bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Properties of the Upper Airway
Authors: Strohl Kingman P. , Butler James P. , Malhotra Atul
Published: June 2012

The importance of the upper airway (nose, pharynx, and larynx) in health and in the pathogenesis of sleep apnea, asthma, and other airway diseases, discussed elsewhere in the Comprehensive Physiology series, prompts this review of the biomechanical properties and functional aspects of the upper airway. There is a literature based on anatomic or structural descriptions in static circumstances, albeit studied in limited numbers of individuals in both health and disease. As for dynamic features, the literature is limited to studies of pressure and flow through all or parts of the upper airway and to the effects of muscle activation on such features; however, the links between structure and function through airway size, shape, and compliance remain a topic that is completely open for investigation, particularly through analyses using concepts of fluid and structural mechanics. Throughout are included both historically seminal references, as well as those serving as signposts or updated reviews. This article should be considered a resource for concepts needed for the application of biomechanical models of upper airway physiology, applicable to understanding the pathophysiology of disease and anticipated results of treatment interventions. © 2012 American Physiological Society.Compr Physiol2:1853‐1872, 2012.
Coping with Thermal Challenges: Physiological Adaptations to Environmental Temperatures
Authors: Tattersall Glenn J. , Sinclair Brent J. , Withers Philip C. , Fields Peter A. , Seebacher Frank , Cooper Christine E. , Maloney Shane K.
Published: June 2012

Temperature profoundly influences physiological responses in animals, primarily due to the effects on biochemical reaction rates. Since physiological responses are often exemplified by their rate dependency (e.g., rate of blood flow, rate of metabolism, rate of heat production, and rate of ion pumping), the study of temperature adaptations has a long history in comparative and evolutionary physiology. Animals may either defend a fairly constant temperature by recruiting biochemical mechanisms of heat production and utilizing physiological responses geared toward modifying heat loss and heat gain from the environment, or utilize biochemical modifications to allow for physiological adjustments to temperature. Biochemical adaptations to temperature involve alterations in protein structure that compromise the effects of increased temperatures on improving catalytic enzyme function with the detrimental influences of higher temperature on protein stability. Temperature has acted to shape the responses of animal proteins in manners that generally preserve turnover rates at animals' normal, or optimal, body temperatures. Physiological responses to cold and warmth differ depending on whether animals maintain elevated body temperatures (endothermic) or exhibit minimal internal heat production (ectothermic). In both cases, however, these mechanisms involve regulated neural and hormonal over heat flow to the body or heat flow within the body. Examples of biochemical responses to temperature in endotherms involve metabolic uncoupling mechanisms that decrease metabolic efficiency with the outcome of producing heat, whereas ectothermic adaptations to temperature are best exemplified by the numerous mechanisms that allow for the tolerance or avoidance of ice crystal formation at temperatures below 0°C. © 2012 American Physiological Society.Compr Physiol2:2151‐2202, 2012.
Kinetic Study of Thermal 1,3‐Dipolar Cycloaddition of Azomethine Ylides by Using Differential Scanning Calorimetry
Authors: Mancebo‐Aracil Juan , Muñoz‐Guillena María J. , Such‐Basáñez Ion , Sansano‐Gil José M.
Published: June 2012

The kinetics of 1,3‐dipolar cycloaddition involving azomethine ylides, generated from thermal 1,2‐prototropy of the corresponding imino ester, employing differential scanning calorimetry (DSC), is surveyed. Glycine and phenylalanine derived imino esters have different behavior. The first one prefers reacting with itself at 75 °C, rather than with the dipolarophile. However, the α‐substituted imino ester gives the cycloadduct at higher temperatures. Thermal dynamic analysis, by using 1H NMR spectroscopy, of the neat reaction mixture of the glycine derivative reveals the presence of signals corresponding to the dipole in small abundance. The non‐isothermal and isothermal DSC curves of the cycloaddition of phenylalaninate and diisobutyl fumarate are obtained from freshly prepared samples. The application of known kinetic models and mathematical multiple non‐linear regressions (NLR) allow the determintion and comparison of Ea, lnA, reaction orders, and reaction enthalpy values. Finally a rate equation for each different temperature studied can be established for this particular thermal cycloaddition.
Interconversion of ephedrine and pseudoephedrine during chemical derivatization
Authors: Wong Colton H. F. , Ho Emmie N. M. , Kwok W. H. , Leung David K. K. , Leung Gary N. W. , Tang Francis P. W. , Wong April S. Y. , Wong Jenny K. Y. , Yu Nola H. , Wan Terence S. M.
Published: June 2012

Gas chromatography–mass spectrometry (GC‐MS) analysis after heptafluorobutyric anhydride (HFBA) derivatization was one of the published methods used for the quantification of ephedrine (EP) and pseudoephedrine (PE) in urine. This method allows the clear separation of the derivatized diastereoisomers on a methyl‐silicone‐based column. Recently the authors came across a human urine sample with apparently high levels (µg/ml) of EP and PE upon initial screening. However, duplicate analyses of this sample using the HFBA‐GC‐MS method revealed an unusual discrepancy in the estimated levels of EP and PE, with the area response ratios of EP/PE at around 29% on one occasion and around 57% on another. The same sample was re‐analyzed for EP and PE using other techniques, including GC‐MS after trimethylsilylation and ultra‐high‐performance liquid chromatography‐tandem mass spectrometry. Surprisingly, the concentration of EP in the sample was determined to be at least two orders of magnitude less than what was observed with the HFBA‐GC‐MS method. A thorough investigation was then conducted, and the results showed that both substances could interconvert during HFBA derivatization. Similar diastereoisomeric conversion was also observed using other fluorinated acylating agents (e.g. pentafluoropropionic anhydride and trifluoroacetic anhydride). The extent of interconversion was correlated with the degree of fluorination of the acylating agents, with HFBA giving the highest conversion. This conversion has never been reported before. A mechanism for the interconversion was proposed. These findings indicated that fluorinated acylating agents should not be used for the unequivocal identification or quantification of EP and PE as the results obtained can be erroneous. Copyright © 2012 John Wiley & Sons, Ltd.
Effectiveness of GH isoform differential immunoassay for detecting rhGH doping on application of various growth factors
Authors: Okano Masato , Nishitani Yasunori , Sato Mitsuhiko , Kageyama Shinji
Published: June 2012

The analytical method for detecting growth hormone (GH) doping, the so‐called GH isoform differential immunoassay, is currently approved by the World Anti‐Doping Agency (WADA).

Anti‐doping laboratories often face challenges by athletes' lawyers and need to have various types of scientific evidence against the claim that the adverse analytical finding (AAF) result was caused by excess ectopic or abnormal excretion. In this work, a population study of Japanese athletes (255 male and 256 female) and administration studies of recombinant human GH (rhGH) in Japanese females were conducted to confirm the applicability of GH isoform differential immunoassay. The present paper describes the effectiveness of the GH isoform differential immunoassay under abnormal excretion of endogenous GH as determined by administration studies of GH releasing hormone (GHRH(1–44)) and insulin‐like growth factor‐1 (IGF‐1). No false positive findings were found in Japanese athletes. The GH isoform differential immunoassays could detect application of rhGH for approximately 12–24 h. The administration of GHRH(1–44) and IGF‐1 as well as ghrelin receptor agonists did not affect the isoform ratio (no false positives). We conclude that the GH isoform differential immunoassay is a highly specific method for detecting rhGH doping. Subject‐based profiling (i.e. athlete biological passport) very likely will represent a highly sensitive approach for detecting rhGH doping. Copyright © 2012 John Wiley & Sons, Ltd.
Psychotropic medication use in anorexia nervosa between 1997 and 2009
Authors: Fazeli Pouneh K. , Calder Genevieve L. , Miller Karen K. , Misra Madhusmita , Lawson Elizabeth A. , Meenaghan Erinne , Lee Hang , Herzog David , Klibanski Anne
Published: June 2012

Objective:

Despite a lack of data demonstrating benefit, psychotropic medications are frequently prescribed for patients with anorexia nervosa.

Method:

We studied 525 women (18–54 years of age) with anorexia nervosa who presented to the Clinical Research Center at the Massachusetts General Hospital between January 1997 and December 2009. For this analysis, participants were a priori divided into two groups based on date of presentation (Group I: participants presenting between 1997 and 2002; Group II: participants presenting between 2003 and 2009).

Results:

Overall, 53% of participants reported current use of any psychotropic medication; 48.4% reported use of an antidepressant and 13% reported use of an antipsychotic. Twice as many participants in Group II (18.5%) reported using atypical antipsychotics as compared to Group I (8.9%) (p = 0.002).

Discussion:

A majority of participants with anorexia nervosa report using psychotropic medications despite lack of data supporting their efficacy. These data are concerning given the known adverse effects of these medications. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
The tyrosine kinase Abl is a component of macrophage podosomes and is required for podosome formation and function
Authors: Baruzzi Anna , Berton Giorgio
Published: June 2012

Myeloid leukocytes form actin‐based plasma membrane protrusions, called podosomes, that are implicated in myeloid cell recruitment into tissues and cell migration within the interstitium. In this study, we show that tyrosine kinases of the Abl family are present in podosomes formed by murine and human macrophages. Silencing of Abl expression in bone marrow‐derived macrophages and monocyte‐derived macrophages by siRNA or Abl enzymatic inhibition with imatinib resulted in the disassembly of macrophage podosomes and the reduction of their capacity to degrade an extracellular matrix and migrate through matrigel matrices and endothelial cell monolayers. Additionally, macrophages deficient in Src‐family kinases, which cross‐talk with Abl in regulating macrophage migration, also demonstrated podosome disassembly. These findings suggest that podosome disassembly induced by Abl targeting may inhibit podosome‐dependent functions such as leukocyte recruitment into inflammatory sites and osteoclast‐dependent bone resorption.
The early cellular signatures of protective immunity induced by live viral vaccination
Authors: Kohler Siegfried , Bethke Nicole , Böthe Matthias , Sommerick Sophie , Frentsch Marco , Romagnani Chiara , Niedrig Matthias , Thiel Andreas
Published: June 2012

Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV‐17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV‐17D specific T‐ and B‐cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV‐17D‐specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen‐specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV‐17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV‐17D‐specific antibodies, correlated with early activation and recruitment of YFV‐17D‐specific CD4+ T cells and higher levels of sIL‐6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity.
Intact B7‐H3 signaling promotes allograft prolongation through preferential suppression of Th1 effector responses
Authors: Ueno Takuya , Yeung Melissa Y. , McGrath Martina , Yang Sunmi , Zaman Nadia , Snawder Benjamin , Padera Robert F. , Magee Ciara N. , Gorbatov Rostic , Hashiguchi Masaaki , Azuma Miyuki , Freeman Gordon J. , Sayegh Mohamed H. , Najafian Nader
Published: June 2012

Ligands of the B7 family provide both positive and negative costimulatory signals to the CD28 family of receptors on T lymphocytes, the balance of which determines the immune response. B7‐H3 is a member of the B7 family whose function in T‐cell activation has been the subject of some controversy: in autoimmunity and tumor immunity, it has been described as both costimulatory and coinhibitory, while in transplantation, B7‐H3 signaling is thought to contribute to graft rejection. However, we now demonstrate results to the contrary. Signaling through a putative B7‐H3 receptor prolonged allograft survival in a fully MHC‐mismatched cardiac model and promoted a shift toward a Th2 milieu; conversely, B7‐H3 blockade, achieved by use of a blocking antibody, resulted in accelerated rejection, an effect associated with enhanced IFN‐γ production. Finally, graft prolongation achieved by CTLA4 Ig was shortened both by B7‐H3 blockade and the absence of recipient B7‐H3. These findings suggest a coinhibitory role for B7‐H3. However, experience with other CD28/B7 family members suggests that immune redundancy plays a crucial role in determining the functions of various pathways. Given the abundance of conflicting data, it is plausible that, under differing conditions, B7‐H3 may have both positive and negative costimulatory functions.
Effect of Lactobacillus plantarum P‐8 on lipid metabolism in hyperlipidemic rat model
Authors: Bao Yan , Wang Zhanli , Zhang Yong , Zhang Jiachao , Wang Lifeng , Dong Ximei , Su Fang , Yao Guoqiang , Wang Shuiquan , Zhang Heping
Published: June 2012

Probiotics have been reported to play an important role in the prevention of metabolic disorders. We recently identified a novel probiotic strain Lactobacillus plantarum (L. plantarum) P‐8. The objective of this study was to determine the effects of L. plantarum P‐8 on lipid metabolism of rats fed with high fat diet. All experimental rats were divided into three groups: control group, model group, and L. plantarum P‐8 group. Changes in serum lipid levels, hepatic lipid deposition, serum oxidative stress‐related parameters, activities of liver function marker enzymes, organ indices, gut microflora, and fecal lipids were assessed. Compared with model group, L. plantarum P‐8 exhibited hypolipidemic effects by lowering serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol levels, accompanied with elevation of high‐density lipoprotein cholesterol level. L. plantarum P‐8 also exerted beneficial effects against high‐fat diet‐induced oxidative stress, curtailed the accumulation of liver lipids and protected healthy liver function. Moreover, L. plantarum P‐8 was able to regulate intestinal bacteria and enhance the fecal excretion of TC, TG, and bile acid. These findings indicate that L. plantarum P‐8 may represent a potential therapeutic agent for controlling hyperlipidemia.
Vegetable oil cast resins via click chemistry: Effects of cross‐linkers
Authors: Hong Jian , Shah Bipin K. , Petrović Zoran S.
Published: June 2012

Polymerization of azidated castor, canola, corn, soybean, and linseed oils with two diynes under thermal click chemistry conditions (without a solvent or a catalyst) yielded fully cross‐linked polymers (1–10) with similar density. The use of an aromatic diyne (1,4‐diethynylbenzene) as a cross‐linker resulted in polymers (1–5) that showed higher glass transition and strength and lower swelling, water absorption, and sol fraction than corresponding polymers (6–10) resulting from an aliphatic diyne (1,7‐octadiyne). These polymers exhibited behaviors ranging from soft rubbers to hard plastics.

Practical applications: Vegetable oil cast resins prepared by click chemistry are potentially useful electroinsulating materials as potting or encapsulating compounds since no by‐products are generated.
AFB1‐induced mutagenesis of the gpt gene in AS52 cells
Authors: Wattanawaraporn Roongtiwa , Kim Min Young , Adams Jillian , Trudel Laura J. , Woo Leslie L. , Croy Robert G. , Essigmann John M. , Wogan Gerald N.
Published: June 2012

Aflatoxin B1 (AFB1) is a potent mutagen and an important risk factor for hepatocellular carcinoma (HCC) in humans. Transgenic mouse strains and cells in culture have been used to detect different types of mutations caused by AFB1 and investigate the molecular determinants of their location and frequency. The AFB1 mutational spectrum in the gpt gene was markedly different in AS52 cells compared with the liver in gpt delta B6C3F1 transgenic mice. The results demonstrate the importance of metabolism, chromosomal location, transcription and selection conditions on mutational spectra. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
Optimizing the cost and performance of parabolic trough solar plants with thermal energy storage in India
Authors: Jain Amit , Vu Tuyet , Mehta Rajeev , Mittal Susheel K.
Published: June 2012

Solar energy is considered a potential source of renewable energy in India, a country blessed with abundant solar energy resources. Using system advisor model, weather data, cost estimates, and local specific assumptions, this work looks at economic and financial feasibility of a 100 MW parabolic trough concentrating solar power plant with energy storage at Jodhpur, Rajasthan, India. Base case scenario is defined as a 100 MW plant without thermal energy storage. The resulting power purchase agreement (PPA) price comes out to be 34.17 US cents/kWh, barely within acceptable range of specified feed‐in tariff indicated by the Indian Government in Jawaharlal Nehru National Solar Mission. This implies that although the system configuration in the base case may be financially feasible, it yields lower returns. Scenario analysis with varying solar multiples and thermal energy storage has been done in this study. It is concluded that the lowest PPA price of about 31.4 US cents/kWh can be achieved in a system configuration having a solar multiple of two and equipped with 3 hours of thermal energy storage. Sensitivity analysis is done to measure the impact of uncertainty of solar radiation on project economics and performance. Theuncertainty in measurement and prediction of solar radiation has a direct impact on the levelized cost of electricity and capacity factor of the 100 MW parabolic trough plant. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 824–829, 2013
Recycling technology—Artificial lightweight aggregates synthesized from sewage sludge and its ash at lowered comelting temperature
Authors: Hu Shao‐Hua , Hu Shen‐Chih , Fu Yen‐Pei
Published: June 2012

Currently, Taiwan's major source of gravel for construction purposes is its river systems; however, over exploitation could potentially deplete this source. To address this problem and reduce dependence on natural aggregate exploitation, this article investigates artificial lightweight aggregates (ALWAs) synthesized from industrial waste such as sewage sludge and sewage‐sludge‐derived ash. The ALWAs were synthesized from the sewage sludge and ash using Na2CO3. The sodium carbonate helps produce the required viscous glassy phase (needed for ALWA sintering) at a lower co‐melting temperature than would otherwise be possible. Water absorption, apparent porosity, bulk density and compressive strength of the ALWAs were tested to assess resource‐recycling feasibility. The required dosages of Na2CO3 were 16 and 22 wt % for conditioned sludge and ash, respectively. The dosed sludge sample required preheating at 400°C for 0.5 h, followed by sintering at 900°C for 5 min. The ash sample required sintering only at 900°C for 15 min. The sludge‐derived ALWAs gave the following percentages 2.84%, 3.31%, 1.20 g/cm3, and 13.0 MPa for water absorption, apparent porosity, bulk density, and compressive strength, respectively. The corresponding values for ash‐derived ALWAs were: 4.85%, 6.55%, 1.41 g/cm3, and 87.3 MPa, respectively. The characteristics of ALWAs derived in this study were then compared to those of commercially available lightweight aggregates—Lytag and Arlita F7. The characteristics mentioned above of the former were superior than those of the latter except that the value ofdensity was an interval value between Lytag and Arlita. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 740–748, 2013
Decomposition of benzene as a surrogate tar in a gliding Arc plasma
Authors: Chun Young Nam , Kim Seong Cheon , Yoshikawa Kunio
Published: June 2012

The pyrolysis and gasification technology uses diverse waste resources, including biomass, urban solid waste, and sewage sludge, to produce synthetic gases for industrial use. The tar in the thermal decomposition gas from the pyrolysis and/or gasification process, however, damages synthetic gas facilities and causes operation trouble. In this study, a gliding‐arc plasma reformer for tar decomposition was developed to address the aforementioned problem. In addition, experiments were performed on the variables that affect the tar removal efficiency, and the optimal operation condition was presented. The experimental variables included the steam flow rate, input benzene concentration, total gas feed rate, specific energy input (SEI), gas nozzle diameter, electrode length, electrode gap, and electrode shape. With the increase in the total gas feed rate, the benzene decomposition efficiency slightly decreased, and with the increase in the SEI, the energy efficiency increased. In the stable plasma discharge condition, a smaller nozzle diameter, a longer electrode gap, and a longer electrode length led to better decomposition and energy efficiencies. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 837–845, 2013
Removal of zinc ions from wastewater using industrial waste sludge: A novel approach
Authors: Mishra Umesh , Paul Supantha , Bandyopadhaya Manas
Published: June 2012

This article presents sorption of zinc by a novel adsorbent derived from steel plant waste sludge. The batch experiments were carried out to investigate the influence of process parameters such as pH, contact time, adsorbent dose, and the initial metal ion concentration. The equilibrium and kinetic study were performed to investigate the adsorption potential of the waste sludge. The maximum adsorption of 7.26 mg/g of Zn(II) on waste sludge was obtained at an initial pH value of 5.0. Particle size range of 75–150 μm yielded the best adsorption capacity for Zn(II). The pseudo‐second‐order rate equation fitted the adsorption kinetic data better than pseudo‐first‐order rate equation. The rate constants and coefficient of determination were determined for the waste sludge. The equilibrium data for the adsorption of Zn(II) on waste sludge was tested with various adsorption isotherm models viz. Langmuir, Freundlich, Redlich–Peterson, and Tempkin. The Langmuir isotherm model was found to be the most suitable one followed by nonlinear Redlich–Peterson isotherm model. The characteristic of the prepared waste sludge was found comparable to the other technically as well as economically feasible and environmentally benign activated carbon. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 576–586, 2013
Simultaneous adsorption and bioaccumulation: A study on continuous mass transfer in column reactor
Authors: Mishra Vishal , Balomajumder Chandrajit , Agarwal Vijay Kumar
Published: June 2012

Zinc sequestering bacteria VMSDCM accession number HQ108109, was immobilized on particles of Cedrus deodar sawdust in continuous column reactor. The bacterium seemed to cluster up with arsenite oxidizing bacteria when plotted in a maximum likelihood tree. The rough texture of the immobilized bacterium indicated the presence of tremendous area on the cell surface. The uptake capacities obtained at saturation and break points for a flow rate of 109 mL/h were 21.33 (g/g) and 19.53 (g/g) at 33.90 g/L of zinc. The uptake capacities at saturation and break points were 58.30 (g/g), and 54.33 (g/g) at an initial concentration of 70.20 g/L of zinc, respectively. The insignificant values of error functions (SSE and χ2) indicated the collateral relationship between experimental and theoretical values of uptake capacities. The physical process parameters like bed height, flow rate, and initial metal ion concentration have shown significant impact on forced convective mass transfer of metal ions in packed bed column studies. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 605–614, 2013
Adsorption behavior of methylene blue dye onto surface modified Strychnos potatorum seeds
Authors: Senthamarai C. , Kumar P. Senthil , Priyadharshini M. , Vijayalakshmi P. , Kumar V. Vinoth , Baskaralingam P. , Thiruvengadaravi K.V. , Sivanesan S.
Published: June 2012

Kinetic, mechanism, equilibrium, and thermodynamic behavior of adsorption of methylene blue (MB) dye onto surface modified Strychnos potatorum seeds (SMSP), in an aqueous solution were studied. Batch adsorption experiments were carried out to analyze the effect of initial solution pH, adsorbent dose, contact time, initial MB dye concentration, and temperature on the removal of MB dye. The kinetics of MB dye adsorption onto SMSP follows a pseudo‐second order kinetic model. The adsorption of MB dye onto SMSP was found to be controlled by both surface diffusion and pore diffusion. The diffusivity values were calculated from Boyd kinetic and Shrinking Core Model for varying initial MB dye concentration from 50 to 250 mg L−1. The adsorption equilibrium data were fitted to different adsorption isotherm models such as Langmuir, Freundlich, and Dubinin‐Radushkevich. The equilibrium data fitted best with the Freundlich adsorption isotherm model, which indicates multilayer adsorption of MB dye onto SMSP. The maximum monolayer adsorption capacity estimated with Langmuir isotherm model was 78.84 mg of MB dye molecules per gram of SMSP. Thermodynamic studies showed that the adsorption of MB dye onto SMSP follows an exothermic process. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 624–632, 2013
The seismic demand hazard and importance of the conditioning intensity measure
Authors: Bradley Brendon A.
Published: June 2012

The seismic demand hazard, which gives the rate/probability of exceeding a specified level of seismic demand/response in a given exposure period, is a key measure used to quantify the seismic performance of structures. Because of its simplicity in implementation, the intensity measure (IM)‐based approach is the most common method for computation of the seismic demand hazard. One observed detrimental consequence of the IM‐based approach is that the practical computation of the seismic demand hazard appears to be dependent on the IM used in its computation. This manuscript demonstrates theoretically that the seismic demand hazard for a particular structure at a specific location is unique irrespective of the conditioning IM used in its computation. More importantly, it is demonstrated that this theoretical result can be consistently obtained in a practical context via a six‐step process based around the selection of ground motion records using the generalised conditional intensity measure (GCIM) approach. Copyright © 2012 John Wiley & Sons, Ltd.
Stochastic subspace identification for output‐only modal analysis: application to super high‐rise tower under abnormal loading condition
Authors: Liu Yi‐Cheng , Loh Chin‐Hsiung , Ni Yi‐Qing
Published: June 2012

The objective of this paper is to develop an online system parameter estimation technique from the response measurements through using the recursive covariance‐driven stochastic subspace identification (SSI‐COV) approach. In developing the recursive SSI‐COV, to avoid time‐consumption of singular value decomposition in recursive SSI, the extended instrumental variable version of the projection approximation subspace tracking method is used in SSI‐COV. Besides, to reduce the effect of noise on the results of identification, the preprocessing of data using recursive singular spectrum analysis technique is also presented to remove the noise contaminant measurements to enhance the stability of data analysis. On the basis of the proposed method, both the ambient vibration and seismic response data of a tower (Canton Tower) are used to observe the time‐varying system natural frequencies of a tower from its operating condition. Results from using off‐line SSI‐COV method under normal operating condition are also presented. Comparison on the identified time‐varying dynamic characteristics of the tower under normal operating condition and earthquake response of distanced earthquake event is discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Exclusion of the 750‐kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1‐linked families
Authors: Kouprina Natalay , Lee Nicholas C. O. , Pavlicek Adam , Samoshkin Alexander , Kim Jung‐Hyun , Lee Hee‐Sheung , Varma Sudhir , Reinhold William C. , Otstot John , Solomon Greg , Davis Sean , Meltzer Paul S. , Schleutker Johanna , Larionov Vladimir
Published: June 2012

Several linkage studies provided evidence for the presence of the hereditary prostate cancer locus, HPCX1, at Xq27‐q28. The strongest linkage peak of prostate cancer overlies a variable region of ∼750 kb at Xq27 enriched by segmental duplications (SDs), suggesting that the predisposition to prostate cancer may be a genomic disorder caused by recombinational interaction between SDs. The large size of SDs and their sequence similarity make it difficult to examine this region for possible rearrangements using standard methods. To overcome this problem, direct isolation of a set of genomic segments by in vivo recombination in yeast (a TAR cloning technique) was used to perform a mutational analysis of the 750 kb region in X‐linked families. We did not detect disease‐specific rearrangements within this region. In addition, transcriptome and computational analyses were performed to search for nonannotated genes within the Xq27 region, which may be associated with genetic predisposition to prostate cancer. Two candidate genes were identified, one of which is a novel gene termed SPANXL that represents a highly diverged member of the SPANX gene family, and the previously described CDR1 gene that is expressed at a high level in both normal and malignant prostate cells, and mapped 210 kb of upstream the SPANX gene cluster. No disease‐specific alterations were identified in these genes. Our results exclude the 750‐kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy. Adjacent regions appear to be the most likely candidates to identify the elusive HPCX1 locus. © 2012 Wiley Periodicals, Inc.
Comprehensive DNA methylation analysis of benign and malignant adrenocortical tumors
Authors: Fonseca Annabelle L. , Kugelberg Johan , Starker Lee F. , Scholl Ute , Choi Murim , Hellman Per , Åkerström Göran , Westin Gunnar , Lifton Richard P. , Björklund Peyman , Carling Tobias
Published: June 2012

The molecular pathogenesis of benign and malignant adrenocortical tumors (ACT) is incompletely clarified. The role of DNA methylation in adrenocortical tumorigenesis has not been analyzed in an unbiased, systematic fashion. Using the Infinium HumanMethylation27 BeadChip, the DNA methylation levels of 27,578 CpG sites were investigated in bisulfite‐modified DNA from 6 normal adrenocortical tissue samples, 27 adrenocortical adenomas (ACA), and 15 adrenocortical carcinomas (ACC). Genes involved in cell cycle regulation, apoptosis, and transcriptional regulation of known or putative importance in the development of adrenal tumors showed significant and frequent hypermethylation. Such genes included CDKN2A, GATA4, BCL2, DLEC1, HDAC10, PYCARD, and SCGB3A1/HIN1. Comparing benign versus malignant ACT, a total of 212 CpG islands were identified as significantly hypermethylated in ACC. Gene expression studies of selected hypermethylated genes (CDKN2A, GATA4, DLEC1, HDAC10, PYCARD, SCGB3A1/HIN1) in 6 normal and 16 neoplastic adrenocortical tissues (10 ACA and 6 ACC), displayed reduced gene expression in benign and malignant ACT versus normal adrenocortical tissue. Treatment with 5‐aza‐2′‐deoxycytidine of adrenocortical cancer H‐295R cells increased expression of the hypermethylated genes CDKN2A, GATA4, DLEC1, HDAC10, PYCARD, and SCGB3A1/HIN1. In conclusion, the current study represents the first unbiased, quantitative, genome‐wide study of adrenocortical tumor DNA methylation. Genes with altered DNA methylation patterns were identified of putative importance to benign and malignant adrenocortical tumor development. © 2012 Wiley Periodicals, Inc.
Functional network connectivity during rest and task conditions: A comparative study
Authors: Arbabshirani Mohammad R. , Havlicek Martin , Kiehl Kent A. , Pearlson Godfrey D. , Calhoun Vince D.
Published: June 2012

Functional connectivity (FC) examines temporal statistical dependencies among distant brain regions by means of seed‐based analysis or independent component analysis (ICA). Spatial ICA also makes it possible to investigate FC at the network level, termed functional network connectivity (FNC). The dynamics of each network (ICA component), which may consist of several remote regions is described by the ICA time‐course of that network; hence, FNC studies statistical dependencies among ICA time‐courses. In this article, we compare comprehensively FNC in the resting state and during performance of an auditory oddball (AOD) task in 28 healthy subjects on relevant (nonartifactual) brain networks. The results show global FNC decrease during the performance of the task. In addition, we show that specific networks enlarge and/or demonstrate higher activity during the performance of the task. The results suggest that performing an active task like AOD may be facilitated by recruiting more neurons and higher activation of related networks rather than collaboration among different brain networks. We also evaluated the impact of temporal filtering on FNC analyses. Results showed that the results are not significantly affected by filtering. Hum Brain Mapp 34:2959–2971, 2013. © 2012 Wiley Periodicals, Inc.
The 5‐HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans
Authors: Haahr Mette Ewers , Fisher Patrick , Holst Klaus , Madsen Karine , Jensen Christian Gaden , Marner Lisbeth , Lehel Szabols , Baaré William , Knudsen Gitte , Hasselbalch Steen
Published: June 2012

The cerebral serotonin (5‐HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5‐HT type 4 receptor (5‐HT4R) facilitates memory and learning and further that the 5‐HT4R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5‐HT4R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [11C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5‐HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BPND, (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BPND and delayed recall (p = 0.014). These findings provide evidence that the 5‐HT4R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory. Hum Brain Mapp 34:3066–3074, 2013. © 2012 Wiley Periodicals, Inc.
Theta‐related gating cells in hippocampal formation: In vivo and in vitro study
Authors: Kowalczyk Tomasz , Konopacki Jan , Bocian Renata , Caban Bartosz
Published: June 2012

In this study we extended our earlier in vitro findings concerning the discovery of a novel type of theta‐related cells, which we have termed gating cells. There were two main objectives of our present investigations. The first was to determine the distribution of theta gating cells in the separated CA1 and CA3 generators in three different pharmacological conditions: (i) the presence of a cholinergic agonist—carbachol, (ii) the presence of carbachol and GABAAergic antagonist—bicuculline, (iii) the presence of carbachol and GABABergic antagonist—2‐hydroxysaclofen. The second objective of our studies was to verify our earlier in vitro findings and to demonstrate, for the first time, gating cells in intact hippocampus during the generation of Type II theta in urethane anaesthetized rats. Two hundred ninety‐nine theta‐related cells were isolated and recorded from in vivo and in vitro hippocampal formation. Twenty out of all 299 neurons (6.6%) were classified as gating cells. The neuron was classified as a gating cell if it met one of the following criteria: (i) the cell discharges occurred precisely in the beginning and at the end of each theta epoch (gating cell A); (ii) the cell began to discharge just before the transition from non‐theta interval/LIA into the theta epoch (gating cell B); (iii) the cell began to discharge just after the transition from the theta epoch into non‐theta interval/LIA (gating cell C). Our data demonstrates that the appearance of theta epochs and their length, as well as the appearance of non‐theta states (in vivo recorded LIA or in vitro recorded intervals between theta epochs) and their length, may require the existence of a specific population of hippocampal neurons which we termed gating cells. © 2012 Wiley Periodicals, Inc.
The project organization as a policy tool in implementing welfare reforms in the public sector
Authors: Jensen Christian , Johansson Staffan , Löfström Mikael
Published: June 2012

Organizational design is considered in policy literature as a forceful policy tool to put policy to action. However, previous research has not analyzed the project organization as a specific form of organizational design and, hence, has not given much attention to such organizations as a strategic choice when selecting policy tools. The purpose of the article is to investigate the project as a policy tool; how do such temporary organizations function as a specific form of organization when public policy is implemented? The article is based on a framework of policy implementation and is illustrated with two welfare reforms in the Swedish public sector, which were organized and implemented as project organizations. The case studies and the analysis show that it is crucial that a project organization fits into the overall governance structure when used as a policy tool. If not, the project will remain encapsulated and will not have sufficient impact on the permanent organizational structure. The concept of encapsulation indicates a need to protect the project from a potential hostile environment. The implication of this is that organizational design as a policy tool is a matter that deserves more attention in the strategic discussion on implementing public policies and on the suitability of using certain policy tools. Copyright © 2012 John Wiley & Sons, Ltd.
Valued ecosystem components for watershed cumulative effects: An analysis of environmental impact assessments in the South Saskatchewan River watershed, Canada
Authors: Ball Murray A , Noble Bram F , Dubé Monique G
Published: June 2012

The accumulating effects of human development are threatening water quality and availability. In recognition of the constraints to cumulative effects assessment (CEA) under traditional environmental impact assessment (EIA), there is an emerging body of research dedicated to watershed-based cumulative effects assessment (WCEA). To advance the science of WCEA, however, a standard set of ecosystem components and indicators is required that can be used at the watershed scale, to inform effects-based understanding of cumulative change, and at the project scale, to inform regulatory-based project based impact assessment and mitigation. A major challenge, however, is that it is not clear how such ecosystem components and indicators for WCEA can or should be developed. This study examined the use of aquatic ecosystem components and indicators in EIA practice in the South Saskatchewan River watershed, Canada, to determine whether current practice at the project scale could be “scaled up” to support ecosystem component and indicator development for WCEA. The hierarchy of assessment components and indicators used in a sample of 35 environmental impact assessments was examined and the factors affecting aquatic ecosystem component selection and indicator use were identified. Results showed that public environmental impact statements are not necessarily publically accessible, thus limiting opportunities for data and information sharing from the project to the watershed scale. We also found no consistent terminology across the sample of impact statements, thus making comparison of assessment processes and results difficult. Regulatory compliance was found to be the dominant factor influencing the selection of ecosystem components and indicators for use in project assessment, rather than scientific reasoning, followed by the mandate of the responsible government agency for the assessment, public input to the assessment process, and preexisting water licensing arrangements external to the assessment process. The current approach to project-based assessment offered little support for WCEA initiatives. It did not provide a standard set of aquatic ecosystem components and indicators or allow the sharing of information across projects and from the project to the watershed scale. We suggest that determining priority assessment parameters for WCEA requires adoption of a standardized framework of component and indicator terminology, which can then be populated for the watershed of concern based on both watershed-based priorities and project-specific regulatory requirements. Integr Environ Assess Manag 2013;9:469–479. © 2012 SETAC
Intratracheal and oral administration of SM‐276001: A selective TLR7 agonist, leads to antitumor efficacy in primary and metastatic models of cancer
Authors: Koga‐Yamakawa Erina , Dovedi Simon J. , Murata Masashi , Matsui Hiroyuki , Leishman Andrew J. , Bell John , Ferguson Douglas , Heaton Simon P. , Oki Toshihiro , Tomizawa Hideyuki , Bahl Ash , Takaku Haruo , Wilkinson Robert W. , Harada Hideyuki
Published: June 2012

Topical TLR7 agonists such as imiquimod are highly effective for the treatment of dermatological malignancies; however, their efficacy in the treatment of nondermatological tumors has been less successful. We report that oral administration of the novel TLR7‐selective small molecule agonist; SM‐276001, leads to the induction of an inflammatory cytokine and chemokine milieu and to the activation of a diverse population of immune effector cells including T and B lymphocytes, NK and NKT cells. Oral administration of SM‐276001 leads to the induction of IFNα, TNFα and IL‐12p40 and a reduction in tumor burden in the Balb/c syngeneic Renca and CT26 models. Using the OV2944‐HM‐1 model of ovarian cancer which spontaneously metastasizes to the lungs following subcutaneous implantation, we evaluated the efficacy of intratracheal and oral administration of SM‐276001 in an adjuvant setting following surgical resection of the primary tumor. We show that both oral and intratracheal TLR7 therapy can reduce the frequency of pulmonary metastasis, and metastasis to the axillary lymph nodes. These results demonstrate that SM‐276001 is a potent selective TLR7 agonist that can induce antitumor immune responses when dosed either intratracheally or orally.
Identification of novel functional and spatial associations between sphingosine kinase 1, sphingosine 1‐phosphate receptors and other signaling proteins that affect prognostic outcome in estrogen receptor‐positive breast cancer
Authors: Ohotski Jan , Edwards Joanne , Elsberger Beatrix , Watson Carol , Orange Clare , Mallon Elizabeth , Pyne Susan , Pyne Nigel J.
Published: June 2012

Sphingosine kinase is an enzyme that catalyses the phosphorylation of sphingosine to form sphingosine 1‐phosphate. Sphingosine 1‐phosphate is a bioactive lipid, which has been shown to have an important role in promoting the survival, growth and invasiveness of cancer cells. Sphingosine 1‐phosphate binds to five different plasma membrane sphingosine 1‐phosphate receptors (S1P1–5) and can regulate intracellular target proteins. We have used immunohistochemical analysis to determine the concurrent expression levels of sphingosine kinase 1 or S1P receptors and other signaling proteins in estrogen receptor‐positive breast cancer tumors and have then assessed the impact of these combinations on clinical outcome. This approach has enabled identification of (i) novel biomarkers and (ii) several spatially controlled associations between either sphingosine kinase 1 or S1P1–3 and other signaling proteins whose combination affect prognosis. For instance, the translocation of sphingosine kinase 1 to the plasma membrane has been shown to be a critical determinant in cancer progression. However, our findings identify an additional novel role for the nuclear localization of sphingosine kinase 1 combined with either ERK‐1/2 or SFK or LYN or AKT or NF‐κB, which significantly shortens disease‐specific survival and/or recurrence. We also demonstrate that nuclear S1P2 receptor and c‐SRC are associated with improved prognosis and this is linked with a reduction in the nuclear localization of sphingosine kinase 1. These findings identify potential novel biomarker associations, which might serve as new targets for drug intervention designed to improve treatment of estrogen receptor‐positive breast cancer.
The Rec protein of HERV‐K(HML‐2) upregulates androgen receptor activity by binding to the human small glutamine‐rich tetratricopeptide repeat protein (hSGT)
Authors: Hanke Kirsten , Chudak Claudia , Kurth Reinhard , Bannert Norbert
Published: June 2012

The expression of endogenous retroviruses of the HERV‐K(HML‐2) family is strongly upregulated in germ cell tumors and several other cancers. Although the accessory Rec protein of HERV‐K(HML‐2) has been shown to induce carcinoma in situ in transgenic mice, to increase the activity of c‐myc and to interact with the androgen receptor (AR), whether or not Rec expression is indeed implicated causally in the initiation or progression of any human malignancies remains unclear. We used the yeast two‐hybrid system involving the Rec protein of a recently integrated HERV‐K(HML‐2) element in an effort to identify potential Rec‐related oncogenic mechanisms. This revealed the human small glutamine‐rich tetratricopeptide repeat (TPR)‐containing protein (hSGT) to be a cellular binding partner. The interaction of Rec with this known negative regulator of the AR was confirmed by coimmunoprecipitation, pull‐down assays and colocalization studies. The interaction involves the TPR motif of hSGT and takes place in the cytoplasm and in the nucleoli. Using an AR‐responsive promoter and gene we could demonstrate that Rec interference with hSGT resulted in an up to five‐fold increase in the activity of AR. Furthermore, in AR positive cells, Rec was shown to act as transactivator by enhancing AR‐mediated activation of the HERV‐K(HML‐2) LTR promoter. This is in line with previous observations of elevated HERV‐K(HML‐2) expression in steroid‐regulated tissues. On the basis of our findings we propose a “vicious cycle” model of Rec‐driven hyperactivation of the AR leading to increased cell proliferation, inhibition of apoptosis and eventually to tumor induction or promotion.