bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Approaches to Drug Discovery for Oxidative Stress‐Related Retinal Diseases
Authors: Nishimura Yuhei , Hara Hideaki
Published: December 2016

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age‐related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high‐throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease‐related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress‐related targets for retinal diseases.
Global Solutions in the Species Competitive Chemotaxis System with Inequal Diffusion Rates
Authors: Cao Huaihuo
Published: December 2016

This paper is devoted to studying the two-species competitive chemotaxis system with signal-dependent chemotactic sensitivities and inequal diffusion rates u1t=Δu1-∇·u1χ1v∇v+μ1u11-u1-a1u2, x∈Ω,  t>0, u2t=Δu2-∇·u2χ2v∇v+μ2u21-a2u1-u2, x∈Ω,  t>0, vt=τΔv-γv+u1+u2, x∈Ω,  t>0, under homogeneous Neumann boundary conditions in a bounded and regular domain Ω⊂Rn  (n≥1). If the nonnegative initial date (u10,u20,v0)∈(C1(Ω¯))3 and v0∈(v_,v¯) where the constants v¯>v_≥0, the system possesses a unique global solution that is uniformly bounded under some suitable assumptions on the chemotaxis sensitivity functions χ1(v), χ2(v) and linear chemical production function -γv+u1+u2.
PWR Containment Shielding Calculations with SCALE6.1 Using Hybrid Deterministic-Stochastic Methodology
Authors: Matijević Mario , Pevec Dubravko , Trontl Krešimir
Published: December 2016

The capabilities of the SCALE6.1/MAVRIC hybrid shielding methodology (CADIS and FW-CADIS) were demonstrated when applied to a realistic deep penetration Monte Carlo (MC) shielding problem of a full-scale PWR containment model. Automatic preparation of variance reduction (VR) parameters is based on deterministic transport theory (SNmethod) providing the space-energy importance function. The aim of this paper was to determine the neutron-gamma dose rate distributions over large portions of PWR containment with uniformly small MC uncertainties. The sources of ionizing radiation included fission neutrons and photons from the reactor and photons from the activated primary coolant. We investigated benefits and differences of FW-CADIS over CADIS methodology for the objective of the uniform MC particle density in the desired tally regions. Memory intense deterministic module was used with broad group library “v7_27n19g” opposed to the fine group library “v7_200n47g” used for final MC simulation. Compared with CADIS and with the analog MC, FW-CADIS drastically improved MC dose rate distributions. Modern shielding problems with large spatial domains require not only extensive computational resources but also understanding of the underlying physics and numerical interdependence betweenSN-MC modules. The results of the dose rates throughout the containment are presented and discussed for different volumetric adjoint sources.
Influence of Chemical Reaction on Heat and Mass Transfer Flow of a Micropolar Fluid over a Permeable Channel with Radiation and Heat Generation
Authors: Singh Khilap , Kumar Manoj
Published: December 2016

The effects of chemical reaction on heat and mass transfer flow of a micropolar fluid in a permeable channel with heat generation and thermal radiation is studied. The Rosseland approximations are used to describe the radiative heat flux in the energy equation. The model contains nonlinear coupled partial differential equations which have been transformed into ordinary differential equation by using the similarity variables. The relevant nonlinear equations have been solved by Runge-Kutta-Fehlberg fourth fifth-order method with shooting technique. The physical significance of interesting parameters on the flow and heat transfer characteristics as well as the local skin friction coefficient, wall couple stress, and the heat transfer rate are thoroughly examined.
A New Nonlinear Contraction Principle in Partial Metric Spaces
Authors: Zhang Yi , Zhu Jiang
Published: December 2016

We present a new nonlinear contraction principle on partial metric spaces and prove the existence of common fixed point. We also give some examples to show our results and apply our results to study the existence of common bounded solution of the system of functional equations.
Multiple Linear Regressions by Maximizing the Likelihood under Assumption of Generalized Gauss-Laplace Distribution of the Error
Authors: Jäntschi Lorentz , Bálint Donatella , Bolboacă Sorana D.
Published: December 2016

Multiple linear regression analysis is widely used to link an outcome with predictors for better understanding of the behaviour of the outcome of interest. Usually, under the assumption that the errors follow a normal distribution, the coefficients of the model are estimated by minimizing the sum of squared deviations. A new approach based on maximum likelihood estimation is proposed for finding the coefficients on linear models with two predictors without any constrictive assumptions on the distribution of the errors. The algorithm was developed, implemented, and tested as proof-of-concept using fourteen sets of compounds by investigating the link between activity/property (as outcome) and structural feature information incorporated by molecular descriptors (as predictors). The results on real data demonstrated that in all investigated cases the power of the error is significantly different by the convenient value of two when the Gauss-Laplace distribution was used to relax the constrictive assumption of the normal distribution of the error. Therefore, the Gauss-Laplace distribution of the error could not be rejected while the hypothesis that the power of the error from Gauss-Laplace distribution is normal distributed also failed to be rejected.
Numerical Analysis of Discrete Switching Prey-Predator Model for Integrated Pest Management
Authors: Xiang Changcheng , Yang Yi , Xiang Zhongyi , Qin Wenjie
Published: December 2016

The switching discrete prey-predator model concerning integrated pest management has been proposed, and the switches are guided by the economic threshold (ET). To begin with, the regular and virtual equilibria of switching system have been discussed and the key parameter bifurcation diagrams for the existence of equilibria have been proposed, which reveal the three different regions of equilibria. Besides, numerical bifurcation analyses show that the switching discrete system may have complicated dynamics behavior including chaos and the coexistence of multiple attractors. Finally, the effects of key parameters on the switching frequencies and switching times are discussed and the sensitivity analysis of varying parameter values for mean switching times has also been given. The results proved that economic threshold (ET) and the growth rate (α) were the key parameters for pest control.
A Myc Activity Signature Predicts Poor Clinical Outcomes in Myc-Associated Cancers
Authors: Jung MoonSun , Russell Amanda J. , Liu Bing , George Joshy , Liu Pei Yan , Liu Tao , DeFazio Anna , Bowtell David D.L. , Oberthuer André , London Wendy B. , Fletcher Jamie I. , Haber Michelle , Norris Murray D. , Henderson Michelle J.
Published: December 2016

Myc transcriptional activity is frequently deregulated in human cancers, but a Myc-driven gene signature with prognostic ability across multiple tumor types remains lacking. Here, we selected 18 Myc-regulated genes from published studies of Myc family targets in epithelial ovarian cancer (EOC) and neuroblastoma. A Myc family activity score derived from the 18 genes was correlated to MYC/MYCN/MYCL1 expression in a panel of 35 cancer cell lines. The prognostic ability of this signature was evaluated in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL), and EOC microarray gene expression datasets using Kaplan–Meier and multivariate Cox regression analyses and was further validated in 42 primary neuroblastomas using qPCR. Cell lines with high MYC, MYCN, and/or MYCL1 gene expression exhibited elevated expression of the signature genes. Survival analysis showed that the signature was associated with poor outcome independently of well-defined prognostic factors in neuroblastoma, breast cancer, DLBCL, and medulloblastoma. In EOC, the 18-gene Myc activity signature was capable of identifying a group of patients with poor prognosis in a "high-MYCN" molecular subtype but not in the overall cohort. The predictive ability of this signature was reproduced using qPCR analysis of an independent cohort of neuroblastomas, including a subset of tumors without MYCN amplification. These data reveal an 18-gene Myc activity signature that is highly predictive of poor prognosis in diverse Myc-associated malignancies and suggest its potential clinical application in the identification of Myc-driven tumors that might respond to Myc-targeted therapies. Cancer Res; 77(4); 971–81. ©2016 AACR.
An Essential Role of Maspin in Embryogenesis and Tumor Suppression
Authors: Dzinic Sijana H. , Bernardo M. Margarida , Li Xiaohua , Fernandez-Valdivia Rodrigo , Ho Ye-Shih , Mi Qing-Sheng , Bandyopadhyay Sudeshna , Lonardo Fulvio , Vranic Semir , Oliveira Daniel S.M. , Bonfil R. Daniel , Dyson Gregory , Chen Kang , Omerovic Almasa , Sheng Xiujie , Han Xiang , Wu Dinghong , Bi Xinling , Cabaravdic Dzenana , Jakupovic Una , Wahba Marian , Pang Aaron , Harajli Deanna , Sakr Wael A. , Sheng Shijie
Published: December 2016

Maspin (SerpinB5) is an epithelial-specific tumor suppressor gene product that displays context-dependent cellular functions. Maspin-deficient mouse models created to date have not definitively established maspin functions critical for cancer suppression. In this study, we generated a mouse strain in which exon 4 of the Maspin gene was deleted, confirming its essential role in development but also enabling a breeding scheme to bypass embryonic lethality. Phenotypic characterization of this viable strain established that maspin deficiency was associated with a reduction in maximum body weight and a variety of context-dependent epithelial abnormalities. Specifically, maspin-deficient mice exhibited pulmonary adenocarcinoma, myoepithelial hyperplasia of the mammary gland, hyperplasia of luminal cells of dorsolateral and anterior prostate, and atrophy of luminal cells of ventral prostate and stratum spinosum of epidermis. These cancer phenotypes were accompanied by increased inflammatory stroma. These mice also displayed the autoimmune disorder alopecia aerate. Overall, our findings defined context-specific tumor suppressor roles for maspin in a clinically relevant model to study maspin functions in cancer and other pathologies. Cancer Res; 77(4); 886–96. ©2017 AACR.
Alisol A 24-Acetate, a Triterpenoid Derived from Alisma orientale, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling
Authors: Xue Xie-Hua , Zhou Xiao-Mao , Wei Wei , Chen Tong , Su Qing-Ping , Tao Jing , Chen Li-Dian
Published: December 2016

Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown antiatherosclerotic actions. The purpose of this study was to evaluate the inhibition of alisol A 24-acetate on oxidized low-density lipoprotein (Ox-LDL)-induced phenotypic transformation and migration of rat vascular smooth muscle cells (VSMCs), and to explore the underlying mechanisms. VSMCs were pretreated with alisol A 24-acetate and a specific extracellular signal-regulated kinase (ERK) inhibitor, U0126, and then stimulated with 50 mg/l Ox-LDL in vitro. The expression of VSMC phenotypic marker SM22α was determined using immunocytochemistry, and the migration of VSMCs was detected using a scratch-wound healing assay. The expression of matrix metalloproteinase (MMP)-9, MMP-2, phosphorylated ERK1/2 (pERK1/2) and total ERK was determined. Ox-LDL treatment caused a reduction in SM22α expression, VSMC transformation to the synthetic phenotype, increased MMP-2 and MMP-9 synthesis, the extension of VSMC migration distance and the upregulation of pERK1/2 expression, while the addition of alisol A 24-acetate or U0126 resulted in the elevation of SM22α expression, VSMC transformation to the contractile phenotype, a reduction in MMP-2 and MMP-9 expression, the shortening of cell migration distance and decreased pERK1/2 expression. The results of this study demonstrate that alisol A 24-acetate effectively reverses the phenotypic transformation and inhibits the migration of VSMCs, which may be associated with the suppression of the ERK1/2 signaling pathway.
Feasibility of Knife-Coagulated Cut in Gastric Endoscopic Submucosal Dissection: A Case-Control Study
Authors: Horikawa Yohei , Toyonaga Takashi , Mizutamari Hiroya , Mimori Nobuya , Kato Yuhei , Fushimi Saki , Okubo Syunji
Published: December 2016

Background/Aims: Intraoperative bleeding remains a challenge during endoscopic submucosal dissection (ESD). Forceps-coagulated cut (FCC) was found to be effective to reduce this bleeding. However, this involved frequent device replacement, and therefore, knife-coagulated cut (KCC) might ensure an easier and smoother procedure. We aimed to assess the effectiveness of KCC with Flushknife-BT at a super-low-output setting. Methods: In this prospective study, we compared the hemostasis condition during ESD in 40 pairs of gastric lesions treated by FCC (Group F) or KCC (Group K). The primary outcome was frequency of major bleeding with an analysis by tumor location. The secondary outcomes included frequency of exchanging devices, procedure time, en bloc resection rate, and adverse event rate. Results: In terms of the frequency of major bleeding, there was no significant difference between Group F and K (0.95 ± 0.12 vs. 0.88 ± 0.17, p = 0.282). Lesions located on the upper third of the stomach involved repeated hemostasis (p = 0.012). The frequency of exchanging devices was higher in Group F than in Group K (6.95 ± 0.42 vs. 0.88 ± 0.17, p = 0.000). Procedure time was reduced in Group K by 15.6%. Other aspects were the same in both groups. Conclusion: KCC prevented intraoperative bleeding just as FCC did. But it decreased device replacement and saved time and only a low risk was involved. This technique could ensure the conduct of a smooth and safe procedure during gastric ESD. UMIN000017229.
Community Perceptions of Biobanking Participation: A Qualitative Study among Mexican-Americans in Three Texas Cities
Authors: Heredia Natalia I. , Krasny Sarah , Strong Larkin L. , Von Hatten Laura , Nguyen Lynne , Reininger Belinda M. , McNeill Lorna H. , Fernández María E.
Published: December 2016

Background: Most biospecimens in the US are collected from non-Hispanic Whites, limiting the generalizability of findings. There is a need to increase participation in biobanking among ethnic and racial minorities. The purpose of this study was to use qualitative methods to identify factors that may influence Mexican-American individuals' willingness to participate in biobanking. Methods: We conducted 15 focus groups in three Texas cities with Mexican-American individuals, in both Spanish and English. Results: Lack of knowledge about medical research and biobanks, lack of information about the specifics of biobanking participation, lack of communication of the results, fear of pain or harm, and distrust of the healthcare system or health research were identified as barriers to biobanking participation. Facilitators to participation were altruism, safety, understanding biobanking procedures and purposes, perceived benefits to participation, and culturally appropriate recruitment strategies. Although Mexican-Americans living in Texas are willing to donate biospecimens for altruistic reasons, such as helping society or advancing science, they want more information about what biobanking entails. They want to be assured that participation will not cause them harm and that the research is conducted with good intentions. Conclusion: Results from this study can inform educational materials or interventions to increase Hispanic participation in biobanking.
Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma
Authors: Mor Joel M. , Heindl Ludwig M.
Published: December 2016

Aim: In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma. Methods: The study provides a PubMed literature review. Results: Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy. Conclusions: The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.
First-Rank Symptoms in Methamphetamine Psychosis and Schizophrenia
Authors: Shelly James , Uhlmann Anne , Sinclair Heidi , Howells Fleur M. , Sibeko Goodman , Wilson Don , Stein Dan J. , Temmingh Henk
Published: December 2016

Background: Methamphetamine psychosis (MAP) symptomatology has been described as indistinguishable from that of schizophrenia (SZ), yet research comparing these two disorders on specific psychotic symptoms such as schneiderian first-rank symptoms (FRS) is lacking. We aimed to determine and compare the occurrence and associations of FRS in patients diagnosed with MAP and with SZ. Sampling and Method: Data from SCID-I interviews performed on patients with either a diagnosis of SZ or MAP were compared. We calculated the prevalence of different FRS between MAP and SZ patients and used logistic regression to assess the association between FRS and diagnosis. Results: 102 patients were included in the study (MAP = 33, SZ = 69). Thought broadcasting occurred significantly more often in SZ (42%) than in MAP (24.2%) patients (adjusted OR = 3.02; 95% CI: 1.12-8.15; p = 0.028), while auditory hallucinations (voices conversing) were significantly higher in MAP (48.5%) than in SZ (20.3%) patients (adjusted OR = 0.27; 95% CI: 0.10-0.66; p = 0.004). However, there was no significant difference in the occurrence of one or more FRS in MAP and SZ, with most FRS showing overlap. Conclusions: We found that first-rank auditory hallucinations were more prevalent in MAP, whereas first-rank delusions of thought broadcasting were more prevalent in SZ. However, there was a substantial overlap in MAP and SZ for most FRS. This is consistent with the finding that FRS may have limited diagnostic specificity and that there is significant overlap in the symptoms of MAP and SZ. Future research into the neurobiology of delusions and hallucinations needs to take FRS into account.
GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats
Authors: Hu Bo , Wu Yuhong , Liu Jie , Shen Xiaohua , Tong Fei , Xu Guangtao , Shen Ruilin
Published: December 2016

Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.
Ex vivo Cutaneous Bioavailability of Topical Mometasone Furoate in an O/W Preparation
Authors: Wohlrab Johannes , Neubert Reinhard H.H. , Sommer Elfi , Michael Julia
Published: December 2016

Mometasone furoate (MMF) is a modern glucocorticoid of the 4th generation, which has been proven not only for inhalation but also for cutaneous treatment. Due to its lipophilic character, it is mainly used in ointments and creams with an outer lipophilic phase (W/O type). However, this study investigated the cutaneous cytotoxicology of MMF and tried to characterize its pharmacokinetic effects on the skin using an O/W preparation. An HPLC method has been developed and validated for the detection of MMF in cutaneous tissue, and concentration-time curves of MMF were created after cutaneous application on unaffected as well as lesional skin. Cytotoxicological characterization was carried out using scratch assays on keratinocytes and cutaneous fibroblasts. Results showed that the condition of the skin had no significant impact on the cutaneous bioavailability of MMF, but the intrinsic effect of the O/W vehicle could be utilized in periods of acute inflammation. Cytotoxicological data gave no new indications regarding the safety of MMF.
Mammalian Meiotic Recombination: A Toolbox for Genome Evolution
Authors: Capilla Laia , Garcia Caldés Montserrat , Ruiz-Herrera Aurora
Published: December 2016

Meiotic recombination is a process that increases genetic diversity and is fundamental for sexual reproduction. Determining by which mechanisms genetic variation is generated and maintained across different phylogenetic groups provides the basis for our understanding of biodiversity and evolution. In this review, we go through different aspects of this essential phenomenon, paying special attention to mammals. We provide a comprehensive view on the organization of meiotic chromosomes and the mechanisms involved in the formation and genomic distribution of recombination hotspots, focusing on the factors influencing the formation and repair of the massive amount of self-induced DNA breaks in early stages of meiosis. At the same time, we discuss the genetic and mechanistic factors that influence recombination landscapes in mammals, as reflected by several layers of regulation. These factors include the selective forces that affect the DNA sequence itself, which can be modulated by genome reshuffling and the evolutionary history of each taxon, and the forces that control how the DNA is packaged into chromosomes during meiosis.
Acupuncture for Blood Pressure Control in Stroke Patients: Case Reports
Authors: Zheng Haizhen , Zhao Xiaofeng , Du Yuzheng , Shi Xuemin
Published: December 2016

Background: Effective control of hypertension is deeply associated with the secondary prevention of stroke. The blood pressure-lowering effect of acupuncture alone is controversial but worthy of exploration, considering the side effects of and the problems of low adherence to drugs. Case Reports: One male patient experienced severe dizziness after overuse of valsartan, which decreased his blood pressure to 110/70 mm Hg. Our acupuncture treatment of 40 sessions alone regulated his blood pressure to about 110/70-130/80 mm Hg, with disappearance of the dizziness after 3 sessions. The second male patient with a suboptimal blood pressure during treatment with 50 mg/day of irbesartan received sole acupuncture treatment of 41 sessions, which decreased his blood pressure to about 120/70-130/80 mm Hg after 6 sessions. The third patient, who refused to take antihypertensive drugs because of their side effects, received acupuncture treatment of 46 sessions over 2 months, which reduced his blood pressure from 150/90 to 120/80 mm Hg. The efficacy continued for 3 months (cases 1 and 3) or 2 months (case 2) post treatment end. Conclusion: Our cases suggest the potential of acupuncture alone to favorably control high blood pressure or regulate low blood pressure in stroke individuals, as a means of secondary prevention of stroke.
Photodynamic Therapy and Skin Appendage Disorders: A Review
Authors: Megna Matteo , Fabbrocini Gabriella , Marasca Claudio , Monfrecola Giuseppe
Published: December 2016

Photodynamic therapy (PDT) is a noninvasive treatment that utilizes light treatment along with application of a photosensitizing agent. In dermatology, PDT is commonly used and approved for the treatment of oncological conditions such as actinic keratosis, Bowen disease and superficial basal cell carcinoma. In the last 2 decades however, PDT has also been used for the treatment of several nonneoplastic dermatological diseases. The present review summarizes published data on PDT application in skin appendage disorders. Our literature review shows that: (a) PDT may be a suitable treatment for acne, folliculitis decalvans, hidradenitis suppurativa, nail diseases, and sebaceous hyperplasia; (b) there is a lack of agreement on PDT features (type, concentrations and incubation period of used substances, number and frequency of PDT sessions, optimal parameters of light sources, and patient characteristics [e.g., failure to previous treatments, disease severity, body surface area involved, etc.] which should guide PDT use in these diseases); (c) further research is needed to establish international guidelines helping dermatologists to choose PDT for the right patient at the right time.
Collateral Flow and White Matter Disease in Patients with Internal Carotid Artery Occlusion
Authors: Ishikawa Mami , Sugawara Hitoshi , Nagai Mutsumi , Kusaka Gen , Tanaka Yuichi , Naritaka Heiji
Published: December 2016

Background: When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA). Methods: In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized. Results: Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow). Conclusion: The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO.
Platelets as a novel source of Gremlin-1: Implications for thromboinflammation
Authors: Chatterjee Madhumita , Behrendt Alexander , Schmid Martina , Beck Sandra , Schneider Martina , Mack Andreas , Müller Iris , Geisler Tobias , Gawaz Meinrad
Published: December 2016

Platelets mediating haemostasis-thrombosis are central players in coronary artery disease (CAD). We characterised platelets as a novel source of Gremlin-1. Platelets express Gremlin-1 like inflammatory and endothelial cells. Gremlin-1 co-localised with P-selectin containing randomly distributed α–granules under resting state, which were peripheralised following platelet activation or adhesion over fibrinogen-coated surface. Gremlin-1 release upon activation with ADP, CRP, and TRAP was detected as enhanced surface expression; also in activated platelet supernatant as detected by Western Blot following CRP activation and by ELISA upon activation with ADP, CRP, PAR-1, and PAR4 agonist. Recombinant (rh)Gremlin-1 synergistically enhanced CRP-triggered intracellular calcium mobilisation, ADP-TRAP induced platelet activation, aggregation, and thrombin-activation triggered apoptosis; also thrombus formation ex vivo. Intracellular localisation of macrophage migration inhibitory factor (MIF) and Gremlin-1 a high-affinity binding partner and functional antagonist of MIF were found in intracoronary thrombus sections from acute coronary syndrome (ACS) patients and showed moderate overlap in α-granules of platelets. Intra-platelet Gremlin-1 levels were significantly decreased in ACS patients as compared to stable CAD (n=235). rhGremlin-1 also counteracted the anti-apoptotic and anti-thrombotic effects of rhMIF on platelets. Platelet-derived-Gremlin-1 prompted monocyte migration, facilitated adhesion under static and dynamic arterial flow conditions to collagen-adherent activated platelets; supported monocyte survival against BH-3-mimetic–induced apoptosis and macrophage differentiation in monocyte-platelet co-culture system, which were counteracted upon Gremlin-1 neutralisation. Thus platelet derived Gremlin-1 might contribute to the elevated circulating levels of Gremlin-1 in ACS and serve as a thrombo-inflammatory mediator in cardiovascular pathophysiologies.
LA CULTURA DE LA VIOLENCIA
Authors: Bentancor Milton Hernán
Published: December 2016

A atual literatura hispano-americana percorre caminhos que se fazem necessários como expressãoartística posterior aotodo-poderoso“Boom”. Nesses novos caminhos aparecem nomes,   obras   e   técnicas   que   oferecem   novas   perspectivas   para   o  trabalho criativo,  tanto   no tocante à temática quanto no que diz respeito às vozes que se escutam. Neste artigo,  desejamos  analisar  como a cultura latino-americana se tem impregnado  de violência - nas suas mais diversas formas - e como essa violência se reflete na criação literária de diversos autores.
Literature and Its Role in the Formation of The Nations
Authors: Rocha Luiz Carlos Moreira da
Published: December 2016

A história de qualquer literatura nacional confunde com a história de sua nação. Uma das razões reside no fato de que, durante o processo de construção de uma nação, a questão da língua padrão emerge e literatura desempenha um papel decisivo na formação tanto do Estado nacional e língua padrão. Assim, este ensaio se concentrar no aumento de Inglês e Literaturas americanas e suas respectivas contribuições para a formação da identidade de Inglaterra e nos EUA
miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition
Authors: He Ming , Chen Zhen , Martin Marcy , Zhang Jin , Sangwung Panjamaporn , Woo Brian , Tremoulet Adriana H. , Shimizu Chisato , Jain Mukesh K. , Burns Jane C. , Shyy John Y.-J.
Published: December 2016

Rationale:

Endothelial–mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell–mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD.

Objective:

We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied.

Methods and Results:

Sera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells. Cardiovascular disease–related miRNAs, CTGF, and EndoMT markers were quantified using reverse transcriptase quantitative polymerase chain reaction, ELISA, and Western blotting. Compared with healthy controls, human umbilical vein endothelial cell incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3′ untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in endothelial cells in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in endothelial cells.

Conclusions:

KD sera suppress the KLF4-miR-483 axis in endothelial cells, leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part, through the restoration of KLF4-miR-483 expression.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01431105.
Changes in Depressive Symptoms and Subsequent Risk of Stroke in the Cardiovascular Health Study
Authors: Gilsanz Paola , Kubzansky Laura D. , Tchetgen Tchetgen Eric J. , Wang Qianyi , Kawachi Ichiro , Patton Kristen K. , Fitzpatrick Annette L. , Kop Willem J. , Longstreth W.T. , Glymour M. Maria
Published: December 2016

Background and Purpose—

Depression is associated with stroke, but the effects of changes in depressive symptoms on stroke risk are not well understood. This study examined whether depressive symptom changes across 2 successive annual assessments were associated with incident stroke the following year.

Methods—

We used visit data from 4319 participants of the Cardiovascular Health Study who were stroke free at baseline to examine whether changes in depressive symptoms classified across 2 consecutive annual assessments predicted incident first stroke during the subsequent year. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression scale (high versus low at ≥10). Survival models were inverse probability weighted to adjust for demographics, health behaviors, medical conditions, past depressive symptoms, censoring, and survival.

Results—

During follow-up, 334 strokes occurred. Relative to stable low scores of depressive symptoms, improved depression symptoms were associated with almost no excess risk of stroke (adjusted hazards ratio, 1.02; 95% confidence interval, 0.66–1.58). New-onset symptoms were nonsignificantly associated with elevated stroke risk (adjusted hazards ratio, 1.44; 95% confidence interval, 0.97–2.14), whereas persistently high depressive symptoms were associated with elevated adjusted hazard of all-cause stroke (adjusted hazards ratio, 1.65; 95% confidence interval, 1.06–2.56). No evidence for effect modification by race, age, or sex was found.

Conclusions—

Persistently high symptoms of depression predicted elevated hazard of stroke. Participants with improved depressive symptoms had no elevation in stroke risk. Such findings suggest that strategies to reduce depressive symptoms may ameliorate stroke risk.
Frequency and Predictors of Dysphagia in Patients With Recent Small Subcortical Infarcts
Authors: Fandler Simon , Gattringer Thomas , Eppinger Sebastian , Doppelhofer Kathrin , Pinter Daniela , Niederkorn Kurt , Enzinger Christian , Wardlaw Joanna M. , Fazekas Franz
Published: December 2016

Background and Purpose—

Detailed data on the occurrence of swallowing dysfunction in patients with recent small subcortical infarcts (RSSI) in the context of cerebral small vessel disease are lacking. This prompted us to assess the frequency of and risk factors for dysphagia in RSSI patients.

Methods—

We identified all inpatients with magnetic resonance imaging–confirmed RSSI between January 2008 and February 2013. Demographic and clinical data were extracted from our stroke database, and magnetic resonance imaging scans were reviewed for morphological changes. Dysphagia was determined according to the Gugging Swallowing Screen.

Results—

We identified 332 patients with RSSI (mean age, 67.7±11.9 years; 64.5% male). Overall, 83 patients (25%) had dysphagia, which was mild in 46 (55.4%), moderate in 26 (31.3%), and severe in 11 patients (13.3%). The rate of dysphagia in patients with supratentorial RSSI was 20%. Multivariate analysis identified a higher National Institutes of Health Stroke Scale score (
P
<0.001), pontine infarction (
P
<0.01), and more severe white matter hyperintensities (Fazekas grades 2 and 3,
P
=0.03) as risk factors for swallowing dysfunction.

Conclusions—

Dysphagia is present in a quarter of patients with RSSI and has to be expected especially in those with higher stroke severity, pontine infarction, and severe white matter hyperintensities.
Border Struggles: Migration, Subjectivity and the Common
Authors: Leonardi Emanuele
Published: December 2016

The review assesses first and foremost the capability of Mezzadra and Neilson’s book to radically tackle some urgent issues concerning both capital’s regulation of migratory movements and the subjective autonomy these latter incessantly express. The main original contribution of the text is a conception of the border as an epistemic device through which to address and act upon a variety of social processes, from migration policies to labour transformations, from capital’s restructuring to governmental regulations. Subsequently, two crucial topics are critically discussed: 1) the methodological link between epistemology and conflictual subjectivity (its roots in theoperaistatradition, the creative way it is employed inBorder as Method, and some problematic elements it raises); 2) the compelling – but problematic from a practical perspective – way in which the issue of political organisation is situated against the current phase of capitalist development by means of concepts such as translation and the common.
Daniel Bensaïd, Melancholic Strategist
Authors: Antentas Josep Maria
Published: December 2016

Daniel Bensaïd was a Marxist philosopher and author of an extensive body of works about political strategy. His writings combine a diversity of singular influences, such as Marx, Lenin, Trotsky and Che Guevara on the one hand, and Benjamin, Péguy and Blanqui on the other. In his work, religious heresies, Marranos, moles and emblematic figures of the resistance to oppression such as Joan of Arc meet with the classic figures of Marxism. The non-linear concept of time and messianic reason support a strategic reading of history and an understanding of political commitment, following Goldmann’s interpretation of Pascal’s Wager as a wager of uncertain outcome.
Meaning Representationalism: between Representationalism and Qualia Realism
Authors: de Sá Pereira Roberto Horácio
Published: December 2016

The purpose of this article is to offer a new view of the key relation between the content and the conscious character of visual experience. The author aims to support the following claims. First, the author rejects the qualia realist claim that conscious character is an intrinsic, nonrepresentational property of visual experience, for example, a pattern of activation of neurons. However, the author also rejects the rival widespread representationalist claim that the conscious character of visual experience is identical to, or supervenes on, any specific property represented by visual experience. The positive proposal is the following. Conscious character is identical with those patterns of activation of neurons that are referentially or representationally alive. Conscious redness, for example, is a pattern of activations of neurons that is created normally only when brains of physical duplicates come in visual contact with some distal property and this pattern of activation is recruited by natural selection to represent that property. This is called meaning representationalism.
Regional Analysis of Construction Permitting Procedures in Slovenia and Croatia
Authors: Sever Tina , Đulabić Vedran , Kovač Polonca
Published: December 2016

Construction permitting and spatial regulations are important for the functioning of modern society as regards enabling basic social needs, the right to a healthy living environment and the possibility to promote business and economic growth. However, what is typical of these real life situations is a collision of several private interests and the public interest. In order to protect the latter, the state needs to set certain limitations also by means of regulations and to ensure the appropriate administrative capacity to implement them. Moreover, the right and possibility to build is important for sustainable regional development. The article addresses the profiles of Slovenia and Croatia, in particular their procedural aspects and administrative systems’ efficiency in the field of construction. The results show that both countries regulate their construction procedures similarly, with a special focus on the simplification of administrative procedures. As such, they continually try to enhance administrative capacity.
Monsoon Gyres of the Northwest Pacific: Influences of ENSO, the MJO, and the Pacific–Japan Pattern
Authors: Molinari John , Vollaro David
Published: December 2016

An objective definition of monsoon gyres in the northwest Pacific was developed in order to construct a gyre climatology. Over a 31-yr period, 53 gyres were identified with a median formation location at 16.5°N, 135°E. More than 80% formed during July–September. More than half of gyres developed during El Niño periods at a median location 1200 km farther to the east-southeast than during La Niña. Cyclonic winds at 850 hPa extended across a diameter of more than 4000 km, with maximum tangential wind near the 1000-km radius. A precipitation maximum extended westward for several thousand kilometers south of the gyre. Typhoons were most common north and east of the gyre centers. More than 70% of gyres developed during large-amplitude MJO events, with a strong preference for Real-time Multivariate MJO (RMM) phases 5–7. In boreal summer these phases contain circulation and convective anomalies that coincide most closely with those of the climatological monsoon trough. Gyres are most likely to form when an active, large-amplitude MJO event superposes with the monsoon trough in the presence of high sea surface temperature. Gyres exhibited 850-hPa wind, height, and vorticity anomalies and surface latent heat flux anomalies that closely resembled the active Pacific–Japan pattern (PJP). This was especially true during La Niña, even though no attempt was made to isolate the PJP. It is hypothesized that an active MJO modulates gyre formation, and the gyres project onto the active phase of the PJP as they move westward.
Statistical–Dynamical Seasonal Forecast of Western North Pacific and East Asia Landfalling Tropical Cyclones using the GFDL FLOR Coupled Climate Model
Authors: Zhang Wei , Vecchi Gabriel A. , Villarini Gabriele , Murakami Hiroyuki , Gudgel Richard , Yang Xiaosong
Published: December 2016

This study attempts to improve the prediction of western North Pacific (WNP) and East Asia (EA) landfalling tropical cyclones (TCs) using modes of large-scale climate variability [e.g., the Pacific meridional mode (PMM), the Atlantic meridional mode (AMM), and North Atlantic sea surface temperature anomalies (NASST)] as predictors in a hybrid statistical–dynamical scheme, based on dynamical model forecasts with the GFDL Forecast-Oriented Low Ocean Resolution version of CM2.5 with flux adjustments (FLOR-FA). Overall, the predictive skill of the hybrid model for the WNP TC frequency increases from lead month 5 (initialized in January) to lead month 0 (initialized in June) in terms of correlation coefficient and root-mean-square error (RMSE). The hybrid model outperforms FLOR-FA in predicting WNP TC frequency for all lead months. The predictive skill of the hybrid model improves as the forecast lead time decreases, with values of the correlation coefficient increasing from 0.56 for forecasts initialized in January to 0.69 in June. The hybrid models for landfalling TCs over the entire East Asian (EEA) coast and its three subregions [i.e., southern EA (SEA), middle EA (MEA), and northern EA (NEA)] dramatically outperform FLOR-FA. The correlation coefficient between predicted and observed TC landfall over SEA increases from 0.52 for forecasts initialized in January to 0.64 in June. The hybrid models substantially reduce the RMSE of landfalling TCs over SEA and EEA compared with FLOR-FA. This study suggests that the PMM and NASST/AMM can be used to improve statistical/hybrid forecast models for the frequencies of WNP or East Asia landfalling TCs.
The Consistent Behavior of Tropical Rain: Average Reflectivity Vertical Profiles Determined by Rain Top Height
Authors: Heiblum Reuven H. , Koren Ilan , Altaratz Orit , Kostinski Alexander B.
Published: December 2016

Sixteen years of Tropical Rain Measuring Mission (TRMM) reflectivity profile data are collected for oceanic, continental, and island tropical regions within the boreal winter intertropical convergence zone (ITCZ). When sorted by the rain top height (RTH), a consistent behavior emerges where the average reflectivity profiles originating at different RTHs form non-overlapping manifolds in the height–reflectivity space, excluding the brightband regions for stratiform type profiles. Based on reflectivity slope (dBZ km−1) profile characteristics and physical considerations, the profiles are divided into three classes: 1) cold profiles, which originate above the −20°C isotherm height and display convergence to a single reflectivity slope profile independent of RTH; 2) warm profiles, which originate below the 0°C isotherm height and display strong reflectivity slope dependence on RTH, with slope values per RTH linearly decreasing with decreased height; and 3) mixed profiles, which originate at the layer located in between the lowest cold rain and highest warm rain profiles and show a gradual transition from cold profile to warm profile reflectivity slope behavior. Stratiform type profiles show similarity for all regions. It is shown that the typical tropical stratiform cold rain profile can be simply parameterized given the temperature profile. Convective type profiles present larger interregional differences. Their deviation from the typical stratiform cold rain profile is used as a measure for convective intensity, where continental and island regions show larger deviations compared to oceanic ones.
Glass/epoxy structural composites with interleaved nylon 6/6 nanofibers
Authors: Anand Anoop , Kumar Narendhara , Harshe Rahul , Joshi Makarand
Published: December 2016

Nylon 6/6 nanofibers of diameter 80–100 nm were electrospun on bidirectional E-glass fabric. The fabric with nanofibers on one surface was used to fabricate glass/epoxy structural composites, through resin film infusion. Mechanical properties of composites with interleaved nylon 6/6 nanofibers were found to be substantially improved from that of the control specimens fabricated under identical conditions, but without nanofibers. Compressive strength of composites showed over 30% increase, while interlaminar shear strength improved by 17% with nylon nanofibers of an areal density as low as 0.4 gsm. Residual compressive strength of laminates after a low-velocity impact event also showed a promising improvement with interleaved electrospun nanofibers.