bluuebunny/crossref_metadata_2025 huggingface dataset:
Hölder Continuity of a Parametric Generalized Variational Inequality
Authors: Wang Li-na , Li Xiao-bing
Published: April 2014

By using the classic metric projection method, we obtain sufficient conditions for Hölder continuity of the nonunique solution mapping for a parametric generalized variational inequality with respect to data perturbation. The result is different from the recent ones in the literature and has a strong geometric flavor.
A Hybrid Multiuser Detector Based on MMSE and AFSA for TDRS System Forward Link
Authors: Yin Zhendong , Jiang Xu , Wu Zhilu , Liu Xiaohui
Published: April 2014

This study mainly focuses on multiuser detection in tracking and data relay satellite (TDRS) system forward link. Minimum mean square error (MMSE) is a low complexity multiuser detection method, but MMSE detector cannot achieve satisfactory bit error ratio and near-far resistance, whereas artificial fish swarm algorithm (AFSA) is expert in optimization and it can realize the global convergence efficiently. Therefore, a hybrid multiuser detector based on MMSE and AFSA (MMSE-AFSA) is proposed in this paper. The result of MMSE and its modified formations are used as the initial values of artificial fishes to accelerate the speed of global convergence and reduce the iteration times for AFSA. The simulation results show that the bit error ratio and near-far resistance performances of the proposed detector are much better, compared with MF, DEC, and MMSE, and are quite close to OMD. Furthermore, the proposed MMSE-AFSA detector also has a large system capacity.
Patterns of Nonemergent Visits to Different Healthcare Facilities on the Same Day: A Nationwide Analysis in Taiwan
Authors: Wu Meng-Hsuan , Wu Meng-Ju , Chou Li-Fang , Chen Tzeng-Ji
Published: April 2014

Doctor shopping is a common phenomenon in many countries. However, patterns of switching healthcare facilities on the same day were little known. The data were obtained from the longitudinal cohort datasets (LHID2010) of Taiwan’s National Health Insurance Research Database in 2010. Of 1,000,000 persons of the cohort with 13,276,928 nonemergent visits, 185,347 patients had visited different healthcare facilities within one day, with a total of 672,478 visits and 337,260 switches between facilities in 329,073 patient-days. While 63.0% (n=212,590) of all switches occurred between facilities of the same accreditation level, 14.1% (n=47,664) moved from lower to higher level, and 22.8% (n=77,006) moved in the opposite direction. In 33,689 switches, patients moved to the same specialty of another facility. In 48,324 switches, patients moved to another facility with the same diagnosis, and the most frequent diagnoses were diseases of the digestive system (11,148) and diseases of the respiratory system (10,393). In a densely populated country without strict referral regulation, a high percentage of Taiwanese people had the experience of visiting different healthcare facilities on the same day. The system of family physicians as personal doctors and gatekeepers to healthcare might ameliorate the harmful impact.
On Generalized Fractional Integral Operators and the Generalized Gauss Hypergeometric Functions
Authors: Baleanu Dumitru , Agarwal Praveen
Published: April 2014

A remarkably large number of fractional integral formulas involving the number of special functions, have been investigated by many authors. Very recently, Agarwal (National Academy Science Letters) gave some integral transform and fractional integral formulas involving theFpα,β·. In this sequel, here, we aim to establish some image formulas by applying generalized operators of the fractional integration involving Appell’s functionF3(·)due to Marichev-Saigo-Maeda. Some interesting special cases of our main results are also considered.
Finite-Time Stability of Fractional-Order BAM Neural Networks with Distributed Delay
Authors: Cao Yuping , Bai Chuanzhi
Published: April 2014

Based on the theory of fractional calculus, the generalized Gronwall inequality and estimates of mittag-Leffer functions, the finite-time stability of Caputo fractional-order BAM neural networks with distributed delay is investigated in this paper. An illustrative example is also given to demonstrate the effectiveness of the obtained result.
Topical Application ofCleome viscosaIncreases the Expression of Basic Fibroblast Growth Factor and Type III Collagen in Rat Cutaneous Wound
Authors: Upadhyay Aadesh , Chattopadhyay Pronobesh , Goyary Danswrang , Mazumder Papiya M. , Veer Vijay
Published: April 2014

Cleome viscosaL. (Cleomaceae) is an important traditional medicine of the Indian-Ayurvedic and Chinese-medicine system documented for rheumatic arthritis, hypertension, malaria, neurasthenia, and wound healing. The plant is also known as Asian spider flower and is distributed throughout the greater part of India. The present study explored the wound healing property ofC. viscosamethanol extract (CvME) and its related mechanism using Wistar rat cutaneous excision wound model. Wound contraction rate, hydroxyproline quantification, and histopathological examination of wound granulation tissue were performed. The healing potential was comparatively assessed with a reference gentamicin sulfate hydrogel (0.01% w/w). Western blot for COL3A1, bFGF, and Smad-2, Smad-3, Smad-4, and Smad-7 was performed with 7-day postoperative granulation tissue. Results revealed that the topical application of CvME (2.5% w/w) significantly accelerated the wound contraction rate (95.14%, 24 postoperative days), increased the hydroxyproline content (3.947 mg/100 mg tissue), and improved histopathology of wound tissue as compared to control groups. Western blot analysis revealed that CvME significantly upregulated the expression of COL3A1 and bFGF and increased the Smad-mediated collagen production in granulation tissue. These findings suggest thatC. viscosapromoted the wound repair process by attenuating the Smad-mediated collagen production in wound granulation tissue.
Association between Smoking and Health Outcomes in Postmenopausal Women Living with Multiple Sclerosis
Authors: Jawahar Rachel , Oh Unsong , Eaton Charles , Wright Nicole , Tindle Hilary , Lapane Kate L.
Published: April 2014

Background. In multiple sclerosis (MS), symptom management and improved health-related quality of life (HrQOL) may be modified by smoking.Objective. To evaluate the extent to which smoking is associated with worsened health outcomes and HrQOL for postmenopausal women with MS.Methods. We identified 251 Women’s Health Initiative Observational Study participants with a self-reported MS diagnosis. Using a linear model, we estimated changes from baseline to 3 years for activities of daily living, total metabolic equivalent tasks (MET) hours per week, mental and physical component scales (MCS, PCS) of the SF-36, and menopausal symptoms adjusting for years since menopause and other confounders.Results. Nine percent were current and 50% past smokers. Age at smoking initiation was associated with significant changes in MCS during menopause. PCS scores were unchanged. While women who had ever smoked experienced an increase in physical activity during menopause, the physical activity levels of women who never smoked declined. Residual confounding may explain this finding. Smoking was not associated with change in menopausal symptoms during the 3-year follow-up.Conclusion. Smoking was not associated with health outcomes among post-menopausal women with MS.
Redox-Reaction Based Spectrophotometric Assay of Isoniazid in Pharmaceuticals
Authors: Swamy N. , Prashanth K. N. , Basavaiah K.
Published: April 2014

Two spectrophotometric methods are described for the determination of isoniazid (INH) in pharmaceuticals. In the first method (FCR method), INH is reacted with Folin-Ciocalteu reagent in Na2CO3medium and the resulting blue colored chromogen measured at 760 nm. Iron(II), formed as a result of reaction between INH and iron(III), is made to react with ferricyanide, and the resulting Prussian blue is measured at 760 nm, basing the second method (FFC method). The conditions for better performance are optimized. Beer’s law is obeyed in the concentration ranges 0.5–10 and 0.2–3.0 μg mL−1for FCR method and FFC methods, respectively, with corresponding molar absorptivity values of1.12×104and4.55×104 L mol−1 cm−1. The methods are validated for accuracy, precision, LOD, LOQ, robustness, and ruggedness as per the current ICH guidelines. The validated methods were successfully applied to quantify INH in its commercial formulation with satisfactory results; hence the methods are suitable for isoniazid determination in bulk drugs and pharmaceuticals.
Nitric Oxide Synthetic Pathway in Patients with Microvascular Angina and Its Relations with Oxidative Stress
Authors: Porro Benedetta , Eligini Sonia , Veglia Fabrizio , Lualdi Alessandro , Squellerio Isabella , Fiorelli Susanna , Giovannardi Marta , Chiorino Elisa , Dalla Cia Alessia , Crisci Mauro , Werba José Pablo , Tremoli Elena , Cavalca Viviana
Published: April 2014

A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.
Estimating Students’ Satisfaction with Web Based Learning System in Blended Learning Environment
Authors: Bauk Sanja , Šćepanović Snežana , Kopp Michael
Published: April 2014

Blended learning became the most popular educational model that universities apply for teaching and learning. This model combines online and face-to-face learning environments, in order to enhance learning with implementation of new web technologies and tools in learning process. In this paper principles of DeLone and Mclean success model for information system are applied to Kano two-dimensional model, for categorizing quality attributes related to satisfaction of students with web based learning system used in blended learning model. Survey results are obtained among the students at “Mediterranean” University in Montenegro. The (dys)functional dimensions of Kano model, including Kano basic matrix for assessment of the degree of students’ satisfaction level, have been considered in some more detail through corresponding numerical, graphical, and statistical analysis.
Phytotherapeutic Information on Plants Used for the Treatment of Tuberculosis in Eastern Cape Province, South Africa
Authors: Lawal I. O. , Grierson D. S. , Afolayan A. J.
Published: April 2014

The current rate of deforestation in Africa constitutes a serious danger to the future of medicinal plants on this continent. Conservation of these medicinal plants in the field and the scientific documentation of our knowledge about them are therefore crucial. An ethnobotanical survey of plants used for the treatment of tuberculosis (TB) was carried out in selected areas of the Eastern Cape, South Africa. These areas were Hala, Ncera, Sheshegu, and Gquamashe, all within the Nkonkobe Municipality. One hundred informants were interviewed. The survey included the identification of scientific and vernacular names of the plants used for treatment of TB as well as the methods of preparation and administration, the part used, dosage, and duration of treatment. The survey revealed 30 plants belonging to 21 families which are commonly used by traditional healers for the treatment of TB and associated diseases. Of these plants Clausena anisata, Haemanthus albiflos, and Artemisia afra were the most cited. The leaves were the most common part used in the medicinal preparations. Our findings are discussed in relation to the importance of the documentation of medicinal plants.
Sample Size Determination for the Polychotomous Randomized Response Model for Sensitive Questions in a Stratified Two-Stage Sampling Survey
Authors: Jin Zongda , Yu Bo , Pu Xiangke , Gao Ge
Published: April 2014

Methods of finding the minimum value and the Lagrange function were applied to deduce the formulae for the optimum sample sizes for polychotomous randomized response technique (RRT) model in stratified two-stage sampling, so as to minimize the cost for specified sampling errors and to minimize the sampling errors under the constraint of a fixed budget. These formulae were successfully applied to sensitive topics survey among men who have sex with men (MSM) in Beijing, China.
Optimal Demand Side Bidding with Carbon Emission by Using MRS Strategy
Authors: Dwivedi Kaustubh , Kumar Yogendra , Agnihotri Ganga
Published: April 2014

A new moderate-random-search strategy (MRPSO) is used for an optimal bidding strategy of a supplier, considering linear bidding curve model with a precise model and emission as constraints, and who delivered electricity to end users in oligopolistic dynamic electricity is studied. Bidding strategy of a supplier is solved by MRPSO, where mean best position (mbest) boosts the diversity and the exploration ability of particle. The MRPSO adopts an attractor pd as the main moving direction of particles, which replaces the velocity update procedure in the particle swarm optimization. The effectiveness of the proposed approach is tested with linear bidding model and the results are compared with the solutions obtained using classical PSO. In this paper, a comparative study has been done by a competitive bidding model tested on IEEE 14- and IEEE 39-bus systems and results motivate the suppliers towards opting green technologies.
An Offline Formulation of MPC for LPV Systems Using Linear Matrix Inequalities
Authors: Bumroongsri P.
Published: April 2014

An offline model predictive control (MPC) algorithm for linear parameter varying (LPV) systems is presented. The main contribution is to develop an offline MPC algorithm for LPV systems that can deal with both time-varying scheduling parameter and persistent disturbance. The norm-bounding technique is used to derive an offline MPC algorithm based on the parameter-dependent state feedback control law and the parameter-dependent Lyapunov functions. The online computational time is reduced by solving offline the linear matrix inequality (LMI) optimization problems to find the sequences of explicit state feedback control laws. At each sampling instant, a parameter-dependent state feedback control law is computed by linear interpolation between the precomputed state feedback control laws. The algorithm is illustrated with two examples. The results show that robust stability can be ensured in the presence of both time-varying scheduling parameter and persistent disturbance.
The Human Epidermal Growth Factor Receptor 2 Screening Tests for Breast Cancer Suggested by the New Updated Recommendation of the American Society of Clinical Oncology/College of American Pathologists Will Involve a Rise of the In-Situ Hybridization Tests for the European Laboratories of Pathology
Authors: Garbar Christian , Savoye Aude-Marie , Mascaux Corinne , Brabencova Eva , Curé Hervé
Published: April 2014

Aims. The differences between the 2007 and the 2013 ASCO/CAP HER2 guidelines have been compared. We also discussed the potential consequences in our pathological practice.Material and Methodology. 189 HER2 fluorescence in situ hybridisation (FISH) tests were performed from 1016 preliminary HER2 immunohistochemical tests (IHC). All cases were reviewed and reclassed following the 2007 and 2013 ASCO/CAP recommendations.Results. The 2013 version decreased false-negative IHC (3/118 versus 1/54,P=ns) and created more 2+ IHC (40/186 versus 89/186,P=0.001) or more 3+ IHC (9/186 versus 39/186,P=0.001). One false-positive IHC was described for the 2013 version (0/9 versus 1/39,P=ns). Equivocal FISH was reduced (8/186 versus 2/186,P=ns). An estimation based on our data for 1000 patients showed a rise of our FISH tests for the control of 2+ IHC (180 tests for the 2007 version versus 274 tests for the 2013 version or FISH work overflow is +52%) and for the control of 2+/3+ IHC (300 for the 2007 version versus 475 for the 2013 version or FISH work overflow is +58%).Conclusions. The new 2013 ASCO/CAP guidelines have detected more HER2 positive cases but have increased the number of FISH tests.
Nonlinear Controllers for a Light-Weighted All-Electric Vehicle Using Chebyshev Neural Network
Authors: Sharma Vikas , Purwar Shubhi
Published: April 2014

Two nonlinear controllers are proposed for a light-weighted all-electric vehicle: Chebyshev neural network based backstepping controller and Chebyshev neural network based optimal adaptive controller. The electric vehicle (EV) is driven by DC motor. Both the controllers use Chebyshev neural network (CNN) to estimate the unknown nonlinearities. The unknown nonlinearities arise as it is not possible to precisely model the dynamics of an EV. Mass of passengers, resistance in the armature winding of the DC motor, aerodynamic drag coefficient and rolling resistance coefficient are assumed to be varying with time. The learning algorithms are derived from Lyapunov stability analysis, so that system-tracking stability and error convergence can be assured in the closed-loop system. The control algorithms for the EV system are developed and a driving cycle test is performed to test the control performance. The effectiveness of the proposed controllers is shown through simulation results.
Climate Change Hotspots Identification in China through the CMIP5 Global Climate Model Ensemble
Authors: Gu Huanghe , Yu Zhongbo , Wang Jigan , Ju Qin , Yang Chuanguo , Fan Chuanhao
Published: April 2014

China is one of the countries vulnerable to adverse climate changes. The potential climate change hotspots in China throughout the 21st century are identified in this study by using a multimodel, multiscenario climate model ensemble that includes Phase Five of the Coupled Model Intercomparison Project (CMIP5) atmosphere-ocean general circulation models. Both high (RCP8.5) and low (RCP4.5) greenhouse gas emission trajectories are tested, and both the mean and extreme seasonal temperature and precipitation are considered in identifying regional climate change hotspots. Tarim basin and Tibetan Plateau in West China are identified as persistent regional climate change hotspots in both the RCP4.5 and RCP8.5 scenarios. The aggregate impacts of climate change increase throughout the 21st century and are more significant in RCP8.5 than in RCP4.5. Extreme hot event and mean temperature are two climate variables that greatly contribute to the hotspots calculation in all regions. The contribution of other climate variables exhibits a notable subregional variability. South China is identified as another hotspot based on the change of extreme dry event, especially in SON and DJF, which indicates that such event will frequently occur in the future. Our results can contribute to the designing of national and cross-national adaptation and mitigation policies.
Ultrastructure of Plant Leaf Cuticles in relation to Sample Preparation as Observed by Transmission Electron Microscopy
Authors: Guzmán Paula , Fernández Victoria , Khayet Mohamed , García María Luisa , Fernández Agustín , Gil Luis
Published: April 2014

The leaf cuticular ultrastructure of some plant species has been examined by transmission electron microscopy (TEM) in only few studies. Attending to the different cuticle layers and inner structure, plant cuticles have been grouped into six general morphological types. With the aim of critically examining the effect of cuticle isolation and preparation for TEM analysis on cuticular ultrastructure, adaxial leaf cuticles of blue-gum eucalypt, grey poplar, and European pear were assessed, following a membrane science approach. The embedding and staining protocols affected the ultrastructure of the cuticles analysed. The solubility parameter, surface tension, and contact angles with water of pure Spurr's and LR-White resins were within a similar range. Differences were however estimated for resin : solvent mixtures, since Spurr’s resin is combined with acetone and LR-White resin is mixed with ethanol. Given the composite hydrophilic and lipophilic nature of plant cuticles, the particular TEM tissue embedding and staining procedures employed may affect sample ultrastructure and the interpretation of the results in physicochemical and biological terms. It is concluded that tissue preparation procedures may be optimised to facilitate the observation of the micro- and nanostructure of cuticular layers and components with different degrees of polarity and hydrophobicity.
Factorization Method in Oscillator with the Aharonov-Casher System
Authors: Sadeghi J. , Naji Jalil , Pourhassan Behnam
Published: April 2014

We review the oscillator with Aharonov-Casher system and study some mathematical foundation about factorization method. The factorization method helps us to obtain the energy spectrum and general wave function for the corresponding system in some spin condition. The factorization method leads us to obtain the raising and lowering operators for the Aharonov-Casher system. The corresponding operators give us the generators of the algebra.
The RAD51-Stimulatory Compound RS-1 Can Exploit the RAD51 Overexpression That Exists in Cancer Cells and Tumors
Authors: Mason Jennifer M. , Logan Hillary L. , Budke Brian , Wu Megan , Pawlowski Michal , Weichselbaum Ralph R. , Kozikowski Alan P. , Bishop Douglas K. , Connell Philip P.
Published: April 2014

RAD51 is the central protein that catalyzes DNA repair via homologous recombination, a process that ensures genomic stability. RAD51 protein is commonly expressed at high levels in cancer cells relative to their noncancerous precursors. High levels of RAD51 expression can lead to the formation of genotoxic RAD51 protein complexes on undamaged chromatin. We developed a therapeutic approach that exploits this potentially toxic feature of malignancy, using compounds that stimulate the DNA-binding activity of RAD51 to promote cancer cell death. A panel of immortalized cell lines was challenged with the RAD51-stimulatory compound RS-1. Resistance to RS-1 tended to occur in cells with higher levels of RAD54L and RAD54B, which are Swi2/Snf2-related translocases known to dissociate RAD51 filaments from dsDNA. In PC3 prostate cancer cells, RS-1–induced lethality was accompanied by the formation of microscopically visible RAD51 nuclear protein foci occurring in the absence of any DNA-damaging treatment. Treatment with RS-1 promoted significant antitumor responses in a mouse model, providing proof-of-principle for this novel therapeutic strategy. Cancer Res; 74(13); 3546–55. ©2014 AACR.
Evaluating TBK1 as a Therapeutic Target in Cancers with Activated IRF3
Authors: Muvaffak Asli , Pan Qi , Yan Haiyan , Fernandez Rafael , Lim Jongwon , Dolinski Brian , Nguyen Thi T. , Strack Peter , Wu Stephen , Chung Rossana , Zhang Weiqun , Hulton Chris , Ripley Steven , Hirsch Heather , Nagashima Kumiko , Wong Kwok-Kin , Jánne Pasi A. , Seidel-Dugan Cynthia , Zawel Leigh , Kirschmeier Paul T. , Middleton Richard E. , Morris Erick J. , Wang Yan
Published: April 2014

TBK1 (TANK-binding kinase 1) is a noncanonical IκB protein kinase that phosphorylates and activates downstream targets such as IRF3 and c-Rel and, mediates NF-κB activation in cancer. Previous reports demonstrated synthetic lethality of TBK1 with mutant KRAS in non–small cell lung cancer (NSCLC); thus, TBK1 could be a novel target for treatment of KRAS-mutant NSCLC. Here, the effect of TBK1 on proliferation in a panel of cancer cells by both genetic and pharmacologic approaches was evaluated. In KRAS-mutant cancer cells, reduction of TBK1 activity by knockdown or treatment with TBK1 inhibitors did not correlate with reduced proliferation in a two-dimensional viability assay. Verification of target engagement via reduced phosphorylation of S386 of IRF3 (pIRF3S386) was difficult to assess in NSCLC cells due to low protein expression. However, several cell lines were identified with high pIRF3S386 levels after screening a large panel of cell lines, many of which also harbor KRAS mutations. Specifically, a large subset of KRAS-mutant pancreatic cancer cell lines was uncovered with high constitutive pIRF3S386 levels, which correlated with high levels of phosphorylated S172 of TBK1 (pTBK1S172). Finally, TBK1 inhibitors dose-dependently inhibited pIRF3S386 in these cell lines, but this did not correlate with inhibition of cell growth. Taken together, these data demonstrate that the regulation of pathways important for cell proliferation in some NSCLC, pancreatic, and colorectal cell lines is not solely dependent on TBK1 activity.

Implications: TBK1 has therapeutic potential under certain contexts and phosphorylation of its downstream target IRF3 is a biomarker of TBK1 activity.

Visual Overview: http://mcr.aacrjournals.org/content/12/7/1055/F1.large.jpg.

Mol Cancer Res; 12(7); 1055–66. ©2014 AACR.
Efficient Induction of Antitumor Immunity by Synthetic Toll-like Receptor Ligand–Peptide Conjugates
Authors: Zom Gijs G. , Khan Selina , Britten Cedrik M. , Sommandas Vinod , Camps Marcel G.M. , Loof Nikki M. , Budden Christina F. , Meeuwenoord Nico J. , Filippov Dmitri V. , van der Marel Gijsbert A. , Overkleeft Hermen S. , Melief Cornelis J.M. , Ossendorp Ferry
Published: April 2014

Chemical conjugates comprising synthetic Toll-like receptor ligands (TLR-L) covalently bound to antigenic synthetic long peptides (SLP) are attractive vaccine modalities, which can induce robust CD8+ T-cell immune responses. Previously, we have shown that the mechanism underlying the power of TLR-L SLP conjugates is improved delivery of the antigen together with a dendritic cell activation signal. In the present study, we have expanded the approach to tumor-specific CD4+ as well as CD8+ T-cell responses and in vivo studies in two nonrelated aggressive tumor models. We show that TLR2-L SLP conjugates have superior mouse CD8+ and CD4+ T-cell priming capacity compared with free SLPs injected together with a free TLR2-L. Vaccination with TLR2-L SLP conjugates leads to efficient induction of antitumor immunity in mice challenged with aggressive transplantable melanoma or lymphoma. Our data indicate that TLR2-L SLP conjugates are suitable to promote integrated antigen-specific CD8+ and CD4+ T-cell responses required for the antitumor effects. Collectively, these data show that TLR2-L SLP conjugates are promising synthetic vaccine candidates for active immunotherapy against cancer. Cancer Immunol Res; 2(8); 756–64. ©2014 AACR.
Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma
Authors: Hodi F. Stephen , Lawrence Donald , Lezcano Cecilia , Wu Xinqi , Zhou Jun , Sasada Tetsuro , Zeng Wanyong , Giobbie-Hurder Anita , Atkins Michael B. , Ibrahim Nageatte , Friedlander Philip , Flaherty Keith T. , Murphy George F. , Rodig Scott , Velazquez Elsa F. , Mihm Martin C. , Russell Sara , DiPiro Pamela J. , Yap Jeffrey T. , Ramaiya Nikhil , Van den Abbeele Annick D. , Gargano Maria , McDermott David
Published: April 2014

Ipilimumab improves survival in advanced melanoma and can induce immune-mediated tumor vasculopathy. Besides promoting angiogenesis, vascular endothelial growth factor (VEGF) suppresses dendritic cell maturation and modulates lymphocyte endothelial trafficking. This study investigated the combination of CTLA4 blockade with ipilimumab and VEGF inhibition with bevacizumab. Patients with metastatic melanoma were treated in four dosing cohorts of ipilimumab (3 or 10 mg/kg) with four doses at 3-week intervals and then every 12 weeks, and bevacizumab (7.5 or 15 mg/kg) every 3 weeks. Forty-six patients were treated. Inflammatory events included giant cell arteritis (n = 1), hepatitis (n = 2), and uveitis (n = 2). On-treatment tumor biopsies revealed activated vessel endothelium with extensive CD8+ and macrophage cell infiltration. Peripheral blood analyses demonstrated increases in CCR7+/−/CD45RO+ cells and anti-galectin antibodies. Best overall response included 8 partial responses, 22 instances of stable disease, and a disease-control rate of 67.4%. Median survival was 25.1 months. Bevacizumab influences changes in tumor vasculature and immune responses with ipilimumab administration. The combination of bevacizumab and ipilimumab can be safely administered and reveals VEGF-A blockade influences on inflammation, lymphocyte trafficking, and immune regulation. These findings provide a basis for further investigating the dual roles of angiogenic factors in blood vessel formation and immune regulation, as well as future combinations of antiangiogenesis agents and immune checkpoint blockade. Cancer Immunol Res; 2(7); 632–42. ©2014 AACR.
A memória em três atos: deslocamentos interdisciplinares
Authors: Dutra Eliana de Freitas
Published: April 2014

Este texto pretende elaborar uma reflexão sobre a problemática do tempo, da memória e do esquecimento no campo do conhecimento histórico. Por essa via pretendemos contribuir para a discussão de como os historiadores tecem as formas atuais da história nas relações que estabelecem entre a história, o tempo e a memória, nas ligações que constroem entre o passado, o presente e o futuro, na sua tensão com os regimes de verdade da disciplina histórica, ou no seu inevitável trânsito nas fronteiras de outras disciplinas e formas de conhecimento, face às suas responsabilidades com a contemporaneidade.
Memória: tipos e mecanismos – achados recentes
Authors: Izquierdo Iván Antonio , Myskiw Jociane de Carvalho , Benetti Fernando , Furini Cristiane Regina Guerino
Published: April 2014

Examinamos as definições e características gerais dos principais tipos de memórias de acordo com sua função, conteúdo e duração, as áreas cerebrais responsáveis por elas e os mecanismos moleculares sinápticos envolvidos na formação e extinção dos diversos tipos de memórias nessas áreas. Damos particular destaque a alguns aspectos de sua biologia, com alguma ênfase na memória de trabalho, na memória de curta duração e na memória de extinção, comentando os principais processos fisiológicos responsáveis por sua formação, evocação e extinção, assim como sobre sua modulação por sistemas cerebrais e periféricos. Encerramos com algumas recomendações para a manutenção das principais formas de memória.
Futebol: sonhos, paixões e cultura
Authors: Bento Jorge Olímpio
Published: April 2014

O autor deste ensaio é um apaixonado pelo futebol. Isso não o inibe de olhar com preocupação o panorama que, paulatinamente, se vai implantando em torno do espetáculo futebolístico. Assim, o ensaio intenta despertar a necessidade de realização de estudos que apresentem o estado da arte no tocante ao ideário desportivo, aos sonhos e virtudes imanentes ao futebol, face ao avanço do pragmatismo e utilitarismo em todas as áreas, nomeadamente no setor da educação. A remissão discursiva e prática daquele ideário impõe-se com carácter de urgência.
Brasil, país do futebol?
Authors: Franco Júnior Hilário
Published: April 2014

Como todo clichê, aquele que define o Brasil como o país do futebol contém algumas verdades e muitos exageros. É preciso examiná-lo criticamente. Verificar o que é que se entende por esse rótulo e analisar cada um de seus componentes de um ponto de vista histórico e comparativo. A conclusão revela, então, tanto sobre o futebol brasileiro quanto sobre o Brasil.
Control of Very Low-Density Lipoprotein Secretion by N-Ethylmaleimide-Sensitive Factor and miR-33
Authors: Allen Ryan M. , Marquart Tyler J. , Jesse Jordan J. , Baldán Ángel
Published: April 2014

Rationale
:

Several reports suggest that antisense oligonucleotides against miR-33 might reduce cardiovascular risk in patients by accelerating the reverse cholesterol transport pathway. However, conflicting reports exist about the impact of anti-miR-33 therapy on the levels of very low-density lipoprotein-triglycerides (VLDL-TAG).

Objective
:

We test the hypothesis that miR-33 controls hepatic VLDL-TAG secretion.

Methods and Results
:

Using therapeutic silencing of miR-33 and adenoviral overexpression of miR-33, we show that miR-33 limits hepatic secretion of VLDL-TAG by targeting N-ethylmaleimide-sensitive factor (NSF), both in vivo and in primary hepatocytes. We identify conserved sequences in the 3′UTR of
NSF
as miR-33 responsive elements and show that
Nsf
is specifically recruited to the RNA-induced silencing complex following induction of miR-33. In pulse-chase experiments, either miR-33 overexpression or knock-down of
Nsf
lead to decreased secretion of apolipoproteins and TAG in primary hepatocytes, compared with control cells. Importantly,
Nsf
rescues miR-33-dependent reduced secretion. Finally, we show that overexpression of
Nsf
in vivo increases global hepatic secretion and raises plasma VLDL-TAG.

Conclusions
:

Together, our data reveal key roles for the miR-33–NSF axis during hepatic secretion and suggest that caution should be taken with anti-miR-33-based therapies because they might raise proatherogenic VLDL-TAG levels.
Decreased Level of Cord Blood Circulating Endothelial Colony–Forming Cells in Preeclampsia
Authors: Muñoz-Hernandez Rocio , Miranda Maria L. , Stiefel Pablo , Lin Ruei-Zeng , Praena-Fernández Juan M. , Dominguez-Simeon Maria J. , Villar Jose , Moreno-Luna Rafael , Melero-Martin Juan M.
Published: April 2014

Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony–forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (
P
=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events.
“The Covenant Made with David”: The King and the Kingdom in 2 Chronicles 21
Authors: Zimran Yisca
Published: April 2014

Abstract

This article examines 2 Chronicles 21 and the description it provides of Jehoram of Judah’s reign, which diverges widely from the parallel in 2 Kings 8. Addressing some of the structural, substantive, and linguistic issues that arise from the text, it suggests that this chapter integrates two perspectives regarding Jehoram, each of which contain different details—that are nonetheless essentially interlinked. The proposal offered herein resolves some of the fundamental questions relating to the text, including the structure of the chapter and the duplications and meaning of the unique phrases it contains. The paper also discusses the Chronicler’s views concerning the family and Israelite kingship and the manner in which the promise to the house of David is presented in the chapter.
Ezekiel’s Temple in Babylonian Context1
Authors: Ganzel Tova , Holtz Shalom E.
Published: April 2014

Abstract

Comparison between Ezekiel’s visionary temple and Neo-Babylonian temples shows similar organization of space and personnel. These formal similarities stem from a similar root purpose: maintaining strict standards of sanctity.
Biblical Hebrew šninɔ: A ‘Cautionary Tale’ of Root Identification
Authors: Vayntrub Jacqueline E. , Hardy Humphrey H.
Published: April 2014

Abstract

The present study comprises a philological examination of the Biblical Hebrew term šninɔ. The contextual semantics, the ancient translations, and the re-identification of the verbal root ŠNN as a by-form of ŠNY ‘to recount’ demonstrate that šninɔ may be realigned as related to this root and translated as a ‘cautionary tale’.
„An dem Tag, als JHWH ihn rettete aus der Hand aller seiner Feinde und aus der Hand Sauls“ (Ps 18,1)
Authors: Weber Beat
Published: April 2014

Abstract

Examining the arrangement of biographical notices in the titles of psalms ascribed to David reveals that these are not placed haphazardly. Their order and correlation conveys a message to the reader of the first two Davidic collections of psalms. There are two main horizons, one reflecting on the conflict between Saul and David (Pss 34; 52-59, followed by Ps 60 with national enemies), another reflecting on the conflict between David and Absalom (Ps 3-7; 63). The headings of Pss 18 (doubling 2 Sam 22) and Ps 51 (in connection with Ps 2 and 72) are of special hermeneutical significance, as they guide the reader’s understanding of such biographical information, signalling relationships between the headings of different psalms als well as back to the narrative of the Book of Samuel (1-2 Sam). In the midst of prayers in which David is struggling with enemies, Ps 18 foregrounds the salvation of JHWH “at the end.” Pss 2; 51 and 72 are interconnected by the common theme of the house of David and the prophetic voice of Nathan adressed twice to king David (2 Sam 7; 12).
The Greek Perfect through Gothic Eyes: Evidence for the Existence of a Unitary Semantic for the Greek Perfect in New Testament Greek
Authors: Crellin Robert
Published: April 2014

The semantics of the later Koine Greek perfect have been the subject of considerable debate in recent years. For the immediately post-Classical language Haug (2004) has suggested that the perfect combines resultant state and XN semantics, unifiable under the framework of event realisation (Bohnemeyer & Swift 2004). The present article presents a modified unitary semantic in terms of participant property (Smith 1997), and assesses its validity with reference to the translation of the perfect indicative active into Gothic. It is found that, while non-state verbs are translated only with past-tense forms in Gothic, contrary to traditional and even many modern views of the Greek perfect, the perfect of both pure state and change-of-state verbs are compatible with both past and non-past tense readings. The fact that this is the case regardless of the diachronic pedigree of the perfect forms concerned is taken as evidence consistent with the existence of the proposed unitary semantic for the Greek perfect in the New Testament in the eyes of the Gothic translator.
The Late Medieval Greek Vernacular Πολιτικὸς Στίχος Poetry: A Modern Linguistic Analysis into Intonation Units
Authors: Soltic Jorie
Published: April 2014

The Late Medieval Greek “vernacular” (12th–15th c.) is one of the least studied stages of the history of the Greek language. The lack of interest by linguists can presumably be ascribed to its major source, i.e. metrical πολιτικὸς στίχος poetry. The language of this type of poetry has been labelled a “Kunstsprache”, because of its oral-formulaic character and because of its mixed idiom incorporating vernacular yet also archaizing elements. In this article, however, I demonstrate that the Late Medieval Greek πολιτικὸς στίχος poetry should not automatically be excluded from linguistic research, given that it clearly possesses a strongly vernacular, i.e. spoken, syntactic base: its underlying syntax runs in a very natural way. This is proven by the fact that we can apply the modern linguistic concept of the Intonation Unit, the basic unit of analysis in contemporary spoken(!) languages, to the texts composed in the πολιτικὸς στίχος: far from having an artificial syntax, the πολιτικὸς στίχος poetry is conceptually made up of short, simple “chunks” of information. More precisely, each verse consists of two (stylized) Intonation Units, demarcated by the fixed caesura, which can thus be equated with an Intonation Unit boundary. This thesis is supported by various arguments, both of a metrical and of a syntactico-semantic nature. Arguments belonging to the former category are the length of each half-line, the possibility of stress on the first syllable of each half-line, the origin of the metre, and especially the avoidance of elision at the caesura. In the second category of (syntactico-semantic) evidence, we can consider the tendency of each half-line for constituting a grammatical sense-unit. I also bring forward some little-studied syntactic features of Late Medieval Greek: first, I pay attention to the distribution of the archaizing “Wackernagel particles”, which do not only appear in second position in the verse, but also occur after the first word/constituent following the caesura and thus further confirm my thesis. The same holds for the position of “corrective afterthoughts”, for the verbs and pronominal objects taking the singular are consistently separated from their plural referents by the caesura. Once the Intonation Unit is thus established as a meaningful methodological tool for the analysis of the πολιτικὸς στίχος poetry, the way is cleared for more linguistic research on the Late Medieval Greek vernacular.
A new species of bunchgrass lizard (Squamata: Phrynosomatidae) from the southern sky islands of the Sierra Madre Occidental, Mexico
Authors: GRUMMER JARED A. , BRYSON JR. ROBERT W.
Published: April 2014

A new species of bunchgrass lizard in the Sceloporus scalaris group is described from the southern portion of the Sierra Madre Occidental in Mexico. The new species, Sceloporus aurantius sp. nov., was previously confused with S. brownorum but differs from this and all but one species within the S. scalaris group by a lack of blue belly patches in males. It shares with S. chaneyi an absence of blue belly patches, but differs from this species in size, number of dorsal scales, number of scales around midbody, and presence of an un-patterned morph. The new species further differs from S. chaneyi, and all other species in the S. scalaris species group, by unique phylogenetic position revealed through species delimitation based on multi-locus nuclear DNA. Principal component analyses of 24 traditional morphological characters used to describe previous S. scalaris group taxa indicate that these characters may be of limited use to delineate species in this species group. However, male lateral and ventral coloration may still be an important character for diagnosing species.
Description of Chlorogomphus auripennis spec. nov. from Guangdong Province, with new records of Chlorogomphidae from Yunnan Province, China (Odonata: Chlorogomphidae)
Authors: ZHANG HAO-MIAO , CAI QING-HUA
Published: April 2014

A new chlorogomphid, Chlorogomphus (Orogomphus) auripennis spec. nov. (holotype male; Mt Nankunshan, Longmen County, Guangdong Province, China, 20. V. 2008) is described and illustrated. It is the first species belonging to the subgenus Orogomphus recorded from mainland China. The holotype will be deposited in the Collection of Aquatic Animals, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan City, Hubei Province, China. Chlorogomphus auratus Martin, 1910 and Chloropetalia selysi (Fraser, 1929) are recoded from Chinese territory for the first time. The total number of Chlorogomphidae in China reaches 20. Description of the hitherto unknown female of Chlorogomphus yokoii Karube, 1995 is provided.
Description of the larva and biological notes on Vermiophis taihangensis Yang & Chen, 1993 (Diptera: Vermileonidae) from China
Authors: OVTSHINNIKOVA O. G. , WANG ZHILIANG , OVCHINNIKOV A. N. , WANG XINLI , KRIVOKHATSKY V. A.
Published: April 2014

Unmixed colonies of larval antlions and wormlions in similar pits were found in the Xiaolongmen National Forest Park in the Taihang Shan, China. A male of Vermiophis taihangensis Yang & Chen, 1993 was reared from a larva and a morphological description of the third instar larval wormlion is presented. The larva of Vermiophis taihangensis differs from the related species V. ganquanensis Yang, 1979 in the well developed sclerotized stigmata on abdominal segment 4, but is similar in the structure of the lateral row of setae and the same number of spines (6) on the pseudopod on the abdominal segment 1.
Moderation of Summertime Heat Island Phenomena via Modification of the Urban Form in the Tokyo Metropolitan Area
Authors: Adachi Sachiho A. , Kimura Fujio , Kusaka Hiroyuki , Duda Michael G. , Yamagata Yoshiki , Seya Hajime , Nakamichi Kumiko , Aoyagi Toshinori
Published: April 2014

This study investigated the moderation of the urban heat island via changes in the urban form in the Tokyo metropolitan area (TMA). Two urban scenarios with the same population as that of the current urban form were used for sensitivity experiments: the dispersed-city and compact-city scenarios. Numerical experiments using the two urban scenarios as well as an experiment using the current urban form were conducted using a regional climate model coupled with a single-layer urban canopy model. The averaged nighttime surface air temperature in TMA increased by ~0.34°C in the dispersed-city scenario and decreased by ~0.1°C in the compact-city scenario. Therefore, the compact-city scenario had significant potential for moderating the mean areal heat-island effect in the entire TMA. Alternatively, in the central part of the TMA, these two urban-form scenarios produced opposite effects on the surface air temperature; that is, severe thermal conditions worsened further in the compact-city scenario because of the denser population. This result suggests that the compact-city form is not always appropriate for moderation of the urban-heat-island effect. This scenario would need to combine with other mitigation strategies, such as the additional greening of urban areas, especially in the central area. This study suggests that it is important to design a plan to adapt to higher urban temperatures, which are likely to ensue from future global warming and the urban heat island, from several perspectives; that is, designs should take into account not only climatological aspects but also impacts on urban inhabitants.