bluuebunny/crossref_metadata_2025 huggingface dataset:
New Catalysts for a Zero-Gap Type Gas-Diffusion Electrode in Chlor-Alkali Membrane Process
Authors: Sudoh Masao , Izawa Yuki , Suzuki Tomohisa , Tanaka Masashi , Nishiki Yoshinori
Published: July 2012

Newly developed gas-diffusion electrodes (GDE) with binary catalyst composed of Ag and Pd were evaluated in a zero-gap type chlor-alkali cell. It was found that the cell voltage was 2.06V at 6kAm-2, which was 120 mV smaller than those of composed of single Ag catalyst or Pd catalyst. The increase of the cell voltage with the binary catalyst after 600 days of operation was only around 20 mV, which is one third of that of Ag catalyst. The particles sizes of the former catalyst were not changed after the electrolysis, but the size of Ag in the latter became large, which quantitatively corresponded to the increase of overvoltage predicted by a porous GDE model calculation. It was suggested that the agglomeration of the Ag catalyst could be inhibited by the existence of Pd.
Excimer Laser Annealing Effects of Silicon-rich Silicon Nitride Films Prepared by Using Catalytic Chemical Vapor Deposition
Authors: Lee Kyoung-Min , Hwang Jae-Dam , Lee Youn-Jin , Kim Sun-Jae , Han Min-Koo , Jang Seunghun , Han Moonsup , Won Sunghwan , Sok Junghyun , Park Kyoungwan , Hong Wan-Shick
Published: July 2012

We studied excimer laser annealing effects on silicon-rich silicon nitride films containing silicon quantum dots to develop silicon based flexible Light emitting diodes. The silicon-rich silicon nitride films were deposited by catalytic chemical vapor deposition system using a mixture of SiH4, NH3 and H2 gas. The substrate temperatures in all deposition process were less than 200 ° to use polyethersulphone substrate. The changing crystallity and density of silicon quantum dots were analyzed by photoluminescence spectra. The change in the luminescence behavior with nucleation of silicon quantum dots was observed after excimer laser annealing.
Investigation of Co Doped CGO Buffer Layer for Intermediate-temperature SOFC
Authors: Wang Z. , Hashimoto S. , Mori M.
Published: July 2012

The sintering characteristics of Ce0.9Gd0.1O1.95 (CGO) with various specific surface areas and Zr0.89Sc0.1Ce0.01O1.95 (ScSZ) content have been measured. Cobalt-doped CGO can be used as a buffer layer on a ScSZ electrolyte for anode-supported solid oxide fuel cells with intermediate-temperature operation. By addition of ScSZ, the densifications of all CGO samples were markedly lowered. The Co-doping of CGO enhanced its densification and improved the increase of densification with increasing specific surface area.
Electronic Properties and Oxygen Nonstoichiometry of Mixed-conducting Oxide La1-χSrχCoO3-δ Thin Films at High Temperature
Authors: Hemmi D. , Iwamoto K. , Hirai N. , Sase M. , Unemoto A. , Nakamura T. , Horikiri F. , Mori Y. , Sato K. , Yashiro K. , Kawada T. , Mizusaki J.
Published: July 2012

Thin films of the perovskite-type oxide La1-χSrχCoO3-δ were deposited onto Ce0.9Gd0.1O1.95, SiO2 and single crystal MgO (100) substrates surface by a pulsed laser deposition (PLD) using a XeCl excimer laser to study the difference of the electronic properties and nonstoichiometry. It was shown that the oxygen nonstoichiometry of thin film is smaller than that of bulk for La1-χSrχCoO3-δ. The conductivity of the films were measured by a DC four probe method in 10-4-1 bar O2 gas at temperatures of 25-800{degree sign}C. The activation energy of the conductivity for thin films strongly depends on substrates due to the mismatch of the thermal expansion coefficient between the thin film and the substrate. Although the temperature coefficient of conductivity of La1-χSrχCoO3-δ bulk was negative for χ≥0.4 and was positive for 0≤χ≤0.3, that of thin film was positive irrespective of χ. At the condition with the Co mean valence of 3.0 for χ=0.4, 0.5, the conductivity shows large values for bulk, on the other hand, the conductivity is close to 0 for thin film. These facts suggest the electron hole in bulk is delocalized and metal like, while that in thin film is localized on cobalt ion.
Influence of estradiol supplementation on neuropeptide Y neurotransmission in skeletal muscle arterioles of F344 rats
Authors: Evanson Kirk W. , Stone Audrey J. , Samraj Enoch , Benson Tyler , Prisby Rhonda , Kluess Heidi A.
Published: July 2012

The effects of estradiol on neuropeptide Y (NPY) neurotransmission in skeletal muscle resistance vessels have not been described. The purpose of this study was to determine the effects of long-term estradiol supplementation on NPY overflow, degradation, and vasoconstriction in gastrocnemius first-order arterioles of adult female rats. Female rats (4 mo; n = 34) were ovariectomized (OVX) with a subset ( n = 17) receiving an estradiol pellet (OVE; 17β-estradiol, 4 μg/day). After conclusion of the treatment phase (8 wk), arterioles were excised, placed in a physiological saline solution (PSS) bath, and cannulated with micropipettes connected to albumin reservoirs. NPY-mediated vasoconstriction via a Y1-agonist [Leu31Pro34]NPY decreased vessel diameter 44.54 ± 3.95% compared with baseline; however, there were no group differences in EC50(OVE: −8.75 ± 0.18; OVX: −8.63 ± 0.10 log M [Leu31Pro34]NPY) or slope (OVE: −1.11 ± 0.25; OVX: −1.65 ± 0.34% baseline/log M [Leu31Pro34]NPY). NPY did not potentiate norepinephrine-mediated vasoconstriction. NPY overflow experienced a slight increase following field stimulation and significantly increased ( P < 0.05) over control conditions in the presence of a DPPIV inhibitor (diprotin A). Estradiol status did not affect DPPIV activity. These data suggest that NPY can induce a moderate decrease in vessel diameter in skeletal muscle first-order arterioles, and DPPIV is active in mitigating NPY overflow in young adult female rats. Long-term estradiol supplementation did not influence NPY vasoconstriction, overflow, or its enzymatic breakdown in skeletal muscle first-order arterioles.
Impact of maternal dexamethasone on coronary PGE2production and prostaglandin-dependent coronary reactivity
Authors: Roghair Robert D. , Volk Kenneth A. , Lamb Fred S. , Segar Jeffrey L.
Published: July 2012

Intrauterine growth restriction is associated with increased fetal glucocorticoid exposure and an increased risk of adult coronary artery disease. Coronary arteries from sheep exposed to early gestation dexamethasone (Dex) have increased constriction to angiotensin II (ANG II). Prostaglandin E2(PGE2) helps maintain coronary dilation, but PGE2production is acutely decreased by Dex administration. We hypothesized early gestation Dex exposure impairs adult coronary PGE2production with subsequent increases in coronary reactivity. Dex was administered to ewes at 27–28 days gestation (term 145 days). Coronary reactivity was assessed by wire myography in offspring at 4 mo of age ( N = 5 to 7). Coronary smooth muscle cells were cultured and prostaglandin production was measured after 90 min incubation with radiolabeled arachidonate. Coronary myocytes from Dex-exposed lambs had a significant decrease in PGE2production that was reversed with ANG II incubation. Dex-exposed coronary arteries had increased constriction to ANG II and attenuated dilatation to arachidonic acid, with the greatest difference seen after the endothelium was inactivated by rubbing. Preincubation with the cyclooxygenase (COX) inhibitor indomethacin altered control responses and recapitulated the heightened coronary tone seen following Dex exposure. We conclude that impaired coronary smooth muscle COX-mediated PGE2production contributes to the coronary dysfunction elicited by early gestation Dex. Programmed inhibition of vasodilatory prostanoid production may link an adverse intrauterine environment with adult coronary artery disease.
3D spheroid defects in NPHP knockdown cells are rescued by the somatostatin receptor agonist octreotide
Authors: Ghosh Amiya K. , Hurd Toby , Hildebrandt Friedhelm
Published: July 2012

Ciliopathies are a heterogeneous group of diseases that exhibit broad clinical phenotypes, including renal cysts, retinal degeneration, and cerebellar vermis aplasia. Nephronophthisis (NPHP) is a renal ciliopathy that causes chronic kidney disease and is characterized by kidney cysts at the cortico-medullary border. Among the 10 different disease-causing genes ( NPHP1-NPHP10), mutations in NPHP3, NPHP6, or NPHP8 cause the most severe ciliopathy variants of NPHP, Joubert syndrome, and Meckel Syndrome. In this study, we tested the hypothesis that loss of function of these three most severe disease-associated genes leads to morphological defects in a three-dimensional (3D) renal cell culture [murine (m) inner medullary collecting duct (IMCD) 3] model by either lack of cilia formation and/or cell polarity defects. Stable knockdown cell lines were examined in 3D spheroid culture followed by rhodamine-phalloidin staining to assess spheroid architecture. We observed significantly higher percentages of abnormal spheroids for all three stable cell lines compared with control short-hairpin RNA cells. In addition, stable knockdown of Nphp3, Nphp6, and Nphp8 results in reduced cilia numbers and elevated cAMP levels in mIMCD3 cells. We demonstrate that, following gene knockdown of Nphp3, Nphp6, or Nphp8, treatment with the somatostatin agonist octreotide (2 μM) reduces the percentage of abnormal spheroids compared with control. This study reveals that the loss of Nphp3, Nphp6, or Nphp8 leads to cilia abnormalities and cell polarity defects, resulting in spheroid abnormalities, which can be rescued by inhibiting cAMP levels with octreotide treatment.
Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε
Authors: Richards Jacob , Greenlee Megan M. , Jeffers Lauren A. , Cheng Kit-Yan , Guo Laijing , Eaton Douglas C. , Gumz Michelle L.
Published: July 2012

Increasing evidence suggests that the circadian clock plays an important role in the control of renal function and blood pressure. We previously showed that the circadian clock protein Period (Per)1, positively regulates the expression of the rate limiting subunit of the renal epithelial sodium channel (αENaC), which contributes to blood pressure regulation. Casein kinases 1δ and 1ε (CK1δ/ε) are critical regulators of clock proteins. CK1δ/ε must phosphorylate the circadian clock protein Per1 in order for the latter to enter the nucleus. We used a commercially available CK1δ/ε inhibitor, PF670462, to test the effect of CK1δ/ε blockade and inhibited Per1 nuclear entry on αENaC in a model of the renal cortical collecting duct (mpkCCDc14cells). CK1δ/ε blockade prevented Per1 and Clock from interacting with an E-box from the αENaC promoter. CK1δ/ε inhibition reduced αENaC mRNA levels by <60%. A similar decrease in αENaC mRNA was observed following siRNA-mediated CK1δ/ε knock-down. Inhibition of CK1δ/ε effectively prevented the transcriptional response of αENaC to aldosterone, suggesting an interaction between the circadian clock and aldosterone-mediated regulation of αENaC. CK1δ/ε inhibition significantly reduced αENaC but increased Caveolin-1 membrane protein levels; transepithelial current, a measure of ENaC activity, was decreased. Importantly, single channel analysis in amphibian renal cells demonstrated a dramatic decrease in the number of patches with observable ENaC current following CK1δ/ε inhibition. The present study shows for the first time that CK1δ/ε inhibition and impaired Per1 nuclear entry results in decreased αENaC expression and ENaC activity, providing further support for direct control of ENaC by the circadian clock.
Effect of a serine protease inhibitor on the progression of chronic renal failure
Authors: Hayata Manabu , Kakizoe Yutaka , Uchimura Kohei , Morinaga Jun , Yamazoe Rika , Mizumoto Teruhiko , Onoue Tomoaki , Ueda Miki , Shiraishi Naoki , Adachi Masataka , Miyoshi Taku , Sakai Yoshiki , Tomita Kimio , Kitamura Kenichiro
Published: July 2012

The number of the chronic renal failure (CRF) patients is increasing explosively. Hypertension, proteinuria, inflammation, fibrosis, and oxidative stress are intertwined in a complicated manner that leads to the progression of CRF. However, the therapeutic strategies to delay its progression are limited. Since serine proteases are involved in many processes that contribute to these risk factors, we investigated the effects of a synthetic serine protease inhibitor, camostat mesilate (CM), on the progression of CRF in 5/6 nephrectomized (Nx) rats. Eighteen male Sprague-Dawley rats were divided into three groups: a sham-operated group ( n = 6), a vehicle-treated Nx group ( n = 6), and a CM-treated Nx group ( n = 6). Following the 9-wk study period, both proteinuria and serum creatinine levels were substantially increased in the vehicle-treated Nx group, and treatment with CM significantly reduced proteinuria and serum creatinine levels. The levels of podocyte-associated proteins in glomeruli, such as nephrin and synaptopodin, were markedly decreased by 5/6 nephrectomy, and this was significantly ameliorated by CM. CM also suppressed the levels of inflammatory and fibrotic marker mRNAs including transforming growth factor-β1, TNF-α, collagen types I, III, and IV, and reduced glomerulosclerosis, glomerular hypertrophy, and interstitial fibrosis in histological studies. Furthermore, CM decreased the expression of NADPH oxidase component mRNAs, as well as reactive oxygen species generation and advanced oxidative protein product levels. Our present results strongly suggest the possibility that CM could be a useful therapeutic agent against the progression of CRF.
Mitochondrial dysfunction induced by heat stress in cultured rat CNS neurons
Authors: White Michael G. , Saleh Osama , Nonner Doris , Barrett Ellen F. , Moraes Carlos T. , Barrett John N.
Published: July 2012

Previous work demonstrated that hyperthermia (43°C for 2 h) results in delayed, apoptotic-like death in striatal neuronal cultures. We investigated early changes in mitochondrial function induced by this heat stress. Partial depolarization of the mitochondrial membrane potential (ΔΨm) began about 1 h after the onset of hyperthermia and increased as the stress continued. When the heat stress ended, there was a partial recovery of ΔΨm, followed hours later by a progressive, irreversible depolarization of ΔΨm. During the heat stress, O2consumption initially increased but after 20–30 min began a progressive, irreversible decline to about one-half the initial rate by the end of the stress. The percentage of oligomycin-insensitive respiration increased during the heat stress, suggesting an increased mitochondrial leak conductance. Analysis using inhibitors and substrates for specific respiratory chain complexes indicated hyperthermia-induced dysfunction at or upstream of complex I. ATP levels remained near normal for ∼4 h after the heat stress. Mitochondrial movement along neurites was markedly slowed during and just after the heat stress. The early, persisting mitochondrial dysfunction described here likely contributes to the later (>10 h) caspase activation and neuronal death produced by this heat stress. Consistent with this idea, proton carrier-induced ΔΨmdepolarizations comparable in duration to those produced by the heat stress also reduced neuronal viability. Post-stress ΔΨmdepolarization and/or delayed neuronal death were modestly reduced/postponed by nicotinamide adenine dinucleotide, a calpain inhibitor, and increased expression of Bcl-xL.
Construction of a Smart Medication Dispenser with High Degree of Scalability and Remote Manageability
Authors: Pak JuGeon , Park KeeHyun
Published: July 2012

We propose a smart medication dispenser having a high degree of scalability and remote manageability. We construct the dispenser to have extensible hardware architecture for achieving scalability, and we install an agent program in it for achieving remote manageability. The dispenser operates as follows: when the real-time clock reaches the predetermined medication time and the user presses the dispense button at that time, the predetermined medication is dispensed from the medication dispensing tray (MDT). In the proposed dispenser, the medication for each patient is stored in an MDT. One smart medication dispenser contains mainly one MDT; however, the dispenser can be extended to include more MDTs in order to support multiple users using one dispenser. For remote management, the proposed dispenser transmits the medication status and the system configurations to the monitoring server. In the case of a specific event such as a shortage of medication, memory overload, software error, or non-adherence, the event is transmitted immediately. All these operations are performed automatically without the intervention of patients, through the agent program installed in the dispenser. Results of implementation and verification show that the proposed dispenser operates normally and performs the management operations from the medication monitoring server suitably.
Genotype × Environment Interaction of Mosaic Disease, Root Yields and Total Carotene Concentration of Yellow-Fleshed Cassava in Nigeria
Authors: Maroya Norbert G. , Kulakow Peter , Dixon Alfred G. O. , Maziya-Dixon Busie B.
Published: July 2012

Twenty-one yellow-fleshed cassava genotypes were evaluated over two years in five major cassava growing agroecological zones in Nigeria. The trials were established in a randomized complete block design with four replications to assess genotype performance and Genotype × Environment interaction for cassava mosaic disease (CMD), fresh and dry root yield (FYLD; DYLD), root dry matter content (DMC), and total carotene concentration (TCC). Combined analysis of variance showed significant differences (P<0.001) among genotypes (G), environment (E), and Genotype × Environment interaction (GE) for all the traits tested. For reaction to CMD, the best genotypes showing stable resistance were TMS 07/0539 and TMS 07/0628. For root yield, the best genotypes were TMS 01/1368 and TMS 07/0553. Genotype TMS 07/0593 was the best for DMC and TCC across the 10 environments. Variation among genotypes accounted for most of the Total Sum of Squares for CMD (72.1%) and TCC (34.4%). Environmental variation accounted for most of the Total Sum of Squares for FYLD (42.8%), DYLD (39.6%), and DMC (29.2%). This study revealed that TMS 07/0593 has the highest and most stable TCC, DMC with the lowest CMD severity score and appeared to be the best genotype.
Gram-Negative Bacterial Infection in Thigh Abscess Can Migrate to Distant Burn Depending on Burn Depth
Authors: Hamrahi Victoria , Hamblin Michael R. , Jung Walter , Benjamin John B. , Paul Kasie W. , Fischman Alan J. , Tompkins Ronald G. , Carter Edward A.
Published: July 2012

Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosaandProteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection. The bioluminescent bacteria migrated from subcutaneous abscesses in the leg to distant burn wounds on the back depending on the severity of the burn injury, and this migration led to increased mortality of the mice. Treatment with ciprofloxacin, injected either in the leg with the bacterial infection or into the burn eschar, prevented this colonization of the wound and decreased mortality. The present data suggest that burn wounds can readily become colonized by infections distant from the wound itself.
Dietary Mercury Exposure Resulted in Behavioral Differences in Mice Contaminated with Fish-Associated Methylmercury Compared to Methylmercury Chloride Added to Diet
Authors: Bourdineaud Jean-Paul , Marumoto Masumi , Yasutake Akira , Fujimura Masatake
Published: July 2012

Methylmercury (MeHg) is a potent neurotoxin, and humans are mainly exposed to this pollutant through fish consumption. However, in classical toxicological studies, pure methylmercury chloride (MeHgCl) is injected, given to drink or incorporated within feed assuming that its effects are identical to those of MeHg naturally associated to fish. In the present study, we wanted to address the question whether a diet containing MeHg associated to fish could result in observable adverse effects in mice as compared to a diet containing the same concentration of MeHg added pure to the diet and whether beneficial nutriments from fish were able to counterbalance the deleterious effects of fish-associated mercury, if any. After two months of feeding, the fish-containing diet resulted in significant observable effects as compared to the control and MeHg-containing diets, encompassing altered behavioral performances as monitored in a Y-shaped maze and an open field, and an increased dopamine metabolic turnover in hippocampus, despite the fact that the fish-containing diet was enriched in polyunsaturated fatty acids and selenium compared to the fish-devoid diets.
Performance Analysis Techniques for Multi-Soft-Core and Many-Soft-Core Systems
Authors: Castells-Rufas David , Fernandez-Alonso Eduard , Carrabina Jordi
Published: July 2012

Multi-soft-core systems are a viable and interesting solution for embedded systems that need a particular tradeoff between performance, flexibility and development speed. As the growing capacity allows it, many-soft-cores are also expected to have relevance to future embedded systems. As a consequence, parallel programming methods and tools will be necessarily embraced as a part of the full system development process. Performance analysis is an important part of the development process for parallel applications. It is usually mandatory when you want to get a desired performance or to verify that the system is meeting some real-time constraints. One of the usual techniques used by the HPC community is the postmortem analysis of application traces. However, this is not easily transported to the embedded systems based on FPGA due to the resource limitations of the platforms. We propose several techniques and some hardware architectural support to be able to generate traces on multiprocessor systems based on FPGAs and use them to optimize the performance of the running applications.
Relativistic Double Barrier Problem with Three Transmission Resonance Regions
Authors: Alhaidari A. D. , Bahlouli H. , Jellal A.
Published: July 2012

We obtain exact scattering solutions of the Dirac equation in 1 + 1 dimensions for a double square barrier vector potential. The potential bottom between the two barriers is chosen to be higher than 2mc2, whereas the top of the barriers is at least 2mc2above the bottom. The relativistic version of the conventional double barrier transmission resonances is obtained for energies within ±mc2from the height of the barriers. However, due to our judicious choice of potential configuration we also find two more (subbarrier) transmission resonance regions below the conventional one. Both are located within the two Klein energy zones and characterized by resonances that are broader than the conventional ones. The design of our double barrier so as to enable us to establish these two new subbarrier transmission resonance regions is our main finding.
Women's and Midwives' Perspectives on the Design of a Text Messaging Support for Maternal Obesity Services: An Exploratory Study
Authors: Soltani H. , Furness P. J. , Arden M. A. , McSeveny K. , Garland C. , Sustar H. , Dearden A.
Published: July 2012

This study was aimed to explore women’s and midwives’ views on the use of mobile technology in supporting obese pregnant women with healthy lifestyle choices. A purposive sample of 14 women and midwives participated in four focus groups in Doncaster, UK. A content analysis of the transcripts from the first focus group led to the emergence of three main constructs with associated subcategories including Benefits (“modernising,” “motivating,” “reminding,” and “reducing” the sense of isolation), Risks and Limitations (possibility of “being offensive,” “creating pressure or guilt,” and “being influenced by mood”), and Service Delivery (making it “available to all pregnant women,” giving attention to the “message tone” and development of “message content”). They also suggested the use of other modalities such as web-based services for weight management during pregnancy. Based on the above results a text messaging service was developed and presented to the 2nd focus group participants who confirmed the positive views from the first focus group on the use of the text messaging as being supportive and informative. The participants also welcomed “women’s engagement and choice” in deciding the content, timing and frequency of messages. The results informed the development of a text messaging service to support maternal obesity management. The implementation and acceptability of this service requires further investigation.
Analysis of Hydrodynamics of Fluid Flow on Corrugated Sheets of Packing
Authors: Subramanian Kumar , Wozny Günter
Published: July 2012

Modelling of the hydrodynamics behaviour of the liquid on the corrugated sheets of packing is studied using three-dimensional, volume-of-fluid (VOF) model that is incorporated in Ansys Fluent 12.0. The flow of three different liquids with different physical properties is modelled. A domain of corrugated sheets of packing resembling the real structured packing with little modifications in the elementary geometry is constructed using ICEM CFD 12.0. The quantitative comparisons of the wetting behavior from the simulations are in good agreement with experiments. Further, the study has been extended to understand the influence of the second corrugated sheet on the flow behavior. The contours from the simulations indicate the liquid hold-up in the crimp of two corrugated sheets, and these results are in good agreement with the earlier experimental studies performed using X-ray tomography in the literature. The result from the simulation shows that even for the high flow rate of around 811 mL/min for silicon-oil (DC5), only 60% of the corrugated sheet has been wetted. Hence, the efficiency of the existing packing can be further increased by increasing the wetted area in the corrugated sheet of packing.
Identification and Analysis of Full Scale Ventilation Events
Authors: Savio Luca , Steen Sverre
Published: July 2012

The present paper deals with propeller ventilation in full scale. The paper is based on full scale monitoring data from an offshore supply ship during normal operation. The data was collected by the on-line monitoring system HeMoS, developed by Rolls Royce Marine. The data covering one year and a half of ship operations were made available within the framework of the Era-Net Martec project PropSeas. The ventilation events are identified by means of an analysis procedure based on fuzzy logic. The paper contains both a basic introduction to fuzzy logic and a detailed description of the analysis procedure. The analysis procedure is then adopted to process the available data, find ventilation events, and form a set which is further analyzed including weather observations.
The Pivotal Role of Integrin β1 in Metastasis of Head and Neck Squamous Cell Carcinoma
Authors: Wang Dongsheng , Müller Susan , Amin A.R.M. Ruhul , Huang Donghai , Su Ling , Hu Zhongliang , Rahman Mohammad Aminur , Nannapaneni Sreenivas , Koenig Lydia , Chen Zhengjia , Tighiouart Mourad , Shin Dong M. , Chen Zhuo G.
Published: July 2012

Purpose: This study aimed to understand the prognostic value of integrin β1 expression in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its association with metastatic HNSCC.

Experimental Design: Archival HNSCC tissues including 99 nonmetastatic primary tumors and 101 metastatic primary tumors were examined for the association of integrin β1 expression with metastasis and disease prognosis by appropriate statistical methods. Fluorescence-activated cell sorting was used to separate the integrin β1high/+ cell population from the integrin β1low/− population in HNSCC cell lines. These two populations and integrin β1 shRNA knockdown HNSCC cells were examined for the effect of integrin β1 on invasion in vitro and on lymph node and lung metastases in a xenograft mouse model. Expression and activation of matrix metalloproteinases (MMP) were examined by zymography.

Results: Statistical analysis showed that integrin β1 expression was significantly higher in the metastatic primary tumors than in the nonmetastatic tumors (42.6% vs. 24.8%, P < 0.0001 and P < 0.0001 by univariate and multivariate analyses, respectively). In patients with lymph node metastasis, integrin β1 expression was inversely correlated with overall survival (P = 0.035). The integrin β1 knockdown or integrin β1low/− HNSCC cells showed a significant reduction in lymph node and lung metastases in vivo (P < 0.001 and P < 0.05, respectively). Significantly reduced Matrigel invasion capability was also found in integrin β1 knockdown or integrin β1low/− HNSCC cells (P < 0.01). Finally, zymography results showed integrin β1-affected HNSCC invasion by regulating MMP-2 activation.

Conclusion: These findings indicate that integrin β1 has a major impact on HNSCC prognosis through its regulation of metastasis. Clin Cancer Res; 18(17); 4589–99. ©2012 AACR.
Apricoxib, a Novel Inhibitor of COX-2, Markedly Improves Standard Therapy Response in Molecularly Defined Models of Pancreatic Cancer
Authors: Kirane Amanda , Toombs Jason E. , Ostapoff Katherine , Carbon Juliet G. , Zaknoen Sara , Braunfeld Jordan , Schwarz Roderich E. , Burrows Francis J. , Brekken Rolf A.
Published: July 2012

Purpose: COX-2 is expressed highly in pancreatic cancer and implicated in tumor progression. COX-2 inhibition can reduce tumor growth and augment therapy. The precise function of COX-2 in tumors remains poorly understood, but it is implicated in tumor angiogenesis, evasion of apoptosis, and induction of epithelial-to-mesenchymal transition (EMT). Current therapeutic regimens for pancreatic cancer are minimally effective, highlighting the need for novel treatment strategies. Here, we report that apricoxib, a novel COX-2 inhibitor in phase II clinical trials, significantly enhances the efficacy of gemcitabine/erlotinib in preclinical models of pancreatic cancer.

Experimental Design: Human pancreatic cell lines were evaluated in vitro and in vivo for response to apricoxib ± standard-of-care therapy (gemcitabine + erlotinib). Tumor tissue underwent posttreatment analysis for cell proliferation, viability, and EMT phenotype. Vascular parameters were also determined.

Results: COX-2 inhibition reduced the IC50 of gemcitabine ± erlotinib in six pancreatic cancer cell lines tested in vitro. Furthermore, apricoxib increased the antitumor efficacy of standard combination therapy in several orthotopic xenograft models. In vivo apricoxib combination therapy was only effective at reducing tumor growth and metastasis in tumors with elevated COX-2 activity. In each model examined, treatment with apricoxib resulted in vascular normalization without a decrease in microvessel density and promotion of an epithelial phenotype by tumor cells regardless of basal COX-2 expression.

Conclusions: Apricoxib robustly reverses EMT and augments standard therapy without reducing microvessel density and warrants further clinical evaluation in patients with pancreatic cancer. Clin Cancer Res; 18(18); 5031–42. ©2012 AACR.
Analysis of mRNA Profiles after MEK1/2 Inhibition in Human Pancreatic Cancer Cell Lines Reveals Pathways Involved in Drug Sensitivity
Authors: Gysin Stephan , Paquette Jesse , McMahon Martin
Published: July 2012

Mutationally activated KRAS, detected in approximately 90% of pancreatic ductal adenocarcinomas (PDA), has proven an intractable pharmacologic target to date. Consequently, efforts to treat KRAS-mutated cancers are focused on targeting RAS-regulated signaling pathways. In mouse models, expression of BRAFV600E combined with dominant-negative TP53 elicits PDA, and pharmacologic blockade of mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibits proliferation of human PDA-derived cell lines. To better understand the role of RAF→MEK→ERK signaling on PDA cell proliferation, we assessed the consequences of MEK inhibition on global patterns of mRNA expression and tumor cell proliferation in a panel of human PDA-derived cell lines. This analysis revealed that RAF→MEK→ERK signaling regulates mRNAs involved in cell-cycle control as well as regulators of the immune system. Linear regression analysis of relative drug sensitivity and mRNA expression revealed mRNAs and pathways correlating with relative drug sensitivity of the cell lines. Mice carrying orthotopically implanted pancreas tumors that were treated with MEK inhibitor displayed reduced tumor growth, concomitant with a reduction of cells in S phase. Furthermore, analysis of tumor mRNA expression revealed PDA cell lines to display similar baseline and MEK inhibitor mRNA expression profiles in vitro and in vivo. Among the proteins subject to downregulation following MEK inhibition, we identified c-MYC as a key driver of cell proliferation downstream of RAF→MEK→ERK signaling. Indeed, in some PDA cell lines, RNA interference–mediated silencing of c-MYC expression had antiproliferative effects similar to that of MEK inhibition, thereby highlighting the importance of c-MYC in key aspects of pancreatic cancer cell maintenance. Mol Cancer Res; 10(12); 1607–19. ©2012 AACR.
Impact of Sex on Cardiovascular Outcome in Patients at High Cardiovascular Risk
Authors: Kappert Kai , Böhm Michael , Schmieder Roland , Schumacher Helmut , Teo Koon , Yusuf Salim , Sleight Peter , Unger Thomas
Published: July 2012

Background—

Epidemiological data suggest that sex independently contributes to cardiovascular risk. Clinical trials are often hampered by the enrollment of few female patients.

Methods and Results—

The Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the parallel Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) included a large proportion of female patients (9378 female versus 22 168 male patients). Differences in male and female patients enrolled in ONTARGET/TRANSCEND were analyzed for the primary 4-fold end point (composite of cardiovascular death, myocardial infarction, stroke, or admission to hospital for heart failure), a secondary 3-fold end point (cardiovascular death, myocardial infarction, stroke), and individual components of the primary composite. Baseline characteristics included age, ethnicity, body mass index, physical activity, tobacco use, alcohol consumption, formal education, clinical diagnosis for study entry, patient history, and concomitant medication. Patients were followed up until death or the end of the study (median, 56 months). Compared with male patients, female patients had a 19% significantly lower risk for the 4-fold end point and 21% for the 3-fold end point (after adjustment for study, treatment, and the above baseline values). Similarly, the adjusted risk for cardiovascular death (17%) and myocardial infarction (22%), but not for stroke and hospitalization for heart failure, was also significantly lower in women. Diabetic female patients were characterized by a higher risk for acute myocardial infarction compared with diabetic male patients, whereas alcohol consumption resulted in significantly lower risk in women.

Conclusions—

In our analysis made up of 70.3% male and 29.7% female patients, an ≈20% lower risk for the combined cardiovascular end points in female patients was observed despite treatment with cardioprotective agents. This difference was driven primarily by a significantly lower incidence of myocardial infarction. Thus, we demonstrate in a large interventional trial that sex greatly affects the occurrence of cardiovascular events in patients with vascular disease or high-risk diabetes mellitus.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00153101.
Dissociation of Structural and Functional Phenotypes in Cardiac Myosin-Binding Protein C Conditional Knockout Mice
Authors: Chen Peter.P , Patel Jitandrakumar R. , Powers Patricia A. , Fitzsimons Daniel P. , Moss Richard L.
Published: July 2012

Background—

Cardiac myosin-binding protein C (cMyBP-C) is a sarcomeric protein that dynamically regulates thick-filament structure and function. In constitutive cMyBP-C knockout (cMyBP-C
−/−
) mice, loss of cMyBP-C has been linked to left ventricular dilation, cardiac hypertrophy, and systolic and diastolic dysfunction, although the pathogenesis of these phenotypes remains unclear.

Methods and Results—

We generated cMyBP-C conditional knockout (cMyBP-C-cKO) mice expressing floxed cMyBP-C alleles and a tamoxifen-inducible Cre-recombinase fused to 2 mutated estrogen receptors to study the onset and progression of structural and functional phenotypes caused by the loss of cMyBP-C. In adult cMyBP-C-cKO mice, knockdown of cMyBP-C over a 2-month period resulted in a corresponding impairment of diastolic function and a concomitant abbreviation of systolic ejection, although contractile function was largely preserved. No significant changes in cardiac structure or morphology were immediately evident; however, mild hypertrophy developed after near-complete knockdown of cMyBP-C. In response to pressure overload induced by transaortic constriction, cMyBP-C-cKO mice treated with tamoxifen also developed greater cardiac hypertrophy, left ventricular dilation, and reduced contractile function.

Conclusions—

These results indicate that myocardial dysfunction is largely caused by the removal of cMyBP-C and occurs before the onset of cytoarchitectural remodeling in tamoxifen-treated cMyBP-C-cKO myocardium. Moreover, near ablation of cMyBP-C in adult myocardium primarily leads to the development of hypertrophic cardiomyopathy in contrast to the dilated phenotype evident in cMyBP-C
−/−
mice, which highlights the importance of additional factors such as loading stress in determining the expression and progression of cMyBP-C–associated cardiomyopathy.
Staying Quartered
Authors: Pion-Berlin David , Esparza Diego , Grisham Kevin
Published: July 2012

This is a multination study of military disobedience in the face of presidential orders to suppress civilian uprisings. Rather than coercively manipulating the government or seizing power themselves, these insubordinate armies prefer to remain quartered. To determine why, the authors draw on rational, ideational, and structural analytical perspectives on military behavior. The study deploys a qualitative case study method of analysis, identifying seven positive cases (disobedience) and then contrasting those with three negative cases (obedience) to discern whether there is a collection of causal agents that can discriminate between these sets. It finds that disobedience grows out of material grievances, stronger affiliation with public as opposed to government interests, rejection of internal public order roles, illegalities, and splits within the services.
Applying the 3M Model of Personality and Motivation to Adventure Travelers
Authors: Schneider Paige P. , Vogt Christine A.
Published: July 2012

More than a decade has passed since the Travel Industry Association investigated adventure travel as a promising market. Despite growth in the adventure industry, studies of adventure travelers remain scarce, particularly in the identification of the psychological underpinnings of consumer adventurers. Mowen’s (2000) 3M Model of Motivation and Personality provided an organizing framework to explain the psychological roots of adventure tourism behavior. Self-administered questionnaires were mailed to a random sample ( N = 1000) of National Geographic Adventure magazine subscribers with a response rate ( n = 339) of 34%. Guttman Scaling Procedure was employed to categorize respondents in hard and soft adventure traveler categories as a context for understanding the demographic and travel behavior characteristics. The personality trait interest in cultural experiences was a consistent predictor of adventure travel propensity for hard and soft adventure traveler groups. The traits need for arousal and need for material resources were significant predictors for the hard adventure traveler group, while competitiveness was the other trait found to be a significant predictor for the soft adventure traveler group. Findings of this study enhance knowledge and understanding of the relationship between personality and tourism behavior.
Spousal Abuse
Authors: Kuo Margaret
Published: July 2012

This article investigates an overlooked aspect of Chinese legal modernity: how legal change influenced changes in individual consciousness. The article traces in particular the emergence of rights thinking in divorce cases from the 1930s and 1940s by examining the process in which grievances about domestic abuse were transformed from mostly informal and inchoate disappointments into formal, legally actionable complaints under the provisions of the Republican Civil Code of 1929–1930. Case records suggest that popular perceptions about the degree of cruelty that was “tolerable” in marriage were shifting as abuse came to be viewed less as a matter of fortune or fate and more of law and justice. The deployment of legal rights by wives seeking to divorce on the basis of intolerable cruelty, however, met with limited success. Judicial decisions mostly affirmed the preservation of marriage, consolidating a modern form of conjugal patriarchy.
Promotion Orientation Explains Why Future-Oriented People Exercise and Eat Healthy
Authors: Joireman Jeff , Shaffer Monte J. , Balliet Daniel , Strathman Alan
Published: July 2012

The authors extended research linking individual differences in consideration of future consequences (CFC) with health behaviors by (a) testing whether individual differences in regulatory focus would mediate that link and (b) highlighting the value of a revised, two-factor CFC-14 scale with subscales assessing concern with future consequences (CFC-Future) and concern with immediate consequences (CFC-Immediate) proper. Exploratory and confirmatory factor analyses of the revised CFC-14 scale supported the presence of two highly reliable factors (CFC-Future and CFC-Immediate; αs from .80 to .84). Moreover, structural equation modeling showed that those high in CFC-Future engage in exercise and healthy eating because they adopt a promotion orientation. Future use of the two-factor CFC-14 scale is encouraged to shed additional light on how concern with future and concern with immediate consequences (proper) differentially impact the way people resolve a host of intertemporal dilemmas (e.g., health, financial, and environmental behavior).
When Women’s Musical Activism is Motivated by an Activist Musician
Authors: Trier-Bieniek Adrienne M.
Published: July 2012

In order to better understand connections between music, healing from trauma, and feminism, in the summer of 2009 I began interviewing and observing women who were fans of the musician Tori Amos. One outcome of this research was the large percentage of women who identified as a feminist and acknowledged that their feminism was influenced by Amos’ displays of feminism in her music and artistic expression. Further, many of the women found themselves motivated to action because they were inspired by Amos’ lyrics, live shows (which are as many parts feminist activism as they are rock shows), and Amos’ work with the Rape, Abuse and Incest National Network (RAINN). Because most fan-based scholarship presents women as the “fanatical” fan, studies which examine female fans and the links between activism, music, and art are rare. A result of this is limited portrayal of women in popular culture. This article serves attempts to challenge this portrait and serves as a call for further research in order to present a more clear definition of a female fan.
Narratives about relationships with parents from the perspective of middle-aged and older adults
Authors: Budziszewska Magdalena , Dryll Elżbieta
Published: July 2012

The paper examines narratives about relationships with parents, written by participants in middle and later adulthood. Empirical material was submitted in writing as responses to the cue “Tell me about your parents.” The material was subjected to quantitative and qualitative analysis, taking into account the following dimensions: themes, type of text, temporal extension, and decentration (different characters perspective). Each age group displayed a characteristic pattern of themes. The narratives of middle-aged adults typically focused on the narrators’ childhood, including the high intensity and variety of emotion associated with it and multidimensional, equivocal evaluations of parents. The narratives of participants in later adulthood were characterized by wider temporal and historical contexts, idealization of childhood, and predominantly positive evaluation of memories.
The Status of Employment Discrimination Suits in Police and Fire Departments Across the United States
Authors: Riccucci Norma M. , Saldivar Karina
Published: July 2012

Research indicates that women and people of color have made progress in gaining entry-level jobs in government, particularly at the federal level, but still lag behind in gaining positions at the upper levels. But, can the same be said for police and fire departments which have had perhaps the worst history of employment discrimination against women and people of color? This study seeks to answer this question by examining the extent to which race, gender or ethnic discrimination suits are being filed against city fire and police departments across the country, and at what level—entry or senior. The U.S. Supreme Court’s recent decision in Ricci v. DeStefano has renewed interest in this issue.

Interestingly enough, while this study expected to find that lawsuits against police and fire departments are being filed by women and people of color in order to improve their representation in the uniformed services, it found just the opposite—the preponderance of the lawsuits filed against police and fire departments are “reverse discrimination” suits, filed by White men.
Late Infantile Neuronal Ceroid Lipofuscinosis
Authors: Pérez-Poyato María S. , Marfa Mercé Pineda , Abizanda Isidre Ferrer , Rodriguez-Revenga Laia , Sánchez Victoria Cusí , González María J Martínez , Puñal Jesús Eiris , Pérez Alfonso Verdú , González M Mar García , Bermejo Antonio Martínez , Hernández Elena Martín , Rosell M Josep Coll , Gort Laura , Milá Montserrat
Published: July 2012

Late infantile neuronal ceroid lipofuscinosis (Jansky-Bielchowsky disease) is a rare disease caused by mutations in the CLN2 gene. The authors report the clinical outcome and correlate with genotype in 12 Spanish patients with this disease. Psychomotor regression, epilepsy, and other clinical symptoms/signs were assessed. Age at onset of clinical symptoms ranged from 18 months to 3.7 years, and they included delayed speech and simple febrile seizures followed by epilepsy. Partial seizures and myoclonic jerks occurred at an earlier age (median 3.4 and 3.7 years, respectively) than ataxia and cognitive decline (median 4 years). Clinical regression was initiated by loss of sentences (median 3.7 years) followed by loss of walking ability and absence of language (median 4.5 years). Patients showed blindness and lost sitting ability at similar age (median 5 years). The authors report 4 novel mutations in the CLN2 gene. This study provides detailed information about the natural history of this disease.