bluuebunny/crossref_metadata_2025 huggingface dataset:
Opposition-Based Improved PSO for Optimal Reactive Power Dispatch and Voltage Control
Authors: Cao Shengrang , Ding Xiaoqun , Wang Qingyan , Chen Bingyan
Published: June 2015

An opposition-based improved particle swarm optimization algorithm (OIPSO) is presented for solving multiobjective reactive power optimization problem. OIPSO uses the opposition learning to improve search efficiency, adopts inertia weight factors to balance global and local exploration, and takes crossover and mutation and neighborhood model strategy to enhance population diversity. Then, a new multiobjective model is built, which includes system network loss, voltage dissatisfaction, and switching operation. Based on the market cost prices, objective functions are converted to least-cost model. In modeling process, switching operation cost is described according to the life cycle cost of transformer, and voltage dissatisfaction penalty is developed considering different voltage quality requirements of customers. The experiment is done on the new mathematical model. Through the simulation of IEEE 30-, 118-bus power systems, the results prove that OIPSO is more efficient to solve reactive power optimization problems and the model is more accurate to reflect the real power system operation.
Model-Based Experimental Development of Passive Compliant Robot Legs from Fiberglass Composites
Authors: Lin Shang-Chang , Hu Chia-Jui , Shih Wen-Pin , Lin Pei-Chun
Published: June 2015

We report on the methodology of developing compliant, half-circular, and composite robot legs with designable stiffness. First, force-displacement experiments on flat cantilever composites made by one or multifiberglass cloths are executed. By mapping the cantilever mechanics to the virtual spring model, the equivalent elastic moduli of the composites can be derived. Next, by using the model that links the curved beam mechanics back to the virtual spring, the resultant stiffness of the composite in a half-circular shape can be estimated without going through intensive experimental tryouts. The overall methodology has been experimentally validated, and the fabricated composites were used on a hexapod robot to perform walking and leaping behaviors.
Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer
Authors: Yeruva Sri Lakshmi Hyndavi , Nwabudike Stanley Madu , Ogbonna Onyekachi Henry , Oneal Patricia
Published: June 2015

Aromatase inhibitors (AIs) are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature.
Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women
Authors: Baldani Dinka Pavicic , Skrgatic Lana , Ougouag Roya
Published: June 2015

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.
Development of Hybrid Models for a Vapor-Phase Fungi Bioreactor
Authors: Spigno Giorgia , Tronci Stefania
Published: June 2015

This study is aimed at the development of a model for an experimental vapour-phase fungi bioreactor, which could be derived in a simple way using the available measurements of a pilot-plant reactor, without the development of ad hoc experiments for the evaluation of fungi kinetics and the estimation of parameters related to biofilm characteristics. The proposed approach is based on hybrid models, obtained by the connection of the mass balance equation (used in traditional phenomenological models) with a feedforward neural network (used in black-box modelling), and the proper use of statistical tools for the model assessment and system understanding. Two different hybrid models were developed and compared by proper performance indexes, and their capability to predict the biological complex phenomena was demonstrated and compared to that of a first-principle model.
The Burden of Hand Injuries at a Tertiary Hospital in Sub-Saharan Africa
Authors: Makobore P. , Galukande M. , Kalanzi E. , Kijjambu S. C.
Published: June 2015

Background. Hand injuries are common worldwide and lead to heavy financial losses in terms of treatment, job loss, and time off duty. There is paucity of data on hand injuries in sub-Saharan Africa. The aim of this study was to determine the burden and early outcomes of hand injuries at a tertiary hospital.Method. A descriptive prospective study. Eligible patients were recruited over 5 months and followed up for four weeks. Pain, nerve function, and gross functions of the hand were assessed.Results. In total 138 patients were enrolled out of 2940 trauma patients. Of these, 122 patients returned for follow-up. The majority of the patients were males (83%). Mean age was 26.7 years (SD 12.8). The commonest places of injury occurrence were the workplace (36%), home (28%), and on the road (traffic crushes) (23%). Machines (21.3%) were the commonest agent of injuries; others were knives (10%) and broken glass (10%). Sixty-three (51%) patients still had pain at one month.Conclusions. Hand injuries accounted for 4.7% of all trauma patients. Road traffic crushes and machines were the commonest causes of hand injuries. Men in their 20s were mostly involved. Sensitization for prevention strategies at the workplace may be helpful.
Educational Applications for Blind and Partially Sighted Pupils Based on Speech Technologies for Serbian
Authors: Lučić Branko , Ostrogonac Stevan , Vujnović Sedlar Nataša , Sečujski Milan
Published: June 2015

The inclusion of persons with disabilities has always represented an important issue. Advancements within the field of computer science have enabled the development of different types of aids, which have significantly improved the quality of life of the disabled. However, for some disabilities, such as visual impairment, the purpose of these aids is to establish an alternative communication channel and thus overcome the user’s disability. Speech technologies play the crucial role in this process. This paper presents the ongoing efforts to create a set of educational applications based on speech technologies for Serbian for the early stages of education of blind and partially sighted children. Two educational applications dealing with memory exercises and comprehension of geometrical shapes are presented, along with the initial tests results obtained from research including visually impaired pupils.
Uncertainty Quantification in Control Problems for Flocking Models
Authors: Albi Giacomo , Pareschi Lorenzo , Zanella Mattia
Published: June 2015

The optimal control of flocking models with random inputs is investigated from a numerical point of view. The effect of uncertainty in the interaction parameters is studied for a Cucker-Smale type model using a generalized polynomial chaos (gPC) approach. Numerical evidence of threshold effects in the alignment dynamic due to the random parameters is given. The use of a selective model predictive control permits steering of the system towards the desired state even in unstable regimes.
Application of the Mechanism Design to Develop the RGB LEDs Color Mixing
Authors: Hung Chih-Ching , Li Yan-Huei , Yang Ping-Han
Published: June 2015

The big advantage of LED is the flexible spectral design to make white light using different color mixing schemes. Recently, the color mixing of RGB LEDs is mostly done by sealing all three chips at single package and regulated the mix ratio of these three colors to produce the color of light. And, by changing the LEDs array alignment, RGB chips can achieve overlapping colors of light and create the fun of changing colors in light mixing. Therefore, the purpose of this study is to propose an innovative technique of light mixing. By applying the mechanism design, a RGB light mixing mechanism is produced. Each of the RGB LEDs lamp-type is installed on the couple link of the three mechanisms, respectively. By driving a crank makes the couple link and an output link to produce the relative motion, this will result in the fact that the RGB lamps can project lights on the same plane in order to obtain the color mixing. Unlike mixing technique by control system, this design generates light mixing and changes of color with the synchronized driving of three mechanisms, thus achieving the dazzling perception of single-color lights or mixing of multiple colors for creating ambience of a space.
A Framework and Improvements of the Korea Cloud Services Certification System
Authors: Jeon Hangoo , Seo Kwang-Kyu
Published: June 2015

Cloud computing service is an evolving paradigm that affects a large part of the ICT industry and provides new opportunities for ICT service providers such as the deployment of new business models and the realization of economies of scale by increasing efficiency of resource utilization. However, despite benefits of cloud services, there are some obstacles to adopt such as lack of assessing and comparing the service quality of cloud services regarding availability, security, and reliability. In order to adopt the successful cloud service and activate it, it is necessary to establish the cloud service certification system to ensure service quality and performance of cloud services. This paper proposes a framework and improvements of the Korea certification system of cloud service. In order to develop it, the critical issues related to service quality, performance, and certification of cloud service are identified and the systematic framework for the certification system of cloud services and service provider domains are developed. Improvements of the developed Korea certification system of cloud services are also proposed.
Vibration Training Triggers Brown Adipocyte Relative Protein Expression in Rat White Adipose Tissue
Authors: Sun Chao , Zeng Ruixia , Cao Ge , Song Zhibang , Zhang Yibo , Liu Chang
Published: June 2015

Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group(n=6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 and inflammatory relative proteins, IL-6 and TNFα. Simultaneously, ATP content and PPARγprotein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve.
(Fuzzy) Ideals of BN‐Algebras
Authors: Dymek Grzegorz , Walendziak Andrzej
Published: June 2015

The notions of an ideal and a fuzzy ideal in BN‐algebras are introduced. The properties and characterizations of them are investigated. The concepts of normal ideals and normal congruences of a BN‐algebra are also studied, the properties of them are displayed, and a one‐to‐one correspondence between them is presented. Conditions for a fuzzy
set to be a fuzzy ideal are given. The relationships between ideals and fuzzy ideals of a BN‐algebra are established. The homomorphic properties of fuzzy ideals of a BN‐algebra are provided. Finally, characterizations of Noetherian BN‐algebras and Artinian BN‐algebras via fuzzy ideals are obtained.
Quantification of Internalized Silica Nanoparticles via STED Microscopy
Authors: Peuschel Henrike , Ruckelshausen Thomas , Cavelius Christian , Kraegeloh Annette
Published: June 2015

The development of safe engineered nanoparticles (NPs) requires a detailed understanding of their interaction mechanisms on a cellular level. Therefore, quantification of NP internalization is crucial to predict the potential impact of intracellular NP doses, providing essential information for risk assessment as well as for drug delivery applications. In this study, the internalization of 25 nm and 85 nm silica nanoparticles (SNPs) in alveolar type II cells (A549) was quantified by application of super-resolution STED (stimulated emission depletion) microscopy. Cells were exposed to equal particle number concentrations (9.2×1010particles mL−1) of each particle size and the sedimentation of particles during exposure was taken into account. Microscopy images revealed that particles of both sizes entered the cells after 5 h incubation in serum supplemented and serum-free medium. According to thein vitrosedimentation, diffusion, and dosimetry (ISDD) model 20–27% of the particles sedimented. In comparison, 102-103NPs per cell were detected intracellularly serum-containing medium. Furthermore, in the presence of serum, no cytotoxicity was induced by the SNPs. In serum-free medium, large agglomerates of both particle sizes covered the cells whereas only high concentrations (≥ 3.8 × 1012particles mL−1) of the smaller particles induced cytotoxicity.
Confrontation Naming and Reading Abilities at Primary School: A Longitudinal Study
Authors: Luoni Chiara , Balottin Umberto , Rosana Laura , Savelli Enrico , Salini Silvia , Termine Cristiano
Published: June 2015

Background. Confrontation naming tasks are useful in the assessment of children with learning and language disorders.Objectives. The aims of this study were (1) providing longitudinal data on confrontation naming; (2) investigating the role of socioeconomic status (SES), intelligence, age, and gender in confrontation naming; (3) identifying relationship between confrontation naming and reading abilities (fluency, accuracy, and comprehension).Method. A five-year longitudinal investigation of confrontation naming (i.e., the Boston Naming Test (BNT)) in a nonclinical sample of Italian primary school children was conducted (n=126), testing them at the end of each school year, to assess nonverbal intelligence, confrontation naming, and reading abilities.Results. Performance on the BNT emerged as a function of IQ and SES. Significant correlations between confrontation naming and reading abilities, especially comprehension, were found; BNT scores correlated better with reading fluency than with reading accuracy.Conclusions. The longitudinal data obtained in this study are discussed with regard to reading abilities, intelligence, age, gender, and socioeconomic status.
SLFN11: Achilles' Heel or Troublemaker
Authors: Kovar Heinrich
Published: June 2015

SLFN11 expression correlates with sensitivity of tumors to topoisomerase and DNA-targeting drugs and consequently with prognosis. Regulation of SLFN11 by ETS factors opens new avenues to treatment optimization, maximizing antitumor activity and minimizing adverse side effects. Interrogating drug-induced gene expression signatures for SLFN11 modulations may affect the design of therapeutic regimens. Clin Cancer Res; 21(18); 4033–4. ©2015 AACR.

See related article by Tang et al., p. 4184
E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer
Authors: Cheng Chao , Varn Frederick S. , Marsit Carmen J.
Published: June 2015

Bladder cancer is a common malignant disease, with non–muscle-invasive bladder cancer (NMIBC) representing the majority of tumors. This cancer subtype is typically treated by transurethral resection. In spite of treatment, up to 70% of patients show local recurrences. Intravesical BCG (Bacillus Calmette-Guerin) immunotherapy has been widely used to treat NMIBC, but it fails to suppress recurrence of bladder tumors in up to 40% of patients. Therefore, the development of prognostic markers is needed to predict the progression of bladder cancer and the efficacy of intravesical BCG treatment. This study demonstrates the effectiveness of an E2F4 signature for prognostic prediction of bladder cancer. E2F4 scores for each sample in a bladder cancer expression dataset were calculated by summarizing the relative expression levels of E2F4 target genes identified by ChIP-seq, and then the scores were used to stratify patients into good- and poor-outcome groups. The molecular signature was investigated in a single bladder cancer dataset and then its effectiveness was confirmed in two meta-bladder datasets consisting of specimens from multiple independent studies. These results were consistent in different datasets and demonstrate that the E2F4 score is predictive of clinical outcomes in bladder cancer, with patients whose tumors exhibit an E2F4 score >0 having significantly shorter survival times than those with an E2F4 score <0, in both non–muscle-invasive, and muscle-invasive bladder cancer. Furthermore, although intravesical BCG immunotherapy can significantly improve the clinical outcome of NMIBC patients with positive E2F4 scores (E2F4>0 group), it does not show significant treatment effect for those with negative scores (E2F4<0 group).

Implications: The E2F4 signature can be applied to predict the progression/recurrence and the responsiveness of patients to intravesical BCG immunotherapy in bladder cancer. Mol Cancer Res; 13(9); 1316–24. ©2015 AACR.
Activation of the PI3K/Akt/mTOR and MAPK Signaling Pathways in Response to Acute Solar-Simulated Light Exposure of Human Skin
Authors: Bermudez Yira , Stratton Steven P. , Curiel-Lewandrowski Clara , Warneke James , Hu Chengcheng , Bowden George T. , Dickinson Sally E. , Dong Zigang , Bode Ann M. , Saboda Kathylynn , Brooks Christine A. , Petricoin Emanuel F. , Hurst Craig A. , Alberts David S. , Einspahr Janine G.
Published: June 2015

The incidence of skin cancer is higher than all other cancers and continues to increase, with an average annual cost over $8 billion in the United States. As a result, identifying molecular pathway alterations that occur with UV exposure to strategize more effective preventive and therapeutic approaches is essential. To that end, we evaluated phosphorylation of proteins within the PI3K/Akt and MAPK pathways by immunohistochemistry in sun-protected skin after acute doses of physiologically relevant solar-simulated ultraviolet light (SSL) in 24 volunteers. Biopsies were performed at baseline, 5 minutes, 1, 5, and 24 hours after SSL irradiation. Within the PI3K/Akt pathway, we found activation of Akt (serine 473) to be significantly increased at 5 hours while mTOR (serine 2448) was strongly activated early and was sustained over 24 hours after SSL. Downstream, we observed a marked and sustained increase in phospho-S6 (serine 235/S236), whereas phospho-4E-BP1 (threonines 37/46) was increased only at 24 hours. Within the MAPK pathway, SSL-induced expression of phospho-p38 (threonine 180/tyrosine 182) peaked at 1 to 5 hours. ERK 1/2 was observed to be immediate and sustained after SSL irradiation. Phosphorylation of histone H3 (serine 10), a core structural protein of the nucleosome, peaked at 5 hours after SSL irradiation. The expression of both p53 and COX-2 was increased at 5 hours and was maximal at 24 hours after SSL irradiation. Apoptosis was significantly increased at 24 hours as expected and indicative of a sunburn-type response to SSL. Understanding the timing of key protein expression changes in response to SSL will aid in development of mechanistic-based approaches for the prevention and control of skin cancers. Cancer Prev Res; 8(8); 720–8. ©2015 AACR.
Two Faces of SIVA
Authors: Resnick-Silverman Lois , Manfredi James J.
Published: June 2015

Summary: In non–small cell lung cancer cells that contain a mutated KRAS gene, SIVA, a p53 target gene that is critical for apoptosis, is overexpressed in a p53-independent manner and promotes tumorigenesis through the stimulation of mTOR signaling. The ablation of Siva in conditional knockout mice results in an inhibition of tumor development that makes SIVA an interesting new candidate therapeutic target for the treatment of a carcinoma with few therapeutic options. Cancer Discov; 5(6); 581–3. ©2015 AACR.

See related article by Van Nostrand and colleagues, p. 622.
Evaluation of the Incremental Prognostic Utility of Increasingly Complex Testing in Chronic Heart Failure
Authors: Ahmad Tariq , O’Brien Emily C. , Schulte Phillip J. , Stevens Susanna R. , Fiuzat Mona , Kitzman Dalane W. , Adams Kirkwood F. , Kraus William E. , Piña Ileana L. , Donahue Mark P. , Zannad Faiez , Whellan David J. , O’Connor Christopher M. , Felker G. Michael
Published: June 2015

Background—

Current heart failure (HF) risk prediction models do not consider how individual patient assessments occur in incremental steps; furthermore, each additional diagnostic evaluation may add cost, complexity, and potential morbidity.

Methods and Results—

Using a cohort of well-treated ambulatory HF patients with reduced ejection fraction who had complete clinical, laboratory, health-related quality of life, imaging, and exercise testing data, we estimated incremental prognostic information provided by 5 assessment categories, performing an additional analysis on those with available N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. We compared the incremental value of each additional assessment (quality of life screen, laboratory testing, echocardiography, and exercise testing) to baseline clinical assessment for predicting clinical outcomes (all-cause mortality, all-cause mortality/hospitalization, and cardiovascular death/HF hospitalizations), gauging incremental improvements in prognostic ability with more information using area under the curve and reclassification improvement (net reclassification index), with and without NT-proBNP availability. Of 2331 participants, 1631 patients had complete clinical data; of these, 1023 had baseline NT-proBNP. For prediction of all-cause mortality, models with incremental assessments sans NT-proBNP showed improvements in
C
-indices (0.72 [clinical model alone]−0.77 [complete model]). Compared with baseline clinical assessment alone, net reclassification index improved from 0.035 (w/laboratory data) to 0.085 (complete model). These improvements were significantly attenuated for models in the subset with measured NT-proBNP data (
c
-indices: 0.80 [w/laboratory data]−0.81 [full model]); net reclassification index improvements were similarly marginal (0.091→0.096); prediction of other clinical outcomes had similar findings.

Conclusions—

In chronic HF patients with reduced ejection fraction, the marginal benefit of complex prognostic evaluations should be weighed against potential patient discomfort and cost escalation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00047437.
Transcatheter Aortic Valve Implantation With the New Balloon-Expandable Sapien 3 Versus Sapien XT Valve System
Authors: Nijhoff Freek , Abawi Masieh , Agostoni Pierfrancesco , Ramjankhan Faiz Z. , Doevendans Pieter A. , Stella Pieter R.
Published: June 2015

Background—

The new balloon-expandable Sapien 3 transcatheter heart valve (S3-THV) incorporates new features to reduce aortic regurgitation (AR) and vascular complications in transcatheter aortic valve implantation. Aim of this study is to compare the outcomes of the S3-THV with the preceding Sapien XT THV (SXT-THV) in patients who underwent transcatheter aortic valve implantation for symptomatic severe native aortic stenosis.

Methods and Results—

Eligible patients were retrospectively identified in our institutional database and periprocedural clinical and imaging data were collected. Non-parsimonious one-to-many propensity score matching was performed to account for differences in baseline characteristics. Between November 2011 and December 2014, 167 patients underwent balloon-expandable transcatheter aortic valve implantation with either the S3-THV (n=49) or SXT-THV (n=118). Forty-four (89.8%) S3-THV patients were matched to 66 (55.9%) SXT-THV patients (mean age 80.3±8.4 and 80.5±7.8 years, median EuroSCORE 15.8 and 16.5%, respectively). In the S3-THV and SXT-THV groups, transfemoral approach (77.3% versus 78.8%) and postdilatation rates (15.9% versus 12.1%) were similar. Predischarge echocardiography demonstrated a lower incidence of ≥mild AR (15.9% versus 46.2%,
P
=0.003) for the S3-THV, despite reduced annulus area to prosthesis oversizing (8.2±5.1 versus 18.2±10.7%,
P
=0.001). Transfemoral access site–related life-threatening or major bleedings and vascular complications were absent in the S3-THV group (0% versus 7.7%,
P
=0.15). No differences were observed in pacemaker implantation rate (9.8% versus 8.8%,
P
=0.94) and 30-day mortality (both 5%).

Conclusions—

In this retrospective, propensity score–matched analysis, the S3-THV performed superiorly to the SXT-THV, as demonstrated by improved valve patency and increased transfemoral access safety.
Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis
Authors: Villa Francesco , Carrizzo Albino , Spinelli Chiara C. , Ferrario Anna , Malovini Alberto , Maciąg Anna , Damato Antonio , Auricchio Alberto , Spinetti Gaia , Sangalli Elena , Dang Zexu , Madonna Michele , Ambrosio Mariateresa , Sitia Leopoldo , Bigini Paolo , Calì Gaetano , Schreiber Stefan , Perls Thomas , Fucile Sergio , Mulas Francesca , Nebel Almut , Bellazzi Riccardo , Madeddu Paolo , Vecchione Carmine , Puca Annibale A.
Published: June 2015

Rationale:

Long living individuals show delay of aging, which is characterized by the progressive loss of cardiovascular homeostasis, along with reduced endothelial nitric oxide synthase activity, endothelial dysfunction, and impairment of tissue repair after ischemic injury.

Objective:

Exploit genetic analysis of long living individuals to reveal master molecular regulators of physiological aging and new targets for treatment of cardiovascular disease.

Methods and Results:

We show that the polymorphic variant rs2070325 (Ile229Val) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) associates with exceptional longevity, under a recessive genetic model, in 3 independent populations. Moreover, the expression of BPIFB4 is instrumental to maintenance of cellular and vascular homeostasis through regulation of protein synthesis. BPIFB4 phosphorylation/activation by protein-kinase-R–like endoplasmic reticulum kinase induces its complexing with 14-3-3 and heat shock protein 90, which is facilitated by the longevity-associated variant. In isolated vessels, BPIFB4 is upregulated by mechanical stress, and its knock-down inhibits endothelium-dependent vasorelaxation. In hypertensive rats and old mice, gene transfer of longevity-associated variant-BPIFB4 restores endothelial nitric oxide synthase signaling, rescues endothelial dysfunction, and reduces blood pressure levels. Furthermore, BPIFB4 is implicated in vascular repair. BPIFB4 is abundantly expressed in circulating CD34
+
cells of long living individuals, and its knock-down in endothelial progenitor cells precludes their capacity to migrate toward the chemoattractant SDF-1. In a murine model of peripheral ischemia, systemic gene therapy with longevity-associated variant-BPIFB4 promotes the recruitment of hematopoietic stem cells, reparative vascularization, and reperfusion of the ischemic muscle.

Conclusions:

Longevity-associated variant-BPIFB4 may represent a novel therapeutic tool to fight endothelial dysfunction and promote vascular reparative processes.
Differential Role of an NF-κB Transcriptional Response Element in Endothelial Versus Intimal Cell VCAM-1 Expression
Authors: Milstone David S. , Ilyama Motoi , Chen Mian , O’Donnell Peter , Davis Vannessa M. , Plutzky Jorge , Brown Jonathan D. , Haldar Saptarsi M. , Siu Allan , Lau Andrew C. , Zhu Su-Ning , Basheer Mayada F. , Collins Tucker , Jongstra-Bilen Jenny , Cybulsky Myron I.
Published: June 2015

Rationale:

Human and murine
Vcam1
promoters contain 2 adjacent nuclear factor-κB (NF-κB)–binding elements. Both are essential for cytokine-induced transcription of transiently transfected promoter–reporter constructs. However, the relevance of these insights to regulation of the endogenous
Vcam1
gene and to pathophysiological processes in vivo remained unknown.

Objective:

Determine the role of the 5′ NF-κB–binding element in expression of the endogenous
Vcam1
gene.

Methods and Results:

Homologous recombination in embryonic stem cells was used to inactivate the 5′ NF-κB element in the
Vcam1
promoter and alter 3 nucleotides in the 5′ untranslated region to allow direct comparison of wild-type versus mutant allele RNA expression and chromatin configuration in heterozygous mice. Systemic treatment with inflammatory cytokines or endotoxin (lipopolysaccharide) induced lower expression of the mutant allele relative to wild-type by endothelial cells in the aorta, heart, and lungs. The mutant allele also showed lower endothelial expression in 2-week atherosclerotic lesions in
Vcam1
heterozygous/low-density lipoprotein receptor-deficient mice fed a cholesterol-rich diet. In vivo chromatin immunoprecipitation assays of heart showed diminished lipopolysaccharide-induced association of RNA polymerase 2 and NF-κB p65 with the mutant promoter. In contrast, expression of mutant and wild-type alleles was comparable in intimal cells of wire-injured carotid artery and 4- to 12-week atherosclerotic lesions.

Conclusions:

This study highlights differences between in vivo and in vitro promoter analyses, and reveals a differential role for a NF-κB transcriptional response element in endothelial vascular cell adhesion molecule-1 expression induced by inflammatory cytokines or a cholesterol-rich diet versus intimal cell expression in atherosclerotic lesions and injured arteries.
Vascular Smooth Muscle LRP6 Limits Arteriosclerotic Calcification in Diabetic LDLR
−/−
Mice by Restraining Noncanonical Wnt Signals
Authors: Cheng Su-Li , Ramachandran Bindu , Behrmann Abraham , Shao Jian-Su , Mead Megan , Smith Carolyn , Krchma Karen , Bello Arredondo Yoanna , Kovacs Attila , Kapoor Kapil , Brill Laurence M. , Perera Ranjan , Williams Bart O. , Towler Dwight A.
Published: June 2015

Rationale:

Wnt signaling regulates key aspects of diabetic vascular disease.

Objective:

We generated
SM22-Cre;LRP6(fl/fl);LDLR
−/−
mice to determine contributions of Wnt coreceptor low-density lipoprotein receptor–related protein 6 (LRP6) in the vascular smooth muscle lineage of male low-density lipoprotein receptor–null mice, a background susceptible to diet (high-fat diet)–induced diabetic arteriosclerosis.

Methods and Results:

As compared with
LRP6(fl/fl);LDLR
−/−
controls,
SM22-Cre;LRP6(fl/fl);LDLR
−/−
(LRP6-VKO) siblings exhibited increased aortic calcification on high-fat diet without changes in fasting glucose, lipids, or body composition. Pulse wave velocity (index of arterial stiffness) was also increased. Vascular calcification paralleled enhanced aortic osteochondrogenic programs and circulating osteopontin (OPN), a matricellular regulator of arteriosclerosis. Survey of ligands and Frizzled (Fzd) receptor profiles in LRP6-VKO revealed upregulation of canonical and noncanonical Wnts alongside Fzd10. Fzd10 stimulated noncanonical signaling and
OPN
promoter activity via an upstream stimulatory factor (USF)–activated cognate inhibited by LRP6. RNA interference revealed that USF1 but not USF2 supports
OPN
expression in LRP6-VKO vascular smooth muscle lineage, and immunoprecipitation confirmed increased USF1 association with
OPN
chromatin. ML141, an antagonist of cdc42/Rac1 noncanonical signaling, inhibited USF1 activation, osteochondrogenic programs, alkaline phosphatase, and vascular smooth muscle lineage calcification. Mass spectrometry identified LRP6 binding to protein arginine methyltransferase (PRMT)-1, and nuclear asymmetrical dimethylarginine modification was increased with LRP6-VKO. RNA interference demonstrated that PRMT1 inhibits
OPN
and
TNAP
, whereas PRMT4 supports expression. USF1 complexes containing the histone H3 asymmetrically dimethylated on Arg-17 signature of PRMT4 are increased with LRP6-VKO.
Jmjd6
, a demethylase downregulated with LRP6 deficiency, inhibits
OPN
and
TNAP
expression, USF1: histone H3 asymmetrically dimethylated on Arg-17 complex formation, and transactivation.

Conclusions:

LRP6 restrains vascular smooth muscle lineage noncanonical signals that promote osteochondrogenic differentiation, mediated in part via USF1- and arginine methylation–dependent relays.
Superoxide Enhances Ca
2+
Entry Through L-Type Channels in the Renal Afferent Arteriole
Authors: Vogel Paul A. , Yang Xi , Moss Nicholas G. , Arendshorst William J.
Published: June 2015

Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in the renal microcirculation is poorly understood. The present experiments examined the acute effect of superoxide generated by paraquat on calcium entry pathways in isolated rat afferent arterioles. The peak increase in cytosolic calcium concentration caused by KCl (40 mmol/L) was 99±14 nmol/L. The response to this membrane depolarization was mediated exclusively by L-type channels because it was abolished by nifedipine but was unaffected by the T-type channel blocker mibefradil. Paraquat increased superoxide production (dihydroethidium fluorescence), tripled the peak response to KCl to 314±68 nmol/L (
P
<0.001) and doubled the plateau response. These effects were abolished by tempol and nitroblue tetrazolium, but not by catalase, confirming actions of superoxide and not of hydrogen peroxide. Unaffected by paraquat and superoxide was calcium entry through store-operated calcium channels activated by thapsigargin-induced calcium depletion of sarcoplasmic reticular stores. Also unresponsive to paraquat was ryanodine receptor–mediated calcium-induced calcium release from the sarcoplasmic reticulum. Our results provide new evidence that superoxide enhances calcium entry through L-type channels activated by membrane depolarization in rat cortical afferent arterioles, without affecting calcium entry through store-operated entry or ryanodine receptor–mediated calcium mobilization.
Tumor Necrosis Factor Receptor–Associated Factor 3 Is a Positive Regulator of Pathological Cardiac Hypertrophy
Authors: Jiang Xi , Deng Ke-Qiong , Luo Yuxuan , Jiang Ding-Sheng , Gao Lu , Zhang Xiao-Fei , Zhang Peng , Zhao Guang-Nian , Zhu Xueyong , Li Hongliang
Published: June 2015

Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor–associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor–related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II– or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3–TBK1–AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process.
AMPK Dilates Resistance Arteries via Activation of SERCA and BK
Ca
Channels in Smooth Muscle
Authors: Schneider Holger , Schubert Kai Michael , Blodow Stephanie , Kreutz Claus-Peter , Erdogmus Serap , Wiedenmann Margarethe , Qiu Jiehua , Fey Theres , Ruth Peter , Lubomirov Lubomir T. , Pfitzer Gabriele , Mederos y Schnitzler Michael , Hardie D. Grahame , Gudermann Thomas , Pohl Ulrich
Published: June 2015

The protective effects of 5′-AMP–activated protein kinase (AMPK) on the metabolic syndrome may include direct effects on resistance artery vasomotor function. However, the precise actions of AMPK on microvessels and their potential interaction are largely unknown. Thus, we set to determine the effects of AMPK activation on vascular smooth muscle tone and the underlying mechanisms. Resistance arteries isolated from hamster and mouse exhibited a pronounced endothelium-independent dilation on direct pharmacological AMPK activation by 2 structurally unrelated compounds (PT1 and A769662). The dilation was associated with a decrease of intracellular-free calcium [Ca
2+
]
i
in vascular smooth muscle cell. AMPK stimulation induced activation of BK
Ca
channels as assessed by patch clamp studies in freshly isolated hamster vascular smooth muscle cell and confirmed by direct proof of membrane hyperpolarization in intact arteries. The BK
Ca
channel blocker iberiotoxin abolished the hyperpolarization but only partially reduced the dilation and did not affect the decrease of [Ca
2+
]
i
. By contrast, the sarcoplasmic/endoplasmic Ca
2+
-ATPase (SERCA) inhibitor thapsigargin largely reduced these effects, whereas combined inhibition of SERCA and BK
Ca
channels virtually abolished them. AMPK stimulation significantly increased the phosphorylation of the SERCA modulator phospholamban at the regulatory T17 site. Stimulation of smooth muscle AMPK represents a new, potent vasodilator mechanism in resistance vessels. AMPK directly relaxes vascular smooth muscle cell by a decrease of [Ca
2+
]
i
. This is achieved by calcium sequestration via SERCA activation, as well as activation of BK
Ca
channels. There is in part a mutual compensation of both calcium-lowering mechanisms. However, SERCA activation which involves an AMPK-dependent phosphorylation of phospholamban is the predominant mechanism in resistance vessels.
Price or Prize: The Artist as Vertreter
Authors: Spieker Sven
Published: June 2015

This article discusses different modes of delegation in Martin Kippenberger's work. Drawing both on the artist's work as a painter in post-II WW Berlin and on his performance of his own life as part of his artistic work, the article contends that Kippenberger keeps in the balance a modernist logic of art as deskilling and delegation that endorses the artist as an entrepreneur; and a postmodern position that emphasizes more performative elements in subjectivity.
When Next We Meet: On the Figure of the Nonposthumous Survivor
Authors: Sadek Walid
Published: June 2015

Framed as posthumous, or that which lives on past its death, the survivor is tagged by official postwar discourses and practices an impediment to the reconstruction of society along normative guidelines. But the persistent conditions of protracted civil war in Lebanon call for a re-conceptualization of the figure of the survivor along another temporal axis. No longer posthumous, the survivor is not an over-liver who aimlessly questions the significance of his brute survival but rather a witness who knows too much, carrying the weight of an unwelcome knowledge gathered from within war and crisis that challenges the official closure of the present to the unfinished past. What is this figure of a non-posthumous survivor and what is the knowledge that it carries? How are we to re-conceptualize the writing of history through this figure and what are the images it continues to safeguard?
Social instability during pregnancy and lactation alters female wild cavy offsprings’ endocrine status and behaviour later in life
Authors: Kaiser Sylvia , Schwerdt Britta , Siegeler Katja , Sachser Norbert
Published: June 2015

The social environment shapes the individual behavioural profile during early phases of life. In guinea pigs the behavioural profile of daughters whose mothers experienced social instability during pregnancy and lactation (UE-daughters) are behaviourally masculinised. Since guinea pigs are domesticated the question arises whether this phenomenon was brought about by domestication or whether it represents an adaptive behavioural mechanism inherited from their wild ancestor, the wild cavy. This study, therefore, investigates the effects of an early unstable social environment on the biobehavioural profile of daughters in wild cavies and compares these effects with the findings in the domestic form. Our results show higher frequencies of aggression and play behaviour in UE-daughters, indicating a comparable behavioural masculinisation as in guinea pigs. Thus, the observed behavioural changes in UE-daughters cannot have been brought about by artificial selection during domestication. Rather they represent maternal effects evolved through natural selection.
Nonapeptide influences on social behaviour: effects of vasotocin and isotocin on shoaling and interaction in zebrafish
Authors: Lindeyer Charlotte M. , Langen Esther M.A. , Swaney William T. , Reader Simon M.
Published: June 2015

Nonapeptides are important regulators of social behaviour across vertebrate taxa. While their role in simple grouping behaviour has been explored in estrildid finches, other taxa are understudied, prompting us to investigate nonapeptide influences on shoaling behaviour in zebrafish. Subjects received injections of isotocin, an isotocin antagonist, vasotocin, a vasotocin antagonist, or saline, followed by a test of grouping behaviour. Vasotocin decreased social interaction with the shoal. Unexpectedly, the vasotocin antagonist also reduced social interaction with the shoal, as well as general shoaling behaviour. Isotocin and its antagonist had minimal effects on grouping behaviours. These results suggest social interaction and shoaling are discrete aspects of sociality differentially influenced by vasotocin, although we cannot discount possible anxiogenic effects of vasotocin. Contrasting these results with studies in other systems demonstrates that each nonapeptide’s role in social behaviour varies across taxa, and cautions against a simplistic characterisation of nonapeptides as prosocial regulators of behaviour.
Black bear marking behaviour at rub trees during the breeding season in northern California
Authors: Taylor A. Preston , Allen Maximilian L. , Gunther Micaela S.
Published: June 2015

We studied the marking behaviour of American black bears (Ursus americanus) during the breeding season 2013. Six remote video cameras captured 529 trapping nights. We collected behaviour, sex, and age class of bears rubbing on trees. Marking events () were observed between 26 April and 27 July with a median of 12 June. The majority (96%) of marking events were performed diurnally. All bears we could accurately identify to sex were males () and 29 of 31 marking bears were adults. The most frequent use of contact with substrate was bipedal marking followed by pede marking, quadrupedal marking. Bears used their back, neck, head, and cheeks in nearly 90% of observations while scratching and biting occurred in less than a third of observations. We documented the novel behaviour ‘groin marking’. This study suggests rub trees are locations for chemical communication through a variety of marking techniques in forested environments.
Emergency powers and constitutional change  in the late Middle Ages
Authors: de Wilde Marc
Published: June 2015

This article gives an account of late medieval theories and practices of emergency powers. More particularly, it examines the relation between emergency powers and constitutional change. It thus seeks to explain how, in the course of the 13th and 14th centuries, European rulers began using their emergency powers to gradually expand their fiscal and legislative competences at the expense of local authorities and the church. As is demonstrated in this article, it was essentially the normalization of emergency powers that made the transition towards a more centralized government possible. This can be explained by a combination of factors, including the government’s claim to an exclusive right to judge what constituted a public necessity, the new focus on prevention and preparation for future necessities, and the increasing identification of necessity with more general claims to ‘public utility’ and the ‘common welfare’.
African Contextual Hermeneutics
Authors: Draper Jonathan A.
Published: June 2015

The role of the missionaries and their widespread dissemination of the Bible in the process of colonisation of Africa problematized the interpretation of its text, particularly in South Africa, where it was used both to legitimate apartheid and in the struggle for liberation. This paper documents the emergence of the “Tri-polar Model” (Grenholm and Patte, as modified by Draper) in African Contextual Hermeneutics, and problematises it in terms of the hegemonic role of the reader’s “ideo-theological orientation” (West). A new way forward is sought through emphasising this role of the reader, but also the possibility of a “willing suspension of disbelief” (Coleridge) in the construction of the “othered self” through “conversation” with the text (Gadamer) and the role of “reading communities” (Fish) in demanding accountability from reader(s).
Orthodoxies in the Field of Production
Authors: McCutcheon Russell T.
Published: June 2015

A revised version of the introduction to my own Entanglements: Marking Place in the Field of Religion (Sheffield: Equinox Publishers, 2014), this essay identifies some of the rhetorical techniques and institutional conditions that make possible the establishment of an exclusive orthodoxy in the modern academic study of religion – an orthodoxy that polices the limits of the field by determining not only what counts as legitimate methods, data, and findings but also who counts as a legitimate practitioner.