bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrodeposition of Zn-Mg Alloy in Ethylene Glycol-ZnCl2-MgCl2 Non-Aqueous Solution
Authors: Yamamoto Hiroaki , Morishita Masao , Miwa Tatsuya , Isono Kousuke
Published: May 2013

The electrodeposition of Zn–Mg alloy was investigated in a non-aqueous solution using ethylene glycol (EG) as solvent at 393 K. ZnCl2 and MgCl2 were used as Zn and Mg ion sources and could be dissolved in EG. Zn electrodeposits containing a certain amount of Mg were obtained in EG–ZnCl2–MgCl2 baths. 8.8 mol% of Mg was coelectrodeposited with Zn in the EG–ZnCl2–MgCl2 (85.0–7.5–7.5 mol%) bath at the cathodic current density of 300 Am–2, and Mg in this specimen was electrodeposited as Zn–Mg intermetallic compound of Mg2Zn11. The red rust occurrence time of Zn–8.8 mol%Mg alloy plated steel in 5 mass% NaCl aqueous solution at 308 K was about 16.0 times longer than that of Zn plated steel.
Electrocatalytic Activity of Pt-Loaded Carbon Nanofilament for Methanol Oxidation Reaction in Fuel Cell
Authors: Toriyama Takahiro , Nakagawa Kiyoharu , Oda Hirokazu , Ando Toshihiro
Published: May 2013

In this study, we synthesized carbon nanofilament on ethylene decomposition from it was using oxidized diamond-supported for Ni catalyst. Precious supported metals were used for synthesized of carbon nanofilament and preparation of electrocatalyst by using for methanol oxidation reaction. The electrocatalytic activity of Pt-loaded catalysts were examined by Cyclic voltammetry (CV) measurement. The result of CV measurement, Pt-loaded synthesized CNF was a high catalytic activity than carbon black (Vulcan® XC-72) and multi walls carbon nanotube (MWCNT).
Performance Evaluation of an Anode-supported Honeycomb Solid Oxide Fuel Cell
Authors: Fukushima Akira , Nakajima Hironori , Kitahara Tatsumi
Published: May 2013

An anode-supported honeycomb SOFC that can achieve high power density and enhanced durability was developed. Electrolyte layer of 8YSZ (8 mol% yittria stabilized zirconia) is employed by dip-coating an anode honeycomb substrate of Ni/YSZ, followed by being coated with cathode layer of La0.7Sr0.3MnO3. Current-voltage and current-power density characteristics of the cells having different anode and cathode flow channel configurations at 850℃ were measured. The results show promising performances of the cell as a starting point to develop stacks composed of multiple honeycomb cells.
Hydrogen in Platinum Films Electrodeposited from Dinitrosulfatoplatinate Solution
Authors: Hisanaga Naoya , Fukumuro Naoki , Yae Shinji , Matsuda Hitoshi
Published: May 2013

The influence of hydrogen on the microstructure of Pt films electrodeposited from a dinitrosulfatoplatinate(II) solution was investigated with thermal desorption spectroscopy, X-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Two pronounced desorption peaks were observed in the thermal desorption spectrum of hydrogen from the Pt films. The total amount of desorbed hydrogen in the range from 300 to 1100 K in the atomic ratio (H/Pt) was 0.1. The deposited Pt film consisted of fine grains (~10 nm) and many nano-voids. The lattice parameter of the Pt grains was lower than that of bulk Pt. Drastic grain growth and reduction in the lattice contraction occurred from heat treatment at a temperature corresponding to the first hydrogen desorption peak of 500 K.
Evaluation of Stress Condition of Operated Anode Supported-Type SOFC under Operating Conditions Based on Raman Scattering Spectroscopy
Authors: Onodera Syo , Nagai Masafumi , Iguchi Fumitada , Sata Noriko , Kawada Tatsuya , Yugami Hiroo
Published: May 2013

We measured stress, temperature and dopant concentration dependences of Raman spectra in rare-earth-doped ceria to improve stress conditions evaluation method in operated solid oxide fuel cells (SOFCs) based on micro Raman scattering spectroscopy, which used the shift of ceria F2g vibration mode Raman peak. In addition to peak shift, we newly focused on the dependences of peak width, i.e. full width half maximum (FWHM). Considering measurement accuracy and predicted stress conditions in operated SOFCs, FWHM was more sensitive to temperature and dopant concentration than peak position. Consequently, the method was improved to evaluate not only stress conditions but also dopant concentration and temperature with high spatial resolution. We demonstrated this method using the model cells of conventional anode-supported type SOFCs, and the results indicated that stress and dopant concentration were distributed in the cell over measurement error. Especially, standard deviation of stress value sometimes reached 30 % of stress values.
Sulfate secretion and chloride absorption are mediated by the anion exchanger DRA (Slc26a3) in the mouse cecum
Authors: Whittamore Jonathan M. , Freel Robert W. , Hatch Marguerite
Published: May 2013

Inorganic sulfate (SO42−) is essential for a multitude of physiological processes. The specific molecular pathway has been identified for uptake from the small intestine but is virtually unknown for the large bowel, although there is evidence for absorption involving Na+-independent anion exchange. A leading candidate is the apical chloride/bicarbonate (Cl−/HCO3−) exchanger DRA (down-regulated in adenoma; Slc26a3), primarily linked to the Cl− transporting defect in congenital chloride diarrhea. The present study set out to characterize transepithelial 35SO42− and 36Cl− fluxes across the isolated, short-circuited cecum from wild-type (WT) and knockout (KO) mice and subsequently to define the contribution of DRA. The cecum demonstrated simultaneous net SO42− secretion (−8.39 ± 0.88 nmol·cm−2·h−1) and Cl− absorption (10.85 ± 1.41 μmol·cm−2·h−1). In DRA-KO mice, SO42− secretion was reversed to net absorption via a 60% reduction in serosal to mucosal SO42− flux. Similarly, net Cl− absorption was abolished and replaced by secretion, indicating that DRA represents a major pathway for transcellular SO42− secretion and Cl− absorption. Further experiments including the application of DIDS (500 μM), bumetanide (100 μM), and substitutions of extracellular Cl− or HCO3−/CO2 helped to identify specific ion dependencies and driving forces and suggested that additional anion exchangers were operating at both apical and basolateral membranes supporting SO42− transport. In conclusion, DRA contributes to SO42− secretion via DIDS-sensitive HCO3−/SO42− exchange, in addition to being the principal DIDS-resistant Cl−/HCO3− exchanger. With DRA linked to the pathogenesis of other gastrointestinal diseases extending its functional characterization offers a more complete picture of its role in the intestine.
SOX9 directly regulates IGFBP-4 in the intestinal epithelium
Authors: Shi Zhongcheng , Chiang Chi-I , Mistretta Toni-Ann , Major Angela , Mori-Akiyama Yuko
Published: May 2013

SOX9 regulates cell lineage specification by directly regulating target genes in a discrete number of tissues, and previous reports have shown cell proliferative and suppressive roles for SOX9. Although SOX9 is expressed in colorectal cancer, only a few direct targets have been identified in intestinal epithelial cells. We previously demonstrated increased proliferation in Sox9-deficient crypts through loss-of-function studies, indicating that SOX9 suppresses cell proliferation. In this study, crypt epithelial cells isolated from Sox9-deficient mice were used to identify potential target genes of SOX9. Insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4), an inhibitor of the IGF/IGF receptor pathway, was significantly downregulated in Sox9-deficient intestinal epithelial cells and adenoma cells of Sox9-deficient Apc Min/+ mice. Immunolocalization experiments revealed that IGFBP-4 colocalized with SOX9 in mouse and human intestinal epithelial cells and in specimens from patients with primary colorectal cancer. Reporter assays and chromatin immunoprecipitation demonstrated direct binding of SOX9 to the IGFBP-4 promoter. Overexpression of SOX9 attenuated cell proliferation, which was restored following treatment with a neutralizing antibody against IGFBP-4. These results suggest that SOX9 regulates cell proliferation, at least in part via IGFBP-4. Furthermore, the antiproliferative effect of SOX9 was confirmed in vivo using Sox9-deficient mice, which showed increased tumor burden when bred with Apc Min/+ mice. Our results demonstrate, for the first time, that SOX9 is a transcriptional regulator of IGFBP-4 and that SOX9-induced activation of IGFBP-4 may be one of the mechanisms by which SOX9 suppresses cell proliferation and progression of colon cancer.
Adaptation of mesenteric lymphatic vessels to prolonged changes in transmural pressure
Authors: Dongaonkar R. M. , Nguyen T. L. , Quick C. M. , Hardy J. , Laine G. A. , Wilson E. , Stewart R. H.
Published: May 2013

In vitro studies have revealed that acute increases in transmural pressure increase lymphatic vessel contractile function. However, adaptive responses to prolonged changes in transmural pressure in vivo have not been reported. Therefore, we developed a novel bovine mesenteric lymphatic partial constriction model to test the hypothesis that lymphatic vessels exposed to higher transmural pressures adapt functionally to become stronger pumps than vessels exposed to lower transmural pressures. Postnodal mesenteric lymphatic vessels were partially constricted for 3 days. On postoperative day 3, constricted vessels were isolated, and divided into upstream (UP) and downstream (DN) segment groups, and instrumented in an isolated bath. Although there were no differences between the passive diameters of the two groups, both diastolic diameter and systolic diameter were significantly larger in the UP group than in the DN group. The pump index of the UP group was also higher than that in the DN group. In conclusion, this is the first work to report how lymphatic vessels adapt to prolonged changes in transmural pressure in vivo. Our results suggest that vessel segments upstream of the constriction adapt to become both better fluid conduits and lymphatic pumps than downstream segments.
Contribution of central vs. peripheral factors to the force loss induced by passive stretch of the human plantar flexors
Authors: Trajano Gabriel S. , Seitz Laurent , Nosaka Kasunori , Blazevich Anthony J.
Published: May 2013

The purpose of the present research was to identify the contribution of central vs. peripheral factors to the force loss after passive muscle stretching. Thirteen men randomly performed both a 5-min constant-torque stretch of the plantar flexors on an isokinetic dynamometer and a resting condition on 2 separate days. The triceps surae electromyogram (EMG) was recorded simultaneously with plantar flexor isometric torque. Measures of central drive, including the EMG amplitude normalized to the muscle compound action potential amplitude (EMG/M), percent voluntary activation and first volitional wave amplitude, and measures of peripheral function, including the twitch peak torque, 20-to-80-Hz tetanic torque ratio and torque during 20-Hz stimulation preceded by a doublet, were taken before and immediately and 15 min after each condition. Peak torque (−15.7%), EMG/M (−8.2%), and both twitch (−9.4%) and 20-Hz peak torques (−11.5%) were reduced immediately after stretch but recovered by 15 min. There were strong correlations between the torque loss and the reductions in central drive parameters ( r = 0.65–0.93). Torque recovery was also strongly correlated with the recovery in EMG/M and percent voluntary activation ( r = 0.77–0.81). The moderate decreases in measures of peripheral function were not related to the torque loss or recovery. These results suggest that 1) central factors were strongly related to the torque reduction immediately after stretch and during torque recovery; and 2) the muscle's contractile capacity was moderately reduced, although these changes were not associated with the torque reduction, and changes in excitation-contraction coupling efficiency were not observed.
Enhanced Inhibition of ERK Signaling by a Novel Allosteric MEK Inhibitor, CH5126766, That Suppresses Feedback Reactivation of RAF Activity
Authors: Ishii Nobuya , Harada Naoki , Joseph Eric W. , Ohara Kazuhiro , Miura Takaaki , Sakamoto Hiroshi , Matsuda Yutaka , Tomii Yasushi , Tachibana-Kondo Yukako , Iikura Hitoshi , Aoki Toshihiro , Shimma Nobuo , Arisawa Mikio , Sowa Yoshihiro , Poulikakos Poulikos I. , Rosen Neal , Aoki Yuko , Sakai Toshiyuki
Published: May 2013

Tumors with mutant RAS are often dependent on extracellular signal–regulated kinase (ERK) signaling for growth; however, MEK inhibitors have only marginal antitumor activity in these tumors. MEK inhibitors relieve ERK-dependent feedback inhibition of RAF and cause induction of MEK phosphorylation. We have now identified a MEK inhibitor, CH5126766 (RO5126766), that has the unique property of inhibiting RAF kinase as well. CH5126766 binding causes MEK to adopt a conformation in which it cannot be phosphorylated by and released from RAF. This results in formation of a stable MEK/RAF complex and inhibition of RAF kinase. Consistent with this mechanism, this drug does not induce MEK phosphorylation. CH5126766 inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity as well. These results suggest that relief of RAF feedback limits pathway inhibition by standard MEK inhibitors. CH5126766 represents a new type of MEK inhibitor that causes MEK to become a dominant-negative inhibitor of RAF and that, in doing so, may have enhanced therapeutic activity in ERK-dependent tumors with mutant RAS. Cancer Res; 73(13); 4050–60. ©2013 AACR.
ETS2 Mediated Tumor Suppressive Function and MET Oncogene Inhibition in Human Non–Small Cell Lung Cancer
Authors: Kabbout Mohamed , Garcia Melinda M. , Fujimoto Junya , Liu Diane D. , Woods Denise , Chow Chi-Wan , Mendoza Gabriela , Momin Amin A. , James Brian P. , Solis Luisa , Behrens Carmen , Lee J. Jack , Wistuba Ignacio I. , Kadara Humam
Published: May 2013

Purpose: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis.

Experimental Design: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non–small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan–Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes.

Results: ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P < 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P < 0.05), and microarray and pathways analysis revealed significant (P < 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P < 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion.

Conclusion(s): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene. Clin Cancer Res; 19(13); 3383–95. ©2013 AACR.
Dietary Chemopreventative Benzyl Isothiocyanate Inhibits Breast Cancer Stem Cells In Vitro and In Vivo
Authors: Kim Su-Hyeong , Sehrawat Anuradha , Singh Shivendra V.
Published: May 2013

A small subset of mammary tumor-initiating cells (also known as breast cancer stem cells; bCSC), characterized by expression of different markers [CD44high/CD24low/epithelial-specific antigen (ESA)+], aldehyde dehydrogenase-1 (ALDH1) activity, and ability to form mammospheres under ultra-low attachment culture conditions, are suspected to evade conventional therapies leading to disease recurrence. Elimination of both therapy-sensitive epithelial tumor cells and therapy-resistant bCSC is therefore necessary for prevention of breast cancer. We have shown previously that a nontoxic small-molecule constituent of edible cruciferous vegetables (benzyl isothiocyanate; BITC) inhibits mammary cancer development in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice by causing epithelial tumor cell apoptosis. The present study shows efficacy of BITC against bCSC in vitro and in vivo. Mammosphere formation frequency and CD44high/CD24low/ESA+ and/or ALDH1+ populations in cultured MCF-7 (estrogen receptor–positive) and SUM159 (triple-negative) human breast cancer cells were decreased significantly in the presence of plasma achievable concentrations of BITC. BITC administration in the diet (3 μmol BITC/g diet for 29 weeks) resulted in a marked decrease in bCSCs in the MMTV-neu mice tumors in vivo. Overexpression of full-length Ron as well as its truncated form (sfRon), but not urokinase-type plasminogen activator receptor, conferred near complete protection against BITC-mediated inhibition of bCSCs in MCF-7 cells. The BITC treatment downregulated protein levels of Ron and sfRon in cultured breast cancer cells and in tumor xenografts. Ron overexpression resulted in upregulation of bCSC-associated genes Oct-4, SOX-2, and Nanog. In conclusion, the present study indicates that BITC treatment eliminates bCSCs in vitro and in vivo. Cancer Prev Res; 6(8); 782–90. ©2013 AACR.
Endothelial Protease Nexin-1 Is a Novel Regulator of A Disintegrin and Metalloproteinase 17 Maturation and Endothelial Protein C Receptor Shedding via Furin Inhibition
Authors: Boulaftali Yacine , François Déborah , Venisse Laurence , Jandrot-Perrus Martine , Arocas Véronique , Bouton Marie-Christine
Published: May 2013

Objective—

Human protein C is a plasma serine protease that plays a key role in hemostasis, and activated protein C (aPC) is known to elicit protective responses in vascular endothelial cells. This cytoprotective activity requires the interaction of the protease with its cell membrane receptor, endothelial protein C receptor. However, the mechanisms regulating the beneficial cellular effects of aPC are not well known. We aimed to determine whether a serine protease inhibitor called protease nexin-1 (PN-1) or serpinE2, expressed by vascular cells, can modulate the effect of aPC on endothelial cells.

Approach and Results—

We found that vascular barrier protective and antiapoptotic activities of aPC were reduced both in endothelial cells underexpressing PN-1 and in endothelial cells whose PN-1 function was blocked by a neutralizing antibody. Our in vitro data were further confirmed in vivo. Indeed, we found that vascular endothelial growth factor–mediated hyperpermeability in the skin of mice was markedly reduced by local intradermal injection of aPC in wild-type mice but not in PN-1–deficient mice. Furthermore, we demonstrated a previously unknown protective role of endothelial PN-1 on endothelial protein C receptor shedding. We provided evidence that PN-1 inhibits furin, a serine protease that activates a disintegrin and metalloproteinase 17 involved in the shedding of endothelial protein C receptor. We indeed evidenced a direct interaction between PN-1 and furin in endothelial cells.

Conclusions—

Our results thus demonstrate an original role of PN-1 as a furin convertase inhibitor, providing new insights for understanding the regulation of endothelial protein C receptor–dependent aPC endothelial protective effects.
Echocardiographic Assessment of Cardiac Valvular Regurgitation With Lorcaserin From Analysis of 3 Phase 3 Clinical Trials
Authors: Weissman Neil J. , Sanchez Matilde , Koch Gary G. , Smith Steven R. , Shanahan William R. , Anderson Christen M.
Published: May 2013

Background—

Lorcaserin is a selective 5-HT
2C
agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT
2C
agonism would avoid valvular heart disease.

Methods and Results—

Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration–defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, −0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (
P
=0.02 and
P
=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration–defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves.

Conclusions—

In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.
Endothelial Shc Regulates Arteriogenesis Through Dual Control of Arterial Specification and Inflammation via the Notch and Nuclear Factor-κ–Light-Chain-Enhancer of Activated B-Cell Pathways
Authors: Sweet Daniel T. , Chen Zhongming , Givens Christopher S. , Owens A. Phillip , Rojas Mauricio , Tzima Ellie
Published: May 2013

Rationale:

Arteriogenesis, the shear stress–driven remodeling of collateral arteries, is critical in restoring blood flow to ischemic tissue after a vascular occlusion. Our previous work has shown that the adaptor protein Shc mediates endothelial responses to shear stress in vitro.

Objective:

To examine the role of the adaptor protein Shc in arteriogenesis and endothelial-dependent responses to shear stress in vivo.

Methods and Results:

Conditional knockout mice in which Shc is deleted from endothelial cells were subjected to femoral artery ligation. Hindlimb perfusion recovery was attenuated in Shc conditional knockout mice compared with littermate controls. Reduced perfusion was associated with blunted collateral remodeling and reduced capillary density. Bone marrow transplantation experiments revealed that endothelial Shc is required for perfusion recovery because loss of Shc in bone marrow–derived hematopoietic cells had no effect on recovery. Mechanistically, Shc deficiency resulted in impaired activation of the nuclear factor κ–light-chain-enhancer of activated B-cell–dependent inflammatory pathway and reduced CD45
+
cell infiltration. Unexpectedly, Shc was required for arterial specification of the remodeling arteriole by mediating upregulation of the arterial endothelial cell marker ephrinB2 and activation of the Notch pathway. In vitro experiments confirmed that Shc was required for shear stress–induced activation of the Notch pathway and downstream arterial specification through a mechanism that involves upregulation of Notch ligands delta-like 1 and delta-like 4.

Conclusions:

Shc mediates activation of 2 key signaling pathways that are critical for inflammation and arterial specification; collectively, these pathways contribute to arteriogenesis and the recovery of blood perfusion.
Reduced Sodium Channel Function Unmasks Residual Embryonic Slow Conduction in the Adult Right Ventricular Outflow Tract
Authors: Boukens Bas J. , Sylva Marc , de Gier-de Vries Corrie , Remme Carol Ann , Bezzina Connie R. , Christoffels Vincent M. , Coronel Ruben
Published: May 2013

Rationale:

In patients with Brugada syndrome, arrhythmias typically originate in the right ventricular outflow tract (RVOT). The RVOT develops from the slowly conducting embryonic outflow tract.

Objective:

We hypothesize that this embryonic phenotype is maintained in the fetal and adult RVOT and leads to conduction slowing, especially after sodium current reduction.

Methods and Results:

We determined expression patterns in the embryonic myocardium and performed activation mapping in fetal and adult hearts, including hearts from adult mice heterozygous for a mutation associated with Brugada syndrome (
Scn5a
1798insD/+
). The embryonic RVOT was characterized by expression of
Tbx2
, a repressor of differentiation, and absence of expression of both
Hey2
, a ventricular transcription factor, and
Gja1
, encoding the principal gap-junction subunit for ventricular fast conduction. Also, conduction velocity was lower in the RVOT than in the right ventricular free wall. Later in the development,
Gja1
and
Scn5a
expression remained lower in the subepicardial myocardium of the RVOT than in RV myocardium. Nevertheless, conduction velocity in the adult RVOT was similar to that of the right ventricular free wall. However, in hearts of
Scn5a
1798insD/+
mice and in normal hearts treated with ajmaline, conduction was slower in the RVOT than in the right ventricular wall.

Conclusions:

The slowly conducting embryonic phenotype is maintained in the fetal and adult RVOT and is unmasked when cardiac sodium channel function is reduced.
Quantifying Options for Reducing Coronary Heart Disease Mortality By 2020
Authors: Huffman Mark D. , Lloyd-Jones Donald M. , Ning Hongyan , Labarthe Darwin R. , Guzman Castillo Maria , O’Flaherty Martin , Ford Earl S. , Capewell Simon
Published: May 2013

Background—

The American Heart Association (AHA) 2020 Strategic Impact Goal proposes a 20% improvement in cardiovascular health of all Americans. We aimed to estimate the potential reduction in coronary heart disease (CHD) deaths.

Methods and Results—

We used data on 40 373 adults free of cardiovascular disease from the National Health and Nutrition Examination Survey (NHANES; 1988–2010). We quantified recent trends for 6 metrics (total cholesterol, systolic blood pressure, physical inactivity, smoking, diabetes mellitus, and obesity) and generated linear projections to 2020. We projected the expected number of CHD deaths in 2020 if 2006 age- and sex-specific CHD death rates remained constant, which would result in ≈480 000 CHD deaths in 2020 (12% increase). We used the previously validated IMPACT CHD model to project numbers of CHD deaths in 2020 under 2 different scenarios: (1) Assuming a 20% improvement in each cardiovascular health metric, we project 365 000 CHD deaths in 2020 (range 327 000–403 000) a 24% decrease reflecting modest reductions in total cholesterol (−41 000), systolic blood pressure (−36 000), physical inactivity (−12 000), smoking (−10 000), diabetes mellitus (−10 000), and obesity (−5000); (2) Assuming that recent risk factor trends continue to 2020, we project 335 000 CHD deaths (range 274 000–386 000), a 30% decrease reflecting improvements in total cholesterol, systolic blood pressure, smoking, and physical activity (≈167 000 fewer deaths), offset by increases in diabetes mellitus and body mass index (≈24 000 more deaths).

Conclusions—

Two contrasting scenarios of change in cardiovascular health metrics could prevent 24% to 30% of the CHD deaths expected in 2020, though with differing effects by age. Unfavorable continuing trends in obesity and diabetes mellitus would have substantial adverse effects. This analysis demonstrates the utility of modelling to inform health policy.
Incidence of First Stroke
Authors: Hilmarsson Agust , Kjartansson Olafur , Olafsson Elias
Published: May 2013

Background and Purpose—

Iceland is an island in the North Atlantic with ≈319 000 inhabitants. The study determines the incidence of first stroke in the adult population of Iceland during 12 months, which has not been previously reported in the entire Icelandic population.

Methods—

The study population consisted of all residents of Iceland, aged ≥18 years, during the 12-month study period. Cases were identified by multiple overlapping approaches. Medical records were reviewed to verify diagnosis, to determine stroke subtype and to determine selected risk factors.

Results—

A total of 343 individuals, aged ≥18 years, had a first stroke during the study period. Incidence was 144 per 100 000 person years; 81% ischemic infarction; 9% intracerebral hemorrhage; 7% subarachnoid hemorrhage; and 3% unknown. Fifty percent of the individuals were men. Mean age for ischemic infarction and intracerebral hemorrhage was 71 years for men and 73 years for women. Atrial fibrillation was previously known in 18% with first ischemic stroke or intracerebral hemorrhage and another 6% were diagnosed on routine admission ECG. Long-term ECG study (24 hours) found that 12% (18/154) of the remaining individuals had paroxysmal atrial fibrillation.

Conclusions—

Incidence of first stroke in Iceland is similar to other Western countries. The high number of paroxysmal atrial fibrillation found during the 24-hour ECG suggests that atrial fibrillation may be underdiagnosed in patients with stroke.
Trends in Risk Factor Prevalence and Management Before First Stroke
Authors: Marshall Iain J. , Wang Yanzhong , McKevitt Christopher , Rudd Anthony G. , Wolfe Charles D.A.
Published: May 2013

Background and Purpose—

Vascular risk factors are suboptimally managed internationally. This study investigated time trends in risk factors diagnosed before stroke and their treatment, and factors associated with appropriate medication use.

Methods—

A total of 4416 patients with a first stroke were registered in the population-based South London Stroke Register from 1995 to 2011. Previously diagnosed risk factors and usual medications were collected from patients’ primary care and hospital records. Trends and associations were assessed using multivariate logistic regression.

Results—

Seventy-two percent of patients were diagnosed previously with 1 or more risk factors; 30% had diagnosed risk factors that were untreated. Hypercholesterolemia increased significantly during the study period; myocardial infarction and transient ischemic attack prevalences decreased. Antiplatelet prescription increased in atrial fibrillation (AF), myocardial infarction, and transient ischemic attack (AF, 37%–51%,
P
<0.001; myocardial infarction, 48%–69%,
P
<0.001; transient ischemic attack, 49%–61%,
P
=0.015). Anticoagulant prescription for AF showed a nonsignificant increase (12%–23%;
P
=0.059). Fewer older patients with AF were prescribed anticoagulants (age, >85 versus <65 years; adjusted relative risk, 0.19; 95% confidence interval, 0.08–0.41). Black ethnicity (adjusted relative risk, 1.17; 95% confidence interval, 1.10–1.23) and female sex (adjusted relative risk, 1.09; 95% confidence interval, 1.03–1.15) were associated with increased antihypertensive drug prescription; other medications did not vary by ethnicity or sex.

Conclusions—

Antiplatelet and cholesterol-lowering treatment prescribing have improved significantly over time; however, only a minority with AF received anticoagulants, and this did not improve significantly. Overall, 30% of strokes occurred in patients with previously diagnosed but untreated risk factors.
Transcranial Laser Therapy and Infarct Volume
Authors: Kasner Scott E. , Rose David Z. , Skokan Alexander , Walker Michael G. , Shi Jing , Streeter Jackson
Published: May 2013

Background and Purpose—

Two randomized trials suggested that transcranial laser therapy (TLT) may benefit patients with acute ischemic stroke, although efficacy has not been confirmed. Supportive proof of concept could be demonstrated if TLT reduces the volume of cortical infarction.

Methods—

The NeuroThera Efficacy and Safety Trial-2 (NEST-2) was a randomized trial of TLT versus sham in patients with acute ischemic stroke treated within 24 hours of onset. Infarct volumes were measured quantitatively and semiquantitatively on all protocol-required computed tomography (or MRI, if clinically indicated) scans performed on day 5 (±2). Two approaches assessed treatment effects on cortex: (1) indirectly, by analyzing total infarct volume among patients with clinical presentations suggesting cortical involvement; and (2) directly, by assessing the cortical Alberta Stroke Program Early CT Score (cASPECTS) components (M1-M6, anterior, posterior) on a 0- to 8-point modified scale.

Results—

A total of 640 subjects had scans (576 computed tomography, 64 MRI) on day 5. The reliability of ASPECTS (intraclass correlation coefficient=0.85) and cASPECTS (intraclass correlation coefficient=0.82) was excellent, and total ASPECTS was correlated with total infarct volume (
r
=0.71). In the overall study population, there was no impact of TLT on total infarct volume (
P
=0.30), total ASPECTS (
P
=0.85), or cASPECTS (
P
=0.89). Similarly, no effect was seen in any of the following prespecified subgroups selected to indicate cortical involvement: baseline National Institutes of Health Stroke Scale score >10, Oxfordshire Total Anterior Circulation Syndrome, subjects with aphasia or extinction at baseline, or subjects with radiographic involvement of cortex.

Conclusions—

TLT was not associated with a reduction in overall or cortical infarct volume as measured on computed tomography in the subacute phase.
Effects of Candesartan in Acute Stroke on Cognitive Function and Quality of Life
Authors: Hornslien Astrid G. , Sandset Else C. , Bath Philip M. , Wyller Torgeir B. , Berge Eivind
Published: May 2013

Background and Purpose—

High blood pressure is common in the acute phase of stroke and is associated with poor outcome. We examined whether blood pressure–lowering treatment with candesartan in the acute phase affects long-term cognitive function and quality of life.

Methods—

Scandinavian Candesartan Acute Stroke Trial was a randomized-controlled and placebo-controlled trial of candesartan in 2029 patients with acute stroke and raised blood pressure. At 6 months, cognitive function was assessed by the Mini Mental State Examination and quality of life by the EuroQol instrument. We used ordinal logistic and multiple linear regression for statistical analysis, adjusting for predefined key variables.

Results—

Median Mini Mental State Examination score was 28 in both groups, and there was no significant difference between the distribution of Mini Mental State Examination scores in the 2 groups (common odds ratio, 1.11; 95% confidence interval, 0.91–1.34;
P
=0.32). Median EuroQol-5D index were 0.74 and 0.78 (
P
=0.034), and the mean EuroQol-visual analogue scale scores were 66.0 and 67.3 in the candesartan and placebo groups, respectively (
P
=0.11).

Conclusions—

Candesartan did not improve cognitive function or quality of life. Rather, there were signs of harmful effects. These findings support the conclusion from our previous report that there is no indication for routine blood pressure–lowering treatment with candesartan in the acute phase of stroke.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT00120003.
Cardiovascular Biomarkers and Subclinical Brain Disease in the Atherosclerosis Risk in Communities Study
Authors: Dadu Razvan T. , Fornage Myriam , Virani Salim S. , Nambi Vijay , Hoogeveen Ron C. , Boerwinkle Eric , Alonso Alvaro , Gottesman Rebecca F. , Mosley Thomas H. , Ballantyne Christie M.
Published: May 2013

Background and Purpose—

Cerebrovascular and cardiovascular disease share common risk factors. Our goal was to determine whether levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T measured with a highly sensitive assay (hs-cTnT) are associated with silent brain infarcts (BIs) and white matter lesions (WMLs) on MRI in the Atherosclerosis Risk in Communities (ARIC) study.

Methods—

At ARIC visit 3 (1993–1995), 1920 participants had brain MRI. NT-proBNP and hs-cTnT were measured in all individuals at ARIC visit 4 (1996–1998). Of 1920 individuals, 1112 had a follow-up MRI [2004–2006]). We analyzed the association of NT-proBNP and hs-cTnT with MRI-defined BI and WML on the initial MRI and incident BI and WML progression on the follow-up MRI in participants without heart failure, coronary heart disease, or stroke.

Results—

In the adjusted model, individuals in the highest NT-proBNP quartile had significantly more BI (odds ratio, 3.50; 95% confidence interval, 2.03–6.20), and WML (β-coefficient, 0.09; SE, 0.03) on the baseline MRI and more incident BI (odds ratio, 2.18; 95% confidence interval, 1.38–3.47) and WML progression (β-coefficient, 0.22; SE, 0.10) on the follow-up MRI. Individuals in the highest hs-cTnT category had more BI (odds ratio, 3.03; 95% confidence interval, 1.57–5.82) and WML (β-coefficient, 0.11; SE, 0.04) on the initial MRI and more WML progression (β-coefficient, 0.43; SE, 0.17) on the follow-up MRI.

Conclusions—

NT-proBNP and hs-cTnT are independently associated with silent MRI-defined BI and WML, suggesting that cardiovascular biomarkers may be useful to identify individuals with subclinical cerebral injury.
Growing Up Roman: Infant Mortality and Reproductive Development
Authors: Pilkington Nathan
Published: May 2013

Variables from modern epidemiological models can be used to reconstruct infant-mortality rates, childhood-growth patterns, and the onset of fertility in the Roman Empire from osteoarchaeological evidence. The anthropometry of Roman sub-adult skeletons compares closely to that of the unhealthiest modern and premodern populations, thus supporting pessimistic estimations of life expectancy at birth for Roman populations. Furthermore, the onset of female fertility was delayed due to childhood morbidity and malnutrition.
Objects and Categories: Feature Statistics and Object Processing in the Ventral Stream
Authors: Tyler Lorraine K. , Chiu Shannon , Zhuang Jie , Randall Billi , Devereux Barry J. , Wright Paul , Clarke Alex , Taylor Kirsten I.
Published: May 2013

Recognizing an object involves more than just visual analyses; its meaning must also be decoded. Extensive research has shown that processing the visual properties of objects relies on a hierarchically organized stream in ventral occipitotemporal cortex, with increasingly more complex visual features being coded from posterior to anterior sites culminating in the perirhinal cortex (PRC) in the anteromedial temporal lobe (aMTL). The neurobiological principles of the conceptual analysis of objects remain more controversial. Much research has focused on two neural regions—the fusiform gyrus and aMTL, both of which show semantic category differences, but of different types. fMRI studies show category differentiation in the fusiform gyrus, based on clusters of semantically similar objects, whereas category-specific deficits, specifically for living things, are associated with damage to the aMTL. These category-specific deficits for living things have been attributed to problems in differentiating between highly similar objects, a process that involves the PRC. To determine whether the PRC and the fusiform gyri contribute to different aspects of an object's meaning, with differentiation between confusable objects in the PRC and categorization based on object similarity in the fusiform, we carried out an fMRI study of object processing based on a feature-based model that characterizes the degree of semantic similarity and difference between objects and object categories. Participants saw 388 objects for which feature statistic information was available and named the objects at the basic level while undergoing fMRI scanning. After controlling for the effects of visual information, we found that feature statistics that capture similarity between objects formed category clusters in fusiform gyri, such that objects with many shared features (typical of living things) were associated with activity in the lateral fusiform gyri whereas objects with fewer shared features (typical of nonliving things) were associated with activity in the medial fusiform gyri. Significantly, a feature statistic reflecting differentiation between highly similar objects, enabling object-specific representations, was associated with bilateral PRC activity. These results confirm that the statistical characteristics of conceptual object features are coded in the ventral stream, supporting a conceptual feature-based hierarchy, and integrating disparate findings of category responses in fusiform gyri and category deficits in aMTL into a unifying neurocognitive framework.
Dynamics of Multiple-Choice Decision Making
Authors: You Hongzhi , Wang Da-Hui
Published: May 2013

Neuroscientists have carried out comprehensive experiments to reveal the neural mechanisms underlying the perceptual decision making that pervades daily life. These experiments have illuminated salient features of decision making, including probabilistic choice behavior, the ramping activity of decision-related neurons, and the dependence of decision time and accuracy on the difficulty of the task. Spiking network models have reproduced these features, and a two-dimensional mean field model has demonstrated that the saddle node structure underlies two-alternative decision making. Here, we reduced a spiking network model to an analytically tractable, partial integro-differential system and characterized not only multiple-choice decision behaviors but also the time course of neural activities underlying decisions, providing a mechanistic explanation for the observations noted in the experiments. First, we observed that a two-bump unstable steady state of the system is responsible for two-choice decision making, similar to the saddle node structure in the two-dimensional mean field model. However, for four-choice decision making, three types of unstable steady states collectively predominate the time course of the evolution from the initial state to the stable states. Second, the time constant of the unstable steady state can explain the fact that four-choice decision making requires a longer time than two-choice decision making. However, the quicker decision, given a stronger motion strength, cannot be explained by the time constant of the unstable steady state. Rather, the decision time can be attributed to the projection coefficient of the difference between the initial state and the unstable steady state on the eigenvector corresponding to the largest positive eigenvalue.
Information Transfer Through Stochastic Transmission of a Linear Combination of Rates
Authors: Smyrnakis Ioannis , Smirnakis Stelios
Published: May 2013

In this work, the Shannon information transfer rate due to the transmission of a linear combination of the firing rates of a number of afferent neurons is examined. The transmission of this linear combination (transfer statistic) takes place through a stochastic firing process, while a rate code is assumed. Constraints are imposed on the transmission process by the requirement that the coefficient of variation for the transfer statistic is small and by the relative variance of the individual terms in the calculation of the statistic. In the regime of no noise or signal correlations among the input neurons, simulations suggest that information transfer for fixed overall input is favored when there are few high-firing neurons, as opposed to more lower-firing neurons. Signal correlations among low-firing neurons can result in aggregates of high firing rates, improving in this way information transfer and calculational robustness. Under reasonable rate code assumptions, information transfer rates obtained are of the order 3 to 10 bit/sec.
Social Revolution in Russian Female Monasticism: The Case of the Convent of the Intercession, 1700–1917
Authors: Miller Marlyn
Published: May 2013

Focusing on central Orthodox regions in post-Petrine Russia, Marlyn Miller investigates the changing social composition of nuns in Orthodox convents from 1700 through 1917 through a case study on the Convent of the Intercession in Suzdal. Primarily based on a careful study of archival documents, Miller reveals a dramatic drop in the percentage of noblewomen among the ranks of the nuns in Russian convents and a growing predominance of women from the ranks of the peasantry—a “democratization”, as Marlyn characterizes it, among the social composition of female monastics. This trend was already in place following Catherine II’s secularlization policies and continued throughout the nineteenth century. In post-reform Russia, this accompanied a general growth in the number of female monastics, which tripled from 1869 to 1914, in part following general population trends, but also corresponding to the spiritual revivalism of this era. Intriguingly, however, Miller finds that key motivations for women to enter monasteries remained largely unchanged and centered on economic need, dedication to their faith, or personal reasons of family or marriage avoidance up to 1917.
Popular Religiosity in the “Closed City” of Soviet Ukraine: Cultural Consumption and Religion during Late Socialism, 1959-1984
Authors: Zhuk Sergei I.
Published: May 2013

Part of a larger research project about Soviet cultural consumption and identity formation, this article explores the connection between rock music and religiosity in the industrial city of Dnepropetrovsk, Ukraine, in the late socialist period. The Committee of State Security [Komitet gosudarstvennoi bezopasnosti, KGB] closed Dnepropetrovsk to foreigners in 1959 when one of the Soviet Union’s biggest missile factories opened there. Because of its “closed” nature, Dnepropetrovsk became a unique Soviet social and cultural laboratory where various patterns of late socialism collided with new Western cultural influences. The closed city of Dnepropetrovsk can be seen as a microcosm of Soviet society as a whole. Drawing from a wide variety of sources, including archival documents, periodicals, personal diaries and interviews, this article demonstrates how popular fascination for Western rock music, such as Andrew Lloyd Webber’s Jesus Christ Superstar, spurred interest in Christianity. Local Protestant and Orthodox church leaders skillfully promoted such interest, even as the Party bosses tried to quash it. This study stands as a reminder of the continued draw of Christianity in Orthodoxy’s heartland—even through alternative, modernizing media—despite the official promotion of atheism.
A True Maverick: The Political Career of Dr. Oswald E. Anderson, 1919-1944
Authors: Altink Henrice
Published: May 2013

Abstract

This article examines the political career of the African-Jamaican Dr. Oswald E. Anderson from his entry into local politics in 1919 till his defeat in the first election under universal suffrage in 1944. It will demonstrate that Anderson differed from other black politicians at the time because of his criticism of Crown Colony government, commitment to the welfare of the masses, nationalist fervour and above all his outspokenness about racial discrimination. In addition to describing and explaining why Anderson was such a ‘true maverick’, the article will also demonstrate that Anderson was a highly ambiguous politician.