bluuebunny/crossref_metadata_2025 huggingface dataset:
Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
Authors: Gattelli Albana , Nalvarte Ivan , Boulay Anne , Roloff Tim C. , Schreiber Martin , Carragher Neil , Macleod Kenneth K. , Schlederer Michaela , Lienhard Susanne , Kenner Lukas , Torres‐Arzayus Maria I. , Hynes Nancy E.
Published: July 2013

We show that elevated levels of Ret receptor are found in different sub‐types of human breast cancers and that high Ret correlates with decreased metastasis‐free survival. The role of Ret in ER+ breast cancer models was explored combining in vitro and in vivo approaches. Our analyses revealed that ligand‐induced Ret activation: (i) stimulates migration of breast cancer cells; (ii) rescues cells from anti‐proliferative effects of endocrine treatment and (iii) stimulates expression of cytokines in the presence of endocrine agents. Indeed, we uncovered a positive feed‐forward loop between the inflammatory cytokine IL6 and Ret that links them at the expression and the functional level. In vivo inhibition of Ret in a metastatic breast cancer model inhibits tumour outgrowth and metastatic potential. Ret inhibition blocks the feed‐forward loop by down‐regulating Ret levels, as well as decreasing activity of Fak, an integrator of IL6‐Ret signalling. Our results suggest that Ret kinase should be considered as a novel therapeutic target in subsets of breast cancer.
Electrochemical Fabrication of Coaxial Wavy‐Channel NiIIIO(OH)/Ni Nanocomposites for High‐Performance Supercapacitor Electrode Materials
Authors: Tsang Chun‐Kwan , Zeng Shanshan , Cheng Hua , Zheng Lingxia , Zhang Jie , Li Hui , Shu Shi‐Wei , Hung Tak Fu , Lu Jian , Li Yang Yang
Published: July 2013

The supercapacitor electrode material reported herein is a type of NiIIIO(OH)/Ni coaxial nanocomposite with NiIIIO(OH) wrapping around a Ni scaffold, featuring vertically oriented nanochannels with periodically‐corrugated channel walls. A Ni scaffold was constructed through the electrodeposition of a Ni–Cu alloy film by using a square‐wave voltage followed by a dealloying treatment to selectively remove Cu. By further coating the fabricated Ni framework with NiIIIO(OH) through anodic electrodeposition, we obtained wavy‐channel NiIIIO(OH)/Ni coaxial nanostructures, which readily served as a supercapacitor electrode. The as‐fabricated supercapacitor electrode exhibited superior performance with a remarkable specific capacitance (SC) of 2372 F g−1 (after the contribution from the bare Ni scaffold was subtracted), measured at the charge and discharge rate of 1 A g−1. This is 48 % higher than the straight‐channel counterpart and is almost a three‐fold increase compared to the compact NiIIIO(OH) thin film. Moreover, superior cycling stability was achieved at high charge and discharge current densities, for example, only 10 % of the SC was lost over the first 200 cycles with no further change in the subsequent 800 cycles at 50 A g−1.
Neurosurgical Treatment of Anorexia Nervosa: Review of the Literature from Leucotomy to Deep Brain Stimulation
Authors: Lipsman Nir , Woodside D. Blake , Giacobbe Peter , Lozano Andres M.
Published: July 2013

This paper reviews the literature on the surgical treatment of refractory anorexia nervosa (AN) and examines how this literature can inform current circuit models of the disease. The literature contains reports of 35 patients undergoing a neurosurgical procedure for the specific treatment of refractory AN, with the first reported operation, a lobotomy, in 1950. All patients were deemed treatment resistant according to contemporary standards, with the nature of the procedure changing with evolving surgical techniques and methods. All procedures targeted the limbic system and, in a majority of cases, were associated with reported symptomatic improvement. Neurosurgery in AN has been, and continues to be, reserved for patients with chronic and life‐threatening illness, for whom conventional treatment has failed. Early procedures, which were viewed as life‐saving measures, were crude by today's standards but targeted anatomic structures and pathways implicated in modern models of AN. The last decade has seen a concerted effort in elucidating the neurocircuitry underlying prominent etiologic and maintaining factors in AN, including mood, anxiety and dysfunctional reward processing. This has translated into the development of novel, focused therapeutic options for patients with treatment‐refractory AN. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.
Evaluating proxies for estimating subaerial beach volume change across increasing time scales and various morphologies
Authors: Theuerkauf Ethan J. , Rodriguez Antonio B.
Published: July 2013

Proxies, such as changes in beach profiles and shoreline positions, are commonly used in management and research for estimating changes in subaerial beach volume; however, the accuracy of these proxies across increasing time scales and complex morphologies is unclear. Volume changes associated with along‐beach morphologic variability may not be captured well by changes in profiles, while volume changes associated with across‐beach morphologic variability may not be captured well by measuring shoreline change. This study assesses the impacts of morphologic variations, associated with beach cusps and nourishment material, on volume change estimates from profiles and shoreline change at 0.5 to 3.5 year time periods. Results indicate that profiles spaced ≥ 150 m apart and the shoreline‐change proxy will likely estimate volume change inaccurately over periods ≤ 1 year at beaches that are consistently eroding or accreting and contain cusps. However, over longer time periods (1–3.5 years), estimates of volume change from both proxies improved at those types of beaches. Volume changes at the edges of nourishment areas are not captured well by profiles. When the nourishment material is graded to a ramped morphology, which minimizes across‐beach morphologic variability, the shoreline‐change proxy does accurately estimate volume changes. Both proxies estimate volume changes inaccurately at beaches where volume changes oscillate between erosion and accretion on both short and long time scales because the magnitude of small‐scale changes in volume from the formation and erosion of morphologic features, such as cusps and berms, will always be similar to the longer‐term net volume change. This study suggests that decadal records of shoreline change, which are commonly developed using aerial photography, can be used to help identify the best proxy for estimating volume change; however, recent anthropogenic modifications that impact patterns of beach sedimentation, including nourishment, terminal groins, and inlet‐channel dredging, makes decadal records less useful. Copyright © 2013 John Wiley & Sons, Ltd.
Using air photos to parameterize landscape predictors of channel wetted width
Authors: Rawlins B. G. , Clark L. , Boyd D. S.
Published: July 2013

We investigated which landscape and climate‐related data (including information on hydrological source of flow) were statistically significant predictors of channel wetted width (WW) across a sizeable (2200 km2) region of the UK. This was conducted specifically when flow was less than mean daily flow (MDF) and where channels are in a near natural state. Orthorectified air photos at 25 cm spatial resolution were used to measure WW, with the magnitude of the errors in these measurements quantified. We used flow information from local gauging stations to ensure that channels were below MDF for the days on which the air photos were captured. The root mean squared difference between the field and air photo measurements of WW (n = 28 sites) was small (0.14 m) in comparison to median WW (3.07 m).

We created points along sections of channels visible in air photos and used a terrain model to create drainage catchments for these points and computed their catchment area (CA). We selected a subset of points (n = 472) and measured their WW from air photos, and computed landscape‐related data for each of their catchments (mean slope, mean annual rainfall, land cover type, elevation) and also mean BFIHOST, a quantitative index relating to hydrological source of flow. We used a linear mixed model to predict WW by including the landscape data (including CA0.5) as fixed effects, plus a spatial covariance function estimated by residual maximum likelihood to determine unbiased estimates of the predictors. There was no evidence for retaining the spatial covariance function. With the exception of land cover, all the predictors were statistically significant and accounted for 76% of the variance of WW. When CA0.5alone was used as a predictor it captured 54% of the variance. The vast majority of this difference was due to inclusion of an interaction between CA and hydrological source of flow (BFIHOST). As catchment area increases, those channels with larger mean catchment BFIHOST values (greater proportion of baseflow contribution) have narrower WW in comparison with those having smaller mean BFIHOST for the same CA. Improved predictions of channel WW (based on our findings) could be used in channel restoration. © 2013 British Geological Survey. Earth Surface Processes and Landforms © 2013 John Wiley & Sons, Ltd.
Niobium Dioxide Facilitating Methanol Electrooxidation on Pt/C Catalyst by Synergistic Effect
Authors: Zhang N. , Zhang S. , Gao Y. , Yin G.
Published: July 2013

In this work, Pt nanoparticles are deposited on NbO2‐modified carbon composites and evaluated as promising direct methanol fuel cell (DMFC) electrocatalysts. Transmission electron microscopy (TEM) and X‐ray diffraction (XRD) indicate that Pt nanoparticles (about 2.5 nm) are uniformly dispersed on NbO2‐modified carbon composites. Electrochemical measurements show that the mass activity toward methanol electrooxidation on Pt/NbO2‐C is as high as 3.0 times that of conventional Pt/C. Meanwhile, the onset potential of CO oxidation is negatively shifted by about 46 mV as compared with that of Pt/C, which means that the synergistic effect between NbO2 and Pt facilitates the feasible removal of poisoning intermediate CO during methanol electrooxidation. X‐ray photoelectron spectroscopy (XPS) characterizations reveal the electron transfer from Nb to Pt, which suppress the poisoning CO adsorption on Pt nanoparticles and facilitate methanol electrooxidation. NbO2 nanoparticles facilitate methanol electrooxidation on Pt/C catalyst by synergistic effect and electronic effect, which represents a step in the right direction for the development of excellent fuel cell anode electrocatalysts.
Analysis of Design Parameters in Anode‐Supported Solid Oxide Fuel Cells Using Response Surface Methodology
Authors: Bozorgmehri S. , Hamedi M.
Published: July 2013

Achieving high performance from a solid oxide fuel cell (SOFC) requires optimal design based on parametric analysis. In this paper, design parameters, including anode support porosity, thicknesses of electrolyte, anode support, and cathode functional layers of a single, intermediate temperature, anode‐supported planar SOFC, are analyzed. The response surface methodology (RSM) technique based on an artificial neural network (ANN) model is used. The effects of the cell parameters on its performance are calculated to determine the significant design factors and interaction effects. The obtained optimum parameters are adopted to manufacture the single units of an SOFC through tape casting and screen‐printing processes. The cell is tested and its electrochemical characteristics, which show a satisfactory performance, are discussed. The measured maximum power density (MPD) of the fabricated SOFC displays a promising performance of 1.39 W cm–2. The manufacturing process planned to fabricate the SOFC can be used for industrial production purposes.
Remanent magnetization and coercivity of rocks under hydrostatic pressure up to 1.4 GPa
Authors: Demory F. , Rochette P. , Gattacceca J. , Gabriel T. , Bezaeva N. S.
Published: July 2013

We designed an Isothermal Remanent Magnetization (IRM) acquisition system based on permanent magnets and sized to accommodate an amagnetic hydrostatic pressure cell. This pressure cell fits in a superconducting rock magnetometer, allowing for the measurement of remanent magnetization of pressurized samples. With this system, we determined the coercivity of remanence (Bcr) at different hydrostatic pressures up to 1.4 GPa for rock and dispersed mineral samples with various magnetic mineralogy and domain state. IRM and Bcr are nearly identical before compression and after decompression, indicating no permanent changes in the magnetic properties during pressure cycling. Hydrostatic pressure up to 1.4 GPa does not significantly increases IRM under pressure except for multidomain pyrrhotite and magnetite which show an increase of about 40%. Relative increase of Bcr under pressure is mild, except for a near single domain titanomagnetite where Bcr doubles.
Winter motion mediates dynamic response of the Greenland Ice Sheet to warmer summers
Authors: Sole Andrew , Nienow Peter , Bartholomew Ian , Mair Douglas , Cowton Thomas , Tedstone Andrew , King Matt A.
Published: July 2013

We present ice velocities from a land‐terminating transect extending >115 km into the western Greenland Ice Sheet during three contrasting melt years (2009–2011) to determine whether enhanced melting accelerates dynamic mass loss. We find no significant correlation between surface melt and annual ice flow. There is however a positive correlation between melt and summer ice displacement, but a negative correlation with winter displacement. This response is consistent with hydro‐dynamic coupling; enhanced summer ice flow results from longer periods of increasing surface melting and greater duration ice surface to bed connections, while reduced winter motion is explicable by drainage of high basal water pressure regions by larger more extensive subglacial channels. Despite mean interannual surface melt variability of up to 70%, mean annual ice velocities changed by <7.5%. Increased summer melting thereby preconditions the ice‐bed interface for reduced winter motion resulting in limited dynamic sensitivity to interannual variations in surface melting.
Systematic ENSO‐driven nutrient variability recorded by central equatorial Pacific corals
Authors: LaVigne Michèle , Nurhati Intan S. , Cobb Kim M. , McGregor Helen V. , Sinclair Daniel , Sherrell Robert M.
Published: July 2013

Variations in ocean productivity are driven largely by nutrient supply to the photic zone, but temporal records of nutrient variability are sparse. Here we show scleractinian coral P/Ca proxy records of variations in phosphate concentrations during El Niño Southern Oscillation (ENSO) cycles in the central equatorial Pacific. Covarying P/Ca records in Porites corals from Christmas and Fanning Islands show a regional ~40% decrease during the upwelling relaxation of the 1997–1998 El Niño, consistent with less frequent nutrient measurements from this area. Similar ~35–45% skeletal P/Ca decreases occur during the 1982–1983 and 1986–1987 El Niño events, which predate satellite color and regional nutrient measurements. After each El Niño event, nutrient increases lag temperature recovery by 4–12 months, likely reflecting uptake by massive phytoplankton blooms that followed resumption of upwelling. The results support the utility of coral P/Ca to probe the mechanisms linking ENSO, equatorial upwelling, and carbon cycling in the past.
A SHORT NOTE ON ECONOMIC DEVELOPMENT AND SOCIOECONOMIC INEQUALITY IN FEMALE BODY WEIGHT
Authors: Deuchert Eva , Cabus Sofie , Tafreschi Darjusch
Published: July 2013

The origin of the obesity epidemic in developing countries is still poorly understood. It has been prominently argued that economic development provides a natural interpretation of the growth in obesity. This paper tests the main aggregated predictions of the theoretical framework to analyze obesity. Average body weight and health inequality should be associated with economic development. Both hypotheses are confirmed: we find higher average female body weight in economically more advanced countries. In relatively nondeveloped countries, obesity is a phenomenon of the socioeconomic elite. With economic development, obesity shifts toward individuals with lower socioeconomic status. Copyright © 2013 John Wiley & Sons, Ltd.
Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor
Authors: Pearlman Brian L. , Ehleben Carole
Published: July 2013

The new standard of care for treatment-naïve patients with hepatitis C virus (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a protease inhibitor. However, patients who achieve a rapid virologic response after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a sustained virologic response (SVR), and we hypothesized that protease inhibitor therapy may be unnecessary in these patients. Treatment-naïve, noncirrhosis patients infected with genotype-1 HCV and a low viral load at baseline were considered for inclusion (n = 233). After 4 weeks of lead-in therapy with peginterferon α-2b and ribavirin, 101 patients (48%) had a rapid virologic response (defined as undetectable levels of hepatitis C virus RNA at 4 weeks) and were eligible to participate. Patients were randomized 1:1 to 20 weeks of additional therapy with peginterferon α-2b and ribavirin (double therapy) or to 24 weeks of peginterferon α-2b, ribavirin, and boceprevir (triple therapy). There was no significant difference in rates of SVR-12 in patients treated with double versus triple therapy. This similarity persisted regardless of viral subtype (genotype 1a or 1b), interleukin (IL)−28b genotype (CC or non-CC), or ethnicity (African American versus non-Hispanic white).

Conclusion :

Protease inhibitor therapy could be obviated in genotype 1-infected treatment-naïve patients with low viral load at baseline who achieve undetectable viremia after 4 weeks of peginterferon/ribavirin.
Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through c-jun-N-terminal kinase (JNK)-dependent and -independent signaling pathways
Authors: Saberi Behnam , Ybanez Maria D. , Johnson Heather S. , Gaarde William A. , Han Derick , Kaplowitz Neil
Published: July 2013

This study examines the role of protein kinase C (PKC) and AMP-activated kinase (AMPK) in acetaminophen (APAP) hepatotoxicity. Treatment of primary mouse hepatocytes with broad-spectrum PKC inhibitors (Ro-31-8245, Go6983), protected against APAP cytotoxicity despite sustained c-jun-N-terminal kinase (JNK) activation. Broad-spectrum PKC inhibitor treatment enhanced p-AMPK levels and AMPK regulated survival-energy pathways including autophagy. AMPK inhibition by compound C or activation using an AMPK activator oppositely modulated APAP cytotoxicity, suggesting that p-AMPK and AMPK regulated energy survival pathways, particularly autophagy, play a critical role in APAP cytotoxicity. Ro-31-8245 treatment in mice up-regulated p-AMPK levels, increased autophagy (i.e., increased LC3-II formation, p62 degradation), and protected against APAP-induced liver injury, even in the presence of sustained JNK activation and translocation to mitochondria. In contrast, treatment of hepatocytes with a classical PKC inhibitor (Go6976) protected against APAP by inhibiting JNK activation. Knockdown of PKC-α using antisense (ASO) in mice also protected against APAP-induced liver injury by inhibiting JNK activation. APAP treatment resulted in PKC-α translocation to mitochondria and phosphorylation of mitochondrial PKC substrates. JNK 1 and 2 silencing in vivo decreased APAP-induced PKC-α translocation to mitochondria, suggesting PKC-α and JNK interplay in a feed-forward mechanism to mediate APAP-induced liver injury. Conclusion: PKC-α and other PKC(s) regulate death (JNK) and survival (AMPK) proteins, to modulate APAP-induced liver injury. (HEPATOLOGY 2014;59:1543-1554)
Cell entry, efficient RNA replication, and production of infectious hepatitis C virus progeny in mouse liver-derived cells
Authors: Frentzen Anne , Anggakusuma  , Gürlevik Engin , Hueging Kathrin , Knocke Sarah , Ginkel Corinne , Brown Richard J.P. , Heim Markus , Dill Michael T. , Kröger Andrea , Kalinke Ulrich , Kaderali Lars , Kuehnel Florian , Pietschmann Thomas
Published: July 2013

Only humans and chimpanzees are susceptible to chronic infection by hepatitis C virus (HCV). The restricted species tropism of HCV is determined by distinct host factor requirements at different steps of the viral life cycle. In addition, effective innate immune targeting precludes efficient propagation of HCV in nonhuman cells. Species-specificity of HCV host factor usage for cell entry and virus release has been explored. However, the reason for inefficient HCV RNA replication efficiency in mouse liver cells remains elusive. To address this, we generated novel mouse liver-derived cell lines with specific lesions in mitochondrial antiviral signaling protein (MAVS), interferon regulatory factor 3 (IRF3), or Interferon-α/β receptor (IFNAR) by

in vivo

immortalization. Blunted innate immune responses in these cells modestly increased HCV RNA replication. However, ectopic expression of liver-specific human microRNA 122 (miR-122) further boosted RNA replication in all knockout cell lines. Remarkably, MAVS−/−miR-122 cells sustained vigorous HCV RNA replication, attaining levels comparable to the highly permissive human hepatoma cell line Huh-7.5. RNA replication was dependent on mouse cyclophilin and phosphatidylinositol-4 kinase III alpha (PI4KIIIα) and was also observed after transfection of full-length viral RNA. Additionally, ectopic expression of either human or mouse apolipoprotein E (ApoE) was sufficient to permit release of infectious particles. Finally, expression of human entry cofactors rendered these cells permissive to HCV infection, thus confirming that all steps of the HCV replication cycle can be reconstituted in mouse liver-derived cells.

Conclusion :

Blunted innate immunity, abundant miR-122, and HCV entry factor expression permits propagation of HCV in mouse liver-derived cell lines.
Progress against laryngeal cancer in The Netherlands between 1989 and 2010
Authors: van Dijk Boukje A.C. , Karim‐Kos Henrike E. , Coebergh Jan Willem , Marres Henri A.M. , de Vries Esther
Published: July 2013

Cancer of the larynx is a frequently occurring head and neck cancer in The Netherlands. The main risk factors are smoking and excessive alcohol consumption. The aim of our study was to evaluate the progress against laryngeal cancer by studying trends in incidence, mortality and survival in The Netherlands. All patients in The Netherlands Cancer Registry diagnosed with invasive primary squamous cell carcinoma of the larynx during the period 1989–2010 were included for analysis. Time trends in incidence, mortality, treatment and survival were described for the total group and stratified by sex and subsite: glottis, supraglottis and subglottis. The most frequently affected subsite for men was the glottis (69%) and for women the supraglottis (55%). Glottic cancer was diagnosed at lower stages than supraglottic cancer. Incidence and mortality rates decreased for males with −2.5 and −2.8% per year, respectively, but remained stable for women, except for an increasing mortality rate in older women (EAPC: +2.5%). Five‐year relative survival rates were stable for glottic (85%) and supraglottic (50%) cancer, whereas patients with high‐staged cancers more often received radiotherapy. Multivariable analysis showed lower relative excess risks of dying for women, younger patients (<75 years), glottic cancer, lower stage cancer and those undergoing surgery. Changes in incidence and mortality rates are in line with changing smoking habits in The Netherlands. Declining incidence with stable survival rates gives rise to hope and worry at the same time.
A STUDY ON SOME PARAMETERS WHICH CAN AFFECT PROJECT IRRIGATION EFFICIENCY IN IRRIGATION NETWORKS
Authors: Koç Cengiz
Published: July 2013

In this study, some parameters that can affect project irrigation efficiency in irrigation schemes operated and constructed by State Hydraulic Works (DSI) in the Büyük Menderes basin, Turkey, were selected, and the effects on the project irrigation efficiency of these parameters were studied. The selected parameters are irrigation rate, density of irrigation facilities, average farm size, density of distribution scheme, and density of personnel per unit area. In order to determine the possible effects on the project irrigation efficiency of these parameters, SPSS‐15 (Statistical Package for the Social Sciences‐15) software was used. With this method, partial correlation coefficients related to selected parameters were calculated, and degrees of relationship and possible effects on project irrigation efficiency were determined. Also, in order to determine the parameter values that may make standardize the project irrigation efficiency, parameter coefficients were calculated. Copyright © 2013 John Wiley & Sons, Ltd.
Tropisetron alleviate early post‐operative pain after gynecological laparoscopy in sevoflurane based general anaesthesia: A randomized, parallel‐group, factorial study
Authors: Mei W. , Li M. , Yu Y. , Cheung C.W. , Cao F. , Nie B. , Zhang Z. , Wang P. , Tian Y.
Published: July 2013

Background

Studies have suggested that 5‐hydroxytryptamine‐3A (5‐HT‐3A) receptor antagonists may have analgesic effects. This randomized, double‐blind, placebo‐controlled, factorial study tested the hypothesis that 5‐HT‐3A receptor antagonist tropisetron attenuates post‐operative pain in women receiving either sevoflurane or propofol based anaesthesia.

Methods

Two hundred and ninety‐six women undergoing gynaecological laparoscopies were randomly assigned to be anaesthetized with either sevoflurane or propofol. Immediately after the induction of anaesthesia, the anaesthesiologist administered either tropisetron 2 mg or a placebo intravenously. Pain score at rest at 0.5 h post‐operatively reported using a numerical rating scale was the primary outcome measure. The secondary outcome measures included pain score at rest every 2 h within the first 24 h post‐operatively, duration of post‐anaesthesia care unit stay, incidence of post‐operative nausea and vomiting, the incidence of shivering and score of the Quality of Recovery Score 40.

Results

Compared with placebo, tropisetron produced a statistically significant decrease on pain report within the first 6 h post‐operatively in the sevoflurane‐based anaesthesia group (3 [2, 4] vs. 5 [4, 5], p < 0.001 in 0.5 h; 2 [0, 4] vs. 3 [3, 5], p < 0.001 in 2 h; 2 [0, 3] vs. 3 [1, 4], p = 0.002 in 4 h; 1 [0, 3] vs. 2 [1, 4], p = 0.016 in 6 h), but not in the propofol‐based group.

Conclusions

A single‐dose intravenous administration of tropisetron after anaesthesia induction is associated with statistically significant decreased early post‐operative pain in patients undergoing gynaecological laparoscopies under sevoflurane based general anaesthesia.
Efficient screening of climate model sensitivity to a large number of perturbed input parameters
Authors: Covey Curt , Lucas Donald D. , Tannahill John , Garaizar Xabier , Klein Richard
Published: July 2013

Modern climate models contain numerous input parameters, each with a range of possible values. Since the volume of parameter space increases exponentially with the number of parameters N, it is generally impossible to directly evaluate a model throughout this space even if just 2–3 values are chosen for each parameter. Sensitivity screening algorithms, however, can identify input parameters having relatively little effect on a variety of output fields, either individually or in nonlinear combination. This can aid both model development and the uncertainty quantification (UQ) process. Here we report results from a parameter sensitivity screening algorithm hitherto untested in climate modeling, the Morris one‐at‐a‐time (MOAT) method. This algorithm drastically reduces the computational cost of estimating sensitivities in a high dimensional parameter space because the sample size grows linearly rather than exponentially with N. It nevertheless samples over much of the N‐dimensional volume and allows assessment of parameter interactions, unlike traditional elementary one‐at‐a‐time (EOAT) parameter variation. We applied both EOAT and MOAT to the Community Atmosphere Model (CAM), assessing CAM's behavior as a function of 27 uncertain input parameters related to the boundary layer, clouds, and other subgrid scale processes. For radiation balance at the top of the atmosphere, EOAT and MOAT rank most input parameters similarly, but MOAT identifies a sensitivity that EOAT underplays for two convection parameters that operate nonlinearly in the model. MOAT's ranking of input parameters is robust to modest algorithmic variations, and it is qualitatively consistent with model development experience.
The WRF nested within the CESM: Simulations of a midlatitude cyclone over the Southern Great Plains
Authors: He Juanxiong , Zhang Minghua , Lin Wuyin , Colle Brian , Liu Ping , Vogelmann Andrew M.
Published: July 2013

This paper describes an integrated modeling system in which the Weather Research and Forecasting model (WRF) is nested within the Community Earth System Model (CESM). This system is validated for the simulation of a midlatitude cyclongesis event over the Southern Great Plains of the United States. The global atmospheric model CAM4 at T42 resolution in the CESM has missed this cyclogenesis, while the nested WRF at 30 km grid spacing (or finer) that is initialized with the CAM4 condition and laterally forced by the CAM4 successfully simulated the deepening midtropospheric trough and associated cyclogenesis. An analysis of the potential velocity evolution and sensitivity experiments show that it is the higher WRF resolution that allowed the realistic sharpening of the Ertel's Potential Vorticity (EPV) gradient and the ensuing cyclogenesis. The terrain resolution and the physical parameterizations, however, play little role in the difference between the CAM4 and the WRF in the CESM. The integrated WRF/CESM system is intended as one method of global climate modeling with regional simulation capabilities. The present case study also serves as a verification of the system by comparing with standalone WRF simulations forced by operational analyses.
Neuroprotective Effects of NicotinamideN‐Methyltransferase and its Metabolite 1‐Methylnicotinamide
Authors: Milani Zeinab H. , Ramsden David B. , Parsons Richard B.
Published: July 2013

NicotinamideN‐methyltransferase (NNMT, E.C. 2.1.1.1) catalyses theN‐methylation of nicotinamide to 1‐methylnicotinamide (MeN). We have previously shown that the ectopic expression of NNMT in SH‐SY5Y human neuroblastoma cells increased adenosine triphosphate synthesis and complex I activity, effects of which were replicated by the addition of MeN. In this study, we investigated whether NNMT expression in SH‐SY5Y conferred protection against mitotoxicity induced by rotenone, potassium cyanide (KCN), 2,4‐dinitrophenol, and 6‐hydroxydopamine, and whether any effects observed were mediated via increased MeN production. NNMT expression abolished the toxic effects of KCN, 2,4‐dinitrophenol, and 6‐hydroxydopamine, and reduced that of rotenone. In contrast, although MeN significantly reduced the toxicity of rotenone, it had no effect upon the toxicity of KCN, 2,4‐dinitrophenol, and 6‐hydroxydopamine. These data show that NNMT is cytoprotective against toxins that inhibit various aspects of mitochondrial function, and that these are not mediated solely via increased MeN production, but in combination with other unidentified mechanisms. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:451‐456, 2013; View this article online atwileyonlinelibrary.com. DOI 10.1002/jbt.21508
Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue
Authors: Schwartz Joseph , Winters Jeffrey L. , Padmanabhan Anand , Balogun Rasheed A. , Delaney Meghan , Linenberger Michael L. , Szczepiorkowski Zbigniew M. , Williams Mark E. , Wu Yanyun , Shaz Beth H.
Published: July 2013

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence‐based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence‐based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the “level of evidence” criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. J. Clin. Apheresis 28:145–284, 2013. © 2013 Wiley Periodicals, Inc.
A protocol to evaluate one electron redox potential for iron complexes
Authors: Kim Hyungjun , Park Joungwon , Lee Yoon Sup
Published: July 2013

Density functional theory calculation has been performed to calculate the redox potential and the correct ground spin state of iron complexes in acetonitrile. Widely used B3LYP functional is applied with the spin state corrected basis sets. The newly developed protocol for the set of 21 iron complexes is to optimize the structure at the level of the B3LYP/6‐31G* and to calculate the single point electronic energy with the same functional and the modified basis sets s6‐31G* for the iron atom and 6‐31+G* for other ligand atoms. The solvation energy is considered through the polarized continuum model and the cavity creation energy is included for the accurate spin state description. Modifying the cavity size by employing the different scaling factor according to the mean absolute value of the natural population analysis charge (MA‐NPA) is introduced. The molecule with the large MA‐NPA requires the cavity size smaller than the less polar one. This protocol gives only 1 wrong ground spin state among the 18 iron complexes for which experimental data are known. For the open circuit voltage (OCV) calculation, our protocol performs well yielding the mean absolute error of 0.112 V for the test set. The close correlation between the calculated and the experimental OCV are obtained. © 2013 Wiley Periodicals, Inc.
Ab initio study of the high‐temperature phase transition in crystalline GeO2
Authors: Deringer Volker L. , Lumeij Marck , Stoffel Ralf P. , Dronskowski Richard
Published: July 2013

Germanium dioxide (GeO2) takes two forms at ambient pressure: a thermodynamically stable rutile‐type structure and a high‐temperature quartz‐type polymorph. Here, we investigate the phase stability at finite temperatures by ab initio phonon and thermochemical computations. We use gradient‐corrected density‐functional theory (PBE‐GGA) and pay particular attention to the modeling of the “semicore” germanium 3d orbitals (ascribing them either to the core or to the valence region). The phase transition is predicted correctly in both cases, and computed heat capacities and entropies are in excellent agreement with thermochemical database values. Nonetheless, the computed formation energies of α‐quartz‐type GeO2 (and, consequently, the predicted transition temperatures) differ significantly depending on theoretical method. Remarkably, the simpler and cheaper computational approach produces seemingly better results, not worse. In our opinion, GeO2 is a nice test case that illustrates both possibilities and limitations of modern ab initio thermochemistry. © 2013 Wiley Periodicals, Inc.
A model‐based approach to characterize the population pharmacokinetics and the relationship between the pharmacokinetic and safety profiles of RBP‐7000, a new, long‐acting, sustained‐released formulation of risperidone
Authors: Gomeni R. , Heidbreder C. , Fudala P.J. , Nasser A.F.
Published: July 2013

RBP‐7000 is a sustained‐release (once‐monthly injection for subcutaneous administration) formulation of risperidone using the ATRIGEL® Delivery System, developed for treatment of schizophrenia to address compliance issues associated with oral administration. The objective of this analysis was to report the results of a population pharmacokinetic analysis and to describe the relationship between risperidone and 9‐hydroxyrisperidone levels with dopamine (DA) D2‐receptor occupancy, prolactin levels, and adverse events using data collected in 45 clinically stable schizophrenic patients receiving RBP‐7000 in single ascending doses (risperidone) of 60, 90, and 120 mg. The population PK model accounted for an initial peak, a delayed and slow delivery, the disposition of risperidone, and the conversion of risperidone to 9‐hydroxyrisperidone. BMI was a covariate affecting absorption of risperidone and ultimately formation of 9‐hydroxyrisperidone. A logistic analysis indicated a correlation between the increase in Active Moiety (risperidone + 9‐OH‐risperidone) exposure (Cmax) and the probability of observing GI disorders. An Emax population PK/prolactin model best described the relationship between the circulating Active Moiety and the serum prolactin levels. Gender was a significant covariate associated with Emax. These data provided a comprehensive characterization of the relationship between circulating Active Moiety and the efficacy/safety profile of RBP‐7000 in clinically stable schizophrenic patients.
The Role of Social Capital in the Experiences of Hispanic Women Engineering Majors
Authors: Martin Julie P. , Simmons Denise R. , Yu Shirley L.
Published: July 2013

Background

Women and minorities remain significantly underrepresented in the undergraduate engineering disciplines despite decades‐long recruitment and retention efforts. As United States demographics shift and the nation continues to recognize the value of workplace diversity, engineering education stakeholders continue to seek ways to increase participation of women and minority students.

Purpose

Our research examines the following question: For Hispanic women whose parents have limited educational attainment, what available sources of potential social capital do they identify, and by what means do they access and activate these resources in their decisions to select and persist in engineering as a college major? We hope to provide insights for United States institutions that serve Hispanic students, as well as those seeking to diversify their student body.

Design/method

Utilizing Lin's network theory of social capital as a framework, we employed semi‐structured interviews in a multiple case study research methodology, taking a constructivist epistemological view.

Results

Three major findings are that (1) lack of available family social capital was supplemented mostly by school personnel; (2) delayed recognition or identification of available resources slowed access and activation of resources, leading to difficult university transitions; and (3) if accessed and activated, peer groups and institutional support systems provided sources of social capital.

Conclusions

Even single instances or weak ties can be effective in bridging gaps in engineering‐related social capital. Facilitating opportunities for students to develop sustained social capital may have potential to attract and retain underrepresented students in engineering.
Indispensable Resource? A Phenomenological Study of Textbook Use in Engineering Problem Solving
Authors: Lee Christine S. , McNeill Nathan J. , Douglas Elliot P. , Koro‐Ljungberg Mirka E. , Therriault David J.
Published: July 2013

Background

Textbooks play an important role in engineering education, influencing instructors' pedagogical approaches and providing much of the information students learn. Research has explored students' recollections of the roles that textbooks played in their educational experiences, but how students actually use textbooks remains largely unexplored.

Purpose

This phenomenological study describes engineering students' textbook use during problem‐solving activities. This study directly examined how students employed a textbook in order to generate detailed descriptions of students' behaviors, approaches, and reflections regarding their actual problem‐solving experiences.

Method

Ten senior materials engineering students (8 males and 2 females) were asked to think aloud while solving engineering problems. Follow‐up retrospective interviews regarding the think aloud session were conducted to gain in‐depth information on students' textbook use during the problem‐solving activities.

Results

Students used the textbook primarily to find information related to problem constraints that were explicitly stated in the problem. Furthermore, textbook example problems exerted a strong influence on students' problem‐solving processes. Students also reported limitations of the textbook, contrasting it to the diversity of resources available via the Internet.

Conclusions

This study provides insight into students' textbook use during engineering problem‐solving activities. Students' limited application of the textbook during problem solving suggests that textbooks may not be serving their intended purposes.
Effects of Course and Instructor Characteristics on Student Evaluation of Teaching across a College of Engineering
Authors: Johnson Michael D. , Narayanan Arunachalam , Sawaya William J.
Published: July 2013

Background

Student evaluations of teaching (SETs) are a widely used metric to evaluate instructor effectiveness and are used to make promotion, tenure, and retention decisions for faculty. There is also growing interest by those outside the university community to use these metrics to evaluate faculty and broader academic performance.

Purpose (Hypothesis)

This study seeks to understand if and how course and instructor characteristics affect SETs and thereby to improve the usefulness of these metrics. This article aims to statistically examine the relationship between course and instructor characteristics and SETs.

Design/Method

SETs from a large engineering college at a major public university were evaluated over a seven‐semester period that covered 3938 courses taught by 549 unique engineering instructors. Course and instructor demographic data were statistically evaluated for their effects on SETs.

Results

Course characteristics such as class size, course level, and whether a course was an elective or required had statistically significant effects on SETs. Instructor characteristics of gender and academic rank affected SETs and average course grades, respectively. Average course grades were positively correlated with SETs.

Conclusions

Data analysis showed that course characteristics, faculty demographics, and average course grades had statistically significant effects on SETs; however, in some cases the effect sizes of these variables were small. Administrators and senior faculty members should be cognizant of these relevant factors and their effects when assigning faculty to certain courses and evaluating their teaching effectiveness using SETs.
Simulation of recurring earthquakes along the Nankai trough and their relationship to the Tokai long‐term slow slip events taking into account the effect of locally elevated pore pressure and subducting ridges
Authors: Hirose Fuyuki , Maeda Kenji
Published: July 2013

Many earthquakes of moment magnitudes greater than 8 associated with subduction of the Philippine Sea plate under Japan have occurred along the Nankai trough with a recurrence interval of 90–150 years. A large‐scale rupture of the Tokai fault segment is believed to be imminent because that segment did not rupture during the most recent Tonankai earthquake in 1944. Recurring long‐term slow slip events (LSSEs) have recently been observed in the Tokai region. To investigate the current stress state in the Tokai region, we numerically simulated earthquake cycles using a three‐dimensional model consisting of triangular cells based on the rate‐ and state‐dependent friction law. Our numerical simulations successfully modeled the Tokai segment not ruptured during the 1944 Tonankai earthquake as well as the recurring LSSEs in the Tokai region. We found that a large characteristic displacement (L) and effective normal stress (σ) in areas of subducted ridges are essential to avoid rupture of the Tokai segment during the 1944 Tonankai earthquake. We also demonstrated that we can reproduce the recurring LSSEs by assigning low values of σ and L to the area beneath Lake Hamana without introducing a velocity‐strengthening friction law at high slip rate. Our simulation showed that the amplitudes of the LSSEs increased following the earthquakes that did not rupture the Tokai segment, which suggests that the recent LSSEs may be related to the accumulation of stresses in the Tokai segment because it did not rupture during the 1944 earthquake.
Shear wave structure in the northeastern Tibetan Plateau from Rayleigh wave tomography
Authors: Li Lun , Li Aibing , Shen Yang , Sandvol Eric A , Shi Danian , Li Hongyi , Li Xinfu
Published: July 2013

The northeastern Tibetan Plateau has undergone active shortening due to the India‐Asia collision and has been an ideal place for studying the growth of the plateau. To reveal deep structure that is responsible for geological observations in NE Tibet, we have constructed a 3‐D shear wave velocity model from Rayleigh waves recorded by 36 stations in the Northeast Tibetan Plateau Seismic experiment. First, the two‐plane‐wave tomography method was applied to compute the average and 2‐D variations of phase velocities in a period range of 20 to 100 s. Then 1‐D and 3‐D shear wave velocity models were developed from the obtained Rayleigh wave dispersions. The entire region is characterized by a weak upper mantle with a relatively thin lithosphere of ~80–100 km thick. This observation helps to explain the active deformation at the Kunlun Mountains and the Qinling Orogen in NE Tibet. Relative low velocity anomalies appear along and to the south of the Kunlun fault (KF) in contrast to high velocity anomalies in the north and northeast. One pronounced slow anomaly centered at ~120 km depth is imaged right beneath the restraining bend of the Kunlun fault, which might be a northern extension of the large‐scale slow anomaly to the south of the fault. We interpret it as a local feature due to its large magnitude and coincidence with the restraining bend. It is probably related to anomalously high temperature and associated partial melting resulted from localized asthenosphere upwelling after the delamination of a thick lithosphere root. The formation of the thick lithosphere root would require coherent shortening in the crust and mantle lithosphere caused by local compression due to the bend of the strike‐slip fault, indicating that the Kunlun fault is probably on lithosphere scale and has played an important role in accommodating the eastward extrusion of the Tibetan Plateau.