhabdomyosaroma with different outcomes to current therapy and offers a strategy to define patient candidates for experimental approaches to treatment.
Tailored Chemotherapy Information Faxed to General Practitioners Improves Confidence in Managing Adverse Effects and Satisfaction With Shared Care: Results From a Randomized Controlled Trial
Authors: Jefford Michael , Baravelli Carl , Dudgeon Paul , Dabscheck Adrian , Evans Melanie , Moloney Michael , Schofield Penelope
Published: May 2008

Purpose

General practitioners (GPs) play a critical role in the treatment of patients with cancer; yet often lack information for optimal care. We developed standardized information for GPs about chemotherapy (CT). In a randomized controlled trial we assessed the impact of sending, by fax, information tailored to the particular patient's CT regimen. Primary end points were: confidence treating patients who were receiving CT (confidence), knowledge of adverse effects and reasons to refer the patient to the treatment center (knowledge), and satisfaction with information and shared care of patients (satisfaction).

Methods

Focus group work informed the development of the CT information which focused on potential adverse effects and recommended management strategies. GPs of patients due to commence CT were randomly assigned to receive usual correspondence with or without the faxed patient/regimen-specific information. Telephone questionnaire at baseline and 1 week postintervention assessed knowledge, confidence, and satisfaction.

Results

Ninety-seven GPs managed 97 patients receiving 23 types of CT. Eighty-one (83.5%) completed the follow-up questionnaire. GPs in the intervention group demonstrated a significantly greater increase in confidence (mean difference, 0.28; 95% CI, 0.10 to 0.47) and satisfaction (mean difference, 0.57; 95% CI, 0.27 to 0.88) compared with usual care, reflecting a 7.1% and 10.5% difference in score, respectively. No differences were detected for knowledge. GPs receiving the CT sheet found correspondence significantly more useful (P < .001) and instructive (P < .001) than GPs who received standard correspondence alone.

Conclusion

Information about CT faxed to GPs is a simple, inexpensive intervention that increases confidence managing CT adverse effects and satisfaction with shared care. This intervention could have widespread application.
Interventions for Alleviating Cancer-Related Dyspnea: A Systematic Review
Authors: Ben-Aharon Irit , Gafter-Gvili Anat , Paul Mical , Leibovici Leonard , Stemmer Salomon M.
Published: May 2008

Purpose

Dyspnea is one of the most distressing symptoms experienced by terminally ill cancer patients. This study aimed to evaluate the role of interventions for the palliation of dyspnea.

Methods

We conducted a systematic review of randomized controlled trials assessing all pharmacologic and nonpharmacologic interventions for dyspnea palliation in cancer patients, and searched the Cochrane Library, MEDLINE, conference proceedings, and references. Two reviewers independently appraised the quality of trials and extracted data.

Results

Our search yielded 18 trials. Fourteen evaluated pharmacologic interventions: seven assessing opioids (a total of 256 patients), five assessing oxygen (137 patients), one assessing helium-enriched air, and one assessing furosemide. Four trials evaluated nonpharmacologic interventions (403 patients). The administration of subcutaneous morphine resulted in a significant reduction in dyspnea Visual Analog Scale (VAS) compared with placebo. No difference was observed in dyspnea VAS score when nebulized morphine was compared with subcutaneous morphine, although patients preferred the nebulized route. The addition of benzodiazepines to morphine was significantly more effective than morphine alone, without additional adverse effects. Oxygen was not superior to air for alleviating dyspnea, except for patients with hypoxemia. Nursing-led interventions improved breathlessness. Acupuncture was not beneficial.

Conclusion

Our review supports the use of opioids for dyspnea relief in cancer patients. The use of supplemental oxygen to alleviate dyspnea can be recommended only in patients with hypoxemia. Nursing-led nonpharmacologic interventions seem valuable. Only a few studies addressing this question were performed. Thus, further studies evaluating interventions for alleviating dyspnea are warranted.
Survival Following Recurrence in Stage II and III Colon Cancer: Findings From the ACCENT Data Set
Authors: O'Connell Michael J. , Campbell Megan E. , Goldberg Richard M. , Grothey Axel , Seitz Jean-François , Benedetti Jacqueline K. , André Thierry , Haller Daniel G. , Sargent Daniel J.
Published: May 2008

Purpose

This study was undertaken to examine five possible prognostic factors in patients with recurrent stage II and III colon cancer: time from randomization on an adjuvant therapy clinical trial to tumor recurrence (< 1 year, 1 to 2 years, 2 to 3 years, 3 to 4 years, > 4 years), initial stage (II v III), initial adjuvant treatment (fluorouracil [FU]-based v surgery alone), the era in which the patient entered an adjuvant therapy clinical trial (1978 to 1985, 1986 to 1992, 1993 to 1999), and patient age at recurrence.

Methods

The Adjuvant Colon Cancer End Points (ACCENT) data set was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study.

Results

5,722 (32.9%) of 17,381 patients experienced recurrence. Median survival following recurrence was 13.3 months. Time from randomization to recurrence was highly prognostic of survival following recurrence (P < .0001). Longer survival following recurrence was seen in patients with initial stage II versus III disease (P < .0001; 14.3% 6-year overall survival after recurrence in initial stage II patients), patients entered more recently onto trials (P < .0001), and patients initially treated with surgery alone versus FU adjuvant treatment (P = .0005). All relationships were maintained in multivariate models.

Conclusion

Time from initial treatment to recurrence and initial stage are important prognostic factors in patients with recurrent colon cancer. Survival following recurrence increased modestly from 1978 to 1999. Patients who had a recurrence following adjuvant therapy had poorer prognosis than those who progressed after surgery alone. These prognostic factors may be useful for clinical trial design and treatment decisions in patients with recurrent colon cancer.
Comparing results of digital photoplethysmography in two groups of chronic obstructive pulmonary disease patients with and without high pulmonary artery pressure
Authors: Sharif-Kashani B , Behzadnia N , Shahabi P
Published: May 2008

Background

Digital photoplethysmography (D-PPG) is a newly introduced method of optical screening of deep vein thrombosis (DVT) by recording changes in the size of limb due to tissue fluid.

Objectives

The objective of this study is to assess the effect of high pulmonary artery pressure (PAP) and consequently increased venous system pressure on D-PPG test results.

Methods

Forty-five patients with and 45 patients without PAP pressure were enrolled in the study and divided into two groups. All the patients had a history of chronic obstructive pulmonary disease (COPD). D-PPG test was performed for both legs of all the patients and the results of the two groups were compared. Also, all patients underwent duplex sonography for ruling out DVT.

Results

Using venous refilling time (RT) of <22 s as the optimal cut-off point, it was found that 32 (35%) legs of patients with and 39 (43%) legs of patients without high PAP had positive D-PPG test. Although the rate of positive D-PPG test was higher in patients with high PAP, this was not statistically significant ( P = 0.28). Moreover, overall correlation between RT and venous pump detected by D-PPG and PAP was r = −0.11 ( P = 0.2) and r = −0.01 ( P = 0.6), respectively.

Conclusion

Our results showed that the rate of positive D-PPG test results is slightly higher in patients with pulmonary hypertension, but this difference is not statistically significant. Therefore, increased PAP could be excluded as a confounding factor of D-PPG test.
Extreme Point-Based Heuristics for Three-Dimensional Bin Packing
Authors: Crainic Teodor Gabriel , Perboli Guido , Tadei Roberto
Published: May 2008

One of the main issues in addressing three-dimensional packing problems is finding an efficient and accurate definition of the points at which to place the items inside the bins, because the performance of exact and heuristic solution methods is actually strongly influenced by the choice of a placement rule. We introduce the extreme point concept and present a new extreme point-based rule for packing items inside a three-dimensional container. The extreme point rule is independent from the particular packing problem addressed and can handle additional constraints, such as fixing the position of the items. The new extreme point rule is also used to derive new constructive heuristics for the three-dimensional bin-packing problem. Extensive computational results show the effectiveness of the new heuristics compared to state-of-the-art results. Moreover, the same heuristics, when applied to the two-dimensional bin-packing problem, outperform those specifically designed for the problem.
Navigating Local Environments with Global Strategies: A Contingency Model of Multinational Subsidiary Performance
Authors: Grewal Rajdeep , Chandrashekaran Murali , Dwyer F. Robert
Published: May 2008

Multinational corporations (MNCs) often pursue global strategies that emphasize efficiency, flexibility, and learning, but globally developed strategies often clash with the environmental idiosyncrasies of MNC country subsidiary markets in which the strategy is actually implemented. Extant research pays little attention to the contingent efficacy of such global strategies from the perspective of MNC country subsidiary markets. We adopt the strategy-environment alignment principle and study how host country task- and institutional environments might influence the efficacy of global strategies for MNC subsidiary performance. We assess MNC subsidiary performance using subjective managerial judgments, and on the basis of recent research on human judgments, we theorize that these judgments embody information about judgment magnitude and uncertainty. A mean-variance function model simultaneously teases out the effects of the explanatory variables on the magnitude and uncertainty of MNC subsidiary performance judgments. To test the hypotheses, we analyze survey data from German and Japanese subsidiaries in the United States. The results support the use of the mean-variance function model and specific theory about the antecedents of performance judgment magnitude and uncertainty. Findings pertaining to interactions between global strategies and the facets of the local country environment reveal ways in which MNCs can adapt “global” strategies to navigate the complex array of country markets they face.
Behavior-Based Discrimination: Is It a Winning Play, and If So, When?
Authors: Pazgal Amit , Soberman David
Published: May 2008

With advances in technology, the collection of information from consumers at the time of purchase is common in many categories. This information allows a firm to straightforwardly classify consumers as either “new” or “past” consumers. This opens the door for firms to implement marketing that (a) discriminates between new and past consumers and (b) entails making offers to them that are significantly different. Our objective is to examine the competitive effects of marketing that tailors offers to consumers based on their past buying behavior. In a two-period model with two competing firms, we assume that each firm is able to commit about whether or not to implement behavior-based discrimination (BBD), i.e., to add benefits to its offer for past consumers in the second period. When the firms are identical in their ability to add value to the second-period offer, BBD generally leads to lower profits for both firms. Past customers are so valuable in the second period that BBD leads to cutthroat competition in the first period. As a result, the payoffs associated with the implementation of BBD form a prisoner's dilemma. Interestingly, when a firm has a significant advantage over its competitor (one firm has the capability to add more benefits for its past customers than the other), it can increase its profit versus the base case even when there is significant competition in the second period. Moreover, the firm at a disadvantage sometimes finds that the best response to BBD by a strong competitor is to respond with a uniform price and avoid the practice completely.
Modeling the Dynamics of Credit Spreads with Stochastic Volatility
Authors: Jacobs Kris , Li Xiaofei
Published: May 2008

This paper investigates a two-factor affine model for the credit spreads on corporate bonds. The first factor can be interpreted as the level of the spread and the second factor is the volatility of the spread. The riskless interest rate is modeled using a standard two-factor affine model, thus leading to a four-factor model for corporate yields. This approach allows us to model the volatility of corporate credit spreads as stochastic, and also allows us to capture higher moments of credit spreads. We use an extended Kalman filter approach to estimate our model on corporate bond prices for 108 firms. The model is found to be successful at fitting actual corporate bond credit spreads, resulting in a significantly lower root mean square error than a standard alternative model both in sample and out of sample. In addition, key properties of actual credit spreads such as the stochastic volatility of the credit spreads and the positive skewness of the credit spread distribution are better captured by the model.
How Do Decision Frames Influence the Stock Investment Choices of Individual Investors?
Authors: Kumar Alok , Lim Sonya Seongyeon
Published: May 2008

This study examines whether the framing mode (narrow versus broad) influences the stock investment decisions of individual investors. Motivated by the experimental evidence, which suggests that separate decisions are more likely to be narrowly framed than simultaneous decisions, we propose trade clustering as a proxy for narrow framing. Using this framing proxy, we show that investors who execute more clustered trades exhibit weaker disposition effects and hold better-diversified portfolios. We also find that the degree of trade clustering is related to investors' stock preferences and portfolio returns. Collectively, the evidence indicates that the choice of decision frames is likely to be an important determinant of investment decisions.
Impact of Supply Learning When Suppliers Are Unreliable
Authors: Tomlin Brian
Published: May 2008

Dual sourcing and inventory are two prevalent and widely studied strategies firms use to manage yield risk. A pervasive but implicit assumption in the literature is that a firm knows its suppliers' yield distributions with certainty. This is a strong assumption in many circumstances. A firm is more likely to have a forecast of a supplier's yield distribution and to update that forecast based on its experiences with the supplier. We introduce and analyze a Bayesian model of “supply learning” (i.e., distribution updating) and investigate how supply learning influences both sourcing and inventory strategies in dual-sourcing and single-sourcing models, respectively. In the case of Bernoulli all-or-nothing yield distributions, we completely characterize the firm's optimal sourcing and inventory decisions for the supply-learning model. Among other results, we prove that for a given expected supplier reliability (i.e., the mean of the firm's forecast for the probability of successful delivery) an increase in the reliability forecast uncertainty increases the attractiveness of a supplier, but it reduces the firm's desire to invest in inventory to protect against future supply failures. We extend our analysis to allow for general yield distributions, multiple sourcing (i.e., more than two suppliers), and inventory carryover in the dual-sourcing model.
SMAD3 Functions as a Transcriptional Repressor of Acid-Sensing Ion Channel 3 (ASIC3) in Nucleus Pulposus Cells of the Intervertebral Disc
Authors: Uchiyama Yoshiyasu , Guttapalli Asha , Gajghate Sachin , Mochida Joji , Shapiro Irving M , Risbud Makarand V
Published: May 2008

The goal of this investigation was to study the regulation of acid-sensing ion channel (ASIC)3 expression by TGFβ in the nucleus pulposus cells of the intervertebral disc. Analysis of human nucleus pulposus tissue indicated decreased ASIC3 and elevated TGFβ expression in the degenerate state. In a parallel study, treatment of nucleus pulposus cells with TGFβ resulted in decreased expression of ASIC3 mRNA and protein. Suppression of ASIC3 promoter activity was evident when the nucleus pulposus cells were treated with TGFβ or co-transfected with the constitutively active ALK5 or a smad3 construct. On the other hand, co-transfection of dominant negative smad3 or smad7 restored ASIC3 promoter activity. We validated the role of smad3 in controlling ASIC3 expression using cells derived from smad3-null mice. ASIC3 promoter activity in the null cells was 2- to 3-fold higher than the wildtype cells. Moreover, expression of smad3 in null cells decreased ASIC3 promoter activity by almost 50%. Further studies using deletion constructs and trichostatin A treatment showed that the full-length smad3 was necessary, and the suppression involved recruitment of histone deacetylase to the promoter. To determine the mechanism, we evaluated the rat ASIC3 promoter sequence and noted the presence of two smad interacting CAGA box motifs. Gel-shift and supershift analysis indicated that smad3 protein was bound to this motif. Chromatin immunoprecipitation analysis confirmed that smad3 bound both the CAGA elements. Results of these studies clearly show that TGFβ is highly expressed in the degenerate disc and through smad3 serves as a negative regulator of ASIC3 expression.
A Missense T(Brachyury) Mutation Contributes to Vertebral Malformations
Authors: Ghebranious Nader , Blank Robert D , Raggio Cathleen L , Staubli Justin , McPherson Elizabeth , Ivacic Lynn , Rasmussen Kristen , Jacobsen F Stig , Faciszewski Thomas , Burmester James K , Pauli Richard M , Boachie-Adjei Oheneba , Glurich Ingrid , Giampietro Philip F
Published: May 2008

No major susceptibility genes for sporadically occurring congenital vertebral malformations (CVM) in humans have been identified to date. Body patterning genes whose mutants cause axial skeletal anomalies in mice are candidates for human CVM susceptibility. T (also known as Brachyury) and TBX6 are critical genes needed to establish mesodermal identity. We hypothesized that mutations in T and/or TBX6 contribute to the pathogenesis of human CVMs. The complete T and TBX6 coding regions, splice junctions, and proximal 500 bp of the promoters were sequenced in 50 phenotyped patients with CVM. Three unrelated patients with sacral agenesis, Klippel-Feil syndrome, and multiple cervical and thoracic vertebral malformations were heterozygous for a c.1013C>T substitution, resulting in a predicted Ala338Val missense alteration in exon 8. A clinically unaffected parent of each patient also harbored the substitution, but the variant did not occur in an ethnically diverse, 443-person reference population. The c.1013C>T variant is significantly associated with CVM (p < 0.001). Alanine 338 shows moderate conservation across species, and valine at this position has not been reported in any species. A fourth patient harbored a c.908–8C>T variant in intron 7. This previously unreported variant was tested in 347 normal control subjects, and 11 heterozygotes and 2 T/T individuals were found. No TBX6 variants were identified. We infer that the c.1013C>T substitution is pathogenic and represents the first report of an association between a missense mutation in the T gene and the occurrence of sporadic CVMs in humans. It is uncertain whether the splice junction variant increases CVM risk. TBX6 mutations do not seem to be associated with CVM. We hypothesize that epistatic interactions between T and other developmental genes and the environment modulate the phenotypic consequences of T variants.
Changing narratives and images the Holocaust: Tim Blake Nelson's film The Grey Zone (2001)
Authors: Bangert Axel
Published: May 2008

This article situates the depiction of the Holocaust in Tim Blake Nelson'sThe Grey Zone(2001) within the discourse of cultural memory. It demonstrates how the film transgresses established aesthetic and ethical boundaries of representation with the aim of constructing a different image of the Jewish Holocaust victim. By depicting the forced assistance of the predominantly JewishSonderkommandoin the extermination process,The Grey Zonechallenges the frequently dichotomised portrayal of victims and perpetrators. Moreover, the film subverts the image of a homogenous and passive Jewish victim group by staging theSonderkommandorevolt which occurred at Auschwitz-Birkenau in October 1944. In terms of narration, Nelson avoids stereotypical patterns of melodrama by drawing upon popular film genres such as the urban resistance movie. With regard to iconography, the explicit representation of the exercise of violence upon the human body raises questions about the limits of representation, questions which appear to form a part of the director's strategy to reaffirm the significance of the Holocaust for collective memory.
Narration in World cinema: Mapping the flows of formal exchange in the era of globalisation
Authors: Thanouli Eleftheria
Published: May 2008

World cinema has become a popular concept in the film studies circles in an effort to arrange the growing terrain of national cinemas across the globe and compensate for a long-standing Eurocentric approach to film criticism. In my article I try to overcome some of the existing orthodoxies
on the topic, such as the dichotomy between Hollywood cinema and the rest of the world, the American hegemony thesis and the hierarchical/linear models of analysis. By focusing on the narration of a number of films from across the globe, I trace a number of formal developments that urge us
to reconsider the notion of western primacy in the production of cinematic forms and to seek new models of complex cultural interactions.
Some peculiarities of the Macedonian verbal system in a Slavonic and Balkan context
Authors: Dimitrova-Schmieger Nina , Schmieger Roland
Published: May 2008

The subject of the article are some peculiarities in the verbal system which give Macedonian a special place within the Slavonic language family and within the Balkan Sprachbund. In concrete terms, Macedonian is characterized by some features which approximate it towards Modern Greek: a tendency towards unification of the means of aspectual shift, exclusively dependent use of the present forms of perfective verbs and the de facto existence of only one past tense with allomorphs for both aspects. The so-called as a Balkanism shows differences in comparison with Bulgarian and proximity with Albanian and Modern Greek, whereas the parallelism of the two perfect forms and leads to a redistribution of their functions.
On the use of habere-perfect in journalistic and administrative style
Authors: Mitkovska Liljana , Bužarovska Eleni
Published: May 2008

The authors analyze the occurrence of habere-perfect in two formal registers that are supposed to be the least influenced by regional use. The goal of the paper is to establish how and why habere-perfect is spread in standard Macedonian. The corpus-based analysis shows that the perfect enters and spreads in the standard in a systematic way, through certain semantic verb classes in privileged contexts. It is claimed that habere-perfect favors light verb collocations with verbs of acquisition in possessive-existential contexts. The findings support the thesis that the most frequently encountered have-perfect type is used in functions characteristic of the early stages of grammaticalization.
Macedonian dialectology and Eurology: areal and typological perspectives
Authors: Friedman Victor A.
Published: May 2008

The relationship between areal linguistics and typology can be illuminated and clarified by Macedonian dialectology, especially in the context of Balkan linguistics. This is especially important in analyses of the Balkan linguistic league, which, as an areal phenomenon, should be seen in historical perspective. On the one hand, Macedonian dialectology helps clarify the graded nature of the phenomenon itself, and on the other helps demonstrate that Macedonian is the most Balkanized of the Balkan languages.
The phonetics of Macedonian
Authors: Sawicka Irena
Published: May 2008

With respect to its morphosyntactic features, the Macedonian language belongs to the same typological group as its closest relative – the Bulgarian language. However, considering their phonetic features, these two languages fall into different linguistic areas. While Bulgarian possesses typical East Slavic phonetics – related to the Eurasian linguistic community – Macedonian phonetics has many more features in common with Serbian than with Bulgarian. Both Serbian and Macedonian are members of a different (more European) phonetic type that, at the same time, is characteristic of Balkan phonetics. This paper presents the features determining the typology of the Macedonian phonetics.
Balkan Sprachbund aspects of Macedonian grammar
Authors: Mišeska Tomić Olga
Published: May 2008

The multi-lingual environment on the Balkans and its intensive contact with non-Slavic languages caused Macedonian to drift away from Common Slavic more than the other Slavic languages and to share with non-Slavic Balkan languages a number of typological features, referred to as Balkan Sprachbund features. Its verbal system is analytical to a considerable degree and its nominal case system is disintegrated. It has a general tendency towards explicit marking of grammatical functions with specific function words and towards uniformity of morphological markers.
Drift Dynamics of Larval Pallid Sturgeon and Shovelnose Sturgeon in a Natural Side Channel of the Upper Missouri River, Montana
Authors: Braaten Patrick J. , Fuller David B. , Holte Landon D. , Lott Ryan D. , Viste William , Brandt Tyrel F. , Legare Robert G.
Published: May 2008

The drift dynamics of larval shovelnose sturgeon Scaphirhynchus platorynchus (1, 2, 6, and 10 d posthatch (dph)) and pallid sturgeon S. albus (1, 2, 5, 9, 11, and 17 dph) were examined in a natural side channel of the Missouri River to quantify the vertical drift location of larvae in the water column, determine the drift velocity of larvae relative to water velocity, and simulate the cumulative distance (km) drifted by larvae during ontogenetic development. Larvae were released at the side-channel inlet and sampled at points 100, 500, 900, and 1,300 m downstream. Larvae drifted primarily near the riverbed, as 58–79% of recaptured shovelnose sturgeon and 63–89% of recaptured pallid sturgeon were sampled in the lower 0.5 m of the water column. The transition from the drifting to the benthic life stage was initiated at 6 dph (mean length, 15.6 mm) for shovelnose sturgeon and at 11–17 dph (mean length, 18.1–20.3 mm) for pallid sturgeon. Across ages, the drift rates of larval shovelnose sturgeon averaged 0.09–0.16 m/s slower than the mean water column velocity. The drift rates of pallid sturgeon were similar to or slightly slower (0.03–0.07 m/s) than the mean water column velocity for 1–11-dph larvae. Conversely, 17-dph larval pallid sturgeon dispersed downstream at a much slower rate (mean, 0.20 m/s slower than the mean water column velocity) owing to their transition to benthic habitats. Drift simulations indicated that the average larval shovelnose sturgeon may drift from 94 to 250 km and the average larval pallid sturgeon may drift from 245 to 530 km, depending on water velocity. Differences in larval drift dynamics between species provide a possible explanation for differences in recruitment between shovelnose sturgeon and pallid sturgeon in the upper Missouri River.
Fluxo de seiva pelo método do balanço de calor: base teórica, qualidade das medidas e aspectos práticos
Authors: Marin Fábio Ricardo , Ribeiro Rafael Vasconcelos , Angelocci Luiz Roberto , Righi Evandro Zanini
Published: May 2008

O método do balanço de calor representa uma técnica importante para estudos sobre fisiologia vegetal, agrometeorologia e irrigação. Sua aplicação tem aumentado nos últimos anos em decorrência da maior facilidade de importação de material e equipamentos e do uso mais disseminado dos sistemas automáticos de aquisição de dados. Avanços importantes em diversas áreas de pesquisa têm sido alcançados com a possibilidade de se quantificar o consumo hídrico em plantas isoladas em diferentes escalas de tempo. Com base na teoria do método, esta revisão tem como objetivo apresentar e discutir os procedimentos de instalação, manutenção e de análise e processamento dos dados com vistas ao uso mais adequado da técnica e à obtenção de dados mais confiáveis e coerentes. Aspectos relacionados à influência das condições ambientais no funcionamento do sensor são abordados; são também discutidas diversas recomendações práticas observadas na literatura disponível. O grande número e a diversidade de procedimentos que envolvem a instalação dos sensores, sua manutenção em condições de campo e a análise dos dados conferem ao método grande aplicação na experimentação científica. Entretanto, o uso do método de balanço de calor em larga escala parece inadequado devido à dificuldade de correta operação, o que facilmente compromete a qualidade das medidas.