bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastasis-Associated Protein 1 and Its Short Form Variant Stimulates Wnt1 Transcription through Promoting Its Derepression from Six3 Corepressor
Authors: Kumar Rakesh , Balasenthil Seetharaman , Manavathi Bramanandam , Rayala Suresh K. , Pakala Suresh B.
Published: August 2010

Although Wnt1 downstream signaling components have been well studied and activated in human cancer, the pathways that regulate Wnt1 itself have not been explored in depth. Here, we provide gain-of-function, loss-of function, and molecular evidence supporting functional interactions between metastasis-associated protein 1 short-form (MTA1s), metastasis-associated protein 1 (MTA1), and Wnt1 signaling components during mammary gland development and tumorigenesis. Using multiple model systems involving overexpression or knockdown of MTA1s or MTA1, we discovered that MTA1s and MTA1 hyperactivate the Wnt1 pathway due to increased expression of Wnt1 transcription. MTA1s and MTA1 physically interact with Six3 chromatin, a protein product of which is a direct histone deacetylase inhibitor–dependent repressor of Wnt1 transcription. Deletion of the MTA1s and MTA1 allele in murine embryonic fibroblasts resulted in the upregulation of Six3 and downregulation of Wnt signaling. In addition, mammary glands from the MTA1s/MTA1−/− mice exhibited increased recruitment of Six3 corepressor complex to the Wnt1 promoter and inhibition of Wnt1 pathway in mammary glands. These findings identify MTA1s and MTA1 as important upstream modifiers of the Wnt1 transcription, and consequently its functions, by directly inhibiting the transcription of Six3, allowing derepression of Wnt1 transcription. Cancer Res; 70(16); 6649–58. ©2010 AACR.
An Open-Label, Phase I Study of the Polo-like Kinase-1 Inhibitor, BI 2536, in Patients with Advanced Solid Tumors
Authors: Hofheinz Ralf-Dieter , Al-Batran Salah-Eddin , Hochhaus Andreas , Jäger Elke , Reichardt Volker L. , Fritsch Holger , Trommeshauser Dirk , Munzert Gerd
Published: August 2010

Purpose: This phase I, open-label, dose-escalation study investigated the maximum tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)–1 inhibitor, in two treatment schedules in patients with advanced solid tumors. Secondary objectives included evaluation of safety, efficacy, and pharmacokinetics.

Experimental Design: Patients received a single i.v. dose of BI 2536 as a 1-hour infusion on days 1 and 8 or a single 24-hour infusion on day 1 of each 21-day treatment course. MTD determination was based on dose-limiting toxicities.

Results: Forty-four and 26 patients received each treatment schedule, respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per administration (200 mg per course). The MTD for the second dosing schedule was not determined; a 225-mg dose was well tolerated. The most frequently reported treatment-related nonhematologic adverse events were gastrointestinal events and fatigue. Hematotoxicity as the most relevant side effect was similar in both schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen patients (32%) treated in the day 1 and 8 dosing schedule had a best overall response of stable disease. Plasma concentrations of BI 2536 increased dose proportionally, with no relevant accumulation of exposure in the day 1 and 8 dosing schedule. The average terminal half-life was 50 hours.

Conclusions: BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase–1 inhibitors. Clin Cancer Res; 16(18); 4666–74. ©2010 AACR.
Biological Evidence for Dual Antiangiogenic-Antiaromatase Activity of the VEGFR Inhibitor PTK787/ZK222584In vivo
Authors: Banerjee Susana , A'Hern Roger , Detre Simone , Littlewood-Evans Amanda J. , Evans Dean B. , Dowsett Mitchell , Martin Lesley-Ann
Published: August 2010

Purpose: Targeting vascular endothelial growth factor (VEGF) and estrogen receptor signaling pathways concomitantly may enhance benefit in estrogen receptor–positive breast cancer. We had shown previously that the VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 (PTK/ZK) is a competitive aromatase inhibitor in vitro. Here we investigated (a) whether PTK/ZK shows both antiangiogenic and antiaromatase inhibitory properties in vivo, and (b) whether the combination of PTK/ZK and letrozole is superior to letrozole alone.

Experimental Design: Estrogen-dependent human breast cancer cells engineered to express aromatase (MCF7 AROM 1 and BT474 AROM) were used. Mice were treated with vehicle, PTK/ZK (25, 50, or 100 mg/kg), letrozole, or PTK/ZK in combination with letrozole.

Results: In MCF7 AROM 1 tumors, all treatments induced growth suppression and were associated with a reduction in cell turnover index, a composite measurement of both proliferation and apoptosis. PTK/ZK significantly reduced vessel density. Whereas letrozole caused tumor regression, PTK/ZK stabilized tumor volumes. The growth suppressive and antiangiogenic effects of PTK/ZK were confirmed in BT474 AROM xenografts. The addition of PTK/ZK did not enhance the growth-suppressive effects of letrozole. However, PTK/ZK decreased progesterone receptor (PgR) and TFF1 expression and uterine weight, indicating that PTK/ZK decreases 17β-estradiol (E2) signaling in vivo.

Conclusion: The VEGF receptor inhibitor PTK/ZK showed effects on E2-dependent gene expression consistent with aromatase inhibition as well as antiangiogenesis in xenograft models of breast cancer. The combination with letrozole was not superior to letrozole alone. Overall, these results provide further support for a potential therapeutic approach of dual inhibition of VEGF and E2 signaling using a single agent. Clin Cancer Res; 16(16); 4178–87. ©2010 AACR.
HER2 Fragmentation and Breast Cancer Stratification
Authors: Arribas Joaquín , Parra-Palau Josep Lluís , Pedersen Kim
Published: August 2010

HER2 is a tyrosine kinase receptor whose overexpression in breast cancers correlates with poor prognosis. A subset of HER2-positive tumors also expresses a series of HER2 fragments, collectively known as p95HER2. These fragments are emerging as a valuable biomarker for this subset of patients, who have a particularly poor prognosis. Clin Cancer Res; 16(16); 4071–3. ©2010 AACR.
X-linked Inhibitor of Apoptosis: A Chemoresistance Factor or a Hollow Promise
Authors: Kashkar Hamid
Published: August 2010

The X-linked inhibitor of apoptosis (XIAP) is the only cellular protein that has evolved to potently inhibit the enzymatic activity of mammalian caspases and promotes resistance to apoptosis. Given its role in apoptosis and its frequently elevated expression in malignant cells, XIAP has garnered the most attention as a promising therapeutic target in cancer to overcome drug resistance. Accordingly, XIAP is thought to render tumor cells resistant to chemotherapy through its ability to inhibit caspases, and it is on this basis that XIAP has been proposed as an important adverse biomarker for chemoresistance in cancer patients. Here, the current understanding of the role of XIAP in cancer is reviewed. Further, the notion is explored that the elevated XIAP expression frequently observed in malignant tissues is, at least, not exclusively responsible for the resistance of tumor cells to conventional therapeutic treatment; rather, the function of XIAP seems to be conducive to the process of malignant transformation and/or progression. Clin Cancer Res; 16(18); 4496–502. ©2010 AACR.
Expression of ABCG2 (BCRP) Is Regulated by Nrf2 in Cancer Cells That Confers Side Population and Chemoresistance Phenotype
Authors: Singh Anju , Wu Hailong , Zhang Ping , Happel Christine , Ma Jinfang , Biswal Shyam
Published: August 2010

ATP-binding cassette, subfamily G, member 2 (ABCG2) is expressed in both normal and cancer cells and plays a crucial role in side population (SP) formation and efflux of xenobiotics and drugs. Nrf2, a redox-sensing transcription factor, on constitutive activation in non–small-cell lung cancer cells upregulates a wide spectrum of genes involved in redox balance, glutathione metabolism, and drug detoxification, which contribute to chemoresistance and tumorigenicity. This study examined the mechanism underlying Nrf2-dependent expression of ABCG2 and its role in the multidrug resistance phenotype. In silico analysis of the 5′-promoter flanking region of ABCG2 identified an antioxidant response element (ARE) at −431 to −420 bp. A detailed promoter analysis using luciferase reporter assays showed that ARE at −431 to −420 bp is critical for the Nrf2-mediated expression in lung cancer cells. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays revealed that Nrf2 interacts with the ABCG2 ARE element at −431 to −420 bp in vitro and in vivo. Disruption of Nrf2 expression in lung and prostate cancer cells, by short hairpin RNA, attenuated the expression of ABCG2 transcript and protein, and dramatically reduced the SP fraction in Nrf2-depleted cancer cells. Moreover, depleted levels of ABCG2 in these Nrf2 knockdown cells sensitized them to mitoxantrone and topotecan, two chemotherapy drugs detoxified mainly by ABCG2. As expected, overexpression of Nrf2 cDNA in lung epithelial cells led to an increase in ABCG2 expression and a 2-fold higher SP fraction. Thus, Nrf2-mediated regulation of ABCG2 expression maintains the SP fraction and confers chemoresistance. Mol Cancer Ther; 9(8); 2365–76. ©2010 AACR.
Dual Targeting of CDK and Tropomyosin Receptor Kinase Families by the Oral Inhibitor PHA-848125, an Agent with Broad-Spectrum Antitumor Efficacy
Authors: Albanese Clara , Alzani Rachele , Amboldi Nadia , Avanzi Nilla , Ballinari Dario , Brasca Maria Gabriella , Festuccia Claudio , Fiorentini Francesco , Locatelli Giuseppe , Pastori Wilma , Patton Veronica , Roletto Fulvia , Colotta Francesco , Galvani Arturo , Isacchi Antonella , Moll Jurgen , Pesenti Enrico , Mercurio Ciro , Ciomei Marina
Published: August 2010

Altered expression and activity of cyclin-dependent kinase (CDK) and tropomyosin receptor kinase (TRK) families are observed in a wide variety of tumors. In those malignancies with aberrant CDK activation, the retinoblastoma protein (pRb) pathway is deregulated, leading to uncontrolled cell proliferation. Constitutive activation of TRKs is instead linked to cancer cell survival and dissemination. Here, we show that the novel small-molecule PHA-848125, a potent dual inhibitor of CDKs and TRKs, possesses significant antitumor activity. The compound inhibits cell proliferation of a wide panel of tumoral cell lines with submicromolar IC50. PHA-848125–treated cells show cell cycle arrest in G1 and reduced DNA synthesis, accompanied by inhibition of pRb phosphorylation and modulation of other CDK-dependent markers. The compound additionally inhibits phosphorylation of TRKA and its substrates in cells, which functionally express this receptor. Following oral administration, PHA-848125 has significant antitumor activity in various human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemia models, with plasma concentrations in rodents in the same range as those found active in inhibiting cancer cell proliferation. Mechanism of action was also confirmed in vivo as assessed in tumor biopsies from treated mice. These results show that the dual CDK-TRK inhibitor PHA-848125 has the potential for being a novel and efficacious targeted drug for cancer treatment. Mol Cancer Ther; 9(8); 2243–54. ©2010 AACR.
γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors
Authors: Kannappan Ramaswamy , Ravindran Jayaraj , Prasad Sahdeo , Sung Bokyung , Yadav Vivek R. , Reuter Simone , Chaturvedi Madan M. , Aggarwal Bharat B.
Published: August 2010

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily, is in clinical trials for cancer therapy, but its anticancer potential is limited by the development of resistance. We investigated the ability of tocotrienol (T3), an unsaturated vitamin E present in palm oil, rice bran, barley, oats, and wheat germ, to sensitize tumor cells to TRAIL. Results from esterase staining, colony formation, caspase activation, and sub-G1 cell cycle arrest revealed that γ-T3 can sensitize human colon cancer cells to TRAIL. When examined for the mechanism, we found that γ-T3 significantly downregulated the expression of antiapoptotic proteins (c-IAP2 and Bcl-xL). We also found that γ-T3, but not tocopherol, induced the expression of the TRAIL receptors death receptor (DR)-4 and DR5. This induction was not cell type specific, as upregulation was also found in pancreatic, kidney, and leukemic cells. Upregulation of DRs by γ-T3 required the production of reactive oxygen species (ROS), and sequestering of ROS abolished both upregulation of the receptors and potentiation of TRAIL-induced apoptosis. Induction of DRs by γ-T3 also required activation of extracellular signal-regulated kinase 1 (ERK1), as silencing of ERK1 by specific siRNA abrogated the upregulation of TRAIL receptors. Further, induction of DRs by γ-T3 required the expression of p53 and Bax, as no induction of the receptors was found in colon cancer cells with deletion of these genes. Overall, our results show that γ-T3 sensitizes tumor cells to TRAIL by upregulating DRs through the ROS/ERK/p53 pathway and by downregulating cell survival proteins. Mol Cancer Ther; 9(8); 2196–207. ©2010 AACR.
Combinations of DNA Methyltransferase and Histone Deacetylase Inhibitors Induce DNA Damage in Small Cell Lung Cancer Cells: Correlation of Resistance with IFN-Stimulated Gene Expression
Authors: Luszczek Wioleta , Cheriyath Venugopalan , Mekhail Tarek M. , Borden Ernest C.
Published: August 2010

Because epigenetic inhibitors can reduce cancer cell proliferation, we tested the hypothesis that concurrent inhibition of histone acetylation and DNA methylation could synergistically reduce the viability of small cell lung cancer (SCLC) cells. Sub-IC50 concentrations of the DNA methyltransferase (DNMT) inhibitor decitabine (5-AZA-dC) and the histone deacetylase (HDAC) inhibitors (LBH589 or MGCD0103) synergistically reduced the proliferation of five of nine SCLC cell lines. Loss of viability of sensitive SCLC cells did not correlate with the inhibition of either DNMT1 or HDACs, suggesting nonepigenetic mechanisms for synergy between these two classes of epigenetic modulators. Because combinations of 5-AZA-dC and HDAC inhibitors had marginal effects on the apoptosis index, Comet assay was undertaken to assess DNA damage. MGCD0103 and 5AZA-dC cotreatment augmented DNA damage in SCLC cells, resulting in increased tail length and moment in Comet assays by 24 hours in sensitive cell lines (P < 0.01). Consistent with augmented DNA damage, combination of a DNMT and HDAC inhibitor markedly increased the levels of phospho-H2A.X in sensitive cells but not in resistant ones. Comparison of basal gene expression between resistant and sensitive cells identified markedly higher basal expression of IFN-stimulated genes in the resistant cell lines, suggesting that IFN-stimulated gene expression may determine SCLC cell sensitivity to epigenetic modulators or other DNA damaging agents. Mol Cancer Ther; 9(8); 2309–21. ©2010 AACR.
Epidermal Growth Factor Receptor–Targeted Radioimmunotherapy of Human Head and Neck Cancer Xenografts Using 90Y-Labeled Fully Human Antibody Panitumumab
Authors: Liu Zhaofei , Liu Yan , Jia Bing , Zhao Huiyun , Jin Xiaona , Li Fang , Chen Xiaoyuan , Wang Fan
Published: August 2010

Panitumumab (ABX-EGF or Vectibix), the first fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR), was approved by the Food and Drug Administration for treatment of patients with metastatic colorectal cancer. Here, we report for the first time the radioimmunotherapy (RIT) of EGFR-positive human head and neck cancer in a nude mouse model using pure β− emitter 90Y-labeled panitumumab. Biodistribution and planar γ-imaging studies were carried out with 111In-DOTA-panitumumab. The RIT efficacy of 90Y-DOTA-panitumumab was evaluated in UM-SCC-22B tumor model. CD31, Ki67, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling, and H&E staining were done on UM-SCC-22B tumor sections after treatment. The tumor uptake of 111In-DOTA-panitumumab in UM-SCC-22B tumor-bearing nude mice was 26.10 ± 4.93, 59.11 ± 7.22, 44.57 ± 9.80, 40.38 ± 7.76, and 14.86 ± 7.23 % injected dose per gram of tissue at 4, 24, 72, 120, and 168 hours after injection, respectively. Immunotherapy with cold panitumumab (four doses of 10 mg/kg) did not cause significant antitumor effect. RIT with a single dose of 100 μCi 90Y-DOTA-panitumumab caused significant tumor growth delay and improved the survival in UM-SCC-22B tumor model. A single dose of 200 μCi 90Y-DOTA-panitumumab led to almost complete tumor regression (tumor volumes were 34.83 ± 11.11 mm3 and 56.02 ± 39.95 mm3 on days 0 and 46 after treatment, respectively). Histopathologic analysis of tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of 90Y-DOTA-panitumumab. The high tumor uptake and prolonged tumor retention, as well as effective therapy, reveal that 90Y-DOTA-panitumumab may be a promising radioimmunotherapeutic agent to treat EGFR-positive solid tumors. Mol Cancer Ther; 9(8); 2297–308. ©2010 AACR.
The Association of Exposure to Lead, Mercury, and Selenium and the Development of Amyotrophic Lateral Sclerosis and the Epigenetic Implications
Authors: Callaghan Brian , Feldman Daniel , Gruis Kirsten , Feldman Eva
Published: August 2010

Metal exposures are an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). For one, there are numerous case reports linking different metals to an ALS phenotype. Furthermore, some investigators have demonstrated higher levels of certain metals in the blood, bone, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. There are also many case-control studies looking at the possible association of certain metals with the development of ALS. We have reviewed the relevant literature regarding metal exposures and the risk of developing ALS. We found that many different metals have been implicated as having a role in ALS, but there is more literature investigating the role of lead than any other metal. Despite many studies, the role, if any, of this metal in the pathogenesis of ALS remains unclear. Similarly, other metals either have inconclusive, conflicting, or insufficient results in order to make a definitive conclusion. One explanation for these findings is that metal exposures alone are insufficient for the development of ALS. Perhaps an interaction between the metal exposure and an individual’s genetic makeup is required to produce epigenetic changes that ultimately lead to ALS.
Estimation of the Age-Dependent Decline of Glomerular Filtration Rate from Formulas Based on Creatinine and Cystatin C in the General Elderly Population
Authors: Christensson Anders , Elmståhl Sölve
Published: August 2010

Background/Aims: To evaluate the performance of estimation formulas for glomerular filtration rate (GFR) based on creatinine and cystatin C in elderly. Methods: This study includes 2,931 men and women comprising nine age cohorts (60–93 years) from a longitudinal population-based project in Sweden. The participants were divided into four age groups. GFR was estimated from four formulas: the Modification of Diet in Renal Disease (MDRD), CKD-EPI and Cockroft-Gault (CG) based on creatinine and one based on cystatin C (eGFR-CysC). CG was also adjusted for body surface area (BSA) to CG/BSA. Results: CG, CG/BSA and eGFR-CysC yielded significantly lower GFR values compared to MDRD and CKD-EPI in the oldest persons (>80 years). A low GFR (<30 ml/min/1.73 m2) was demonstrated with MDRD in 3.3% (80–89 years) and in 6.3% (>90 years). With CG/BSA it was 8.0% (80–89 years) and 27.2% (>90 years), and with eGFR-CysC it was 12.1% (80–89 years) and 27% (>90 years), respectively. The individual formulas showed different eGFR in the four age cohorts and also different slopes by increasing age. CG/BSA and eGFR-CysC both show steeper declines than MDRD and CKD-EPI. Conclusion: Age-associated decline of renal function is common in elderly and increases immensely after the age of 80 years. More than 25% of the oldest demonstrate eGFR <30 ml/min/1.73 m2. CG and eGFR-CysC yielded the highest prevalence of decline and MDRD the lowest.
C-Reactive Protein Is a Predictor for Developing Proteinuria in a Screened Cohort
Authors: Iseki Kunitoshi , Iseki Chiho , Kinjo Kozen
Published: August 2010

Background: The relationship between C-reactive protein (CRP) and proteinuria is not known. Methods: We examined 20,077 screenees (men: 52.4%) of the Okinawa General Health Maintenance Association (OGHMA) registry who were examined between 2004 and 2006. Cross-sectional and longitudinal relationships between CRP and dipstick proteinuria were examined. The OGHMA central laboratory measured creatinine and CRP levels using an autoanalyzer (normal: <0.30 mg/dl). The glomerular filtration rate was estimated using the Japanese formula. Results: The prevalence of dipstick-positive proteinuria increased from 5.2% in screenees with a low CRP level of <0.10 mg/dl to 12.3% in those with high CRP levels (0.30–0.90 mg/dl). The CRP values did not affect the mean (SD) estimated glomerular filtration rate: 76.9 (13.7) with low CRP and 76.4 (15.1) with high CRP levels. We examined the relationship between baseline CRP and the development of proteinuria among subjects screened in 2004. Of 8,315 subjects without proteinuria examined again by 2006, 370 (4.4%) had developed proteinuria. The odds ratio (95% CI) for high CRP levels (0.30–0.90 mg/dl; reference CRP: <0.10 mg/dl) was 1.433 (1.013–2.028; p = 0.0422) after adjusting for multivariate variables, suggesting that CRP is closely associated with the prevalence and incidence of proteinuria. Conclusion: A prospective study on the development of proteinuria among those with high CRP levels is warranted. Screenees with high CRP levels may need to be followed up carefully despite the absence of traditional risk factors for proteinuria.
Fibroblast Growth Factor 23 in Hemodialysis Patients: Effects of Phosphate Binder, Calcitriol and Calcium Concentration in the Dialysate
Authors: Cancela Ana L.E. , Oliveira Rodrigo B. , Graciolli Fabiana G. , dos Reis Luciene M. , Barreto Fellype , Barreto Daniela V. , Cuppari Lilian , Jorgetti Vanda , Carvalho Aluizio B. , Canziani Maria Eugênia , Moysés Rosa M.A.
Published: August 2010

Background: Fibroblast growth factor 23 (FGF23) concentrations increase early in chronic kidney disease (CKD), and the influence of current CKD-mineral and bone disorder (MBD) therapies on serum FGF23 levels is still under investigation. Methods: In this post-hoc analysis of a randomized clinical trial, phosphate binders and calcitriol were washed out of 72 hemodialysis patients who were then submitted to bone biopsy, coronary tomography and biochemical measures, including FGF23. They were randomized to receive sevelamer or calcium acetate for 1 year and the prescription of calcitriol and the calcium concentration in the dialysate were adjusted according to serum calcium, phosphate and PTH and bone biopsy diagnosis. Results: At baseline, bone biopsy showed that 58.3% had low-turnover bone disease, whereas 38.9% had high-turnover bone disease, with no significant differences between them with regard to FGF23. Median baseline FGF23 serum levels were elevated and correlated positively with serum phosphate. After 1 year, serum FGF23 decreased significantly. Repeated measures ANOVA analysis showed that the use of a 3.5-mEq/l calcium concentration in the dialysate, as well as the administration of calcitriol and a calcium-based phosphate binder were associated with higher final serum FGF23 levels.Conclusions: Taken together, our results confirm that the current CKD-MBD therapies have an effect on serum levels of FGF23. Since FGF23 is emerging as a potential treatment target, our findings should be taken into account in the decision on how to manage CKD-MBD therapy.
Re-evaluating Dissociations between Implicit and Explicit Category Learning: An Event-related fMRI Study
Authors: Gureckis Todd M. , James Thomas W. , Nosofsky Robert M.
Published: August 2010

Recent fMRI studies have found that distinct neural systems may mediate perceptual category learning under implicit and explicit learning conditions. In these previous studies, however, different stimulus-encoding processes may have been associated with implicit versus explicit learning. The present design was aimed at decoupling the influence of these factors on the recruitment of alternate neural systems. Consistent with previous reports, following incidental learning in a dot-pattern classification task, participants showed decreased neural activity in occipital visual cortex (extrastriate region V3, BA 19) in response to novel exemplars of a studied category compared to members of a foil category, but did not show this decreased neural activity following explicit learning. Crucially, however, our results show that this pattern was primarily modulated by aspects of the stimulus-encoding instructions provided at the time of study. In particular, when participants in an implicit learning condition were encouraged to evaluate the overall shape and configuration of the stimuli during study, we failed to find the pattern of brain activity that has been taken to be a signature of implicit learning, suggesting that activity in this area does not uniquely reflect implicit memory for perceptual categories but instead may reflect aspects of processing or perceptual encoding strategies.
Formation of the Philippine Twin Tropical Cyclones during the 2008 Summer Monsoon Onset
Authors: Chen Tsing-Chang , Tsay Jenq-Dar , Yen Ming-Cheng , Cayanan Esperanza O.
Published: August 2010

Stretched from Indochina, across the South China Sea, to the Philippine Sea, a monsoon cyclonic shear flow was formed by easterlies of the cold surge-like flow in the north and monsoon westerlies in the south before the onset of the tropical Southeast Asian monsoon on 12 May 2008. On this date, two named tropical cyclones (Halong and Matmo) evolved with a 12-h lag from a closed vortex adjacent to the coast of central Vietnam and another closed vortex near Palawan Island (Philippines) within this shear flow. These two cyclones, named the twin Philippine tropical cyclones, moved almost on the same track, along the anomalous shear line (departure from the climatological one) across the Philippines, and turned northeastward to the ocean south of Japan. It was revealed from synoptic analysis that the cold surge-like flow was coupled with the midlatitude eastward-propagating short wave in northeast Asia, and part of the monsoon westerlies were fed by the cross-equatorial flow, the downstream flow of easterlies around the northern rim of the Southern Hemisphere subtropical high. The environment favorable for the formation of the twin cyclones was developed from the tropics–midlatitude interaction between synoptic systems in these two latitudinal zones. Formations of these cyclones were a result of drastic spinups of the two closed vortices (within the monsoon shear flow) following the surge of monsoon westerlies, which coincided with those of easterlies of the cold surge-like flow, and the cross-equatorial flow originating from easterlies between the Southern Hemisphere subtropical high and the Southern Hemisphere shear flow.
Effect of Glucose and Insulin on Oxidized Low-Density Lipoprotein Phagocytosis by Human Monocytes: A Pilot Study
Authors: Sarigianni Maria , Bekiari Eleni , Tsapas Apostolos , Topouridou Konstantina , Kaloyianni Martha , Koliakos George , Paletas Konstantinos
Published: August 2010

We assessed the effect of glucose and insulin on human monocytes. Monocytes were isolated from 16 healthy obese and 10 lean healthy participants. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese participants were subdivided into 2 subgroups: insulin sensitive (IS) and insulin resistant (IR). Monocyte oxidized low-density lipoprotein (oxLDL) phagocytosis was assessed pre and poststimulation in vitro with glucose or insulin. Experiments were repeated after incubation with a Na+/H+ exchanger-1 inhibitor ([NHE-1]; cariporide) or rosiglitazone. Glucose increased oxLDL phagocytosis in all groups studied (at 1 or 3 hours incubation; P = .037-.002). Insulin increased oxLDL phagocytosis in all groups studied after 1-hour incubation (P = .027-.015) but not at 3 hours. Incubation with cariporide attenuated oxLDL phagocytosis except in the obese IS group. Rosiglitazone eliminated glucose- and insulin-induced increase in oxLDL phagocytosis in all studied groups. Glucose and insulin induce oxLDL phagocytosis.
Effects of 10 Weeks Walk Training With Leg Blood Flow Reduction on Carotid Arterial Compliance and Muscle Size in the Elderly Adults
Authors: Ozaki Hayao , Miyachi Motohiko , Nakajima Toshiaki , Abe Takashi
Published: August 2010

High-intensity resistance training increases muscle size, but reduces arterial compliance. Muscular blood flow reduction (BFR) during low-intensity training has been shown to elicit muscle hypertrophy. However, the effect on arterial compliance is unknown. We examined the effects of walk training with BFR on carotid arterial compliance and muscle size in the elderly adults. Both BFR-walk training (BFR-W, n = 13, 66 ± 1 year) and control-walk training (CON-W, n = 10, 68 ± 1 year) groups performed 20 minutes treadmill walking at an exercise intensity of 45% of heart rate reserve, 4 days/week for 10 weeks. The BFR-W group wore pressure cuffs on both legs during training. Maximum knee joint strength (∼15%) and MRI-measured thigh muscle cross-sectional area (3%) increased in the BFR-W, but not in the CON-W. Carotid arterial compliance improved in both BFR-W (50%) and CON-W (59%) groups. Walk training with blood flow reduction can improve thigh muscle size/strength as well as carotid arterial compliance, unlike high-intensity training, in the elderly.
Correlates of Teacher Practices Influencing Student Outcomes in Reading Instruction for Advanced Readers
Authors: Hunsaker Scott L. , Nielsen Aubree , Bartlett Brianne
Published: August 2010

In a professional development project, six teaching practices were posited as necessary for improving affective and cognitive outcomes for identified advanced readers. These practices were identification, organization for instruction, content, instructional strategies, continuous improvement assessment, and ambassadorship. Sixty-one teachers received training in these practices and were evaluated on their implementation, with usable data from 37. Implementation ratings were correlated with measure of reading attitude and literary analysis. Several correlations were discovered that have implications for understanding teaching style and the influence of teacher practice on student outcomes.
An evolutionary tuning technique for type-2 fuzzy logic controller
Authors: Mohammadi S.M.A. , Gharaveisi A.A. , Mashinchi M. , Vaezi-Nejad S.M.
Published: August 2010

Uncertainty is an inherent part of control systems used in real world applications. Various instruments used in such systems produce uncertainty in their measurements and thus influence the integrity of the data collection. Type-1 fuzzy sets used in conventional fuzzy systems cannot fully handle the uncertainties present but type-2 fuzzy sets that are used in type-2 fuzzy systems can handle such uncertainties in a better way because they provide more parameters and more design degrees of freedom. There are membership functions that can be parameterized by a few variables and when optimized, the membership optimization problem can be reduced to a parameter optimization problem. This paper deals with the parameter optimization of the type-2 fuzzy membership functions using a new proposed reinforcement learning algorithm in automatic voltage regulator. The results of the proposed method referred to as the Extended Discrete Action Reinforcement Learning Automata algorithm are compared with the results obtained by the Discrete Action Reinforcement Learning Automata algorithm and well known genetic algorithm. The performance of the proposed method on initial error reduction and error convergence issues are investigated by computer simulations.
Decentralized control design for a class of non-linear large-scale systems with matched and unmatched uncertainties
Authors: Liu Wen-Jeng
Published: August 2010

In this paper, based on sliding mode control (SMC) theory, a new robust decentralized control scheme is proposed for a class of uncertain large-scale interconnected systems with matched and unmatched uncertainties. The proposed decentralized SMC law ensures the global reaching condition of the sliding mode of the uncertain composite system in the presence of matched and/or unmatched uncertainties. The so-called sliding coefficient matching condition can be extended for the decentralized SMC of the uncertain large-scale systems (LSS). Also, in the sliding mode, the investigated uncertain composite system still possesses the insensitivity to the uncertainties and disturbances and behaves like a system just with matched uncertainties. Furthermore, it shows that the proposed control law can be applied to stabilize the uncertain LSS with matched and unmatched uncertainties. Furthermore, they ensure that the system trajectories not only converge but also globally exponentially converge to the sliding mode within a specified rate. Finally, an illustrative example is included to demonstrate the validity of the proposed decentralized SMC law.
User Agency in the Middle Range: Rumors and the Reinvention of the Internet in Accra, Ghana
Authors: Burrell Jenna
Published: August 2010

This article is an analysis of rumors about Internet scamming told by Internet café users in the West African capital city of Accra, Ghana. Rumors provided accounts of how the Internet can be effectively operated by young Ghanaians to realize ‘‘big gains’’ through foreign connections. Yet these accounts were contradicted by the less promising direct experiences users had at the computer interface. Rumors amplified evidence of wildly successful as well as especially harmful encounters with the Internet. Rather than simply transferring information, through the telling of rumors, Internet users reclaimed a social stability that was disrupted by the presence of the Internet. These stories cast young Ghanaian Internet users as both good and effective in relation to the Internet. The study of accounts as they relate to the activities accounted for is an established area of interest in social theory. By considering how rumors function as accounts and how such interpretations of the technology are propagated among users, this analysis contributes to a broader understanding of user agency.
Experiencing and Managing Urinary Incontinence: A Qualitative Study
Authors: Hayder Daniela , Schnepp Wilfried
Published: August 2010

Urinary incontinence is a complex problem from which millions of people are affected worldwide. How the affected persons experience and organize their day-to-day lives has hardly been studied. This was the motive for a 2½-year study in the German-speaking region. Thirty-two problem-centered interviews were conducted with 22 women and 10 men, which were then analyzed using the grounded theory method, after Strauss and Corbin. The experience of urinary incontinence is dependent on the cause of the incontinence and on whether the episode of incontinence took place in private or in public. Incontinence itself influences social, cultural, and sportive activities and partner relationships. The results show that persons with incontinence use complex strategies to regain control. These include (a) being prepared for the next urge to urinate or the next episode of incontinence, (b) searching for possible therapies, and (c) forming a circle of trust.
Job Satisfaction Ratings: Measurement Equivalence Across Nurses and Physicians
Authors: Etchegaray Jason M. , Sexton J. Bryan , Helmreich Robert L. , Thomas Eric J.
Published: August 2010

The measurement equivalence of job satisfaction ratings from physicians and nurses working in intensive care units was tested in the present study. Seventy-two nurses and 72 physicians completed the Safety Attitudes Questionnaire, which contains five items about job satisfaction. Measurement equivalence across nurses and physicians of the job satisfaction ratings was examined via multiple-group confirmatory factor analysis. The results indicated that physicians and nurses use the same metric when providing ratings for this job satisfaction measure. The primary implication from the present study is that nurses and physicians conceptualize job satisfaction in a similar manner. This implication needs to be extended to other survey measures of interest to health services researchers. Future areas of research are discussed.
Animal Models of Orthopoxvirus Infection
Authors: Chapman J. L. , Nichols D. K. , Martinez M. J. , Raymond J. W.
Published: August 2010

Smallpox was one of the most devastating diseases known to humanity. Although smallpox was eradicated through a historically successful vaccination campaign, there is concern in the global community that either Variola virus (VARV), the causative agent of smallpox, or another species of Orthopoxvirus could be used as agents of bioterrorism. Therefore, development of countermeasures to Orthopoxvirus infection is a crucial focus in biodefense research, and these efforts rely on the use of various animal models. Smallpox typically presented as a generalized pustular rash with 30 to 40% mortality, and although smallpox-like syndromes can be induced in cynomolgus macaques with VARV, research with this virus is highly restricted; therefore, animal models with other orthopoxviruses have been investigated. Monkeypox virus causes a generalized vesiculopustular rash in rhesus and cynomolgus macaques and induces fatal systemic disease in several rodent species. Ectromelia virus has been extensively studied in mice as a model of orthopoxviral infection in its natural host. Intranasal inoculation of mice with some strains of vaccinia virus produces fatal bronchopneumonia, as does aerosol or intranasal inoculation of mice with cowpox virus. Rabbitpox virus causes pneumonia and fatal systemic infections in rabbits and can be naturally transmitted between rabbits by an aerosol route similar to that of VARV in humans. No single animal model recapitulates all known aspects of human Orthopoxvirus infections, and each model has its advantages and disadvantages. This article provides a brief review of the Orthopoxvirus diseases of humans and the key pathologic features of animal models of Orthopoxvirus infections.
Aerobiology and Inhalation Exposure to Biological Select Agents and Toxins
Authors: Roy C. J. , Reed D. S. , Hutt J. A.
Published: August 2010

Aerosol is the most likely route of dissemination of biological select agents and toxins in a bioterrorist attack, regardless of the natural route of exposure to the agent. The use of animal models for testing preventative and therapeutic countermeasures requires knowledge of the pathogenesis of disease after inhalation exposure. Factors that relate to outcome after respiratory exposure include the inherent infectivity and virulence and/or toxicity of the agent in the host under investigation, in addition to characteristics of the aerosol particle and host that affect the delivered dose of, and host response to, the inhaled material. This introductory article discusses the emerging science of aerobiology and the unique features of respiratory tract anatomy, physiology, and immunology that are relevant to the pathogenesis of aerosolized biothreat agents.
Correctional Officers’ Perceptions of a Solution-Focused Training Program
Authors: Pan Peter Jen Der , Deng Liang-Yu F. , Chang Shona Shih Hua , Jiang Karen Jye-Ru
Published: August 2010

The purpose of this exploratory study was to explore correctional officers’ perceptions and experiences during a solution-focused training program and to initiate development of a modified pattern for correctional officers to use in jails. The study uses grounded theory procedures combined with a follow-up survey. The findings identified six emergent themes: obstacles to doing counseling work in prisons, offenders’ amenability to change, correctional officers’ self-image, advantages of a solution-focused approach (SFA), potential advantages of applying SFA to offenders, and the need for the consolidation of learning and transformation. Participants perceived the use of solution-focused techniques as appropriate, important, functional, and of only moderate difficulty in interacting with offenders. Finally, a modified pattern was developed for officers to use when working with offenders in jails. Suggestions and recommendations are made for correctional interventions and future studies.
Hygroscopic thickness swelling rate of wood polymer nanocomposite
Authors: Kord Behzad , Kiaeifar Azadeh
Published: August 2010

In this study, the effects of nanoclay and coupling agent content on the clay dispersion and thickness swelling behavior of PP/WF composites were investigated. To meet this objective, the blend nanocomposites were prepared by melt mixing PP and beech WF at 50% weight ratios, with various amounts of nanoclay (0, 3, and 6 phc) and MAPP (0, 2, and 4 phc) in Hakee internal mixer. The samples were then made by injection molding. The thickness swelling rate of the composites was evaluated by immersing them in water at room temperature for several weeks (up to 3000 h). A swelling model developed by Shi and Gardner (2006) was used to study the thickness swelling process of composites, from which the parameter, K SR, can be used to quantify the swelling rate. The results indicated that equilibrium thickness swelling and also shorter equilibrium time (the time to reach the equilibrium thickness swelling) decreased with increase of clay loading, and also the effect of compatibilizer was positive in terms of enhancing the dimensional stability of the composites. The swelling model developed was a good predictor of the hygroscopic swelling process of wood plastic composites. The composites containing PP had a higher KSR than those containing MAPP or nanoclay. The minimum KSR values were observed in composites made of 3 phc of nanoclay and 4 phc of MAPP. The micrographs of XRD and TEM confirmed the intercalation morphology in nanocomposite samples.
Probation Officer Recommendations for Sentencing Relative to Judicial Practice: The Implications for African Americans
Authors: Leiber Michael , Reitzel John , Mack Kristin
Published: August 2010

A number of studies have been conducted that assess the role of the prosecutor on judicial decision making in regard to the differential treatment African Americans may receive relative to Whites. Missing from this inquiry has been consideration of the influence that probation officers may have on this process. In the present study, the focal concerns perspective and prior research are used as background to understand the concordance between probation officer sentencing recommendations and decision making by judges and the extent to which this relationship may be tempered by the race of the offender.
Light Still Shines in the Darkness
Authors: Karpf Ted , Ferguson J. Todd , Swift Robin Y.
Published: August 2010

Health care is in crisis at the global, national, and local levels, with hundreds of millions living without basic care, or with insufficient care. Current health care models seem to have ignored, muted, or excluded the voices of the people they were intended to serve, resulting in health systems and care delivery models that do not respond to the needs of the people. This article describes a values-based approach to health and health care services in which the voices of the people are heard and listened to, and in which individuals and communities are informed participants in their own care. We draw parallels between contemporary concerns for decency in care giving to Florence Nightingale’s path-breaking work, first with the British military medical system and then Great Britain as a whole.
Shorter Stay, Longer Life: Age at Migration and Mortality Among the Older Mexican-Origin Population
Authors: Angel Ronald J. , Angel Jacqueline L. , Díaz Venegas Carlos , Bonazzo Claude
Published: August 2010

Objectives: In this article, we investigate the association between age at migration and mortality during a 13-year period in a sample of Mexican American immigrants 65 and older at baseline. Method: We employ the Hispanic Established Populations for Epidemiologic Studies of the Elderly (H-PESE) to control for mortality-related health and social factors. Results: Our analyses show that the immigrant generation does not represent a homogeneous mortality risk category. Individuals who migrated to the United States in mature adulthood have a considerably lower risk of death than individuals who migrated in childhood or midlife. Chronic conditions or functional capacity do not account for these differences. Conclusion: Our findings suggest that standard risk pools may differ significantly on the basis of genetic and unmeasured life-course factors. A better understanding of the late-life immigrant mortality advantage has important implications for more effective and targeted social and medical interventions.
Systemic lupus erythematosus complicated with pulmonary hemorrhage in a 17-year-old female
Authors: Vijatov-Djuric G. , Stojanovic V. , Tomic J. , Konstantinidis N. , Konstantinidis G.
Published: August 2010

Pulmonary hemorrhage is a rare and life-threatening complication of systemic lupus erythematosus. In this report, we described a 17-year-old female with pulmonary hemorrhage as an initial manifestation of systemic lupus erythematosus, along with lupus nephritis and central nervous system lupus. High doses of corticosteroids and pulse cyclophosphamide therapy resulted in rapid improvement of respiratory function in our patient.
Disseminating Effective Community Prevention Practices: Opportunities for Social Work Education
Authors: Hawkins J. David , Shapiro Valerie B. , Fagan Abigail A.
Published: August 2010

In the United States, about 17% of adolescents meet diagnostic criteria for mental, emotional, and behavioral (MEB) disorders. Six million young people receive treatment services annually for mental, emotional, or behavioral problems. These problems affect one in five families and cost $247 million annually. Some strategies for preventing MEB disorders in young people have been developed, tested, and found to be effective in preventing the onset, persistence, and severity of psychological disorders, drug abuse, and delinquency. Unfortunately, tested and effective prevention policies, programs, and practices are not widely used. This article highlights recent advances in prevention science and describes some opportunities and challenges in advancing the use of science-based prevention in communities. The chapter concludes by exploring the potential role of social work education in developing a workforce ready to increase community access to effective prevention strategies.
Commentary: Cultural Adaptation, Collaboration, and Exchange
Authors: Palinkas Lawrence Albert
Published: August 2010

This commentary reviews three articles linked together by two themes (a) the use of cultural adaptation of evidence-based practices to reduce disparities in health and services delivery and (b) the importance of collaboration involving intervention developers, practitioners, and consumers when delivering services. Both themes illustrate a process of cultural exchange, enabling researchers to develop interventions that are more meaningful and acceptable to consumers; providers to develop a stronger therapeutic alliance with consumers; and consumers to develop greater understanding and acceptance of treatment process. Such exchanges lead to improved consumer outcomes and greater satisfaction with services. By serving as a culture broker or change agents, social workers can play a leadership role in the translation of research to practice.