bluuebunny/crossref_metadata_2025 huggingface dataset:
Earth pressures exerted on an induced trench cast-in-place double-cell rectangular box culvert
Authors: Oshati Olajide Samuel , Valsangkar Arun J. , Schriver Allison B.
Published: November 2012

Earth pressure data from the field instrumentation of a cast-in-place reinforced rectangular box culvert are presented in this paper. The instrumented culvert is a 2.60 m by 3.60 m double-cell reinforced cast-in-place rectangular box buried under 25.10 m of fill constructed using the induced trench installation (ITI) method. The average earth pressure measured across the roof was 0.42 times the overburden pressure, and an average of 0.52 times the overburden pressure was measured at mid-height of the culvert on the sidewalls. Base contact pressure under the rectangular box culvert was also measured, providing field-based data demonstrating increased base pressure resulting from downward drag forces developed along the sidewalls of the box culvert. An average increase of 25% from the measured vertical earth pressures on the roof plus the culvert dead load (DL) pressure was calculated at the culvert base. A model culvert was also tested in a geotechnical centrifuge to obtain data on earth pressures at the top, sides, and base of the culvert. The data from the centrifuge testing were compared with the prototype structure, and the centrifuge test results agreed closely with the measured field prototype pressures, in spite of the fact that full similitude was not attempted in centrifuge testing.
SIGNATURE CHANGE IN NONCOMMUTATIVE FRW COSMOLOGY
Authors: GHANEH T. , DARABI F. , MOTAVALLI H.
Published: November 2012

The conditions for which the no boundary proposal may have a classical realization of a continuous change of signature, are investigated for a cosmological model described by FRW metric coupled with a self-interacting scalar field, having a noncommutative phase space of dynamical variables. The model is then quantized and a good correspondence is shown between the classical and quantum cosmology indicating that the noncommutativity does not destruct the classical-quantum correspondence. It is also shown that the quantum cosmology supports a signature transition where the bare cosmological constant takes a vast continuous spectrum of negative values. The bounds of bare cosmological constant are limited by the values of noncommutative parameters. Moreover, it turns out that the physical parameters are constrained by the noncommutativity parameters.
NOTE ON HAWKING–UNRUH EFFECTS IN GRAPHENE
Authors: CHEN PISIN , ROSU HARET
Published: November 2012

Beltrami-shaped graphene sheets have been recently proposed as analogs of curved spacetimes with Hawking–Unruh effects detected through typical condensed matter measurements involving scanning tunneling microscopes and spectroscopy. However, such deformed sheets, if ever fabricated, will contain large strain-induced pseudo-magnetic fields with important guiding effects on the motion of the electrons in the conduction band. Besides, possible surface polariton and plasmon modes are known to be important players in the radiative heat transfer which takes place in the natural near-field nanoscale experimental conditions. Therefore, we suggest that the latter class of experiments could shed light on phenomena related to the black hole membrane paradigm instead.
Sorcin modulates mitochondrial Ca2+ handling and reduces apoptosis in neonatal rat cardiac myocytes
Authors: Suarez Jorge , McDonough Patrick M. , Scott Brian T. , Suarez-Ramirez Angelica , Wang Hong , Fricovsky Eduardo S. , Dillmann Wolfgang H.
Published: November 2012

Sorcin localizes in cellular membranes and has been demonstrated to modulate cytosolic Ca2+ handling in cardiac myocytes. Sorcin also localizes in mitochondria; however, the effect of sorcin on mitochondrial Ca2+ handling is unknown. Using mitochondrial pericam, we measured mitochondrial Ca2+ concentration and fluxes in intact neonatal cardiac myocytes overexpressing sorcin. Our results showed that sorcin increases basal and caffeine-stimulated mitochondrial Ca2+ concentration. This effect was associated with faster Ca2+ uptake and release. The effect of sorcin was specific for mitochondria, since similar results were obtained with digitonin-permeabilized cells, where cytosolic Ca2+ flux was disrupted. Furthermore, mitochondria of cardiac myocytes in which sorcin was overexpressed were more Ca2+-tolerant. Experiments analyzing apoptotic signaling demonstrated that sorcin prevented 2-deoxyglucose-induced cytochrome c release. Furthermore, sorcin prevented hyperglycemia-induced cytochrome c release and caspase activation. In contrast, antisense sorcin induced caspase-3 activation. Thus, sorcin antiapoptotic properties may be due to modulation of mitochondrial Ca2+ handling in cardiac myocytes.
Regional distribution of SGLT activity in rat brain in vivo
Authors: Yu Amy S. , Hirayama Bruce A. , Timbol Gerald , Liu Jie , Diez-Sampedro Ana , Kepe Vladimir , Satyamurthy Nagichettiar , Huang Sung-Cheng , Wright Ernest M. , Barrio Jorge R.
Published: November 2012

Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.
Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis
Authors: Ichiki Tomoko , Boerrigter Guido , Huntley Brenda K. , Sangaralingham S. Jeson , McKie Paul M. , Harty Gail J. , Harders Gerald E. , Burnett John C.
Published: November 2012

In heart failure (HF), the cardiac hormone natriuretic peptides (NPs) atrial (ANP), B-type (BNP), and C-type (CNP) play a key role to protect cardiac remodeling. The proprotein convertases corin and furin process their respective pro-NPs into active NPs. Here we define in a canine model of HF furin and corin gene and protein expression in normal and failing left atrium (LA) or ventricle (LV) testing the hypothesis that the NP proproteins convertases production is altered in experimental HF. Experimental canine HF was produced by rapid right ventricular pacing for 10 days. NPs, furin, and corin mRNA expression were determined by quantitative RT-PCR. Protein concentration or expression was determined by immunostaining, radioimmunoassay, or Western blot. Furin and corin proteins were present in normal canine LA and LV myocardium and vasculature and in smooth muscle cells. In normal canines, expression of NPs was dominant in the atrium compared with the ventricle. In experimental early stage HF characterized with marked atrial fibrosis, ANP, BNP, and CNP mRNA, and protein concentrations were higher in HF LA but not HF LV compared with normals. In LA, corin mRNA and protein expressions in HF were lower, whereas furin mRNA and protein expressions were higher than normals. NPs and furin expressions were augmented in the atrium in experimental early stage HF and, conversely, corin mRNA and protein expressions were decreased with atrial remodeling. Selective changes of these NP convertases may have significance in the regulation of pro-NP processing and atrial remodeling in early stage HF.
An Af9 cis-element directly targets Dot1a to mediate transcriptional repression of the αENaC gene
Authors: Zhang Wenzheng , Yu Zhiyuan , Wu Hongyu , Chen Lihe , Kong Qun , Kone Bruce C.
Published: November 2012

The epithelial Na+ channel subunit-α ( αENaC) of the distal nephron is essential for salt balance. We previously demonstrated that the histone methyltransferase Dot1a and its protein partner Af9 basally repress αENaC transcription in mouse inner medullary collecting duct type 3 (mIMCD3) cells and link aldosterone-elicited chromatin modifications to αENaC transcriptional activation. Af9 DNA-binding activity has never been demonstrated, and whether and where Af9 binds to the αENaC promoter to target Dot1a are unknown. The present study sought to identify functional Af9 cis-element(s) in the −57/+439 “R3” subregion of αENaC, the principal site for Dot1a-Af9 interaction, in mIMCD3 cells. We also exploited connecting tubule/collecting duct-specific Dot1l-deficient mice ( Dot1l AC) to determine the impact of Dot1l inactivation on renal αENaC expression in vivo. mIMCD3 cell lines expressing αENaC promoter-reporter constructs harboring deletion of +74/+107 demonstrated greatly reduced association of Af9 and Dot1a by ChIP/qPCR. Aldosterone treatment resulted in further decrements in Af9 and Dot1a association with the αENaC promoter. Gel shift and antibody competition assays using wild-type and mutant oligomers revealed Af9-containing +78/+92 αENaC DNA-protein complexes in nuclear extracts of mIMCD3 cells. Mutation of the +78/+92 element resulted in higher basal αENaC promoter activity and impaired Dot1a-mediated inhibition in trans-repression assays. In agreement, mice with connecting tubule/collecting duct-specific knockout of Dot1l exhibited greater αENaC mRNA levels in kidney compared with control. Thus, we conclude that +78/+92 of αENaC represents the primary Af9 binding site involved in recruiting Dot1a to repress basal and aldosterone-sensitive αENaC transcription and that Dot1l inactivation promotes αENaC mRNA expression by eliminating Dot1a-mediated repression.
Critical role of trkB receptors in reactive axonal sprouting and hyperexcitability after axonal injury
Authors: Aungst Stephanie , England Pamela M. , Thompson Scott M.
Published: November 2012

Traumatic brain injury (TBI) causes many long-term neurological complications. Some of these conditions, such as posttraumatic epilepsy, are characterized by increased excitability that typically arises after a latent period lasting from months to years, suggesting that slow injury-induced processes are critical. We tested the hypothesis that trkB activation promotes delayed injury-induced hyperexcitability in part by promoting reactive axonal sprouting. We modeled penetrative TBI with transection of the Schaffer collateral pathway in knock-in mice having an introduced mutation in the trkB receptor (trkBF616A) that renders it susceptible to inhibition by the novel small molecule 1NMPP1. We observed that trkB activation was increased in area CA3 1 day after injury and that expression of a marker of axonal growth, GAP43, was increased 7 days after lesion. Extracellular field potentials in stratum pyramidale of area CA3 in acute slices from sham-operated and lesioned mice were normal in control saline. Abnormal bursts of population spikes were observed under conditions that were mildly proconvulsive but only in slices taken from mice lesioned 7–21 days earlier and not in slices from control mice. trkB activation, GAP43 upregulation, and hyperexcitability were diminished by systemic administration of 1NMPP1 for 7 days after the lesion. Synaptic transmission from area CA3 to area CA1 recovered 7 days after lesion in untreated mice but not in mice treated with 1NMPP1. We conclude that trkB receptor activation and reactive axonal sprouting are critical factors in injury-induced hyperexcitability and may contribute to the neurological complications of TBI.
Histone Deacetylase Inhibitor AR-42 Differentially Affects Cell-cycle Transit in Meningeal and Meningioma Cells, Potently Inhibiting NF2-Deficient Meningioma Growth
Authors: Burns Sarah S. , Akhmametyeva Elena M. , Oblinger Janet L. , Bush Matthew L. , Huang Jie , Senner Volker , Chen Ching-Shih , Jacob Abraham , Welling D. Bradley , Chang Long-Sheng
Published: November 2012

Meningiomas constitute about 34% of primary intracranial tumors and are associated with increased mortality in patients with neurofibromatosis type 2 (NF2). To evaluate potential medical therapies for these tumors, we have established a quantifiable orthotopic model for NF2-deficient meningiomas. We showed that telomerase-immortalized Ben-Men-1 benign meningioma cells harbored a single nucleotide deletion in NF2 exon 7 and did not express the NF2 protein, merlin. We also showed that AR-42, a pan-histone deacetylase inhibitor, inhibited proliferation of both Ben-Men-1 and normal meningeal cells by increasing expression of p16INK4A, p21CIP1/WAF1, and p27KIP1. In addition, AR-42 increased proapoptotic Bim expression and decreased anti-apoptotic BclXL levels. However, AR-42 predominantly arrested Ben-Men-1 cells at G2–M whereas it induced cell-cycle arrest at G1 in meningeal cells. Consistently, AR-42 substantially decreased the levels of cyclin D1, E, and A, and proliferating cell nuclear antigen in meningeal cells while significantly reducing the expression of cyclin B, important for progression through G2, in Ben-Men-1 cells. In addition, AR-42 decreased Aurora A and B expression. To compare the in vivo efficacies of AR-42 and AR-12, a PDK1 inhibitor, we generated and used luciferase-expressing Ben-Men-1-LucB cells to establish intracranial xenografts that grew over time. While AR-12 treatment moderately slowed tumor growth, AR-42 caused regression of Ben-Men-1-LucB tumors. Importantly, AR-42–treated tumors showed minimal regrowth when xenograft-bearing mice were switched to normal diet. Together, these results suggest that AR-42 is a potential therapy for meningiomas. The differential effect of AR-42 on cell-cycle progression of normal meningeal and meningioma cells may have implications for why AR-42 is well-tolerated while it potently inhibits tumor growth. Cancer Res; 73(2); 792–803. ©2012 AACR.
Brachytherapy Using Injectable Seeds That Are Self-Assembled from Genetically Encoded Polypeptides In Situ
Authors: Liu Wenge , McDaniel Jonathan , Li Xinghai , Asai Daisuke , Quiroz Felipe Garcia , Schaal Jeffery , Park Ji Sun , Zalutsky Michael , Chilkoti Ashutosh
Published: November 2012

Brachytherapy is a common clinical technique involving implantation of sealed radioactive “seeds” within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with 131I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (∼85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy. Cancer Res; 72(22); 5956–65. ©2012 AACR.
Prospective Study of Helicobacter pylori Biomarkers for Gastric Cancer Risk among Chinese Men
Authors: Epplein Meira , Zheng Wei , Xiang Yong-Bing , Peek Richard M. , Li Honglan , Correa Pelayo , Gao Jing , Michel Angelika , Pawlita Michael , Cai Qiuyin , Shu Xiao-Ou
Published: November 2012

Background:Helicobacter pylori is the leading risk factor for gastric cancer, yet only a fraction of infected individuals ever develop neoplasia.

Methods: To identify potential predictive biomarkers, we assessed the association of 15 antibodies to H. pylori proteins and gastric cancer in a nested case–control study. Blood levels of antibodies were assessed using multiplex serology for 226 incident cases and 451 matched controls from the Shanghai Men's Health Study. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression.

Results: Seropositivity to four (Omp, HP0305, HyuA, and HpaA) proteins was associated with a 1.5- to 3-fold increased risk for gastric cancer. When excluding cases diagnosed within 2 years of study enrollment, seropositivity to two additional proteins (CagA and VacA) showed significant associations with risk. Compared with individuals with three or fewer seropositive results to the six virulent proteins identified in this population, individuals with four to five seropositive results were at a 2-fold increased risk (OR, 2.08; 95% CI, 1.31–3.30) and individuals seropositive to all six proteins had a 3.5-fold increase in risk (OR, 3.49; 95% CI, 2.00–6.11) for gastric cancer. Among individuals diagnosed at least 2 years after study enrollment, these associations were even stronger (ORs, 2.79 and 4.16, respectively).

Conclusions: Increasing number of seropositives to six H. pylori proteins may be a risk marker for distal gastric cancer in China.

Impact: In a population with a 90% prevalence of CagA-positive H. pylori infection, assessment of additional virulent H. pylori proteins might better identify individuals at high risk for gastric cancer. Cancer Epidemiol Biomarkers Prev; 21(12); 2185–92. ©2012 AACR.
Associations between Arsenic Exposure and Global Posttranslational Histone Modifications among Adults in Bangladesh
Authors: Chervona Yana , Hall Megan N. , Arita Adriana , Wu Fen , Sun Hong , Tseng Hsiang-Chi , Ali Eunus , Uddin Mohammad Nasir , Liu Xinhua , Zoroddu Maria Antonietta , Gamble Mary V. , Costa Max
Published: November 2012

Background: Exposure to arsenic (As) is associated with an increased risk of several cancers as well as cardiovascular disease, and childhood neuro-developmental deficits. Arsenic compounds are weakly mutagenic, alter gene expression and posttranslational histone modifications (PTHMs) in vitro.

Methods: Water and urinary As concentrations as well as global levels of histone 3 lysine 9 di-methylation and acetylation (H3K9me2 and H3K9ac), histone 3 lysine 27 tri-methylation and acetylation (H3K27me3 and H3K27ac), histone 3 lysine 18 acetylation (H3K18ac), and histone 3 lysine 4 trimethylation (H3K4me3) were measured in peripheral blood mononuclear cells (PBMC) from a subset of participants (N = 40) of a folate clinical trial in Bangladesh (FACT study).

Results: Total urinary As (uAs) was positively correlated with H3K9me2 (r = 0.36, P = 0.02) and inversely with H3K9ac (r = −0.47, P = 0.002). The associations between As and other PTHMs differed in a gender-dependent manner. Water As (wAs) was positively correlated with H3K4me3 (r = 0.45, P = 0.05) and H3K27me3 (r = 0.50, P = 0.03) among females and negatively correlated among males (H3K4me3: r = −0.44, P = 0.05; H3K27me3: r = −0.34, P = 0.14). Conversely, wAs was inversely associated with H3K27ac among females (r = −0.44, P = 0.05) and positively associated among males (r = 0.29, P = 0.21). A similar pattern was observed for H3K18ac (females: r = −0.22, P = 0.36; males: r = 0.27, P = 0.24).

Conclusion: Exposure to As is associated with alterations of global PTHMs; gender-specific patterns of association were observed between As exposure and several histone marks.

Impact: These findings contribute to the growing body of evidence linking As exposure to epigenetic dysregulation, which may play a role in the pathogenesis of As toxicity. Cancer Epidemiol Biomarkers Prev; 21(12); 2252–60. ©2012 AACR.
Urinary Concentrations of Estrogens and Estrogen Metabolites and Smoking in Caucasian Women
Authors: Gu Fangyi , Caporaso Neil E. , Schairer Catherine , Fortner Renee T. , Xu Xia , Hankinson Susan E. , Eliassen A. Heather , Ziegler Regina G.
Published: November 2012

Background: Smoking has been hypothesized to decrease biosynthesis of parent estrogens (estradiol and estrone) and increase their metabolism by 2-hydroxylation. However, comprehensive studies of smoking and estrogen metabolism by 2-, 4-, or 16-hydroxylation are sparse.

Methods: Fifteen urinary estrogens and estrogen metabolites (jointly called EM) were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in luteal phase urine samples collected during 1996 to 1999 from 603 premenopausal women in the Nurses' Health Study II (NHSII; 35 current, 140 former, and 428 never smokers). We calculated geometric means and percentage differences of individual EM (pmol/mg creatinine), metabolic pathway groups, and pathway ratios, by smoking status and cigarettes per day (CPD).

Results: Total EM and parent estrogens were nonsignificantly lower in current compared with never smokers, with estradiol significant (Pmultivariate = 0.02). We observed nonsignificantly lower 16-pathway EM (P = 0.08) and higher 4-pathway EM (P = 0.25) and similar 2-pathway EM in current versus never smokers. EM measures among former smokers were similar to never smokers. Increasing CPD was significantly associated with lower 16-pathway EM (P-trend = 0.04) and higher 4-pathway EM (P-trend = 0.05). Increasing CPD was significantly positively associated with the ratios of 2- and 4-pathway to parent estrogens (P-trend = 0.01 and 0.002), 2- and 4-pathway to 16-pathway (P-trend = 0.02 and 0.003), and catechols to methylated catechols (P-trend = 0.02).

Conclusions: As hypothesized, we observed lower urinary levels of total EM and parent estrogens in active smokers. Our results also suggest smoking is associated with altered estrogen metabolism, specifically increased 2- and 4-hydroxylation, decreased 16-hydroxylation, and decreased catechol methylation.

Impact: Our study suggests how smoking might influence estrogen-related cancers and conditions. Cancer Epidemiol Biomarkers Prev; 22(1); 58–68. ©2012 AACR.
Postdiagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project
Authors: Kwan Marilyn L. , Chen Wendy Y. , Flatt Shirley W. , Weltzien Erin K. , Nechuta Sarah J. , Poole Elizabeth M. , Holmes Michelle D. , Patterson Ruth E. , Shu Xiao Ou , Pierce John P. , Caan Bette J.
Published: November 2012

Background: Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear.

Methods: We conducted an investigation of postdiagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors from three prospective US cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire. HR and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors.

Results: After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (≥0.36 g/day of alcohol, ≥0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with nondrinking, regular alcohol intake (≥6.0 g/day) was not associated with risk of recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86–1.24; HR for 12 to less than 24 g/day, 1.12; 95% CI, 0.93–1.34; HR for ≥24 g/day, 1.04; 95% CI, 0.84–1.31). However, risk varied significantly by menopausal status (P for interaction < 0.05). Postmenopausal women who regularly consumed alcohol (≥6.0 g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01–1.40). Alcohol intake was not associated with mortality.

Conclusions: Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women.

Impact: The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev; 22(1); 32–41. ©2012 AACR.
Variation in Genes Related to Obesity, Weight, and Weight Change and Risk of Contralateral Breast Cancer in the WECARE Study Population
Authors: Brooks Jennifer D. , Bernstein Leslie , Teraoka Sharon N. , Knight Julia A. , Mellemkjær Lene , John Esther M. , Malone Kathleen E. , Reiner Anne S. , Lynch Charles F. , Concannon Patrick , Haile Robert W. , Bernstein Jonine L. ,   for the WECARE Study Collaborative Group
Published: November 2012

Background: Body mass index (BMI), a known breast cancer risk factor, could influence breast risk through mechanistic pathways related to sex hormones, insulin resistance, chronic inflammation, and altered levels of adipose-derived hormones. Results from studies of the relationship between BMI and second primary breast cancer have been mixed. To explore the relationship between BMI and asynchronous contralateral breast cancer (CBC), we examined whether variants in genes related to obesity, weight, and weight change are associated with CBC risk.

Methods: Variants in 20 genes [182 single-nucleotide polymorphisms (SNP)] involved in adipose tissue metabolism, energy balance, insulin resistance, and inflammation, as well as those identified through genome-wide association studies (GWAS) of BMI and type II-diabetes were evaluated. We examined the association between variants in these genes and the risk of CBC among Caucasian participants [643 cases with CBC and 1,271 controls with unilateral breast cancer (UBC)] in the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study using conditional logistic regression.

Results: After adjustment for multiple comparisons, no statistically significant associations between any variant and CBC risk were seen. Stratification by menopausal or estrogen receptor (ER) status did not alter these findings.

Conclusion: Among women with early-onset disease who survive a first breast cancer diagnosis, there was no association between variation in obesity-related genes and risk of CBC.

Impact: Genetic variants in genes related to obesity are not likely to strongly influence subsequent risk of developing a second primary breast cancer. Cancer Epidemiol Biomarkers Prev; 21(12); 2261–7. ©2012 AACR.
Metabolic Gene Remodeling and Mitochondrial Dysfunction in Failing Right Ventricular Hypertrophy Secondary to Pulmonary Arterial Hypertension
Authors: Gomez-Arroyo Jose , Mizuno Shiro , Szczepanek Karol , Van Tassell Benjamin , Natarajan Ramesh , dos Remedios Cristobal G. , Drake Jennifer I. , Farkas Laszlo , Kraskauskas Donatas , Wijesinghe Dayanjan S. , Chalfant Charles E. , Bigbee John , Abbate Antonio , Lesnefsky Edward J. , Bogaard Harm J. , Voelkel Norbert F.
Published: November 2012

Background—

Right ventricular (RV) dysfunction (RVD) is the most frequent cause of death in patients with pulmonary arterial hypertension. Although abnormal energy substrate use has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in RVD remain incomplete. Thus, we sought to characterize metabolic gene expression changes and mitochondrial dysfunction in functional and dysfunctional RV hypertrophy.

Methods and Results—

Two different rat models of RV hypertrophy were studied. The model of RVD (SU5416/hypoxia) exhibited a significantly decreased gene expression of peroxisome proliferator-activated receptor-γ coactivator-1α, peroxisome proliferator-activated receptor-α and estrogen-related receptor-α. The expression of multiple peroxisome proliferator-activated receptor-γ coactivator-1α target genes required for fatty acid oxidation was similarly decreased. Decreased peroxisome proliferator-activated receptor-γ coactivator-1α expression was also associated with a net loss of mitochondrial protein and oxidative capacity. Reduced mitochondrial number was associated with a downregulation of transcription factor A, mitochondrial, and other genes required for mitochondrial biogenesis. Electron microscopy demonstrated that, in RVD tissue, mitochondria had abnormal shape and size. Lastly, respirometric analysis demonstrated that mitochondria isolated from RVD tissue had a significantly reduced ADP-stimulated (state 3) rate for complex I. Conversely, functional RV hypertrophy in the pulmonary artery banding model showed normal expression of peroxisome proliferator-activated receptor-γ coactivator-1α, whereas the expression of fatty acid oxidation genes was either preserved or unregulated. Moreover, pulmonary artery banding-RV tissue exhibited preserved transcription factor A mitochondrial expression and mitochondrial respiration despite elevated RV pressure-overload.

Conclusions—

Right ventricular dysfunction, but not functional RV hypertrophy in rats, demonstrates a gene expression profile compatible with a multilevel impairment of fatty acid metabolism and significant mitochondrial dysfunction, partially independent of chronic pressure-overload.
Heterogeneity of Ryanodine Receptor Dysfunction in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Loaiza Randall , Benkusky Nancy A. , Powers Patricia P. , Hacker Timothy , Noujaim Sami , Ackerman Michael J. , Jalife José , Valdivia Héctor H.
Published: November 2012

Rationale:

Most cardiac ryanodine receptor (RyR2) mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) are postulated to cause a distinctive form of Ca
2+
release dysfunction. Considering the spread distribution of CPVT mutations, we hypothesized that dysfunctional heterogeneity also was feasible.

Objective:

To determine the molecular and cellular mechanisms by which a novel RyR2-V2475F mutation associated with CPVT in humans triggers Ca
2+
-dependent arrhythmias in whole hearts and intact mice.

Methods and Results:

Recombinant channels harboring CPVT-linked RyR2 mutations were functionally characterized using tritiated ryanodine binding and single-channel recordings. Homologous recombination was used to generate a knock-in mouse bearing the RyR2-V2475F mutation. Ventricular myocytes from mice heterozygous for the mutation (RyR2-V2475F
+/−
) and their wild-type littermates were Ca
2+
-imaged by confocal microscopy under conditions that mimic stress. The propensity of wild-type and RyR2-V2475F
+/−
mice to have development of arrhythmias was tested at the whole heart level and in intact animals. Recombinant RyR2-V2475F channels displayed increased cytosolic Ca
2+
activation, abnormal protein kinase A phosphorylation, and increased activation by luminal Ca
2+
. The RyR2-V2475F mutation appears embryonic-lethal in homozygous mice, but heterozygous mice have no alterations at baseline. Spontaneous Ca
2+
release events were more frequent and had shorter latency in isoproterenol-stimulated cardiomyocytes from RyR2-V2475F
+/−
hearts, but their threshold was unchanged with respect to wild-type. Adrenergically triggered tachyarrhythmias were more frequent in RyR2-V2475F
+/−
mice.

Conclusions:

The mutation RyR2-V2475F is phenotypically strong among other CPVT mutations and produces heterogeneous mechanisms of RyR2 dysfunction. In living mice, this mutation appears too severe to be harbored in all RyR2 channels but remains undetected under basal conditions if expressed at relatively low levels. β-adrenergic stimulation breaks the delicate Ca
2+
equilibrium of RyR2-V2475F
+/−
hearts and triggers life-threatening arrhythmias.
Religious Studies as a Life Science
Authors: Bulbulia Joseph , Bulbulia Joseph , Slingerland Edward
Published: November 2012

Abstract

Religious studies assumes that religions are naturally occurring phenomena, yet what has scholarship uncovered about this fascinating dimension of the human condition? The manifold reports that classical scholars of religion have gathered extend knowledge, but such knowledge differs from that of scientific scholarship. Classical religious studies scholarship is expansive, but it is not cumulative and progressive. Bucking the expansionist trend, however, there are a small but growing number of researchers who approach religion using the methods and models of the life sciences. We use the biologist’s distinction between “proximate” and “ultimate” explanations to review a sample of such research. While initial results in the biology of religion are promising, current limitations suggest the need for greater collaboration with classically trained scholars of religion. It might appear that scientists of religion and scholars of religion are strange bedfellows; however, progress in the scholarly study of religions rests on the extent to which members of each camp find a common intellectual fate.
Give a Dog a Bad Name and Hang Him: Evaluating Big, Black Dog Syndrome
Authors: Woodward Lucinda , Milliken Jennifer , Humy Sonya
Published: November 2012

Abstract

Two studies examined human perceptions of dog personality attributes based upon exposure to pictures of dogs of select breeds. The proposed hypotheses evaluated the validity of “big, black dog syndrome”—whereby large, black dog breeds are reportedly spurned for adoption due to negatively perceived personality attributes—by assessing each dog’s relative trait dominance and affiliation based upon a taxonomy drawn from the eight-factor interpersonal circumplex. Results of two separate studies indicated that among participants’ ratings, breed-specific differences were more powerful predictors of interpersonal trait attributions than the color or size of the dog. In general, with the exception of the golden retriever, black labs were perceived as consistently less dominant and less hostile than other large breeds, contrary to the assumption that large, black dogs are viewed negatively.
End of the Era of Productivist Welfare Capitalism? Diverging Welfare Regimes in East Asia
Authors: Choi Young Jun
Published: November 2012

Abstract

The purpose of this paper is to examine the nature of recent transformations in East Asian welfare regimes, applying a ‘real-typical’ perspective, based on the ‘productivist welfare capitalism’ thesis of Ian Holliday (2000). Unlike Western welfare-state regimes in which the politics of austerity has dominated, the politics of welfare expansion has been noticeable in East Asian welfare regimes. This paper will analyse whether these changes have fundamentally dismantled the productivist feature where social policy is subordinate to economic objectives. While the trajectories are different depending on different political institutional contexts, this study shows that there are two strong signs that these states are moving out of their productivist nature and also that they are in the process of establishing their own welfare states. Japan seems to still be a productivist welfare-state regime struggling to accommodate rapid socio-economic changes, whereas Korea is a welfare state regime with strong liberal characteristics via modern welfare politics. Since the needs for social policy expansion in China correspond to economic and political needs, the productivist feature has been significantly weakened. However, this study argues that these transitory welfare regimes are in critical stages of formulating their new welfare regimes and that welfare politics based on contingent events could affect the future trajectories of these regimes.
Le Yahwiste salomonien au regard des sciences sociales
Authors: Marx A.
Published: November 2012

Abstract

La présente étude se propose de revisiter la thèse traditionnelle d’un Yahwiste salomonien en faisant appel aux données des sciences sociales. Après un examen critique des arguments pro et contra et une nouvelle proposition de critères de datation, elle s’efforce de démontrer que le Yahwiste est un écrit de propagande rédigé à la cour royale, à la fin du règne de David ou, plus vraisemblablement, au début de règne de Salomon, en vue de renforcer la cohésion de ce jeune Etat dont la création est largement artificielle et qui, au vu de son caractère composite, est extrêmement fragile. L’hypothèse présentée se fonde, non sur tel ou tel détail censé référer à la situation du royaume uni, mais sur une lecture d’ensemble des textes habituellement attribués au Yahwiste.

Die vorliegende Untersuchung beabsichtigt, die traditionelle These eines salomonischen Jahwisten neu zu beleuchten anhand der Sozialwissenschaft. Nach einer kritischen Prüfung der Pro- und Contra-Argumente und der Vorstellung eines neuen Vorschlags zu den Datierungskriterien soll der Versuch unternommen werden, zu beweisen, dass es sich beim Jahwisten um eine auf dem königliche Hof gegen Ende der Herrschaft Davids oder eher zu Beginn derjenigen Salomos verfasste Propagandaschrift handelt, die mit dem Ziel entstanden ist, den Zusammenhang dieses jungen Staates zu stärken, dessen Gründung angesichts seiner Verschiedenartigkeit weitgehend künstlich und somit höchst brüchig ist. Die aufgestellte Hypothese stützt sich nicht auf dieses oder jenes Detail, das auf die Lage des vereinten Königsreichs verweisen soll, sondern auf eine Gesamtlektüre der Texte, die gewöhnlich dem Jahwisten zugeschrieben werden.
From Universals to Topics: The Realism of Rudolph Agricola, with an Edition of his Reply to a Critic
Authors: Nauta Lodi
Published: November 2012

Abstract

Rudolph Agricola’s De inventione dialectica has rightly been regarded as the most original and influential textbook on argumentation, reading, writing, and communication in the Renaissance. At the heart of his treatment are the topics (loci), such as definition, genus, species, place, whole, parts, similars, and so on. While their function in Agricola’s system is argumentative and rhetorical, the roots of the topics are metaphysical, as Agricola himself explicitly acknowledges. It has led scholars to characterize Agricola as a realist or even an extreme realist. This article studies two little treatises on universals by Agricola that throw further light on his realism. It is suggested that they could be viewed as an early step in his long-term project of revising and re-organizing the systems of topics as he encountered them in Aristotle, Cicero, and Boethius. The article offers a close analysis of the treatises, suggesting that Agricola’s realism owes a (general) debt to the school of the Scotists. In both earlier and later work Agricola emphasizes the common aspects of things that enable us to categorize and talk about things without denying their fundamental unicity and individuality. An edition of Agricola’s second treatise on universals—a reply to a critic—is added.
Determinants of Household Access to Formal Credit in the Rural Areas of the Mekong Delta, Vietnam
Authors: Duy Vuong Quoc , D’Haese Marijke , Lemba Jacinta , Hau Le Long , D’Haese Luc
Published: November 2012

Abstract

This paper investigates the factors affecting the access of rural individual and group-based households to formal credit in the Mekong Delta (MD), Vietnam. Poverty levels in the Mekong Delta have reduced significantly over the last decades, but in the rural areas they remain significant. If it is assumed that access to credit is a vehicle for poverty alleviation, it is necessary to assess how households decide on borrowing. This paper identifies the determinants of the decision to borrow and of the amount that is borrowed by using the double hurdle model and Heckman selection model. Data used in this paper was obtained from a survey of 325 rural households, conducted between May and October 2009. The results indicate that household’s capital endowments, marital status, family size, distance to the market center, and locations affect the probability to ask for and amount of credit.
Does Import Substitution Industrialisation Strategy Hurt Growth?: New Evidence from Brazil and South Africa
Authors: Adewale Aregbeshola R.
Published: November 2012

Abstract

More economies have sprung up through home-grown import substitution industrialisation (ISI) strategy in the developing world as compared to those that have plummeted by adopting the prescripts of the Washington Consensus. The recurring economic and financial crises, essentially the 2008/2009 experiences, present another perspective for macroeconomic policy embracement. For instance, major economies, especially those of the United States and the countries in the European Union, jettisoned their neoliberal ideology for protectionist measures in dealing with the 2008/2009 financial and economic turbulence. This lends credence to a rethink of macroeconomic policies for the less developed and developing economies. Using data generated from the World Development Indicators (WDI), an organ of the World Bank, in regression analyses, this article argues that the macroeconomic policy of import-substitution industrialisation contributed to the current economic developments in Brazil and South Africa. The article suggests that an import-substitution industrialisation policy is not only appropriate to galvanise industrialisation in less industrialised economies, but also augments a sustainable economic growth.
Latent Class Analysis of Reproductive Decision Making in Zambia
Authors: Pillai Vijayan K. , Opollo Diana
Published: November 2012

Abstract

Coale (1973) pointed out that a first step in the transition to modern contraceptive use involves making calculated choices with respect to fertility and use of contraception. As women become aware of the fertility choices, they are likely to actively seek information and become engaged in reproductive decision making. Research studies on the role of social network on contraceptive decision making in Zambia are few and far. The objective of this study is to examine women’s strategies and approaches to fertility decision making in Zambia. The sample is gathered from two poor income neighborhoods in Kitwe, Zambia. The sample consists of women from 163 households. Latent class analysis provides a useful technique for identifying the presence of distinct strategies with respect to birth control. Though several heterogeneous categories with respect to various reproductive strategies were expected, only two categories were identified. The first category (latent class) is composed of women who engage in spousal communication with respect to fertility, acquire information though seeking and receiving advices from close social relations on reproductive issues, and are aware of the high cost of raising children. Implications of our finding for family planning programs are discussed.
‘Native’ Conversion to Islam in Southern Côte d’Ivoire: The Perils of Double Identity
Authors: Miran-Guyon Marie
Published: November 2012

Abstract

This article presents a synthetic, historical-cum-anthropological overview of the collective trajectory of Ivoirian converts to Islam from southern autochthonous lineages who can be referred to—albeit unsatisfyingly—as ‘native’ Muslims. It focuses on what is effectively an invisible and silent minority within southern native groups and the majority Dioula Muslim society alike: a community that has barely received any attention from social scientists despite the transformative impact of its slow but steady Islamization process. The study aims first at shedding light on salient socio-religious and political aspects of this group’s development, from colonial to postcolonial times. Given that this plural group is situated at the crossroads of various ethnic, national, and religious controversies, having enflamed Côte d’Ivoire in olden days as much as in recent years, the article eventually makes use of this group’s distinct prism to question the contested Ivoirian interface between Islam, ethnic geography, and nationalism at large, and attempt some nuanced answers.
Just War, Just Peace and the Jus post Bellum
Authors: Österdahl Inger
Published: November 2012

Justice after war is becoming an increasingly pressing concern. The cases of Afghanistan, Iraq and most recently Libya illustrate the importance of as well as the difficulties involved in the efforts to manage the outcome of armed conflict in a constructive way. The jus post bellum is meant to serve as the normative framework for the efforts to stabilise the post-conflict situation. The jus post bellum also has the future peaceful and arguably democratic and human rights respecting development of the post-conflict society in view. This article aims at drawing the conceptual and substantive contours of the jus post bellum and to discuss its relationship with other parts of international law, primarily the other bodies of law making up the law of armed conflict. Depending on one’s perspective the jus post bellum can be claimed not yet to exist, to exist already or irrespective of which to be superfluous as a separate category of law. The article recognises the apparent need for a comprehensive post-conflict law to serve as a bridge between war and stable peace. What way the international community should take in order to arrive at a just and useful normative framework for building peace is far from certain, however.
Bridging Islamic Juristic Differences in Contemporary Islamic Finance
Authors: Soualhi Younes
Published: November 2012

Abstract

This article is an attempt to formulate a viable Sharīʿah framework for juristic differences in contemporary Islamic finance. While acknowledging the legitimacy of juristic differences as an inherent feature of Islamic law, such differences could jeopardize a nascent Islamic finance industry, leading to what has come to be arbitrarily termed ‘Sharīʿah risk’ in Islamic finance. Two blocks appear to represent the two disputing sides since the launch of this industry, i.e., the Middle Eastern and South East Asian markets. Thus, this article aims to bridge differences in Islamic finance by proposing a framework and set of parameters that can be applied to all Islamic banking, Islamic capital market and takāful products. Apart from the outlined framework that aims to circumvent juristic disputes, this article concludes that juristic dispute resolution in Islamic finance will not be attainable until one can appreciate the legal and regulatory differences in which Islamic finance operates worldwide.
Force Majeure in Libyan Law: Current Issues
Authors: Abderrahmane Dahmane Ben
Published: November 2012

Abstract

Force majeure is undoubtedly recognized as an instrument of Libyan law. In Libyan law, the legal regime of force majeure is marked by specific features not found in other legal systems based at least in part on Roman–Germanic legal tradition.