bluuebunny/crossref_metadata_2025 huggingface dataset:
Francophonie
Authors: Vigouroux Cécile B.
Published: August 2013

This review unravels different facets of la Francophonie, both as an international institution dedicated to the defense of French and as a group of people who speak or are united by French. Having been highly ideological since its beginnings and its association with France's colonial history, the very idea of la Francophonie has aroused passionate debates both within and without. Although it was officially launched as a cultural community seeking to develop economic partnership, it has evolved into a political organization promoting human rights and democracy and defending cultural diversity against Anglo-American hegemony. From a linguistic point of view, la Francophonie is approached in light of the centuries-long ideology of French as a universal language whose vitality is threatened by other languages. This review also shows that the political discourse of the institutional Francophonie has not always been in tune with that of its main agents, the Francophones.
Mathematical Modeling of Eukaryotic Cell Migration: Insights Beyond Experiments
Authors: Danuser Gaudenz , Allard Jun , Mogilner Alex
Published: August 2013

A migrating cell is a molecular machine made of tens of thousands of short-lived and interacting parts. Understanding migration means understanding the self-organization of these parts into a system of functional units. This task is one of tackling complexity: First, the system integrates numerous chemical and mechanical component processes. Second, these processes are connected in feedback interactions and over a large range of spatial and temporal scales. Third, many processes are stochastic, which leads to heterogeneous migration behaviors. Early on in the research of cell migration it became evident that this complexity exceeds human intuition. Thus, the cell migration community has led the charge to build mathematical models that could integrate the diverse experimental observations and measurements in consistent frameworks, first in conceptual and more recently in molecularly explicit models. The main goal of this review is to sift through a series of important conceptual and explicit mathematical models of cell migration and to evaluate their contribution to the field in their ability to integrate critical experimental data.
Preindustrial Human Impacts on Global and Regional Environment
Authors: Doughty Christopher E.
Published: August 2013

Humans have had an impact on regional and global environments even prior to the Industrial Revolution through anthropogenic fire, agriculture, and the extinction of the Pleistocene megafauna. The preindustrial impact of anthropogenic fire to modify ecosystems and affect climate may have been small because in regions where impacts were once thought to be large, such as in Australia, the evidence now suggests a smaller effect. Both the extinction of the megafauna, which evidence indicates to be at least partially caused by humans, and preindustrial agriculture may have affected climate, but the effects may have offset each other. For instance, climate simulations indicate that megafauna extinctions may have led to a slight global warming, but later, agriculture led to a slight global cooling. Prior to the industrial era, the largest ecological and climate anomaly may have been associated with forest expansion during the early and mid-Holocene when there were few megafauna and agriculturalists to reduce this expansion.
Corporate Governance: What’s Special About Banks?
Authors: Laeven Luc
Published: August 2013

This review surveys the literature on the corporate governance of banks. Traditional corporate governance mechanisms, such as concentrated ownership and takeover threats, in principle, also apply to banks. However, banks have special traits and are heavily regulated, preventing natural forms of governance to arise and rendering many of these governance mechanisms ineffective. Financial regulation can in principle compensate for weaknesses in corporate governance but in practice has had limited effectiveness in protecting the interests of banks’ stakeholders, because of, for instance, unproductive interactions between regulatory restraints and existing governance arrangements. The review concludes with a discussion of corporate governance and regulatory reforms to enhance the safety and soundness of banks. These proposals range from placing more emphasis on value creation for bank stakeholders other than shareholders to reducing risk-shifting incentives for bank managers and shareholders.
Rheology of Adsorbed Surfactant Monolayers at Fluid Surfaces
Authors: Langevin D.
Published: August 2013

When surfactants adsorb at liquid surfaces, they not only decrease the surface tension, they also confer rheological properties to the surfaces. The most common rheological parameters are the surface compression elasticity and viscosity and the surface shear viscosity. These parameters usually depend on the timescale of the deformation, owing to surface relaxations, and on its amplitude, owing to nonlinear responses. In addition, surfactants can exchange between the bulk and surface, in a way that depends on the amount of bulk surfactant locally available. This complexity explains why the topic has progressed slowly over the years. This review describes the current knowledge, focusing on recent advances, and gives examples of phenomena in which surface rheology plays an important role.
Effect of short-term cold exposure on skeletal muscle protein breakdown in rats
Authors: Manfredi L. H. , Zanon N. M. , Garófalo M. A. , Navegantes L. C. C. , Kettelhut I. C.
Published: August 2013

Although it is well established that carbohydrate and lipid metabolism are profoundly altered by cold stress, the effects of short-term cold exposure on protein metabolism in skeletal muscle are still poorly understood. Because cold acclimation requires that an organism adjust its metabolic flux, and muscle amino acids may be an important energy source for heat production, we hypothesize that muscle proteolysis is increased and protein synthesis is decreased under such a stress condition. Herein, cold exposure for 24 h decreased rates of protein synthesis and increased overall proteolysis in both soleus and extensor digitorum longus (EDL) muscles, but it did not affect muscle weight. An increase in proteolysis was accompanied by hyperactivity of the ubiquitin-proteasome system (UPS) in both soleus and EDL, and Ca2+-dependent proteolysis in EDL. Furthermore, muscles of rats exposed to cold showed increased mRNA and protein levels of atrogin-1 and muscle RING finger enzyme-1 (MuRF1). Additionally, cold stress reduced phosphorylation of Akt and Forkhead box class O1 (FoxO1), a well-known effect that increases FoxO translocation to the nucleus and leads to activation of proteolysis. Plasma insulin levels were lower, whereas catecholamines, corticosterone, and thyroid hormones were higher in cold-exposed rats compared with control rats. The present data provide the first direct evidence that short-term cold exposure for 24 h decreases rates of protein synthesis and increases the UPS and Ca2+-dependent proteolytic processes, and increases expression of atrogin-1 and MuRF1 in skeletal muscles of young rats. The activation of atrophy induced by acute cold stress seems to be mediated at least in part through the inactivation of Akt/FoxO signaling and activation of AMP-activated protein kinase.
EMD and Wavelet Transform Based Fault Diagnosis for Wind Turbine Gear Box
Authors: Yang Qingyu , An Dou
Published: August 2013

Wind turbines are mainly located in harsh environment, and the maintenance is therefore very difficult. The wind turbine faults are mostly from the gear box, and the fault signal is generally nonlinear and nonstationary. The traditional fault diagnosis methods such as Fast Fourier transform (FFT) and the inverted frequency spectrum identification method based on FFT are not satisfactory in processing this kind of signal. This paper proposes a hybrid fault diagnosis method which combines the empirical mode decomposition (EMD) and wavelet transform. The vibration signal is analyzed through wavelet transform, and the aliasing in high-frequency signals is then addressed by conducting EMD to the original signals. The experimental results based on a specific wind turbine gear box demonstrate that this method can diagnose the faults and locate their positions accurately.
Molecular Identification of Fungal Communities in a Soil Cultivated with Vegetables and Soil Suppressiveness toRhizoctonia solani
Authors: Val-Moraes Silvana Pompéia , Nascimbem Pedrinho Eliamar Aparecida , Lemos Eliana Gertrudes Macedo , Carareto-Alves Lucia Maria
Published: August 2013

Fungi constitute an important part of the soil ecosystem, playing key roles in decomposition, cycling processes, and biotic interactions. Molecular methods have been used to assess fungal communities giving a more realistic view of their diversity. For this purpose, total DNA was extracted from bulk soils cultivated with tomato (STC), vegetables (SHC), and native forest (SMS) from three sites of the Taquara Branca river basin in Sumaré County, São Paulo State, Brazil. This metagenomic DNA was used as a template to amplify fungal 18S rDNA sequences, and libraries were constructed inEscherichia coliby cloning PCR products. The plasmid inserts were sequenced and compared to known rDNA sequences in the GenBank database. Of the sequenced clones, 22 were obtained from the SMS sample, 18 from the SHC sample, and 6 from the STC sample. Although most of the clone sequences did not match the sequences present in the database, individual amplified sequences matched with Glomeromycota (SMS), Fungi incertae sedis (SMS), and Neocallimastigomycota (SHC). Most of the sequences from the amplified taxa represent uncultured fungi. The molecular analysis of variance (AMOVA) indicated that fluctuations observed of haplotypes in the composition may be related to herbicide application.
Disulfide Bonding in Neurodegenerative Misfolding Diseases
Authors: Mossuto Maria Francesca
Published: August 2013

In recent years an increasing number of neurodegenerative diseases has been linked to the misfolding of a specific protein and its subsequent accumulation into aggregated species, often toxic to the cell. Of all the factors that affect the behavior of these proteins, disulfide bonds are likely to be important, being very conserved in protein sequences and being the enzymes devoted to their formation among the most conserved machineries in mammals. Their crucial role in the folding and in the function of a big fraction of the human proteome is well established. The role of disulfide bonding in preventing and managing protein misfolding and aggregation is currently under investigation. New insights into their involvement in neurodegenerative diseases, their effect on the process of protein misfolding and aggregation, and into the role of the cellular machineries devoted to disulfide bond formation in neurodegenerative diseases are emerging. These studies mark a step forward in the comprehension of the biological base of neurodegenerative disorders and highlight the numerous questions that still remain open.
The Rendu-Osler-Weber Disease Revealed by a Refractory Hypoxemia and Severe Cerebral Fat Embolism
Authors: Barreto Leonel , Amiel Jean-Bernard , Dugard Anthony , Pichon Nicolas , Clavel Marc , François Bruno , Vignon Philippe
Published: August 2013

The Rendu-Osler-Weber disease is a genetic disease which may lead to severe hemorrhage and less frequently to severe organ dysfunction. We report the case of a 22-year-old patient with no personal medical history who was involved in a motorcycle accident and exhibited severe complications related to large arteriovenous pulmonary shunts during his ICU stay. The patient developed an unexplained severe hypoxemia which was attributed to several arteriovenous shunts of the pulmonary vasculature by a contrast study during a transesophageal echocardiographic examination. The course was subsequently complicated by a prolonged coma associated with hemiplegia which was attributed to a massive paradoxical fat embolism in the setting of an untreated femoral fracture. In addition to hemorrhagic complications which may lead to intractable shock, arteriovenous malformations associated with the Rendu-Osler-Weber disease may involve the pulmonary vasculature and result in unexpected complications, such as hypoxemia or severe cerebral fat embolism in high-risk patients.
Alternative Splicing Programs in Prostate Cancer
Authors: Sette Claudio
Published: August 2013

Prostate cancer (PCa) remains one of the most frequent causes of death for cancer in the male population. Although the initial antiandrogenic therapies are efficacious, PCa often evolves into a hormone-resistant, incurable disease. The genetic and phenotypic heterogeneity of this type of cancer renders its diagnosis and cure particularly challenging. Mounting evidence indicates that alternative splicing, the process that allows production of multiple mRNA variants from each gene, contributes to the heterogeneity of the disease. Key genes for the biology of normal and neoplastic prostate cells, such as those encoding for the androgen receptor and cyclin D1, are alternatively spliced to yield protein isoforms with different or even opposing functions. This review illustrates some examples of genes whose alternative splicing regulation is relevant to PCa biology and discusses the possibility to exploit alternative splicing regulation as a novel tool for prognosis, diagnosis, and therapeutic approaches to PCa.
A Two-Agent Single-Machine Scheduling Problem with Learning and Deteriorating Considerations
Authors: Wu Wen-Hsiang
Published: August 2013

Recently, interest in scheduling with deteriorating jobs and learning effects has kept growing. However, research in this area has seldom considered the multiagent setting. Motivated by these observations, we consider two-agent scheduling on a single machine involving the learning effects and deteriorating jobs simultaneously. In the proposed model, we assume that the actual processing time of a job of the first (second) agent is a decreasing (increasing) function of the total processing time of the jobs already processed in a schedule. The objective is to minimize the total weighted completion time of the jobs of the first agent with the restriction that no tardy job is allowed for the second agent. We develop a branch-and-bound and a simulated annealing algorithms for the problem. We perform extensive computational experiments to test the performance of the algorithms.
Development of an Efficient Hull Form Design Exploration Framework
Authors: Jeong Shinkyu , Kim Hyunyul
Published: August 2013

A high-efficiency design exploration framework for hull form has been developed. The framework consists of multiobjective shape optimization and design knowledge extraction. In multiobjective shape optimization, a multiobjective genetic algorithm (MOGA) using the response surface methodology is introduced to achieve efficient design space exploration. As a response surface methodology, the Kriging model, which was developed in the field of spatial statistics and geostatistics, is applied. A new surface modification method using shifting method and radial basis function interpolation is also adopted here to represent various hull forms. This method enables both global and local modifications of hull form with fewer design variables. In design knowledge extraction, two data mining techniques—functional analysis of variance (ANOVA) and self-organizing map (SOM)—are applied to acquire useful design knowledge about a hull form. The present framework has been applied to hull form optimization exploring the minimum wave drag configuration under a wide range of speeds. The results show that the present method markedly reduced the design period. From the results of data mining, it is possible to identify the design variables controlling wave drag performances at different speed regions and their corresponding geometric features.
Archaeal Assemblages Inhabiting Temperate Mixed Forest Soil Fluctuate in Taxon Composition and Spatial Distribution over Time
Authors: Swanson Colby A. , Sliwinski Marek K.
Published: August 2013

This study explored the persistence and spatial distribution of a diverse Archaeal assemblage inhabiting a temperate mixed forest ecosystem. Persistence under native conditions was measured from 2001 to 2010, 2011, and 2012 by comparison of 16S rRNA gene clone libraries. The Archaeal assemblages at each of these time points were found to be significantly different (AMOVA,P<0.01), and the nature of this difference was dependent on taxonomic rank. For example, the cosmopolitan genus g_Ca.Nitrososphaera (I.1b) was detected at all time points, but within this taxon the abundance of s_SCA1145, s_SCA1170, and s_Ca.N. gargensis fluctuated over time. In addition, spatial heterogeneity (patchiness) was measured at these time points using 1D TRFLP-SSCP fingerprinting to screen soil samples covering multiple spatial scales. This included soil collected from small volumes of 3 cubic centimeters to larger scales—over a surface area of 50 m2, plots located 1.3 km apart, and a separate locality 23 km away. The spatial distribution of Archaea in these samples changed over time, and while g_Ca.Nitrososphaera (I.1b) was dominant over larger scales, patches were found at smaller scales that were dominated by other taxa. This study measured the degree of change for Archaeal taxon composition and patchiness over time in temperate mixed forest soil.
Src Family Kinases as Novel Therapeutic Targets to Treat Breast Cancer Brain Metastases
Authors: Zhang Siyuan , Huang Wen-Chien , Zhang Lin , Zhang Chenyu , Lowery Frank J. , Ding Zhaoxi , Guo Hua , Wang Hai , Huang Suyun , Sahin Aysegul A. , Aldape Kenneth D. , Steeg Patricia S. , Yu Dihua
Published: August 2013

Despite better control of early-stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer and we show how Src-targeting combinatorial regimens can treat HER2+ brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood–brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat patients with breast cancer suffering from brain metastasis. Cancer Res; 73(18); 5764–74. ©2013 AACR.
Integrative Genomics Analysis Identifies Candidate Drivers at 3q26-29 Amplicon in Squamous Cell Carcinoma of the Lung
Authors: Wang Jing , Qian Jun , Hoeksema Megan D. , Zou Yong , Espinosa Allan V. , Rahman S.M. Jamshedur , Zhang Bing , Massion Pierre P.
Published: August 2013

Purpose: Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.

Experimental Design: We conducted a meta-analysis of seven independent datasets containing a total of 593 human primary SCC samples to identify consensus candidate drivers in 3q26-29 amplicon. Through integrating protein–protein interaction network information, we further filtered for candidates that may function together in a network. Computationally predicted candidates were validated using RNA interference (RNAi) knockdown and cell viability assays. Clinical relevance of the experimentally supported drivers was evaluated in an independent cohort of 52 lung SCC patients using survival analysis.

Results: The meta-analysis identified 20 consensus candidates, among which four (SENP2, DCUN1D1, DVL3, and UBXN7) are involved in a small protein–protein interaction network. Knocking down any of the four proteins led to cell growth inhibition of the 3q26-29–amplified SCC. Moreover, knocking down of SENP2 resulted in the most significant cell growth inhibition and downregulation of DCUN1D1 and DVL3. Importantly, a gene expression signature composed of SENP2, DCUN1D1, and DVL3 stratified patients into subgroups with different response to adjuvant chemotherapy.

Conclusion: Together, our findings show that SENP2, DCUN1D1, and DVL3 are candidate driver genes in the 3q26-29 amplicon of SCC, providing novel insights into the molecular mechanisms of disease progression and may have significant implication in the management of SCC of the lung. Clin Cancer Res; 19(20); 5580–90. ©2013 AACR.
Chronic Hyperinsulinemia Does Not Increase the Production Rate of High-Density Lipoprotein Apolipoprotein AI
Authors: Duvillard Laurence , Florentin Emmanuel , Pont Frédéric , Petit Jean-Michel , Baillot-Rudoni Sabine , Penfornis Alfred , Vergès Bruno
Published: August 2013

Objective—

In vitro studies showed that insulin stimulates the production of apolipoprotein AI (apoAI). Thus, we hypothesized that chronic hyperinsulinemia could contribute to the increase in the production of high-density lipoprotein apoAI that is observed in metabolic syndrome.

Approach and Results—

We performed an in vivo kinetic study with stable isotope in 7 patients with insulinoma who showed hyperinsulinemia but no insulin resistance, 8 patients with insulin resistance, and 16 controls. Insulinemia was 3.1× (
P
<0.01) higher in patients with insulinoma or insulin resistance than in controls in the fasting state and, respectively, 3.5× and 2.6× (
P
<0.05) higher in the fed state. The high-density lipoprotein apoAI pool size was smaller in patients with insulin resistance than in controls (49.3±5.4 versus 59.6±7.7 mg·kg
−1
;
P
<0.01), whereas both the high-density lipoprotein apoAI fractional catabolic rate and the high-density lipoprotein apoAI production rate were higher (0.30±0.07 versus 0.20±0.04 pool·d
−1
;
P
<0.0001 and 14.6±1.5 versus 11.5±1.9 mg·kg
−1
·d
−1
;
P
<0.01, respectively). In contrast, no significant difference was observed for these parameters between patients with insulinoma and controls. In patients with insulinoma, the apoAI pool size tended to be greater than in patients with insulin resistance (56.3±8.6 versus 49.3±5.4 mg·kg
−1
;
P
=0.078), whereas both the apoAI fractional catabolic rate and the production rate were lower (0.20±0.06 versus 0.30±0.07 pool·d
−1
;
P
<0.01 and 11.1±1.6 versus 14.6±1.5 mg·kg
−1
·d
−1
;
P
<0.01, respectively). The apoAI fractional catabolic rate was the only variable associated with the apoAI production rate in multivariate analysis and explained 80% of its variance.

Conclusions—

Chronic endogenous hyperinsulinemia does not induce any increase in the apoAI production rate, which seems to be more dependent on the apoAI fractional catabolic rate.
Molecular Imaging Reveals Rapid Reduction of Endothelial Activation in Early Atherosclerosis With Apocynin Independent of Antioxidative Properties
Authors: Khanicheh Elham , Qi Yue , Xie Aris , Mitterhuber Martina , Xu Lifen , Mochizuki Michika , Daali Youssef , Jaquet Vincent , Krause Karl-Heinz , Ruggeri Zaverio M. , Kuster Gabriela M. , Lindner Jonathan R. , Kaufmann Beat A.
Published: August 2013

Objective—

Antioxidative drugs continue to be developed for the treatment of atherosclerosis. Apocynin is an nicotinamide adenine dinucleotide phosphate oxidase inhibitor with anti-inflammatory properties. We used contrast-enhanced ultrasound molecular imaging to assess whether short-term apocynin therapy in atherosclerosis reduces vascular oxidative stress and endothelial activation

Approach and Results—

Genetically modified mice with early atherosclerosis were studied at baseline and after 7 days of therapy with apocynin (4 mg/kg per day IP) or saline. Contrast-enhanced ultrasound molecular imaging of the aorta was performed with microbubbles targeted to vascular cell adhesion molecule 1 (VCAM-1; MB
V
), to platelet glycoprotein Ibα (MB
Pl
), and control microbubbles (MB
Ctr
). Aortic vascular cell adhesion molecule 1 was measured using Western blot. Aortic reactive oxygen species generation was measured using a lucigenin assay. Hydroethidine oxidation was used to assess aortic superoxide generation. Baseline signal for MB
V
(1.3±0.3 AU) and MB
Pl
(1.5±0.5 AU) was higher than for MB
Ctr
(0.5±0.2 AU;
P
<0.01). In saline-treated animals, signal did not significantly change for any microbubble agent, whereas short-term apocynin significantly (
P
<0.05) reduced vascular cell adhesion molecule 1 and platelet signal (MB
V
: 0.3±0.1; MB
Pl
: 0.4±0.1; MB
Ctr
: 0.3±0.2 AU;
P
=0.6 between agents). Apocynin reduced aortic vascular cell adhesion molecule 1 expression by 50% (
P
<0.05). However, apocynin therapy did not reduce reactive oxygen species content, superoxide generation, or macrophage content.

Conclusions—

Short-term treatment with apocynin in atherosclerosis reduces endothelial cell adhesion molecule expression. This change in endothelial phenotype can be detected by molecular imaging before any measurable decrease in macrophage content and is not associated with a detectable change in oxidative burden.
Profiling of Atherosclerotic Lesions by Gene and Tissue Microarrays Reveals PCSK6 as a Novel Protease in Unstable Carotid Atherosclerosis
Authors: Perisic Ljubica , Hedin Erika , Razuvaev Anton , Lengquist Mariette , Osterholm Cecilia , Folkersen Lasse , Gillgren Peter , Paulsson-Berne Gabrielle , Ponten Fredrik , Odeberg Jacob , Hedin Ulf
Published: August 2013

Objective—

Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways is still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in a biobank of carotid endarterectomies followed by characterization of identified candidates, as a platform for discovery of novel proteins differentially regulated in unstable carotid lesions.

Approach and Results—

Genes highly upregulated in symptomatic versus asymptomatic plaques were selected from Affymetrix microarray analyses (n=127 plaques), and tissue microarrays constructed from 34 lesions were assayed for 21 corresponding proteins by immunohistochemistry. Quantification of stainings demonstrated differential expression of CD36, CD137, and DOCK7 (
P
<0.05) in unstable versus stable lesions and the most significant upregulation of a proprotein convertase, PCSK6 (
P
<0.0001). Increased expression of PCSK6 in symptomatic lesions was verified by quantitative real-time polymerase chain reaction (n=233), and the protein was localized to smooth muscle α-actin positive cells and extracellular matrix of the fibrous cap by immunohistochemistry. PCSK6 expression positively correlated to genes associated with inflammation, matrix degradation, and mitogens in microarrays. Stimulation of human carotid smooth muscle cells in vitro with cytokines caused rapid induction of PCSK6 mRNA.

Conclusions—

Using a combination of transcriptomic and tissue microarray profiling, we demonstrate a novel approach to identify proteins differentially expressed in unstable carotid atherosclerosis. The proprotein convertase PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. Further studies are needed to clarify the role of PCSK6 in atherosclerosis.
Restriction of Calpain3 Expression to the Skeletal Muscle Prevents Cardiac Toxicity and Corrects Pathology in a Murine Model of Limb-Girdle Muscular Dystrophy
Authors: Roudaut Carinne , Le Roy Florence , Suel Laurence , Poupiot Jérôme , Charton Karine , Bartoli Marc , Richard Isabelle
Published: August 2013

Background—

Genetic defects in calpain3 (
CAPN3
) lead to limb-girdle muscular dystrophy type 2A, a disease of the skeletal muscle that affects predominantly the proximal limb muscles. We previously demonstrated the potential of adeno-associated virus–mediated transfer of the
CAPN3
gene to correct the pathological signs in a murine model for limb-girdle muscular dystrophy type 2A after intramuscular and locoregional administrations.

Methods and Results—

Here, we showed that intravenous injection of calpain3-expressing vector in mice can induce mortality in a dose-dependent manner. An anatomopathological investigation revealed large areas of fibrosis in the heart that we related to unregulated proteolytic activity of calpain3. To circumvent this toxicity, we developed new adeno-associated virus vectors with skeletal muscle–restricted expression by using new muscle-specific promoters that include the
CAPN3
promoter itself and by introducing a target sequence of the cardiac-specific microRNA-208a in the cassette. Our results show that
CAPN3
transgene expression can be successfully suppressed in the cardiac tissue, preventing the cardiac toxicity, whereas expression of the transgene in skeletal muscle reverts the pathological signs of calpain3 deficiency.

Conclusions—

The molecular strategies used in this study may be useful for any gene transfer strategy with potential toxicity in the heart.
A Relational Approach to the Study of Religious Survival Units
Authors: Reeh Niels
Published: August 2013

Abstract

The article departs from the finding that religious texts and actors relate to other religions as for instance The Old Testament relates to Canaanites, the New Testament to Jews, Pagans etc. A consequence of this inter-relatedness of religion is that religion can be studied as a relational phenomenon and that religions are engaged in a more or less intense struggle against other competing religions. Further, using John Searle’s notion of collective subjectivity, the article posits that religions are in fact an example of such collective subjectivity (Searle 1995). In this perspective, a religion can be defined and studied as the result of complex set of dynamic relations, where a central tenet of a religion is that it relates to the significant religious other. As such religion is not a stable phenomenon but embedded in a dynamic historical process, which can explain the difficulties scholars have had in defining religion.
Second record of the West African hairy bush viper Atheris hirsuta Ernst & Rödel, 2002 (Serpentes: Viperidae)
Authors: PENNER JOHANNES , GONWOUO LEGRAND NONO , RÖDEL MARK-OLIVER
Published: August 2013

The African bush vipers of the genus Atheris Cope, 1862 currently comprises 15 species, this includes A. barbouri Loveridge, 1930 (often assigned to the genus Adenorhinos; but see Lenk et al. 2001). All species occur exclusively on the African continent with most species occurring in East and Central Africa. West Africa, defined as the eco-region including Nigeria and all countries westwards, excluding Cameroon (see Penner et al. 2011), currently harbours three species of Atheris. (i) Atheris squamigera (Hallowell, 1854) which has a wide range across Central Africa and can be found in south-eastern Nigeria (Spawls & Branch 1995; Luiselli et al. 2000). However, the taxonomy of central African Atheris is still under debate and several hidden species might be included (see Broadley 1998; Lawson 1999; Lawson & Ustach 2000; Lawson et al. 2001). Concerning distribution,we follow Chippaux (2006) and others in regarding all records of A. squamigera west of Nigeria as doubtful. A true West African species is (ii) Atheris chlorechis (Pel, 1851) which ranges from Guinea, through Sierra Leone, Liberia, Côte d’Ivoire and Ghana to Togo. Its occurrence in Nigeria is unclear. So far no records exist for Benin (Ullenbruch et al. 2010; Hughes 2013; C. Toudonou pers. comm.). The third species, (iii) Atheris hirsuta Ernst & Rödel, 2002, was described from a single specimen found near the ecological research station in the Taï National Park, Côte d’Ivoire. No further records existed until this study.
Developments in the CSU-RAMS Aerosol Model: Emissions, Nucleation, Regeneration, Deposition, and Radiation
Authors: Saleeby Stephen M. , van den Heever Susan C.
Published: August 2013

The Colorado State University (CSU) Regional Atmospheric Modeling System (RAMS) has undergone development focused on improving the treatment of aerosols in the microphysics model, with the goal of examining the impacts of aerosol characteristics, scavenging, and regeneration processes, among others, on precipitation processes in clouds ranging from stratocumulus to deep convection and mixed-phase orographic clouds. Improvements in the representation of aerosols allow for more comprehensive studies of aerosol effects on cloud systems across scales. In RAMS there are now sub- and supermicrometer modes of sulfate, mineral dust, sea salt, and regenerated aerosol. All aerosol species can compete for cloud droplet nucleation, and they are regenerated via hydrometeor evaporation. A newly applied heterogeneous ice nuclei parameterization accounts for deposition nucleation and condensation and immersion freezing of aerosols greater than 0.5-μm diameter. There are also schemes for trimodal sea salt emissions and bimodal dust lofting that are functions of wind speed and surface properties. Aerosol wet and dry deposition accounts for collection by falling hydrometeors as well as gravitational settling of aerosols on water, soil, and vegetation. Aerosol radiative effects are parameterized via the Mie theory. An examination of the simulated impact of aerosol characteristics, sources, and sinks reveals mixed sensitivity among cloud types. For example, reduced aerosol solubility has little impact on deep convection since supersaturations are large and nearly all accumulation-mode aerosols activate. In contrast, reduced solubility results in reduced aerosol activation in precipitating stratocumulus. This leads to lower cloud droplet concentration, larger droplet size, and more efficient warm rain processes.
Correction of Radar QPE Errors Associated with Low and Partially Observed Brightband Layers
Authors: Qi Youcun , Zhang Jian
Published: August 2013

The melting of aggregated snow/crystals often results in an enhancement of the reflectivity observed by weather radars, and this is commonly referenced as the bright band (BB). The locally high reflectivity often causes overestimation in radar quantitative precipitation estimates (QPE) if no appropriate correction is applied. When the melting layer is high, a complete BB layer profile (including top, peak, and bottom) can be observed by the ground radar, and a vertical profile of reflectivity (VPR) correction can be made to reduce the BB impact. When a melting layer is near the ground and the bottom part of the bright band cannot be observed by the ground radar, a VPR correction cannot be made directly from the Weather Surveillance Radar-1988 Doppler (WSR-88D) radar observations. This paper presents a new VPR correction method under this situation. From high-resolution precipitation profiler data, an empirical relationship between BB peak and BB bottom is developed. The empirical relationship is combined with the apparent BB peak observed by volume scan radars and the BB bottom is found. Radar QPEs are then corrected based on the estimated BB bottom. The new method was tested on 13 radars during seven low brightband events over different areas in the United States. It is shown to be effective in reducing the radar QPE overestimation under low brightband situations.
Intensification of Hurricane Sandy (2012) through Extratropical Warm Core Seclusion
Authors: Galarneau Thomas J. , Davis Christopher A. , Shapiro Melvyn A.
Published: August 2013

Hurricane Sandy's landfall along the New Jersey shoreline at 2330 UTC 29 October 2012 produced a catastrophic storm surge stretching from New Jersey to Rhode Island that contributed to damage in excess of $50 billion—the sixth costliest U.S. tropical cyclone on record since 1900—and directly caused 72 fatalities. Hurricane Sandy's life cycle was marked by two upper-level trough interactions while it moved northward over the western North Atlantic on 26–29 October. During the second trough interaction on 29 October, Sandy turned northwestward and intensified as cold continental air encircled the warm core vortex and Sandy acquired characteristics of a warm seclusion. The aim of this study is to determine the dynamical processes that contributed to Sandy's secondary peak in intensity during its warm seclusion phase using high-resolution numerical simulations. The modeling results show that intensification occurred in response to shallow low-level convergence below 850 hPa that was consistent with the Sawyer–Eliassen solution for the secondary circulation that accompanied the increased baroclinicity in the radial direction. Additionally, cyclonic vertical vorticity generated by tilting of horizontal vorticity along an axis of frontogenesis northwest of Sandy was axisymmetrized. The axis of frontogenesis was anchored to the Gulf Stream in a region of near-surface differential diabatic heating. The unusual northwestward track of Sandy allowed the cyclonic vorticity over the Gulf Stream to form ahead of the main vortex and be readily axisymmetrized. The underlying dynamics driving intensification were nontropical in origin, and supported the reclassification of Sandy as extratropical prior to landfall.
Innovation-Framing Regulation
Authors: Ford Cristie
Published: August 2013

This article provides insights into the effective regulation of private sector innovation. It coins a term—“innovation-framing regulation”—to describe a particular quality of much of financial regulation in the recent era. It sketches a particular financial innovation (securitization and the marketing of securitized assets on derivatives markets), and describes three regulatory interactions having to do with that innovation. I identify three key assumptions that are ripe for re-evaluation: the notion that private sector innovation is beneficial, virtually by definition; the assumption that the regulatory moment is the crucial moment in regulatory design; and the belief that regulation somehow sits outside innovation and can be untouched by it. I argue that effective regulation of private sector innovation requires a clearer and more nuanced understanding of innovation, and engagement with the normative choices underpinning innovation-framing regulation.
Relative rebel strength and the onset and outcome of civil war mediation
Authors: Clayton Govinda
Published: August 2013

To what extent does the relative strength of a rebel movement impact upon the likelihood of a peace settlement in civil conflict? This article argues that relatively stronger rebels are more likely to overcome the strategic bargaining problems that can prevent the resolution of war. Relatively strong insurgents are better equipped to significantly challenge core government interests and fundamentally threaten the survival of a regime. The incumbent’s fear of future violence therefore makes mediation more likely to be undertaken in high-stakes conflicts between states and strong rebel groups. Relatively strong insurgencies are also those with the greatest leverage to negotiate enforcement mechanisms and the best equipped to defend themselves in the event that the government reneges on an agreement. This reduces the scale of the commitment problem and increases the probability of relatively strong rebel groups agreeing to a settlement with an incumbent. This argument is tested using dyadic data that capture the relative position of insurgents in civil war from 1946 to 2004. This represents an important methodological shift within the mediation literature, which has in the past largely relied upon aggregate country-level data. The results suggest that relatively stronger insurgents are more likely to force the state to open a mediation process and eventually concede some form of settlement. This is further evidence of the need to capture the dyadic relations between actors with fine-grained disaggregated data.
Prospects for the UK Economy
Authors: Kirby Simon
Published: August 2013

The production of this forecast is supported by the Institute's Corporate Members: Bank of England, HM Treasury, Mizuho Research Institute Ltd, the Office for National Statistics, Santander (UK) plc and by the members of the NiGEM users group.
Is ‘Holy Scripture’ Christian?: A Lucan perspective
Authors: Twelftree Graham H.
Published: August 2013

The view of large sections of the Church that the Bible alone is the source for Christian thought and living is tested against the writings of Luke. While Luke took Scripture to be important, he considered that without the interpretative role of ideal figures it could be mute. Further, theological creativity did not come through exploring the text, but in using the text to explain a perceived act of God. In this there was a reciprocal relationship between the meaning of the text and understanding God’s activity: Scripture predicted and explained God’s activity, and God’s activity explained Scripture. Moreover, Luke proposed that God guided believers independent of, and sometimes over against, the sacred text. For Luke Scripture was not the supreme or only source consulted for Christian thought and behaviour, and the raw material of theological creativity was the experience of divine activity rather than exegesis.
Motivated Reflection on Attitude-Inconsistent Information
Authors: Clarkson Joshua J. , Valente Matthew J. , Leone Christopher , Tormala Zakary L.
Published: August 2013

The mere thought effect is defined in part by the tendency of self-reflective thought to heighten the generation of and reflection on attitude-consistent thoughts. By focusing on individuals’ fears of invalidity, we explored the possibility that the mere opportunity for thought sometimes motivates reflection on attitude-inconsistent thoughts. Across three experiments, dispositional and situational fear of invalidity was shown to heighten reflection on attitude-inconsistent thoughts. This heightened reflection, in turn, interacted with individuals’ thought confidence to determine whether attitude-inconsistent thoughts were assimilated or refuted and consequently whether individuals’ attitudes and behavioral intentions depolarized or polarized following a sufficient opportunity for thought, respectively. These findings emphasize the impact of motivational influences on thought reflection and generation, the importance of thought confidence in the assimilation and refutation of self-generated thought, and the dynamic means by which the mere thought bias can impact self-persuasion.
Lake Amenities, Environmental Degradation, and Great Lakes Regional Growth
Authors: Stephens Heather M. , Partridge Mark D.
Published: August 2013

Regional migration and growth are increasingly associated with high-quality in situ natural amenities. However, most of the previous US research has focused on the natural amenities of the Mountain West or the South. The Great Lakes, with their abundant fresh water and natural amenities, would also appear well positioned to provide the foundation for this type of economic growth. Yet, while some parts of the western Great Lakes region are prime examples of amenity-led growth, other areas in the eastern Great Lakes may not have capitalized on their natural amenities, perhaps because of their strong industrial legacy. Using a unique county-level data set for the Great Lakes region (including Indiana, Illinois, Michigan, Minnesota, New York, Ohio, Pennsylvania, and Wisconsin), we test whether growth in the region is associated with proximity to lake amenities and whether there are offsetting industrial legacy or pollution effects. We also examine whether amenities have additional attraction value for those with high levels of human capital. Consistent with theory that suggests that natural amenities are normal or superior goods, we find that coastal areas in the region are positively associated with increases in shares of college graduates. However, we find little evidence that lake amenities contribute to broader household migration, especially after 2000. Based on these results, there may be opportunities to leverage Great Lake amenities to support economic growth in terms of attracting individuals with high levels of human capital who are most likely to make quality of life migration decisions.
A “Three-Plus-One” Evaluation Model for Clinical Research Management
Authors: Dilts David M.
Published: August 2013

Clinical research management (CRM) is a critical resource for the management of clinical trials and it requires proper evaluation. This article advances a model of evaluation that has three local levels, plus one global level, for evaluating the value of CRM. The primary level for evaluation is that of the study or processes level. The managerial or aggregate level concerns management of the portfolio of trials under the control of the CRM office. The third, often overlooked level of evaluation, is the strategic level, whose goal is encapsulated in the phrase, “doing the right trials, while doing trials right.” The global (“plus one”) evaluation level concerns the need to evaluate the ever-increasing number of multi-institutional and multinational studies. As there are host of evaluation metrics, this article provides representative examples of metrics at each level and provides methods that can aid in the selecting appropriate metrics for an organization.
Mediating the Paradoxes of Organizational Governance through Numbers
Authors: Michaud Valérie
Published: August 2013

Despite abundant prescriptions regarding what boards should do, we know little about what they actually do, especially in the face of the paradoxical goals of both ensuring control (as expressed in agency theory) and fostering collaboration (as expressed in stewardship theory) simultaneously. Drawing from the study of a co-operative over a 10-year period (including ethnographic data collection spanning 3 years), this paper shows the role of numbers in mediating paradoxes of governance. We show that numbers from very different spheres support different models of governance, prompt their change, but also their coexistence. Paradoxical control–collaboration dynamics are embraced, fed by two number-supported micro-practices: personalizing/professionalizing issues and creating new calculable spaces. These practices enable board members to both “act at a distance” and control, while they are also “kept at a distance” from the general manager, who ensures the board’s collaboration.
Intergenerational Assistance to Adult Children
Authors: Goodsell Todd L. , James Spencer L. , Yorgason Jeremy B. , Call Vaughn R. A.
Published: August 2013

This study considers how the number of sisters and brothers affects the flow of aid from older parents to adult children. Using data from the 2004 Middletown Kinship Survey ( N = 338), the authors find that the aid adults receive from their parents varies by the gender composition of the sibship. Adults with more sisters tend to receive less assistance from their older parents. This holds true across a range of helping behaviors, including financial, gifts, transportation, housework and yard work, and technology. The pattern does not hold for brothers. Possible explanations include resource dilution (daughters drawing more on parents’ resources, leaving fewer resources to go around) or cooperative networks created among sisters (thus rendering aid from parents less necessary).