bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Expression of Id Family Proteins in Small Cell Lung Cancer and its Prognostic Significance
Authors: Kamalian Laleh , Gosney John R. , Forootan Shiva S. , Foster Christopher S. , Bao Zheng Z. , Beesley Carol , Ke Youqiang
Published: April 2008

Purpose: To study the molecular pathology of human small cell lung cancer (SCLC), molecular biology approaches were used to identify genes involved in malignant progression of the cancer cells.

Experimental Design: Microquantity differential display was used initially to identify genes expressed differentially between normal and malignant cell lines. The differences were verified by Western blot. Immunohistochemical analysis was done on paired normal and malignant lung tissues and on tissues taken by biopsy to assess the expression status of candidate genes and their prognostic significance.

Results: Inhibitor of DNA/differentiation (Id)1 gene was up-regulated in SCLC cells. Levels of Id1 in 8 of 10 cell lines were increased by 1.7- to 21.4-fold when compared with the benign cells. A similar increase was also found in levels of Id2 and Id3. On 26 pairs of lung tissues, all four Id proteins were significantly (Wilcoxon Signed Rank Test, P < 0.001-0.005) overexpressed in cytoplasm of the malignant cells. In nuclei of SCLC cells, Id1 expression was significantly reduced, whereas the levels of Id2, Id3, and Id4 were significantly (Wilcoxon Signed Rank Test, P < 0.001) increased. Immunohistochemical staining on biopsy specimens showed that the increased expression of Id2 in cytoplasm of cancer cells, not the other three proteins, was significantly associated with the increased survival of SCLC patients.

Conclusion: Changed expression profiles of Id proteins may play important roles in malignant progression of SCLC, and the increased Id2 in cytoplasm is a novel prognostic factor to predict the patient outcomes.
LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis
Authors: Melisi Davide , Ishiyama Satoshi , Sclabas Guido M. , Fleming Jason B. , Xia Qianghua , Tortora Giampaolo , Abbruzzese James L. , Chiao Paul J.
Published: April 2008

Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor β (TGF-β) plays a key role in cancer metastasis, signaling through the TGF-β type I/II receptors (TβRI/II). We hypothesized that targeting TβRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins (L3.6pl/GLT). To determine whether pancreatic cancer cells or the cells in the liver microenvironment were involved in LY2109761-mediated reduction of liver metastasis, we used a model of experimental liver metastasis. LY2109761 significantly inhibited the L3.6pl/GLT soft agar growth, suppressed both basal and TGF-β1−induced cell migration and invasion, and induced anoikis. In vivo, LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. Results from the experimental liver metastasis models indicate an important role for targeting TβRI/II kinase activity on tumor and liver microenvironment cells in suppressing liver metastasis. Targeting TβRI/II kinase activity on pancreatic cancer cells or the cells of the liver microenvironment represents a novel therapeutic approach to prevent pancreatic cancer metastasis. [Mol Cancer Ther 2008;7(4):829–40]
Antitumor activity of fibroblast growth factor receptor 3–specific immunotoxins in a xenograft mouse model of bladder carcinoma is mediated by apoptosis
Authors: Martínez-Torrecuadrada Jorge L. , Cheung Lawrence H. , López-Serra Paula , Barderas Rodrigo , Cañamero Marta , Ferreiro Sergio , Rosenblum Michael G. , Casal J. Ignacio
Published: April 2008

Human single-chain Fv directed against fibroblast growth factor receptor 3 (FGFR3) have been shown to block proliferation of RT112 bladder carcinoma cells in vitro. Here, we examined the ability of the recombinant gelonin toxin (rGel) to enhance this inhibitory effect in vitro and in vivo on the bladder cancer cell line RT112 and the corresponding xenografts. Immunotoxins were genetically engineered by fusing FGFR3-specific Fv fragments (3C) to the NH2 terminus of rGel and expressed as a soluble protein in Escherichia coli. The 3C/rGel fusion construct showed an IC50 of 200 nmol/L against log-phase RT112 cells compared with 1,500 nmol/L for free rGel. Immunofluorescence studies showed that the 3C/rGel construct internalized rapidly into the cytoplasm of RT112 cells within 1 h of exposure. The mechanism of immunotoxin-induced cell death was found to be mediated by apoptosis. RT112 tumor xenografts in severe combined immunodeficient mice treated with 50 mg/kg 3C/rGel exhibited considerable growth delay relative to control tumors and a significant reduction of 55% to 70% in mean tumor size. Immunohistochemical analysis showed that tumors from mice treated with 3C/rGel displayed considerable apoptotic damage compared with control groups. Subcellular location of FGFR3 in immunotoxin-treated tumors indicated a translocation of FGFR3 to the nuclear membrane in contrast to tumors from saline-treated controls. These results show that FGFR3-driven immunotoxins may be an effective therapeutic agent against human bladder and other tumor types overexpressing FGFR3. [Mol Cancer Ther 2008;7(4):862–73]
Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53
Authors: Supiot Stéphane , Hill Richard P. , Bristow Robert G.
Published: April 2008

Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. Whether Nutlin-3 alters cell toxicity following DNA damage under oxic versus hypoxic conditions has not been studied. The potential radiosensitization (0-10 Gy) properties of Nutlin-3 (dose range, 2-10 μmol/L for up to 24 h) were investigated in vitro using three prostate cancer cell lines, 22RV1 [wild-type p53 (WTp53)], DU145 (mutated p53), and PC-3 (p53-null) under oxic (21% O2), hypoxic (0.2% O2), and anoxic (0% O2) conditions. As a single agent, Nutlin-3 (2-10 μmol/L) stabilized p53 and p21WAF levels and was toxic to WTp53-22RV1 cells (IC50, 4.3 μmol/L) but had minimal toxicity toward p53-deficient cells (IC50, >10 μmol/L). When combined with radiation under oxic conditions, Nutlin-3 decreased clonogenic survival in all three cell lines: 22RV1 [sensitizing enhancement ratio (SER), 1.24], DU145 (SER, 1.27), and PC-3 (SER, 1.12). Anoxia induced p53 protein expression in 22RV1 cells and this was augmented by Nutlin-3 treatment. Furthermore, Nutlin-3 was more effective as a radiosensitizer under hypoxic conditions particularly in WTp53-expressing cells: 22RV1 (SER, 1.78), DU145 (SER, 1.31), and PC-3 (SER, 1.28). The decrease in clonogenic survival with Nutlin-3 was not correlated to altered levels of radiation-induced apoptosis within the three cell lines. Our results indicate that Nutlin-3 can act as a radiosensitizer via p53-independent mechanisms under low O2 levels. Nutlin-3 may be a useful adjunct to improve the therapeutic ratio using precision radiotherapy targeted to hypoxic cells and warrants further study in vivo. [Mol Cancer Ther 2008;7(4):993–9]
Vitamin E succinate induces NAG-1 expression in a p38 kinase-dependent mechanism
Authors: Shim Minsub , Eling Thomas E.
Published: April 2008

NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor-β superfamily, is involved in many cellular processes, such as inflammation, apoptosis/survival, and tumorigenesis. Vitamin E succinate (VES) is the succinate derivative of α-tocopherol and has antitumorigenic activity in a variety of cell culture and animal models. In the current study, the regulation and role of NAG-1 expression in PC-3 human prostate carcinoma cells by VES was examined. VES treatment induced growth arrest and apoptosis as well as an increase in NAG-1 protein and mRNA levels in a time- and concentration-dependent manner. VES treatment induced nuclear translocation and activation of p38 kinase. Pretreatment with p38 kinase inhibitor blocked the VES-induced increase in NAG-1 protein and mRNA levels, whereas an inhibition of protein kinase C, Akt, c-Jun NH2-terminal kinase, or MEK activity had no effect on VES-induced NAG-1 levels. Forced expression of constitutively active MKK6, an upstream kinase for p38, induced an increase in NAG-1 promoter activity, whereas p38 kinase inhibitor blocked MKK6-induced increase in NAG-1 promoter activity. VES treatment resulted in >3-fold increase in the half-life of NAG-1 mRNA in a p38 kinase-dependent manner and transient transfection experiment showed that VES stabilizes NAG-1 mRNA through AU-rich elements in 3′-untranslated region of NAG-1 mRNA. The inhibition of NAG-1 expression by small interfering RNA significantly blocked VES-induced poly(ADP-ribose) polymerase cleavage, suggesting that NAG-1 may play an important role in VES-induced apoptosis. These results indicate that VES-induced expression of NAG-1 mRNA/protein is regulated by transcriptional/post-transcriptional mechanism in a p38 kinase-dependent manner and NAG-1 can be chemopreventive/therapeutic target in prostate cancer. [Mol Cancer Ther 2008;7(4):961–71]
WTp53 induction does not override MTp53 chemoresistance and radioresistance due to gain-of-function in lung cancer cells
Authors: Cuddihy Andrew R. , Jalali Farid , Coackley Carla , Bristow Robert G.
Published: April 2008

New molecular cancer treatment strategies aim to reconstitute wild-type p53 (WTp53) function in mutant p53 (MTp53)–expressing tumors as a means of resensitizing cells to chemotherapy or radiotherapy. The success of this approach may depend on whether MTp53 proteins are acting in a dominant-negative or independent gain-of-function mode. Herein, we describe an isogenic, temperature-sensitive p53 model (p53A138V) in p53-null human H1299 lung cancer cells in which WTp53 can be selectively coexpressed with a temperature-sensitive MTp53 allele (A138V) during initial DNA damage and subsequent DNA repair. Cells expressing MTp53 alone or coexpressing induced WTp53 and MTp53 were tested for p53 transcription, G1 and G2 cell cycle checkpoints, apoptosis, and long-term clonogenic survival following DNA damage. Transient transfection of WTp53 into H1299 cells, or shift-down of H1299-p53A138V stable transfectants to 32°C to induce WTp53, led to increased p21WAF1 expression and G1 and G2 arrests following DNA damage but did not increase BAX expression or apoptosis. In contrast, both transient and stable expression of the p53A138V mutant in p53-null H1299 cells (e.g. testing gain-of-function) at 37°C blocked p21WAF1 induction following DNA damage. Cell death was secondary to mitotic catastrophe and/or tumor cell senescence. Overexpression of WTp53 did not resensitize resistant MTp53-expressing cells to ionizing radiation, cisplatinum, or mitomycin C. Our results suggest that human MTp53 proteins can lead to resistant phenotypes independent of WTp53-mediated transcription and checkpoint control. This should be considered when using p53 as a prognostic factor and therapeutic target. [Mol Cancer Ther 2008;7(4):980–92]
UBE1L represses PML/RARα by targeting the PML domain for ISG15ylation
Authors: Shah Sumit J. , Blumen Steven , Pitha-Rowe Ian , Kitareewan Sutisak , Freemantle Sarah J. , Feng Qing , Dmitrovsky Ethan
Published: April 2008

Acute promyelocytic leukemia (APL) is characterized by expression of promyelocytic leukemia (PML)/retinoic acid (RA) receptor α (RARα) protein and all-trans-RA-mediated clinical remissions. RA treatment can confer PML/RARα degradation, overcoming dominant-negative effects of this oncogenic protein. The present study uncovered independent retinoid degradation mechanisms, targeting different domains of PML/RARα. RA treatment is known to repress PML/RARα and augment ubiquitin-activating enzyme-E1-like (UBE1L) protein expression in NB4-S1 APL cells. We previously reported RA-induced UBE1L and the IFN-stimulated gene, 15-kDa protein ISG15ylation in APL cells. Whether the ubiquitin-like protein ISG15 directly conjugates with PML/RARα was not explored previously and is examined in this study. Transient transfection experiments with different PML/RARα domains revealed that RA treatment preferentially down-regulated the RARα domain, whereas UBE1L targeted the PML domain for repression. As expected, ubiquitin-specific protease 18 (UBP43/USP18), the ISG15 deconjugase, opposed UBE1L but not RA-dependent PML/RARα degradation. In contrast, the proteasomal inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal, inhibited both UBE1L- and RA-mediated PML/RARα degradation. Notably, UBE1L induced ISG15ylation of the PML domain of PML/RARα, causing its repression. These findings confirmed that RA triggers PML/RARα degradation through different domains and distinct mechanisms. Taken together, these findings advance prior work by establishing two pathways converge on the same oncogenic protein to cause its degradation and thereby promote antineoplastic effects. The molecular pharmacologic implications of these findings are discussed. [Mol Cancer Ther 2008;7(4):905–14]
Enhancement of antitumor properties of TRAIL by targeted delivery to the tumor neovasculature
Authors: Cao Lin , Du Pan , Jiang Shu-Han , Jin Guang-Hui , Huang Qi-Lai , Hua Zi-Chun
Published: April 2008

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent with tumor-selective apoptotic activity. TRAIL plays a role in the innate and adaptive immune response and autoimmune disease and may also be involved in hepatic cell death and inflammation. For these reasons, chronic exposure to TRAIL may have deleterious side effects in patients as a cancer therapeutic. In this study, we have improved the antitumor activity of TRAIL by targeted delivery to the tumor vasculature, leading to dramatic enhancement of its therapeutic properties. TRAIL was fused to the ACDCRGDCFC peptide (named RGD-L-TRAIL), a ligand of αVβ3 and αVβ5 integrins. Biological activity was evaluated in vitro and antitumor efficacy was investigated in vivo as a single agent and in combination with irinotecan hydrochloride (CPT-11). The fusion protein RGD-L-TRAIL, but not TRAIL or RGE-L-TRAIL, specifically bound to microvascular endothelial cells in a dose-dependent manner and showed enhanced apoptosis-inducing activity (caspase-3 and caspase-8 activation) in αVβ3 and αVβ5 integrin-positive cancer cells. In addition, RGD-L-TRAIL was more effective in suppressing tumor growth of COLO-205 tumor-bearing mice than an equivalent dose of TRAIL. The antitumor effect of RGD-L-TRAIL was further enhanced by combination with CPT-11 in both TRAIL-sensitive COLO-205 and TRAIL-resistive HT-29 tumor xenograft models. Our findings suggest that the novel fusion protein RGD-L-TRAIL can directly target tumor endothelial cells as well as αVβ3 and αVβ5 integrin-positive tumor cells. The tumor-targeted delivery of TRAIL derivatives, such as RGD-L-TRAIL, may prove to be a promising lead candidate for cancer therapy. [Mol Cancer Ther 2008;7(4):851–61]
2-Deoxyglucose induces Akt phosphorylation via a mechanism independent of LKB1/AMP-activated protein kinase signaling activation or glycolysis inhibition
Authors: Zhong Diansheng , Liu Xiuju , Schafer-Hales Katherine , Marcus Adam I. , Khuri Fadlo R. , Sun Shi-Yong , Zhou Wei
Published: April 2008

The compound 2-deoxyglucose (2-DG) enhances chemotherapy/radiotherapy in cell lines and animal models, prompting two phase I clinical trials with this cancer therapeutic. Although its mechanism of action has not been fully elucidated, it is hypothesized that the molecular basis of 2-DG activity is related to glycolysis inhibition. Here, we report that 2-DG induced Akt phosphorylation at Thr308 and Ser473 as early as 15 min post-treatment. These phosphorylation events required phosphatidylinositol-3-kinase activity but were not related to LKB1/AMP-activated protein kinase signaling, the inhibition of glycolysis or epidermal growth factor receptor signaling. The 2-DG-mediated Akt phosphorylation also led to the phosphorylation of Akt downstream targets, such as Foxo3a, GSK3β, and Chk1. Because the functional consequence of Akt activation includes chemotherapy/radiotherapy resistance, our data suggested that the combination of phosphatidylinositol-3-kinase/Akt inhibitory agents in 2-DG-based chemotherapy/radiotherapy may result in enhanced therapeutic efficacy. [Mol Cancer Ther 2008;7(4):809–17]
Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction
Authors: Westermann Dirk , Kasner Mario , Steendijk Paul , Spillmann Frank , Riad Alexander , Weitmann Kerstin , Hoffmann Wolfgang , Poller Wolfgang , Pauschinger Matthias , Schultheiss Heinz-Peter , Tschöpe Carsten
Published: April 2008

Background—

Increased left ventricular stiffness is a distinct finding in patients who have heart failure with normal ejection fraction (HFNEF). To elucidate how diastolic dysfunction contributes to heart failure symptomatology during exercise, we conducted a study using an invasive pressure-volume loop approach and measured cardiac function at rest and during atrial pacing and handgrip exercise.

Methods and Results—

Patients with HFNEF (n=70) and patients without heart failure symptoms (n=20) were enrolled. Pressure-volume loops were measured with a conductance catheter during basal conditions, handgrip exercise, and atrial pacing with 120 bpm to analyze diastolic and systolic left ventricular function. During transient preload reduction, the diastolic stiffness constant was measured directly. Diastolic function with increased stiffness was significantly impaired in patients with HFNEF during basal conditions. This was associated with increased end-diastolic pressures during handgrip exercise and with decreased stroke volume and a leftward shift of pressure-volume loops during atrial pacing.

Conclusions—

Increased left ventricular stiffness contributed to increased end-diastolic pressure during handgrip exercise and decreased stroke volume during atrial pacing in patients with HFNEF. These data suggest that left ventricular stiffness modulates cardiac function in HFNEF patients and suggests that diastolic dysfunction with increased stiffness is a target for treating HFNEF.
Blood Pressure and Renal Sodium Handling in Relation to Genetic Variation in the
DRD1
Promoter and
GRK4
Authors: Staessen Jan A. , Kuznetsova Tatiana , Zhang Haifeng , Maillard Marc , Bochud Murielle , Hasenkamp Sandra , Westerkamp Judith , Richart Tom , Thijs Lutgarde , Li Xinli , Brand-Herrmann Stefan-Martin , Burnier Michel , Brand Eva
Published: April 2008

Activation of type-1 dopamine receptors (
DRD1
) reduces renal sodium reabsorption. In a family-based random sample of 611 untreated whites (women, 45.0%; mean age, 38.6 years), we measured blood pressure (BP). We used the endogenous lithium clearance to assess fractional sodium excretion (FE
Na
) and proximal (RNa
prox
) and distal (RNa
dist
) tubular sodium reabsorption. We investigated multivariate-adjusted associations with the
DRD1
promoter (
A
−
48G
,
G
−
94A
, and
C
−
800T
) and
GRK4 (Ala142Val
). The frequent
DRD1
haplotypes were
AGC
(48.2%),
GGT
(34.4%), and
AAC
(14.3%). While standardizing to mean sodium excretion (8.7 mmol/h) and adjusting for covariates and relatedness, RNa
dist
was lower in
DRD1
−
94GG
homozygotes than −
94A
allele carriers (effect size, −0.94%;
P
=0.005) with opposite findings for FE
Na
(+0.084%;
P
=0.014).
AGC
carriers (−0.88%;
P
=0.012) and
AAC
carriers (+1.00%;
P
=0.004) had different RNa
dist
compared to corresponding noncarriers. Furthermore, FE
Na
was lower in
AAC
carriers than in noncarriers (−0.082%;
P
=0.019). The family-based analyses identified a significant between-family component in the variance of the renal phenotypes associated with the
DRD1
polymorphisms. Transmission of the
DRD1 AGC
haplotype was also associated with lower systolic (−3.54 mm Hg;
P
=0.016) and diastolic (−2.80 mm Hg;
P
=0.0064) BPs without significant between-family variance component. Plasma renin activity and urinary aldosterone excretion were not associated with
DRD1
variation. The GRK4
Ala142Val
polymorphism did not contribute to the phenotypes under study. In conclusion, renal sodium handling and BP were associated with genetic variation in the
DRD1
promoter. The between-family variance component excluded population stratification for BP, but not for the renal phenotypes.
Orthostatic Hypercoagulability
Authors: Masoud Muhannad , Sarig Galit , Brenner Benjamin , Jacob Giris
Published: April 2008

Orthostatic stress causes significant plasma shift and raises transmural pressure in lower extremities, resulting in an increase in endothelial activation and plasma proteins concentrations, possibly including coagulation factors. This may lead to activation of the coagulation system during standing. To test this hypothesis, we recruited 18 healthy volunteers (9 females and 9 males; mean age: 25±1.2 years; body mass index: 21.7±0.5 kg/m
2
). Hemodynamics, plasma shift (extrapolated from sequential hematocrit concentration), plasma proteins, and coagulation tests, including procoagulants; fibrinogen, factor V, and factor VIII activity; prothrombin fragments 1 and 2; and endothelial activation–related factors (tissue factor and von Willebrand factor), as well as protein C global pathway, were determined at rest supine and at 15 minutes, 30 minutes, and 60 minutes of still standing. Thirty minutes of standing caused a decrease in plasma volume by 12.0±0.5% and an increase in plasma protein by 13.0±0.7%. Fibrinogen, factor V, and factor VIII activity rose by 12.0±1.2%, 13.0±1.0%, and 40.0±6.0% (
P
<0.002 for all), respectively. Prothrombin fragments 1 and 2 were elevated by 150.0±30.0%. Tissue factor and von Willebrand factor increased by 30.0±9.0% and 17.4±51.0% (
P
<0.02 for both), respectively. However, protein C assay results decreased from 0.95±0.20 to 0.83±0.16 (
P
<0.001). We hereby introduce a novel physiological mechanism, “orthostatic procoagulation,” that should be considered during coagulation tests. Furthermore, it could be extrapolated to the pathophysiology of stasis and venous thromboembolism.
The Impact of Snow Model Complexity at Three CLPX Sites
Authors: Feng Xia , Sahoo Alok , Arsenault Kristi , Houser Paul , Luo Yan , Troy Tara J.
Published: April 2008

Many studies have developed snow process understanding by exploring the impact of snow model complexity on simulation performance. This paper revisits this topic using several recently developed land surface models, including the Simplified Simple Biosphere Model (SSiB); Noah; Variable Infiltration Capacity (VIC); Community Land Model, version 3 (CLM3); Snow Thermal Model (SNTHERM); and new field measurements from the Cold Land Processes Field Experiment (CLPX). Offline snow cover simulations using these five snow models with different physical complexity are performed for the Rabbit Ears Buffalo Pass (RB), Fraser Experimental Forest headquarters (FHQ), and Fraser Alpine (FA) sites between 20 September 2002 and 1 October 2003. These models simulate the snow accumulation and snowpack ablation with varying skill when forced with the same meteorological observations, initial conditions, and similar soil and vegetation parameters.

All five models capture the basic features of snow cover dynamics but show remarkable discrepancy in depicting snow accumulation and ablation, which could result from uncertain model physics and/or biased forcing. The simulated snow depth in SSiB during the snow accumulation period is consistent with the more complicated CLM3 and SNTHERM; however, early runoff is noted, owing to neglected water retention within the snowpack. Noah is consistent with SSiB in simulating snow accumulation and ablation at RB and FA, but at FHQ, Noah underestimates snow depth and snow water equivalent (SWE) as a result of a higher net shortwave radiation at the surface, resulting from the use of a small predefined maximum snow albedo. VIC and SNTHERM are in good agreement with each other, and they realistically reproduce snow density and net radiation. CLM3 is consistent with VIC and SNTHERM during snow accumulation, but it shows early snow disappearance at FHQ and FA. It is also noted that VIC, CLM3, and SNTHERM are unable to capture the observed runoff timing, even though the water storage and refreezing effects are included in their physics.

A set of sensitivity experiments suggest that Noah’s snow simulation is improved with a higher maximum albedo and that VIC exhibits little improvement with a larger fresh snow albedo. There are remarkable differences in the vegetation impact on snow simulation for each snow model. In the presence of forest cover, SSiB shows a substantial increase in snow depth and SWE, Noah and VIC show a slight change though VIC experiences a later onset of snowmelt, and CLM3 has a reduction in its snow depth. Finally, we observe that a refined precipitation dataset significantly improves snow simulation, emphasizing the importance of accurate meteorological forcing for land surface modeling.
Anger and Stress
Authors: Kweon Byoung-Suk , Ulrich Roger S. , Walker Verrick D. , Tassinary Louis G.
Published: April 2008

Anger and stress management have become important issues in the modern workplace. One out of four American workers report themselves to be chronically angry, which has been linked to negative outcomes such as retaliatory behavior, revenge, interpersonal aggression, poor work performance, absenteeism, and increased turnover. We hypothesized that people who work in office environments decorated with aesthetically engaging art posters would experience less stress and anger in response to task-related frustration. Two hundred and ten college students were randomly assigned to different office conditions where abstract and nature paintings were hung on the walls. Participants performed four mild anger-provoking computer tasks and then reported their levels of state anger and stress. Results indicate that different office conditions had a significant influence on state anger and stress for males but not for females. Males experienced less state anger and stress when art posters were present. Through mediation analysis, we found that increased proportions of nature paintings decreased state anger because of decreased levels of stress.
Developing alternative masculinities as a strategy to address gender-based violence
Authors: Sathiparsad Reshma
Published: April 2008

English

This article discusses research using focus groups and personal interviews with rural male youth on gender-based violence. The findings revealed that many of the youth considered relationship violence acceptable, but the article highlights the fluid, multiple and contextual nature of masculinity that surfaced. The significance of these alternative responses for interventions is emphasized.

French

Cet article commente une recherche menée au moyen de groupes de discussion et d'entrevues personnelles auprès de jeunes hommes de milieux ruraux sur le sujet de la violence sexospécifique. Les résultats révèlent que bon nombre de ces jeunes considèrent acceptable la violence relationnelle, mais l'article met en relief la nature variable, multiple et contextuelle de la masculinité qui s'en est dégagée. L'accent est donc mis sur le sens de ces nouvelles réponses en intervention.

Spanish

Este artículo discute la investigación utilizando grupos focales y entrevistas personales, con jóvenes varones rurales, sobre violencia de género. Los hallazgos revelan que muchos de los jóvenes consideraron aceptable la violencia en las relaciones, pero el artículo destaca la naturaleza fluida, múltiple y contextual de la masculinidad que sale a la superficie. Se enfatiza la significación de estas respuestas alternativas para las intervenciones.
The intersection of cultural practices and ethics in a rights-based society
Authors: Ross Eleanor
Published: April 2008

English

This article interrogates various African cultural beliefs and practices, and advocates for the development of an indigenous Afro-centric model of social work to promote the healing process, and as a way of teaching social work students about the dilemmas inherent in respecting cultural practices which impinge on the rights of others.

French

Cet article se penche sur différentes croyances et pratiques culturelles africaines et plaide en faveur du développement d'un modèle de travail social propre à l'Afrique. Ce modèle permettrait non seulement de promouvoir le processus de guérison, mais aussi de sensibiliser les étudiants en travail social sur les dilemmes que suscite le respect des pratiques culturelles qui affectent les droits des autres.

Spanish

Este artículo cuestiona varias creencias y prácticas culturales africanas y aboga por el desarrollo de un modelo de trabajo social indígena Afro-céntrico, para promover el proceso terapéutico y como una forma de enseñanza en trabajo social acerca de los dilemas inherentes respecto de las prácticas culturales que afectan los derechos de otros.
Correlation between ethnicity and filial responsibility among three ethnic groups in Israel
Authors: Sultany Tom , Lavie Yotam , Haimov Iris
Published: April 2008

English

This study examines the association between ethnicity and culture to attitude toward filial responsibility in Israel. The results revealed that Ethiopian immigrant students scored significantly higher on all the dimensions. The study's results support the role of culture as an important factor in shaping perceptions of filial responsibilities toward aging parents.

French

Cette étude examine les liens qui existent entre l'origine ethnique, la culture et l'attitude envers la responsabilité filiale en Israël. Les résultants révèlent que les étudiants immigrants éthiopiens enregistrent des scores plus élevés dans toutes les dimensions. Les résultats de cette étude confirment que la culture est un facteur important dans la définition des perceptions de la responsabilité filiale à l'égard de parents âgés

Spanish

Este estudio examina la relación entre etnicidad y cultura en la actitud hacia la responsabilidad filial en Israel. Los resultados revelaron que los estudiantes etíopes inmigrantes obtuvieron una calificación significativamente más alta en todas las dimensiones. Los resultados del estudio respaldan el papel de la cultura como un factor importante en las formas de percepción de las responsabilidades filiales.
Future Concerns of Adult Siblings of Persons With Traumatic Brain Injury
Authors: Degeneffe Charles Edmund , Olney Marjorie F.
Published: April 2008

This study examined future concerns conveyed by adult siblings who provided regular caregiving support to their brothers and sisters with traumatic brain injury (TBI). The authors surveyed a national sample of 280 adult siblings of persons with TBI. Using a constant comparative approach to text analysis, the authors analyzed responses to the question “What are your concerns regarding the future for your sibling with TBI?” Common themes of such concerns were related to the caregiving siblings' roles as future caregivers and their perceptions of the quality of professional care provided to their injured family members. Also, participants endorsed concerns for their injured siblings' independence, recovery, and relationships with family and friends. Clinical, advocacy, and research implications of these findings are discussed.
Local Governance in Mexico: The Cases of Two Historic-centre Partnerships
Authors: Guarneros-Meza Valeria
Published: April 2008

This paper contends that the British understanding of governance as networks has travelled and discusses the extent to which it can be applied in the Mexican context. The paper comes at a time when Rod Rhodes, one of the first inventors of the concept, reflects on how governance is now understood after a decade of research, including its potential to be transferred beyond the British context. The paper begins by underlining the relevance of Mexico's political economy, with particular regard to the neo-liberal and democratic processes experienced over the past 25 years. The next section discusses the three main premises of governance (fragmentation, networks and self-government) and the way they have been questioned by two criticisms significant to this paper: the role of government as having a strong interventionist character and the threat posed by the classical concept of governance to democratic accountability. These criticisms are relevant for understanding the Mexican reality and the implementation of governance through public—private partnerships. The third section develops the research fieldwork, arguing that the premises on fragmentation and networks are relevant to the Mexican case when considered within the context of the historic-centre regeneration partnerships of Querétaro and San Luis Potosí. In presenting the findings, the paper argues that the applicability of the concept reinforces the aforementioned criticisms, underlining their general relevance when used for comparative analysis.
Labour Underutilisation in Metropolitan Labour Markets in Australia: Individual Characteristics, Personal Circumstances and Local Labour Markets
Authors: Baum Scott , Bill Anthea , Mitchell William
Published: April 2008

There has been a growing awareness that the issue of labour market disadvantage is substantially greater than merely considering unemployment and the ability to find a job. There is an increasing literature that points to the advantages of considering a broader concept which accounts not only for those people who are traditionally unemployed, but also for individuals who are underemployed and those who are sub-unemployed or discouraged workers. Taking multidimensional survey and census data for Australian metropolitan regions, this paper applies a broad employability framework to an understanding of labour underutilisation which presents the risk of underutilisation as a function of individual characteristics, personal circumstances and the impact of local labour market characteristics. The analysis finds that the risk of labour underutilisation is associated with a range of individual characteristics and personal circumstances together with the characteristics of the metropolitan local labour market.
Urbanism, Political Uncertainty and Democratisation
Authors: Bollens Scott A.
Published: April 2008

This paper examines how political leaders and urbanists employ city policies and strategies during and after political transformation periods and whether these local policies figure into larger processes of democratisation. It brings the city and the urban scale into contemporary debates about democratic transformations in ethnically diverse countries. Four settings are investigated—Basque Country and Barcelona (Spain) and Sarajevo and Mostar (Bosnia—Herzegovina)—that have experienced intergroup conflict, war and major national transformations. Findings come primarily from over 100 interviews with urban professionals, community officials, academics and political leaders in these cities. It is found that urban interventions are capable of making distinct contributions to national peace-building and can supplement and catalyse transitional paths toward democracy. The paper discusses why some cities play a constructive role in shaping democratisation while others do not, how this progressive city function is actualised and how this type of urbanism can be misplaced or neglected.
Tax Deductions, Tax Credits and the Homeownership Rate of Young Urban Adults in the United States
Authors: Bourassa Steven C. , Ming Yin
Published: April 2008

The US President's Advisory Panel on Federal Tax Reform has recommended changes to income tax concessions for homeowners. Consistent with the opinions of many economists, the tax reform panel concluded that the existing tax concessions are not particularly effective. The housing and mortgage industry have opposed the reforms, in part due to a fear that the reforms will reduce the homeownership rate. In this paper, 1998 American Housing Survey data are used to estimate a tenure choice equation and to simulate hypothetical changes in tax concessions. Focusing on young households who are likely to be on the margin between renting and owning, it is concluded that the mortgage interest and property tax deductions reduce the homeownership rate for these households due to effects on house prices. The tax credit proposed by the Advisory Panel would be likely to have a similar effect.
Strategy Versus Understanding
Authors: Rojas Hernando
Published: April 2008

This study combines empirical political communication research models with theoretical accounts provided by the theory of communicative action to expand the understanding of how communication matters for democratic political functioning, particularly under conditions of social instability. Building on the Habermasian distinction between strategic orientations versus understanding orientations in conversation, the author explores the role of conversation orientations as antecedents to political engagement. Examination of conversation orientations in Colombia, a society characterized by social conflict, provides evidence of the democratic benefits of orientations toward reaching understanding and the deleterious effects of strategic orientations for political involvement, associational membership, and ultimately participation, as well as the importance of including conversation orientations as explanatory factors in models that seek to explain political involvement. These findings speak to the potential for communicative rationality to transcend the use of force and bring about action coordination based on understanding in communities experiencing civil strife.
Revisiting Interpersonal Media Competition
Authors: Ramirez Artemio , Dimmick John , Feaster John , Lin Shu-Fang
Published: April 2008

The theory of niche proposes that a new medium competes with older, more established media to fulfill users' needs. This study uses niche theory, a macrolevel theory, as well as social information processing theory and the theory of electronic propinquity, both microlevel theories, to examine the niche of instant messaging (IM) in providing general gratifications. Results indicate that IM is characterized by a broad niche, surpassed only by that of the cell phone. IM had substantial niche overlap with e-mail and the cell phone, indicating a degree of substitutability between them; the least overlap was with the landline telephone (LLP). The hierarchy that emerged indicated that the cell phone was superior to IM, which was superior to e-mail, followed by the LLP for providing general gratifications. Finally, displacement tests indicated that IM use displaced e-mail and LLP but not cell phone use. Implications and directions for future research are discussed.
Rheological Behavior, Tensile Properties, Morphology, and Thermal Stability of Recycled Poly(vinyl chloride)/Acrylonitrile Butadiene Rubber (PVCr/NBR) Blends: The Effect of Maleic Acid
Authors: Ismail H. , Supri A.G.
Published: April 2008

Blends of recycled poly(vinyl chloride) (PVCr) and acrylonitrile butadiene rubber (NBR) modified by addition of maleic acid (MAc) are prepared by using a Haake Rheomix. The effect of MAc on melt Rheological behavior, tensile properties, morphology, and thermal stability of PVCr/NBR blends are investigated. The recorded data obtained from the Haake Rheomix are converted into values of apparent shear rate, apparent shear stress, and apparent viscosity. The apparent viscosity of the blends is found to decrease with increase in the shear rate and follow the pseudoplasticity behavior. At a similar shear rate, the presence of MAc in PVCr/NBR blends exhibits higher apparent viscosity than PVCr/NBR blends without MAc. Activation energy, Ea decreases with increasing shear rate, obviously due to the strong non-Newtonian behavior of PVCr/NBR blends. The addition of MAc in PVCr/NBR blends exhibits higher stress at peak and stress at 100% elongation but lower elongation at break and thermal stability than PVCr/NBR blends without the addition of MAc. Scanning electron microscopic (SEM) examination of extracted surfaces of PVCr/NBR+MAc blends indicates the increase of the interfacial interaction between PVCr and NBR phases with the presence of Mac.
Effect of Fillers on Mechanical Properties of Dynamically Crosslinked Styrene Butadiene Rubber/High Density Polyethylene Blends
Authors: Jayasree T.K. , Predeep P.
Published: April 2008

The effect of fillers on the mechanical properties such as stress— strain behavior, tensile strength, percentage strain at-break, Young's modulus and tear strength have been investigated. Different filled crosslinked thermoplastic elastomers of styrene butadiene rubber (SBR)/high density polyethylene blends (HDPE) blends were prepared using silica, HAF-carbon black, china clay and TiO2. The extent of polymer-filler interaction has been analyzed by Kraus as well as Cunneen—Russell equation. The reinforcement ability of the filler was increased in the order of silica>HAF-black>clay>TiO 2. The nature of the filler and filler loading has a dramatic effect on the mechanical properties of SBR/ HDPE blends. Filled blends showed improved mechanical properties such as enhanced of strain at-break, when fillers are incorporated. The initial trend of properties for all filled system is the enhancement of properties. When HAF-black is used as the filler, at higher loading strain at- break is found to decrease due to the stiffness of the matrix. In the case of clay, there is a deterioration of properties occurs on higher loading, which is attributed to dilution effect and all TiO 2 filled system have lower elongation at break than the base polymer. Theoretical models namely Guith's and Kerner's model have been compared with the experimental values of Young's modulus of filled system. The experimental values of modulus are found to be higher than the theoretical values indicating strong interaction between the filler and the matrix. SEM studies of the tensile and tear fractured surfaces of the filled blends have been carried out. The variation in properties was correlated with the morphology of the system.
Synthesis and Characterization of Polyurethane Elastomers
Authors: Huibo Zhang  , Yadong Chen  , Yongchun Zhang  , Xiangdong Sun  , Haiya Ye  , Wen Li
Published: April 2008

This study reports the synthesis and characterization of polyurethane (PU) elastomers, with emphasis on the effect of different methods and order for raw materials feeding. First, a series of PU elastomers is synthesized using polyether glycol, TDI, and extender chain reagent. The results show that after diisocyanate is dipped into the dried polyether, the elastomers synthesized using extender chain reagent exhibit the best properties. The subsequent characterization and measurements further show that by an optimum synthetic route, considerable hard segments can be formed uniformly in the soft segments, and the extent of micro-phase separation is relatively perfect. Moreover, it is demonstrated that the relative molecular weight of polyether glycol has an important effect on the properties of the synthesized PU elastomers. The more the relative molecular weight, the more soft segments are contained, and the smaller the tensile strength, rupture strength, and rigidity. In addition, the investigation on the effect of different raw materials indicates that the prepared polyether-type elastomers exhibit an excellent water/solvent resistance.
The Importance of the Organization of Partner Knowledge in Understanding Perceptions of Relationship Quality and Conflict Resolution Behavior in Married Couples
Authors: Campbell Lorne , Butzer Bethany , Wong Joanne
Published: April 2008

This research investigated how the organization of partner knowledge was related to global relationship evaluations and specific interpersonal behaviors in a sample of 107 married couples. Spouses first completed several questionnaires and later participated in a 12-min videotaped conflict resolution task. As expected, wives in older relationships exhibited greater marital quality (self-reported and observed) when they had (a) an integrative knowledge structure and used many negative traits to describe their spouse or (b) a compartmentalized knowledge structure and used few negative traits to describe their spouse. Greater marital quality, however, was found for husbands when they were (a) in older relationships and possessed an integrative structure or (b) in newer relationships and possessed a compartmentalized structure. Exploratory analyses suggested that in some circumstances people may have greater marital quality when they share an organizational style with their spouse.
Beyond the Search for Competition in Social Service Contracting
Authors: Lamothe Meeyoung , Lamothe Scott
Published: April 2008

The authors argue it is time to move beyond thinking of competition in social service contracting simply in terms of whether competitive tendering procedures are used. Although the procurement process is important, other factors should be examined as well. In particular, they look at how market consolidation and accountability are related to competitive procurement. Findings indicate that demand side—driven consolidation (i.e., governments purposely choosing to go with fewer and larger contracts in which lead agencies manage vendor networks) has both competitive and noncompetitive aspects that are in need of further study and that the competition—accountability link is more complex than generally assumed. Although, as expected, there is evidence that competition, in and of itself, leads to some contractor turnover, it does not appear that competitive vendors are held to higher standards than their noncompetitive counterparts regarding performance (as measured by adherence to contract terms).
Leflunomide-induced subacute cutaneous lupus erythematosus with erythema multiforme-like lesions
Authors: Marzano AV , Ramoni S , Del Papa N , Barbareschi M , Alessi E
Published: April 2008

Leflunomide is an immunosuppressive agent that acts by inhibiting pyrimidine synthesis in lymphocytes and other rapidly proliferating cells, as well as by suppressing tumor necrosis factor-α–induced cellular responses. A number of leflunomide-related adverse events have been reported. Among cutaneous side effects, a few cases of subacute cutaneous lupus erythematosus have been described. We report a previously undocumented reaction to leflunomide, manifesting as subacute cutaneous lupus erythematosus and erythema multiforme-like lesions, in a young woman treated with this drug for ankylosing spondylitis. Withdrawal of leflunomide combined with a short cycle of systemic corticosteroid led to the resolution of the patient’s rash, indicating this drug as being responsible for the development of the disease. We conclude that leflunomide might have triggered the occurrence of both subacute cutaneous lupus erythematosus and erythema multiforme in a patient with pre-existing autoimmune diathesis. The suppressive effect of this drug on tumor necrosis factor-α–related mechanisms might have played a role in the induction of such a unique reaction to leflunomide.