bluuebunny/crossref_metadata_2025 huggingface dataset:
A Historic Breakthrough on the Crime of Aggression
Authors: Barriga Stefan , Grover Leena
Published: August 2011

At 12:20 in the morning on Saturday, June 12, 2010, the Review Conference of the Rome Statute of the International Criminal Court in Kampala, Uganda, adopted by consensus a comprehensive package of amendments on the crime of aggression. States parties to the Rome Statute thereby delivered on their promise, reflected in Article 5 (2) of the Statute, to define the crime of aggression and to agree on the conditions for the Court’s exercise of jurisdiction over that crime. Despite a thorough and more than decadelong preparatory process, few, if any, had predicted such a substantive outcome on the crime of aggression in light of the serious disagreements on major questions, which persisted until the last days of the conference. The key elements of the final package are a definition of the crime of aggression, which limits criminal responsibility to leaders who are responsible for the most serious forms of the illegal use of force between states, and a complicated set of conditions for exercising jurisdiction. Investigations would be based on either a Security Council referral or state consent.
High Salt Intake and Risk of Chronic Bronchitis: The Copenhagen Male Study—A 10-Year Followup
Authors: Suadicani Poul , Hein Hans Ole , Gyntelberg Finn
Published: August 2011

Objective. The role of salt intake as a risk factor for asthma, bronchial hyperresponsiveness, and other bronchial symptoms has been addressed in a number of studies. Collectively, these studies indicate an increased risk of bronchial symptoms with high consumption of salt, but the issue remains controversial. We tested prospectively the hypothesis that salt intake would be an independent risk factor for chronic bronchitis (CB). Design. A 10-year prospective study of 2,183 men aged 46 to 65 years without any relevant lung symptoms at baseline. Main Outcome. Chronic bronchitis. Results. During the 10-year followup, the overall incidence of CB was 7.1% among men without any relevant lung symptoms at baseline. In a multiple logistic regression analysis, controlling for age, smoking habits, occupational dust exposure, alcohol use, and social class, the odds ratio associated with self-assessed high salt preference (reported by 24%) was 1.6 (1.1–2.4). Interpretation. The results suggest that salt restriction may prevent chronic bronchitis.
Propagation of Plane Waves in a Thermally Conducting Mixture
Authors: Singh Baljeet
Published: August 2011

The governing equations for generalized thermoelasticity of a mixture of an elastic solid and a Newtonian fluid are formulated in the context of Lord-Shulman and Green-Lindsay theories of generalized thermoelasticity. These equations are solved to show the existence of three coupled longitudinal waves and two coupled transverse waves, which are dispersive in nature. Reflection from a thermally insulated stress-free surface is considered for incidence of coupled longitudinal wave. The speeds and reflection coefficients of plane waves are computed numerically for a particular model.
Predictors of Nonsentinel Nodal Involvement to Aid Intraoperative Decision Making in Breast Cancer Patients with Positive Sentinel Lymph Nodes
Authors: Tan Ern Yu , Ho Bernard , Chen Juliana J. C. , Ho Pey Woei , Teo Christine , Earnest Arul , Chan Patrick M. Y.
Published: August 2011

Background. Up to 60% of patients with a positive sentinel lymph node (SLN) have no additional nodal involvement and do not benefit from completion axillary lymph node dissection (ALND). We aim to identify factors predicting for non-SLN involvement and to validate the MSKCC nomogram and Tenon score in our population.Methods. Retrospective review was performed of 110 consecutive patients with positive SLNs who underwent ALND over an 8-year period.Results. Fifty patients (45%) had non-SLN involvement. Non-SLN involvement correlated positively with the number of positive SLNs (P=0.04), macrometastasis (P=0.01), and inversely with the total number of SLNs harvested (P=0.03). The MSKCC nomogram and Tenon score both failed to perform as previously reported.Conclusions. The MSKCC nomogram and Tenon score have limited value in our practice. Instead, we identified three independent predictors, which are more relevant in guiding the intraoperative decision for ALND.
Clinical and molecular characterization of chromosome 7p22.1 microduplication detected by array CGH
Authors: Chui Jacqueline V. , Weisfeld‐Adams James D. , Tepperberg James , Mehta Lakshmi
Published: August 2011

A 28‐month‐old Peruvian male presented with speech delay and unusual facial features including prominent forehead, anteverted nares, ocular hypertelorism, and low‐set and posteriorly rotated ears with a unilateral preauricular pit. The patient had poor speech with no other developmental delays. Height and weight were normal, although closure of the anterior fontanel and bone age were delayed. Head circumference approximated the 95th centile for age. Following normal routine chromosome analysis and subtelomeric FISH, whole genome microarray revealed a novel interstitial duplication at 7p22.1, approximately 1.7 Mb in size, and containing 13 OMIM annotated genes. FISH studies on the propositus and his parents confirmed that the duplication had occurred de novo. This finding represents the smallest interstitial 7p duplication reported to date, and does not include genes previously implicated as candidates for a 7p duplication syndrome. Common phenotypic features of 7p duplication include distinctive facies with hypertelorism, large anterior fontanel, and intellectual disability. Based on the findings in our patient, and those in previously reported cases of 7p duplication, we propose that genes within this duplicated interval may have a role in skeletal maturation, craniofacial development, and speech acquisition. © 2011 Wiley‐Liss, Inc.
A comparative study of the stress‐relaxation behavior of untreated and alkali‐treated jute fibers
Authors: Ray Dipa , Das Mahuya , Mitra Debarati
Published: August 2011

In this study, we examined the effect of alkali treatment and its variables, namely, the time (2, 4, 6, or 8 h) and the concentration of alkali (1, 5, or 17.5% w/w), on the linear density, strength, and stress‐relaxation properties of jute fiber. It was demonstrated that this kind of treatment led to the creation of several voids and fiber fibrillation. Properties were measured for the alkali‐treated and dewaxed fibers. The linear density and tenacity of the fibers were reduced at higher alkali concentration and at longer dipping times. The strength increased with treatment with mild alkali and decreased with treatment with the strong alkali. A very low alkali treatment (1%) rendered low relaxation. At a 5% alkali concentration, interfibrillar matrix softening also played an important role and was prominent in the stress‐relaxation behavior. The stress‐relaxation value was much higher in the fibers treated with 17.5% NaOH compared to the dewaxed fibers; this was probably due to a loss in the fibrillar arrangement. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Magnetic Silyl Scaffold Enables Efficient Recycling of Protecting Groups
Authors: Schaetz Alexander , Zeltner Martin , Michl Thomas D. , Rossier Michael , Fuhrer Roland , Stark Wendelin J.
Published: August 2011

A novel organic/inorganic hybrid material comprising carbon‐coated cobalt nanoparticles and a poly(benzylchloride)styrene shell is the first magnetic support that complies with important requirements for immobilized reagents and scavengers, that is, stability under harsh conditions (e.g., acids), sufficient loading (up to 2 mmol g−1), and satisfying magnetization. The durability of the scaffold was demonstrated by immobilization of a trialkylsilane reagent, which served as a “magnetic” protecting group for a number of primary and secondary alcohols. Importantly, the scaffold could be efficiently separated, recycled, and reused after alcohol cleavage (HF⋅pyridine) via regeneration of the silyl chloride moiety with BCl3.
Non‐Woven Fibrous Materials with Antibacterial Properties Prepared by Tailored Attachment of Quaternized Chitosan to Electrospun Mats from Maleic Anhydride Copolymer
Authors: Ignatova Milena , Petkova Zhanina , Manolova Nevena , Markova Nadya , Rashkov Iliya
Published: August 2011

In order to impart antibacterial properties to microfibrous electrospun materials from styrene/maleic anhydride copolymers, quaternized chitosan derivatives (QCh) containing alkyl substituents of different chain lengths are covalently attached to the mats. A complete inhibition of the growth of bacteria, S. aureus (Gram‐positive) and E. coli (Gram‐negative), for a contact time of 30–120 min or a decrease of the bacterial titer by 2–3 log units is observed depending on the quaternization degree, the chain length of the alkyl substituent, and the molar mass of QCh. The modified mats are also effective in suppressing the adhesion of pathogenic S. aureus bacteria.

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MR‐compatible treadmill for exercise stress cardiac magnetic resonance imaging
Authors: Foster Eric L. , Arnold John W. , Jekic Mihaela , Bender Jacob A. , Balasubramanian Vijay , Thavendiranathan Paaladinesh , Dickerson Jennifer A. , Raman Subha V. , Simonetti Orlando P.
Published: August 2011

This article describes an MR‐safe treadmill that enables cardiovascular exercise stress testing adjacent to the MRI system, facilitating cardiac MR imaging immediately following exercise stress. The treadmill was constructed of nonferromagnetic components utilizing a hydraulic power system. Computer control ensured precise execution of the standard Bruce treadmill protocol commonly used for cardiovascular exercise stress testing. The treadmill demonstrated no evidence of ferromagnetic attraction and did not affect image quality. Treadmill performance met design specifications both inside and outside the MRI environment. Ten healthy volunteers performed the Bruce protocol with the treadmill positioned adjacent to the MRI table. Upon reaching peak stress (98 ± 8% of age‐predicted maximum heart rate), the subjects lay down directly on the MRI table, a cardiac array coil was placed, an intravenous line connected, and stress cine and perfusion imaging performed. Cine imaging commenced on average within 24 ± 4 s and was completed within 40 ± 7 s of the end of exercise. Subject heart rates were 86 ± 9% of age‐predicted maximum heart rate at the start of imaging and 81 ± 9% of age‐predicted maximum heart rate upon completion of cine imaging. The MRI‐compatible treadmill was shown to operate safely and effectively in the MRI environment. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Factors controlling T2 mapping from partially spoiled SSFP sequence: Optimization for skeletal muscle characterization
Authors: de Sousa Paulo Loureiro , Vignaud Alexandre , Caldas de Almeida Araújo Ericky , Carlier Pierre G.
Published: August 2011

A fast and robust methodology for in vivo T2 mapping is presented. The approach is based on the partially spoiled steady state free precession technique recently proposed by Bieri et al. (Magn Reson Med 2011). The accuracy of this method was demonstrated in simulations and phantom experiments. Variations in skeletal muscle T2 relaxation time have been correlated with cell damage and inflammatory response. Nonetheless, the lack of easily implementable, fast, accurate and reproducible methods has hampered the adoption of T2 measurement as a noninvasive tool for skeletal muscle characterization. The applicability of the partially spoiled steady state free precession method for tissue characterization in muscle disease is illustrated in this work by several examples. Quantitative MRI, in particular T2 mapping based on partially spoiled steady state free precession acquisitions, might provide objective markers of muscle damage and degenerative changes, and an alternative to serial muscle biopsies. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
A Sequential Bayesian Cumulative Conformance Count Approach to Deterioration Detection in High Yield Processes
Authors: Toubia‐Stucky Gracia , Liao Haitao , Twomey Janet
Published: August 2011

Cumulative conformance count (CCC) control chart is a powerful alternative to the traditional p‐control chart, particularly in monitoring high yield processes with extremely low proportions of nonconformance. However, a prevalent limitation of the CCC control chart is its inability to detect small process deterioration. A sequential Bayesian CCC approach capable of detecting small process deterioration is proposed in this paper. The new approach outperforms the traditional CCC chart in that it does not require a large sample of initial observations of the process, which may be difficult, if not impossible to obtain in practice. Moreover, the approach is self‐starting, and thus may be used in short production runs. A Bayesian updating procedure is developed, which allows for the determination of initial control limits based on only three initial observations or some prior knowledge about the proportion of nonconformance of the process. Values of proportions of nonconformance, ranging from 0.1 to 0.00001, are tested to demonstrate the deterioration detection capability of the new approach in conjunction with the proposed deterioration detection rules. Copyright © 2011 John Wiley & Sons, Ltd.
STABLE ISOTOPE ANALYSIS REVEALS ANTHROPOGENIC EFFECTS ON FISH ASSEMBLAGES IN A TEMPERATE RESERVOIR
Authors: Freedman J. A. , Curry R. A. , Munkittrick K. R.
Published: August 2011

Effluent from anthropogenic inputs can affect fish assemblages in aquatic ecosystems by altering species richness, diversity and trophic structure. To investigate the effects of a bleached kraft pulp mill effluent (PME) and municipal sewage treatment plant (STP) discharge on fish assemblages in a temperate reservoir, we combined standard ecological methodologies with stable isotope analysis of δ13C and δ15N. Total catch, species richness, diversity and coefficient of community loss indicated lower species richness and diversity at sites exposed to PME, whereas sewage‐exposed assemblages had intermediate richness and diversity relative to reference sites. Stable isotope analysis of δ13C and δ15N revealed that many species fed at higher relative trophic positions in the presence of both effluents and showed shifts towards increased reliance on littoral‐derived and benthic‐derived carbon at sites downstream of the PME discharge. Fishes at PME‐influenced sites had also generally higher condition factor whereas fishes at STP‐influenced sites were more variable in condition factor. These differences may, in part, be due to decreased species diversity at these sites and to nutrient enrichment manifest from the effluent discharge. While standard fisheries and ecological methodologies and stable isotope analysis have been separately used in other studies of anthropogenic effects on fishes, their integration in this study provides greater resolution than either could alone. Copyright © 2011 John Wiley & Sons, Ltd.
A facile method for fabrication of superhydrophobic coating on aluminum alloy
Authors: Yin B. , Fang L. , Hu J. , Tang A. Q. , He J. , Mao J. H.
Published: August 2011

A superhydrophobic coating applied in corrosion protection was successfully fabricated on the surface of aluminum alloy by chemical etching and surface modification. The water contact angle on the surface was measured to be 161.2° ± 1.7° with sliding angle smaller than 8°, and the superhydrophobic coating showed a long service life. The surface structure and composition were then characterized by means of SEM and XPS. The electrochemical measurements showed that the superhydrophobic coating significantly improved the corrosion resistance of aluminum alloy. The superhydrophobic phenomenon of the prepared surface was analyzed with Cassie theory, and it was found that only about 6% of the water surface is in contact with the metal substrate and 94% is in contact with the air cushion. Copyright © 2011 John Wiley & Sons, Ltd.
Significant inverse associations of serumn-6 fatty acids with plasma plasminogen activator inhibitor-1
Authors: Lee Sunghee , Curb J. David , Kadowaki Takashi , Evans Rhobert W. , Miura Katsuyuki , Takamiya Tomoko , Shin Chol , El-Saed Aiman , Choo Jina , Fujiyoshi Akira , Otake Teruo , Kadowaki Sayaka , Seto Todd , Masaki Kamal , Edmundowicz Daniel , Ueshima Hirotsugu , Kuller Lewis H. , Sekikawa Akira
Published: August 2011

Epidemiological studies suggested thatn-6 fatty acids, especially linoleic acid (LA), have beneficial effects on CHD, whereas somein vitrostudies have suggested thatn-6 fatty acids, specifically arachidonic acid (AA), may have harmful effects. We examined the association of serumn-6 fatty acids with plasminogen activator inhibitor-1 (PAI-1). A population-based cross-sectional study recruited 926 randomly selected men aged 40–49 years without CVD during 2002–2006 (310 Caucasian, 313 Japanese and 303 Japanese-American men). Plasma PAI-1 was analysed in free form, both active and latent. Serum fatty acids were measured with gas-capillary liquid chromatography. To examine the association between totaln-6 fatty acids (including LA and AA) and PAI-1, multivariate regression models were used. After adjusting for confounders, totaln-6 fatty acids, LA and AA, were inversely and significantly associated with PAI-1 levels. These associations were consistent across three populations. Among 915 middle-aged men, serumn-6 fatty acids had significant inverse associations with PAI-1.
Health Ideologies, Objectivism, and the Common Good: On the Rights of Dissidents
Authors: STRAND ROGER
Published: August 2011

With the development of large-scale health registries and human biobanks to be used as research infrastructures, bioethicists, lawyers, philosophers, and social scientists have worked intensely to cast light on current challenges to the principle of informed consent.
Ferroic investigations in LuFe2O4 multiferroic ceramics
Authors: Viana D. S. F. , Gotardo R. A. M. , Cótica L. F. , Santos I. A. , Olzon-Dionysio M. , Souza S. D. , Garcia D. , Eiras José A. , Coelho A. A.
Published: August 2011

In this paper, the ferroic properties of polycrystalline LuFe2O4 samples were carefully investigated, and a dissimilar charge ordered state was identified. Strong dielectric dispersion, between 350 K and 225 K; the formation of cluster glass magnetic phases in the same temperature range; and the existence of a ferrimagnetic transition at 230 K indicate the coupling between the ferroelectric and the magnetic orders. Mössbauer spectroscopic investigations, at room temperature, revealed unbalanced contributions of the ferric and ferrous iron ions to the charge ordered state.
Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice
Authors: Jones Alex , Kumar Sandeep , Zhang Ning , Tong Zongzhong , Yang Jia-Hui , Watt Carl , Anderson James , Amrita  , Fillerup Heather , McCloskey Manabu , Luo Ling , Yang Zhenglin , Ambati Balamurali , Marc Robert , Oka Chio , Zhang Kang , Fu Yingbin
Published: August 2011

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. Wet AMD includes typical choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV). The etiology and pathogenesis of CNV and PCV are not well understood. Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, the precise role of HTRA1 in AMD remains elusive. By transgenically expressing human HTRA1 in mouse retinal pigment epithelium, we showed that increased HTRA1 induced cardinal features of PCV, including branching networks of choroidal vessels, polypoidal lesions, severe degeneration of the elastic laminae, and tunica media of choroidal vessels. In addition, HTRA1 mice displayed retinal pigment epithelium atrophy and photoreceptor degeneration. Senescent HTRA1 mice developed occult CNV, which likely resulted from the degradation of the elastic lamina of Bruch's membrane and up-regulation of VEGF. Our results indicate that increased HTRA1 is sufficient to cause PCV and is a significant risk factor for CNV.
Evidence of neutron leakage at the Fukushima nuclear plant from measurements of radioactive35S in California
Authors: Priyadarshi Antra , Dominguez Gerardo , Thiemens Mark H.
Published: August 2011

A recent earthquake and the subsequent tsunami have extensively damaged the Fukushima nuclear power plant, releasing harmful radiation into the environment. Despite the obvious implication for human health and the surrounding ecology, there are no quantitative estimates of the neutron flux leakage during the weeks following the earthquake. Here, using measurements of radioactive35S contained in sulfate aerosols and SO2gas at a coastal site in La Jolla, California, we show that nearly 4 × 1011neutrons per m2leaked at the Fukushima nuclear power plant before March 20, 2011. A significantly higheractivity as measured on March 28 is in accord with neutrons escaping the reactor core and being absorbed by the coolant seawater35Cl to produce35S by a (n,p) reaction. Once produced,35S oxidizes toandand was then transported to Southern California due to the presence of strong prevailing westerly winds at this time. Based on a moving box model, we show that the observed activity enhancement inis compatible with long-range transport of the radiation plume from Fukushima. Our model predicts that, the concentration in the marine boundary layer at Fukushima, was approximately 2 × 105 atoms per m3, which is approximately 365 times above expected natural concentrations. These measurements and model calculations imply that approximately 0.7% of the total radioactive sulfate present at the marine boundary layer at Fukushima reached Southern California as a result of the trans-Pacific transport.
Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases
Authors: Gutschner Tony , Baas Marion , Diederichs Sven
Published: August 2011

Zinc finger nucleases (ZFNs) allow site-specific manipulation of the genome. So far, the use of ZFNs to create gene knockouts has been restricted to protein-coding genes. However, non-protein-encoding RNAs (ncRNA) play important roles in the cell, although the functions of most ncRNAs are unknown. Here, we describe a ZFN-based method suited for the silencing of protein-coding and noncoding genes. This method relies on the ZFN-mediated integration of RNA destabilizing elements into the human genome, e.g., poly(A) signals functioning as termination elements and destabilizing downstream sequences. The biallelic integration of poly(A) signals into the gene locus of the long ncRNA MALAT1 resulted in a 1000-fold decrease of RNA expression. Thus, this approach is more specific and 300 times more efficient than RNA interference techniques. The opportunity to create a variety of loss-of-function tumor model cell lines in different cancer backgrounds will promote future functional analyses of important long noncoding RNA transcripts.
Improving the quality of e‐learning: lessons from the eMM
Authors: Marshall S.
Published: August 2011

The quality of e‐learning can be defined in many different ways, reflecting different stakeholders and the complexity of the systems and processes used in higher education. These different conceptions of quality can be mutually contradictory and, while politically significant, may also be beyond the direct control or influence of institutional leaders. The e‐learning maturity model (eMM) provides a framework for e‐learning quality improvement that measures the capability of institutions to sustainably engage in e‐learning and visualizes that capability in a way that assists leaders and managers using that information to undertake systematic and targeted improvements in their institution's e‐learning activities. This paper synthesizes the outcomes of multiple international eMM assessments to extract a set of starting points for institutions intending to improve the quality of e‐learning experienced by their students.
The relative contribution of band number to phylogenetic accuracy in AFLP data sets
Authors: GARCÍA‐PEREIRA M. J. , CABALLERO A. , QUESADA H.
Published: August 2011

We examined the effect of increasing the number of sampled amplified fragment length polymorphism (AFLP) bands to reconstruct an accurate and well‐supported AFLP‐based phylogeny. In silico AFLP was performed using simulated DNA sequences evolving along balanced and unbalanced model trees with recent, uniform and ancient radiations and average branch lengths (from the most internal node to the tip) ranging from 0.02 to 0.05 substitutions per site. Trees were estimated by minimum evolution (ME) and maximum parsimony (MP) methods from both DNA sequences and virtual AFLP fingerprints. The comparison of the true tree with the estimated AFLP trees suggests that moderate numbers of AFLP bands are necessary to recover the correct topology with high bootstrap support values (i.e. >70%). Fewer numbers of bands are necessary for shorter tree lengths and for balanced than for unbalanced tree topologies. However, branch length estimation was rather unreliable and did not improve substantially after a certain number of bands were sampled. These results hold for different levels of genome coverage and number of taxa analysed. In silico AFLP using bacterial genomic DNA sequences recovered a well‐supported tree topology that mirrored an empirical phylogeny based on a set of 31 orthologous gene sequences when as few as 263 AFLP bands were scored. These results suggest that AFLPs may be an efficient alternative to traditional DNA sequencing for accurate topology reconstruction of shallow trees when not very short ancestral branches exist.
Effects of alpha‐lipoic acid supplementation on antioxidative ability and performance of sows and nursing piglets
Authors: Bai X. M. , Ma Q. G. , Zhao L. H. , Xi L. , Ji C.
Published: August 2011

The current study was carried out to determine the effects of alpha‐lipoic acid (LA) supplementation during late‐gestation and lactation on antioxidative ability and performance of sows and their nursing piglets. A total of 160 multiparous sows were randomly allocated to four treatments with 40 replicates per treatment according to parity number and backfat (BF) thickness. Sows were fed 1 of 4 diets from day 85 of gestation to day 21 of lactation. Diets were control without LA; 400 ppm LA supplementation; 600 ppm LA supplementation; and 800 ppm LA supplementation. BF thickness of sows was determined on day 85 and 110 of gestation and days 1 and 21 of lactation. Piglet bodyweight was measured at birth, days 7, 14 and 21. Blood samples were obtained from the sows, and average daily feed intake (ADFI) of the sows during lactation was recorded. There were no differences in BF thickness or ADFI among treatment groups. Dietary LA supplementation resulted in a decrease in blood urea nitrogen (p < 0.01) concentration at days 110 of gestation. Dietary 800 ppm LA increased serum glutathione peroxidase (GSH‐Px) activity (p < 0.05) and reduced maleic dialdehyde levels (p < 0.01) of sows compared with the control diet at days 21 of lactation. Alpha‐lipoic acid supplementation increased the birthweight and weaning weight of piglets (p < 0.01) compared with the control group. Weight gains of piglets from sows fed the 800 ppm LA diets were greater (p < 0.01) between days 7 and 14 compared with piglets from control sows. Weight gains of piglets from sows fed the LA‐supplemented diets were greater between days 14 and 21 (p < 0.05) and between days 1 and 21 (p < 0.01) compared with piglets from control‐fed sows. In conclusion, the results indicate that antioxidant LA was effective in enhancing antioxidant enzymes activity and improving the performance of sows and their nursing piglets.
Decomposition of Inequality among Groups by Counterfactual Modeling: An Analysis of the Gender Wage Gap in Japan
Authors: Yamaguchi Kazuo
Published: August 2011

This paper introduces a new method for decomposing group differences in the mean of a variable into various within-group and between-group components with respect to group categories of intermediary variables. This is accomplished by considering counterfactual outcomes that would be realized by social interventions that change the relationship among variables. Because such a change does not by itself determine the counterfactual outcome, the paper introduces and juxtaposes two different mechanisms—the mechanism of realizing the counterfactual state that deviates least from the existing state, and the mechanism of holding relations among variables other than those that are modified by a given intervention unchanged—and demonstrates that despite the large difference in the mechanisms, they yield highly congruent outcomes. As an illustrative example, the paper analyzes gender inequality in hourly wages in Japan and thereby demonstrates the usefulness of the new method for deriving policy implications.
Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum
Authors: Torres‐Altoro Melissa I. , Mathur Brian N. , Drerup Justin M. , Thomas Rachel , Lovinger David M. , O’Callaghan James P. , Bibb James A.
Published: August 2011

J. Neurochem. (2011) 119, 303–313.

The neurological effects of organophosphate (OP) pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here, we characterized the effects of the broadly used insecticide chlorpyrifos (CPF) on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. CPF potentiated protein kinase A (PKA)‐dependent phosphorylation of the striatal protein dopamine‐ and cAMP‐regulated phosphoprotein of Mr 32 kDa (DARPP‐32) and the glutamate receptor 1 (GluR1) subunit of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide N,N‐diethyl‐meta‐toluamide (DEET). This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle‐associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus, consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration.
Erythrocytapheresis versus phlebotomy in the initial treatment of HFE hemochromatosis patients: results from a randomized trial
Authors: Rombout‐Sestrienkova Eva , Nieman Fred H.M. , Essers Brigitte A.B. , van Noord Paulus A.H. , Janssen Mirian C.H. , van Deursen Cees Th.B.M. , Bos Laurens P. , Rombout Ferdinand , van den Braak Rogier , de Leeuw Peter W. , Koek Ger H.
Published: August 2011

BACKGROUND:Standard treatment of newly diagnosed HFE hemochromatosis patients is phlebotomy. Erythrocytapheresis provides a new therapeutic modality that can remove up to three times more red blood cells per single procedure and could thus have a clinical and economic benefit.

STUDY DESIGN AND METHODS:To compare the number of treatment procedures between erythrocytapheresis and phlebotomy needed to reach the serum ferritin (SF) target level of 50 µg/L, a two‐treatment‐arms, randomized trial was conducted in which 38 newly diagnosed patients homozygous for C282Y were randomly assigned in a 1:1 ratio to undergo either erythrocytapheresis or phlebotomy. A 50% decrease in the number of treatment procedures for erythrocytapheresis compared to phlebotomy was chosen as the relevant difference to detect.

RESULTS:Univariate analysis showed a significantly lower mean number of treatment procedures in the erythrocytapheresis group (9 vs. 27; ratio, 0.33; 95% confidence interval [CI], 0.25‐0.45; Mann‐Whitney p < 0.001). After adjustments for the two important influential factors initial SF level and body weight, the reduction ratio was still significant (0.43; 95% CI, 0.35‐0.52; p < 0.001). Cost analysis showed no significant difference in treatment costs between both procedures. The costs resulting from productivity loss were significantly lower for the erythrocytapheresis group.

CONCLUSION:Erythrocytapheresis is highly effective treatment to reduce iron overload and from a societal perspective might potentially also be a cost‐saving therapy.
In situ Particle Generation and Splat Formation During Solution Precursor Plasma Spraying of Yttria‐Stabilized Zirconia Coatings
Authors: Govindarajan Sivakumar , Dusane Rajiv Onkar , Joshi Shrikant Vishwanath
Published: August 2011

Thermal barrier coatings (TBCs) based on Yttria‐stabilized Zirconia (YSZ) deposited by the solution precursor plasma spray (SPPS) technique have been claimed to exhibit superior durability compared to conventional plasma spraying and even electron‐beam physical vapor deposition. This has been attributed to the interesting features, like vertical cracks, nanosized pores, and fine splats that are inherent to SPPS‐deposited YSZ coatings. However, the mechanism of coating formation during SPPS processing is not yet well understood. This study is aimed at understanding the influence of some key SPPS process variables on in situ generated particles and subsequent splat formation to augment the current level of understanding. The plasma power employed was found to play a major role in governing the morphology and phase constitution of in situ generated particles. The shape and size of the YSZ splats were also significantly influenced by the plasma power, but the substrate pre‐heat was also noted to be a major determining factor. It was further observed that the SPPS typically involved in situ generation of very fine particulates (50–500 nm) and splats (typically 200–2000 nm), which lead to its nano‐porous and homogeneous microstructure. The YSZ coating characteristics were also found to correlate well with the above results.
Use of Computed Tomography Adrenal Gland Measurement for Differentiating ACTH Dependence from ACTH Independence in 64 Dogs with Hyperadenocorticism
Authors: Rodríguez Piñeiro M.I. , de Fornel‐Thibaud P. , Benchekroun G. , Garnier F. , Maurey‐Guenec C. , Delisle F. , Rosenberg D.
Published: August 2011

Background:The measurement of adrenal gland size on computed tomography (CT) scan has been proposed for the etiological diagnosis of hyperadrenocorticism (HAC) in dogs. Symmetric adrenal glands are considered to provide evidence for ACTH‐dependent hyperadrenocorticism (ADHAC), whereas asymmetry suggests ACTH‐independent hyperadrenocorticism (AIHAC). However, there are currently no validated criteria for such differentiation.

Objective:The aim of this retrospective study was to compare various adrenal CT scan measurements and the derived ratios in ADHAC and AIHAC cases, and to validate criteria for distinguishing between these conditions in a large cohort of dogs.

Animals:Sixty‐four dogs with HAC (46 ADHAC, 18 AIHAC).

Methods:Dogs with confirmed HAC and unequivocal characterization of its origin were included. Linear measurements of adrenal glands were made on both cross‐sectional and reformatted images.

Results:An overlap was systematically observed between the AIHAC and ADHAC groups for all measurements tested. Overlaps also were observed for ratios tested. For the maximum adrenal diameter ratio derived from reformatted images (rADR), only 1/18 AIHAC dogs had a rADR within the range for ADHAC. For a threshold of 2.08, the 95% confidence intervals for estimated sensitivity and specificity extended from 0.815 to 1.000 and from 0.885 to 0.999, respectively, for AIHAC diagnosis.

Conclusion and Clinical Importance:Measurements from cross‐sectional or reformatted CT scans are of little use for determining the origin of HAC. However, rADR appears to distinguish accurately between ADHAC and AIHAC, with a rADR > 2.08 highly suggestive of AIHAC.
Mitigating Blockage Effects on Flow Over a Circular Cylinder in an Adaptive-Wall Wind Tunnel
Authors: Bishop Michael , Yarusevych Serhiy
Published: August 2011

The effect of wall streamlining on flow development over a circular cylinder was investigated experimentally in an adaptive-wall wind tunnel. Experiments were carried out for a Reynolds number of 57,000 and three blockage ratios of 5%, 8%, and 17%. Three test section wall configurations were investigated, namely, geometrically straight walls (GSW), aerodynamically straight walls (ASW), and streamlined walls (SLW). The results show that solid blockage effects are evident in cylinder surface pressure distributions for the GSW and ASW configurations, manifested by an increased peak suction and base suction. Upon streamlining the walls, pressure distributions for each blockage ratio investigated closely match distributions expected for low blockage ratios. Wake blockage limits wake growth in the GSW configuration at 7.75 and 15 diameters downstream of the cylinder for blockages of 17% and 8%, respectively. This adverse effect can be rectified by streamlining the walls, with the resulting wake width development matching that expected for low blockage ratios. Wake vortex shedding frequency and shear layer instability frequency increase in the GSW and ASW configurations with increasing blockage ratio. The observed invariance of the near wake width with wall configuration suggests that the frequency increase is caused by the increased velocity due to solid blockage effects. For all the blockage ratios investigated, this increase is rectified in the SLW configuration, with the resulting Strouhal numbers of about 0.19 matching that expected for low blockage ratios at the corresponding Reynolds number. Blockage effects on the shear layer instability frequency are also successfully mitigated by streamlining the walls.
Type‐2 Fuzzy Modeling for Acoustic Emission Signal in Precision Manufacturing
Authors: Ren Qun , Baron Luc , Balazinski Marek
Published: August 2011

This paper presents an application of type‐2 fuzzy logic on acoustic emission (AE) signal modeling in precision manufacturing. Type‐2 fuzzy modeling is used to identify the AE signal in precision machining. It provides a simple way to arrive at a definite conclusion without understanding the exact physics of the machining process. Moreover, the interval set of the output from the type‐2 fuzzy approach assesses the information about the uncertainty in the AE signal, which can be of great value for investigation of tool wear conditions. Experiments show that the development of the AE signal uncertainty trend corresponds to that of the tool wear. Information from the AE uncertainty scheme can be used to make decisions or investigate the tool condition so as to enhance the reliability of tool wear.
Glutamatergic Pathway Targeting in Melanoma: Single-Agent and Combinatorial Therapies
Authors: Lee Hwa Jin , Wall Brian A. , Wangari-Talbot Janet , Shin Seung-Shick , Rosenberg Stephen , Chan Joseph L-K. , Namkoong Jin , Goydos James S. , Chen Suzie
Published: August 2011

Purpose: Melanoma is a heterogeneous disease where monotherapies are likely to fail due to variations in genomic signatures. B-RAF inhibitors have been clinically inadequate but response might be augmented with combination therapies targeting multiple signaling pathways. We investigate the preclinical efficacy of combining the multikinase inhibitor sorafenib or the mutated B-RAF inhibitor PLX4720 with riluzole, an inhibitor of glutamate release that antagonizes metabotropic glutamate receptor 1 (GRM1) signaling in melanoma cells.

Experimental Design: Melanoma cell lines that express GRM1 and either wild-type B-RAF or mutated B-RAF were treated with riluzole, sorafenib, PLX4720, or the combination of riluzole either with sorafenib or with PLX4720. Extracellular glutamate levels were determined by glutamate release assays. MTT assays and cell-cycle analysis show effects of the compounds on proliferation, viability, and cell-cycle profiles. Western immunoblotting and immunohistochemical staining showed apoptotic markers. Consequences on mitogen-activated protein kinase pathway were assessed by Western immunoblotting. Xenograft tumor models were used to determine the efficacy of the compounds in vivo.

Results: The combination of riluzole with sorafenib exhibited enhanced antitumor activities in GRM1-expressing melanoma cells harboring either wild-type or mutated B-RAF. The combination of riluzole with PLX4720 showed lessened efficacy compared with the combination of riluzole and sorafenib in suppressing the growth of GRM1-expressing cells harboring the B-RAFV600E mutation.

Conclusions: The combination of riluzole with sorafenib seems potent in suppressing tumor proliferation in vitro and in vivo in GRM1-expressing melanoma cells regardless of B-RAF genotype and may be a viable therapeutic clinical combination. Clin Cancer Res; 17(22); 7080–92. ©2011 AACR.
Parallel Anticancer Drug Development and Molecular Stratification to Qualify Predictive Biomarkers: Dealing with Obstacles Hindering Progress
Authors: Garcia Victor Moreno , Cassier Philippe A. , de Bono Johann
Published: August 2011

Current anticancer drug development still largely follows the classic designs developed for chemotherapeutic agents over the past 4 to 5 decades, remaining slow, costly, and inefficient, with continuing high risks of costly late drug attrition. A Pharmacologic Audit Trail has been described to decrease these risks, incorporating pharmacokinetic, pharmacodynamic, intermediate efficacy endpoints, as well as patient stratification molecular biomarkers. Molecular biomarker–based patient selection in hypothesis-testing early clinical trials is critical to clinically qualify putative predictive biomarkers for rationally designed, molecularly targeted drugs as early as possible. Nevertheless, major concerns have been raised about the impact of using such biomarkers in early trials, in view of the costs and time involved to develop multiple certified assays for clinical use. The rapid evolution of novel technologies of utility to this field, such as next-generation sequencing and circulating tumor-cell isolation, makes these valid concerns of critical importance. We therefore propose a more efficient parallel predictive biomarker and clinical anticancer drug development process to deal with the obstacles hindering progress. Cancer Discovery; 1(3); 207–12. © 2011 AACR.
Functional Subtyping of Breast Cancer
Authors: Beijersbergen Roderick L. , Bernards René
Published: August 2011

Breast cancers can be subdivided in several different ways. In this issue, Brough and colleagues describe a functional subtyping of breast cancers based on their responses to specific perturbations. Cancer Discovery; 1(3); 205–6. © 2011 AACR.

Commentary on Brough et al., p. 260.
Detection and Molecular Characterization of Human Group C Rotavirus in Brazil
Authors: Araújo Irene Trigueiros , Heinemann Marcos Bryan , Fialho Alexandre Madi , Leite José Paulo Gagliardi
Published: August 2011

Objective: The aim of the present study was to characterize 24 isolates of group C rotavirus (RV-C) by analysis of DNA sequences of the VP4, VP6, VP7 and NSP4 genes of several Brazilian states. Methods: All RV-C strains were confirmed by polyacrylamide gel electrophoresis and were characterized by sequence and phylogenetic analysis of the genes encoding NSP4, VP6, VP4, and VP7 proteins. Results: Analysis of the NSP4 gene from Brazilian strains revealed that the isolates are more closely related to each other than to those of other strains previously published. The VP6 gene showed high homology to Indian strains. The sequences of VP4 and VP7 genes showed two lineages circulating in Brazil in the same region and at the same time. Conclusion: These results confirm the transmission of RV-C in Brazil. RV-C infection appears to occur occasionally despite the low detection rate of the virus.
The Influence of the Cloud Shell on Tracer Budget Measurements of LES Cloud Entrainment
Authors: Dawe Jordan T. , Austin Philip H.
Published: August 2011

Direct measurements of rates of entrainment into and detrainment from cumulus cloud cores obtained from LES model cloud fields produce values twice as large as those produced from tracer budget calculations. This difference can be explained by two effects: the presence of a shell of air around the cloud cores that is moister than the mean environment and air at the edge of the cloud core that is drier than the mean core, and the tendency for the mean tracer values of the entrained fluid to be greater than the mean tracer values of the cloud shell. Preferential entrainment of shell air that is moving upward faster than the mean shell creates strong vertical momentum fluxes into the cumulus cloud core, thereby making the assumption that cumulus cloud cores entrain fluid with zero vertical momentum incorrect. Variability in the properties of the moist cloud shell has strong impacts on entrainment values inferred from tracer budget calculations. These results indicate that the dynamics of the cloud shell should be included in parameterization of cumulus clouds used in general circulation models.
Estimating the lifetime economic burden of stroke according to the age of onset in South Korea: a cost of illness study
Authors: Kang Hye-Young , Lim Seung-Ji , Suh Hae Sun , Liew Danny
Published: August 2011

Background

The recently-observed trend towards younger stroke patients in Korea raises economic concerns, including erosion of the workforce. We compared per-person lifetime costs of stroke according to the age of stroke onset from the Korean societal perspective.

Methods

A state-transition Markov model consisted of three health states ('post primary stroke event', 'alive post stroke', and 'dead') was developed to simulate the natural history of stroke. The transition probabilities for fatal and non-fatal recurrent stroke by age and gender and for non-stroke causes of death were derived from the national epidemiologic data of the Korean Health Insurance Review and Assessment Services and data from the Danish Monitoring Trends in Cardiovascular Disease study. We used an incidence-based approach to estimate the long-term costs of stroke. The model captured stroke-related costs including costs within the health sector, patients' out-of-pocket costs outside the health sector, and costs resulting from loss of productivity due to morbidity and premature death using a human capital approach. Average insurance-covered costs occurring within the health sector were estimated from the National Health Insurance claims database. Other costs were estimated based on the national epidemiologic data and literature. All costs are presented in 2008 Korean currency values (Korean won = KRW).

Results

The lifetime costs of stroke were estimated to be: 200.7, 81.9, and 16.4 million Korean won (1,200 KRW is approximately equal to one US dollar) for men who suffered a first stroke at age 45, 55 and 65 years, respectively, and 75.7, 39.2, and 19.3 million KRW for women at the same age. While stroke occurring among Koreans aged 45 to 64 years accounted for only 30% of the total disease incidence, this age group incurred 75% of the total national lifetime costs of stroke.

Conclusions

A higher lifetime burden and increasing incidence of stroke among younger Koreans highlight the need for more effective strategies for the prevention and management of stroke especially for people between 40 and 60 years of ages.