bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Study of the BRAF Inhibitor Vemurafenib in Combination With the Mammalian Target of Rapamycin Inhibitor Everolimus in Patients With BRAF-Mutated Malignancies
Authors: Subbiah Vivek , Sen Shiraj , Hess Kenneth R. , Janku Filip , Hong David S. , Khatua Soumen , Karp Daniel D. , Munoz Javier , Falchook Gerald S. , Groisberg Roman , Tsimberidou Apostolia M. , Sherman Steven I. , Hwu Patrick , Meric-Bernstam Funda
Published: September 2018

Purpose

Parallel activation of the phosphatidylinositol 3-kinase–mammalian target of rapamycin pathway represents a mechanism of primary and acquired resistance to BRAF-targeted therapy, but the two pathways have yet to be cotargeted in humans. We performed a phase I study to evaluate the safety and activity of the BRAF inhibitor vemurafenib in combination with the mammalian target of rapamycin inhibitor everolimus in BRAF-mutated advanced solid tumors.

Patients and Methods

We performed a 3+3 dose-escalation study with escalating doses of both oral (PO) vemurafenib administered twice a day and PO everolimus administered daily.

Results

Twenty patients with advanced cancers were enrolled. The median adult age was 64 years (range, 17 to 85 years); two pediatric patients were 10 and 13 years old. Patients were heavily pretreated with prior BRAF or MEK inhibitors (n = 11), phase I clinical trial therapy (n = 10), surgery (n = 18), radiation therapy (n = 11), and chemotherapy (n=13). One of the two pediatric patients initially experienced grade 3 rash, but after dermatologic intervention, the patient remains on trial with partial response and no dose reduction at time of analysis. Four dose-limiting toxicities (rash, n = 1; fatigue, n = 3) were observed at dose level 2. Therefore, dose level 1 (vemurafenib 720 mg PO twice a day and everolimus 5 mg PO daily) was the maximum-tolerated dose. Overall, four patients (22%) had a partial response and nine patients (50%) had stable disease as best response. One pediatric patient with pleomorphic xanthroastrocytoma remains on protocol with continued clinical response after 38 cycles.

Conclusion

The combination of vemurafenib 720 mg PO twice a day and everolimus 5 mg PO daily is safe and well tolerated and has activity across histologies, with partial responses noted in advanced non–small-cell lung cancer, melanoma, optic nerve glioma, and xanthroastrocytoma, including patients who previously experienced progression on BRAF and/or MEK inhibitor therapy. Further investigation in a larger cohort of molecularly matched patients is warranted.
The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons
Authors: Kurabayashi Nobuhiro , Tanaka Aiki , Nguyen Minh Dang , Sanada Kamon
Published: September 2018

Newborn neurons in the developing neocortex undergo radial migration, a process that is coupled with their precise passage from multipolar to bipolar shape. The cell-extrinsic signals that govern this transition are, however, poorly understood. Here, we find that lysophosphatidic acid (LPA) signaling contributes to the establishment of a bipolar shape in mouse migratory neurons through LPA receptor 4 (LPA4). LPA4 is robustly expressed in migratory neurons. LPA4-depleted neurons show impaired multipolar-to-bipolar transition and become arrested in their migration. Further, LPA4-mediated LPA signaling promotes formation of the pia-directed process in primary neurons overlaid on neocortical slices. In addition, LPA4 depletion is coupled with altered actin organization as well as with destabilization of the F-actin-binding protein filamin A (FlnA). Finally, overexpression of FlnA rescues the morphology and migration defects of LPA4-depleted neurons. Thus, the LPA-LPA4 axis regulates bipolar morphogenesis and radial migration of newborn cortical neurons via remodeling of the actin cytoskeleton.
Value of PET/MRI for assessing tumor resectability in NSCLC—intra-individual comparison with PET/CT
Authors: Messerli Michael , de Galiza Barbosa Felipe , Marcon Magda , Muehlematter Urs J , Stolzmann Paul , Warschkow René , Delso Gaspar , ter Voert Edwin EGW , Huellner Martin W , Frauenfelder Thomas , Veit-Haibach Patrick
Published: September 2018

Objective:

The purpose of this study was to compare the diagnostic accuracy of positron emission tomography (PET)/MRI with PET/CT for determining tumor resectability of non-small cell lung cancer (NSCLC).

Methods:

Sequential trimodality PET/CT/MRI was performed in 36 patients referred with the clinical question of resectability assessment in NSCLC. PET/CT and PET/MR images including T  1 weighted sequence (T  1-Dixon) and respiration gated T  2 weighted sequence (T  2-Propeller) were evaluated for resectability-defining factors; i.e. longest diameter of the tumor, minimal tumor distance to the carina, mediastinal invasion, invasion of the carina, pleural infiltration, pericardial infiltration, diaphragm infiltration, presence of additional nodules.

Results:

There was no significant difference of maximal axial diameter measurements of the primary lung tumors and narrow limits of agreement in Bland–Altman analysis ranging from −11.1  mm to + 11.8  mm for T  2-Propeller and from −14.3  mm to + 13.8  mm for T  1-Dixon sequence. A high agreement of PET/MR with PET/CT for the different resectability-defining factors was observed (k from 0.769 to 1.000). There was an excellent agreement of T  2-Propeller sequence and CT for additional pulmonary nodule detection (k of 0.829 and 0.833), but only a moderate and good agreement using T  1-Dixon sequence (k of 0.484 and 0.722).

Conclusion:

In NSCLC the use of PET/MRI, including a dedicated pulmonary MR imaging protocol, provides a comparable diagnostic value for determination of tumor resectability compared to PET/CT.

Advances in knowledge:

Our findings suggest that whole body PET/MRI can safely be used for the local staging of NSCLC patients. Further studies are warranted to determine whether it is feasible to integrate an imaging sequence in a whole body PET/MRI setting with the potential advantage of detection of liver or brain metastases.
Dual-layer transposon repression in heads of Drosophila melanogaster
Authors: van den Beek Marius , da Silva Bruno , Pouch Juliette , Ali Chaouche Mohammed el amine , Carré Clément , Antoniewski Christophe
Published: September 2018

piRNA-mediated repression of transposable elements (TE) in the germline limits the accumulation of mutations caused by their transposition. It is not clear whether the piRNA pathway plays a role in adult, nongonadal tissues in Drosophila melanogaster. To address this question, we analyzed the small RNA content of adult Drosophila melanogaster heads. We found that the varying amount of piRNA-sized, ping–pong positive molecules in heads correlates with contamination by gonadal tissue during RNA extraction, suggesting that most of the piRNAs detected in heads originate from gonads. We next sequenced the heads of wild-type and piwi mutants to address whether piwi loss of function would affect the low amount of piRNA-sized, ping-pong negative molecules that are still detected in heads hand-checked to avoid gonadal contamination. We find that loss of piwi does not significantly affect these 24–28 nt RNAs. Instead, we observe increased siRNA levels against the majority of Drosophila TE families. To determine the effect of this siRNA level change on transposon expression, we sequenced the transcriptome of wild-type, piwi, dicer-2 and piwi, dicer-2 double-mutant heads. We find that RNA expression levels of the majority of TE in piwi or dicer-2 mutants remain unchanged and that TE transcripts increase only in piwi, dicer-2 double-mutants. These results lead us to suggest a dual-layer model for TE repression in adult somatic tissues. Piwi-mediated gene silencing established during embryogenesis constitutes the first layer of TE repression whereas Dicer-2-dependent siRNA-mediated silencing provides a backup mechanism to repress TEs that escape silencing by Piwi.
Case Report: A nine year follow-up for a pacemaker generator poly-tetra-fluoro-ethylene coating for allergic reactions to pacemaker compounds
Authors: Slim Mehdi , Neffati Elies , Lagren Afef , Kortas Chokri , Tarmiz Amine , Gribba Rym , Boughzela Essia
Published: September 2018

Background: Allergic reaction to pacemaker compounds is a rare complication of cardiac pacing. Initial management is difficult because accurate diagnosis is often delayed. The tendency is to initially suspect a bacterial infection, rather than to quickly rule out an allergy to the pacemaker components. Management of this condition is difficult and not well established.

Case presentation: A 75-year-old man underwent a dual chamber pacemaker implantation. The patient needed two generator re-implantations because of sterile skin necrosis. Pace maker allergic reaction was suspected despite non-conclusive skin patch testing. The patient underwent pacemaker system removal and re-implantation of poly-tetra-fluoro-ethylene sheet coated generator in a retropectoral position. Subsequently, there has been no externalization or recurrence in nine years of follow-up.

Take-away lesson: Contact allergy to pacemakers is often unrecognized. Once infection has been excluded, allergy testing must be performed. The only valuable treatment is the removal of all the system components, followed by a replacement with hypoallergenic material. Polytetrafluoroethylene coated materials can be effective to prevent recurrence.
seqCAT: a Bioconductor R-package for variant analysis of high throughput sequencing data
Authors: Fasterius Erik , Al-Khalili Szigyarto Cristina
Published: September 2018

High throughput sequencing technologies are flourishing in the biological sciences, enabling unprecedented insights into e.g. genetic variation, but require extensive bioinformatic expertise for the analysis. There is thus a need for simple yet effective software that can analyse both existing and novel data, providing interpretable biological results with little bioinformatic prowess. We present seqCAT, a Bioconductor toolkit for analysing genetic variation in high throughput sequencing data. It is a highly accessible, easy-to-use and well-documented R-package that enables a wide range of researchers to analyse their own and publicly available data, providing biologically relevant conclusions and publication-ready figures. SeqCAT can provide information regarding genetic similarities between an arbitrary number of samples, validate specific variants as well as define functionally similar variant groups for further downstream analyses. Its ease of use, installation, complete data-to-conclusions functionality and the inherent flexibility of the R programming language make seqCAT a powerful tool for variant analyses compared to already existing solutions. A publicly available dataset of liver cancer-derived organoids is analysed herein using the seqCAT package, demonstrating that the organoids are genetically stable. A previously known liver cancer-related mutation is additionally shown to be present in a sample though it was not listed in the original publication. Differences between DNA- and RNA-based variant calls in this dataset are also analysed revealing a high median concordance of 97.5%.
A thermodynamic description for physiological transmembrane transport
Authors: Herrera-Valdez Marco Arieli
Published: September 2018

A generic formulation for both passive and active transmembrane transport is derived from basic thermodynamical principles. The derivation takes into account the energy required for the motion of molecules across membranes, and includes the possibility of modeling asymmetric flow. Transmembrane currents can then be described by the generic model in the case of electrogenic flow. As it is desirable in new models, it is possible to derive other well known expressions for transmembrane currents as particular cases of the generic formulation. For instance, the conductance-based formulation for current turns out to be a linear approximation of the generic current. Also, under suitable assumptions, other formulas for current based on electrodiffusion, like the constant field approximation by Goldman, can also be recovered from the generic formulation. The applicability of the generic formulations is illustrated first with fits to existing data, and after, with models of transmembrane potential dynamics for pacemaking cardiocytes and neurons. The generic formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport.
Establishing an international laboratory network for neglected tropical diseases: Understanding existing capacity in five WHO regions
Authors: Dean Laura , Njelesani Janet , Mulamba Charles , Dacombe Russell , Mbabazi Pamela S. , Bates Imelda
Published: September 2018

Background. Limited laboratory capacity is a significant bottleneck in meeting global targets for the control and elimination of neglected tropical diseases (NTD). Laboratories are essential for providing clinical data and monitoring data about the status and changes in NTD prevalence, and for detecting early drug resistance. Currently NTD laboratory networks are informal and specialist laboratory expertise is not well publicised, making it difficult to share global expertise and provide training, supervision, and quality assurance for NTD diagnosis and research. This study aimed to identify laboratories within five World Health Organisation regions (South-East Asia, Eastern Mediterranean, Americas, Western Pacific and Europe) that provide NTD services and could be regarded as national or regional reference laboratories, and to conduct a survey to document their networks and capacity to support NTD programmes.

Methods. Potential NTD reference laboratories were identified through systematic searches, snowball sampling and key informants.

Results. Thirty-two laboratories responded to the survey. The laboratories covered 25 different NTDs and their main regional and national roles were to provide technical support and training, research, test validation and standard setting. Two thirds of the laboratories were based in academic institutions and almost half had less than 11 staff. Although greater than 90 per cent of the laboratories had adequate technical skills to function as an NTD reference laboratory, almost all laboratories lacked systems for external verification that their results met international standards.

Conclusions. This study highlights that although  many laboratories believed they could act as a reference laboratory, only a few had all the characteristics required to fulfil this role as they fell short in the standard and quality assurance of laboratory processes. Networks of high quality laboratories are essential for the control and elimination of disease and this study presents a critical first step in the development of such networks for NTDs.
Cash Hedging in a Supply Chain
Authors: Kouvelis Panos , Wu Xiaole , Xiao Yixuan
Published: September 2018

We study hedging cash-flow risks in a supply chain where firms invest internal funds to improve production efficiencies. We offer a decomposition framework to capture the cost-reduction and flexibility effect of hedging. It allows us to understand how a firm’s hedging choice depends on its supply chain partner’s decision, and how such interaction is affected by supply chain characteristics such as market size, cash-flow volatility, and correlation. When firms’ cash flows are independent of each other, they are more likely to hedge with a larger market size. When cash flows are correlated, the impact of market size and volatility on firms’ hedging decisions presents multiple patterns, contingent on whether their risks amplify or offset each other.

This paper was accepted by Gustavo Manso, finance.
O IMPERATIVO EM LIVROS DIDÁTICOS DE LÍNGUA PORTUGUESA: A DISTÂNCIA ENTRE PESQUISA E ENSINO
Authors: Rumeu Márcia Cristina de Brito , Carvalho Luiz Fernando de
Published: September 2018

O objetivo deste artigo é discutir a incorporação dos resultados das pesquisas linguísticas sobre a expressão variável do imperativo nas aulas de língua portuguesa com base na análise de livros didáticos do ensino médio licenciados pelo Programa Nacional do Livro Didático (PNLD) em suas versões dos anos de 2015 e de 2018. Trazemos à cena a perspectiva da tradição em relação ao imperativo e alguns dos resultados das pesquisas linguísticas acerca do estatuto variável do imperativo gramatical no português brasileiro. Assim sendo, constatamos que a abordagem do imperativo se dá conservadoramente em consonância com os preceitos da tradição gramatical, reforçando-se tão somente o seu valor ilocucionário para a construção do sentido.
Why the hell are cuss words not included in teaching Portuguese as foreign language?!
Authors: Sharma Manjulata
Published: September 2018

This brief study of Brazilian swear words is an attempt to understand the non-inclusion of swear words in the teaching of Portuguese as a foreign language as they are considered as taboo lexicon from the point of view of the institutionalized normative standard language supervised periodically by the Academies. I argue that, since the swear words form a part of the repertoire of popular colloquial vocabulary, they represent the popular culture through their intensity of emotional expression and contextual use. I use the Theory of Lexiculture, proposed by Galisson (1987), and Functional Grammar, by Halliday (2004), to argue that swear words should be introduced through figures of speech such as euphemism and dysphemism, as well as comparisons between swear words of native language of the learner and that of the target language to give the learner a better understanding of the emotional aspect of the language and to foster better pragma-linguistic, socio-pragmatic competence and intercultural competence for the learner of Portuguese as a Foreign Language.
The effects of fires on plants and wildlife species diversity and soil physical and chemical properties at Aberdare Ranges, Kenya
Authors: NJERI WANGARI FAITH , GITHAIGA J. M. , MWALA AGGREY K.
Published: September 2018

Njeri WF, Githaiga JM, Mwala AK. 2018. The effects of fires on plant and wildlife species diversity and soil physical and chemical properties at Aberdare Ranges, Kenya. Asian J For 2: 25-38. This study was aimed to determine the effects of fires on species diversity (plants, animals, birds), and soil physical and chemical properties at the Aberdare Ranges forest, Kenya. Data were collected on five sites that experienced fires in 2002, 2009, 2012, 2013, and 2014 from both burnt and unburnt areas. Point Centered Quarter and quadrant methods were used for woody vegetation sampling and herbaceous vegetation sampling, respectively. Foot count was done for animal census and point count for birds. The data showed that the herbaceous vegetation in burnt sites had significantly higher species diversity than the unburnt sites in the areas that experienced fire before 2014. The fire had triggered the regeneration of the herbaceous plants. The burnt sites had a significantly higher percentage cover. The fire has an immediate adverse effect on the population of animals as demonstrated on the site consumed in 2014. No animal species was found on the site seven days after the fire when data was collected. The animal diversity was proportional to the vegetation density caused by the vegetation regeneration due to fires. All the burnt sites had fewer birds than the unburnt sites. Effects of fires were prominent in the upper layer of the soil for all the soil properties under study. Burning caused an increase in pH, potassium, organic carbon and cation exchange capacity. The study demonstrated that fires lead to an immediate adverse effect on vegetation, wildlife and soil chemical properties. Postfire management is necessary on sites that have recently experienced fires to rehabilitate them. Authorities responsible for the management of forests must ensure that people are kept out of those sites to allow vegetation to recover without interference. Reforestation can also be done on the burnt sites to increase plant and habitat for the wildlife.
Blockchain: an entangled political economy approach
Authors: Allen Darcy W.E. , Berg Chris , Novak Mikayla
Published: September 2018

This paper incorporates blockchain activities into the broader remit of entangled political economy theory, emphasising economic and other social phenomena as the emergent byproduct of human interactions. Blockchains are a digital technology combining peer-to-peer network computing and cryptography to create an immutable decentralised public ledger. The blockchain contrasts vintage ledger technologies, either paper-based or maintained by in-house databases, largely reliant upon hierarchical, third-party trust mechanisms for their maintenance and security. Recent contributions to the blockchain studies literature suggest that the blockchain itself poses as an institutional technology that could challenge existing forms of coordination and governance organised on the basis of vintage ledgers. This proposition has significant implications for the relevance of existing entangled relationships in the economic, social and political domains. Blockchain enables non-territorial ‘crypto-secession’, not only reducing the costs associated with maintaining ledgers, but radically revising and deconcentrating data-conditioned networks to fundamentally challenge the economic positions of legacy firms and governments. These insights are further illuminated with reference to finance, property and identity cases. Entangled political economy provides a compelling lens through which we can discern the impact of blockchain technology on some of our most important relationships.
SCC-S2 Facilitates Tumor Proliferation and Invasion via Activating Wnt Signaling and Depressing Hippo Signaling in Colorectal Cancer Cells and Predicts Poor Prognosis of Patients
Authors: Yang Chuanjia , Xu Weixue , Meng Xiangzhen , Zhou Siqi , Zhang Minglu , Cui Dongxu
Published: September 2018

Summary

SCC-S2 overexpression has been implicated in several human cancers, its correlation with prognosis and the mechanism how it reserved biological roles are still uncertain. The current study demonstrated that, in 142 archived colorectal carcinoma (CRC) tissue samples, SCC-S2 expression was significantly correlated with higher histological grade ( p=0.001), tumor invasion ( p=0.001), advanced Dukes staging ( p=0.002), positive regional lymph node metastasis ( p=0.024), and poor overall survival ( p<0.001). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Transwell assays showed that SCC-S2 significantly promoted the proliferation and invasion. SCC-S2 expression was also accompanied by the overexpression CyclinD1, matrix metalloproteinase-7 (MMP-7), active-β-catenin, yes-associated protein (YAP), and connective tissue growth factor (CTGF), as well as the depression of p-large tumor suppressor kinase 1 (p-LATS1) and p-YAP. Moreover, SCC-S2 interacted and colocalized with LATS1, the interaction may interrupt Hippo signaling and thereafter activate canonical Wnt signaling. In conclusion, our data suggested that SCC-S2 was associated with the progression and unfavorable prognosis of CRCs. Meanwhile, SCC-S2 facilitated canonical Wnt signaling and its downstream effectors (CyclinD1, MMP-7) and promoted tumor proliferation and invasion, which depended on the inhibition of Hippo signaling induced by SCC-S2-LATS1 interaction. These results indicated that SCC-S2 might be used as a novel target for the prevention and treatment of colorectal cancer.
Cross-border reproduction: the reproductive market in Angola and Brazil
Authors: Machin Rosana , Augusto Maria Helena Oliva , Mendosa Douglas
Published: September 2018

Las tecnologías de reproducción asistida (ART) han crecido significativamente desde el primer registro de nacimiento a través de la fertilización in vitro en 1978 en el Reino Unido. A pesar de la expansión global masiva de estos servicios en los últimos años, en el África Subsahariana continúan siendo inaccesibles. En este artículo nos centramos en la movilidad transnacional en torno a las ART a través de una investigación sobre la búsqueda de tratamiento de la infertilidad de parejas de Angola en Brasil apoyándonos en el material empírico producido con los servicios de reproducción asistida en Brasil. Para la investigación, se utilizó metodología tanto cuantitativa como cualitativa. La encuesta cuantitativa online, respondida por 84 de las 141 clínicas de fertilidad del país, mostró que hay un número significativo de personas provenientes de países de África, Europa, América del Norte y del Sur en busca de tratamiento de fertilidad, especialmente de parejas de Angola. Con el fin de explorar estos hallazgos, se llevaron a cabo entrevistas cualitativas con profesionales de salud en Brasil (Sao Paulo) y Angola y parejas en tratamiento reproductivo. El estudio discute las dinámicas involucradas en la búsqueda de tratamiento de países en desarrollo (relación sur-sur), las estrategias reproductivas y sus implicaciones en términos de las prácticas culturales y la comunidad.
Queer Border Objects and the Sucio Material Politics of Migration in the U.S.–Mexico Borderlands
Authors: Masri Hana
Published: September 2018

Although the dynamic role of the material in migration captivates scholarly imagination, little attention has been given to the ways that objects left behind in the U.S.–Mexico borderlands indicate sexuality and gender. This article brings together queer migration scholarship and new materialist perspectives to examine the rhetoric of images from the photo series “El Sueño Americano,” which depicts things confiscated from migrants by U.S. Customs and Border Protection. What I call the queer border objects of the series offer up fruitful ground for moving toward a politics that disentangles itself from fixed identities in order to move toward coalitional queerness, the likes of which, as Cathy J. Cohen describes, is built from a shared marginality to power. Whether or not the people who discarded them identify as queer, border objects can be read queerly because they communicate how sexuality and gender, as regimes, shape migration and designate whole groups of people as surplus to the nation.
“Codo con codo TEA”. Un modelo de colaboración entre el museo y aulas de integración preferente para alumnos con trastornos del espectro autista
Authors: Gamoneda Marijuan Alberto , Piedrola Sanandrés Carmen
Published: September 2018

Este artículo recoge la experiencia del proyecto “Codo con codo TEA”. Educadores del museo junto con la maestra de pedagogía terapéutica y tutora de una de las aulas de apoyo se plantean un acercamiento a diferentes obras de la colección. Este acercamiento se realiza a través de distintas unidades didácticas y experiencias con el aula recogidas en fichas de comunicación aumentativa. Las fichas preparan las visitas al museo y el acercamiento a las obras incorporando puntos del currículo de manera transversal.
La música en el aula activa
Authors: Gancedo Huércanos Eva F.
Published: September 2018

La música se considera una de las disciplinas que puede desarrollar las inteligencias múltiples en equilibrio con mayor facilidad, siempre que el proceso de enseñanza-aprendizaje se lleve a cabo de manera lúdica a través de pedagogías activas. A pesar de ello, esta materia se encuentra poco presente en la educación obligatoria debido al horario escolar estipulado por la ley de educación española. En cuanto al proceso de enseñanza-aprendizaje de la música en las aulas de las escuelas de música y conservatorios, está evolucionando hacia las pedagogías activas, pero aún de manera lenta y desigual.
Neruda
Authors: Machuca Ahumada Antonio , Pereira Domínguez Carmen
Published: September 2018

En 1948, el poeta y senador comunista Pablo Neruda, como algunos de sus compañeros, es perseguido una vez que el partido comunista es declarado ilegal en Chile. Neruda es una gran referencia para la gente sencilla chilena. Por petición del presidente Gabriel González Videla, el policía Óscar Peluchonneau se encarga de su persecución y se obceca con su captura. Neruda es ahora un poeta convertido en arma, en el punto de mira. Vive en la clandestinidad, en casas de conocidos, junto a su mujer, la pintora Delia del Carril. Escribe su épico Canto General en 1950, e intenta huir del país.  Mientras tanto, en Europa, ante la búsqueda obsesiva del policía, aumenta la leyenda del poeta apoyado por artistas, especialmente por su amigo Picasso. Pero Neruda utiliza este seguimiento para recrearse transformándose en un símbolo universal de libertad y en un mito literario.
Implementation of Irrigation Policy in the Decentralized Government: A Case Study of West Java, Indonesia
Authors: DIGDOWISEISO Kumba , SUGIYANTO Eko , DJUMADIN Zainul
Published: September 2018

The damage on irrigation networks has a substantial effect on the declining in the productivity of farming, which further implies the farmers’ welfare. One of the possible causes of such problem is related to the implementation of irrigation policy. This paper tries to analyze existing model and provide the alternative model of irrigation implementation in Indonesia through qualitative approach with a case study on West Java. In general, the existing model of irrigation implementation is still territorial based on government affairs. Therefore, the alternative model should adopt a collaborative one.
Allocation of Financial Resources from EARDF in the Context of Typology of Slovak Regions
Authors: BACULÁKOVÁ Kristína , HARAKAĽOVÁ Ľubica
Published: September 2018

The Common Agricultural Policy of the European Union (CAP EU) is one of the common EU policies that support vulnerable and disadvantaged EU regions. The allocation of EU structural funds is for a long time considered unequal and unjust. Especially money from European agricultural fund is not distributed directly to farmers. In the paper, we use cluster analysis to define the distribution of funds from the EAFRD (European Agriculture Fund for Rural Development) to individual regions of the Slovak Republic at NUTS 3 level in the previous programming period 2007 – 2013. The main objective of the paper is to identify the regions where most of the money form EARDF was allocated during this period. The results of the cluster analysis are clear - funds were not concentrated only in regions that are classified as predominantly rural (according the OECD methodology) but also in regions that were classified as intermediate or even predominantly urban.
Electrodermal Activity Monitoring During Painful Stimulation in Sedated Adult Intensive Care Unit Patients: a Pilot Study
Authors: Aslanidis Theodoros , Grosomanidis Vasilios , Karakoulas Konstantinos , Chatzisotiriou Athanasios
Published: September 2018

Introduction-Aim: Newer methods, such as infrared digital pupillometry and electrodermal activity (EDA) measurement have been suggested as good alternatives for analgesia monitoring in critically ill patients. This study analyzed EDA changes due to pain stimulus in sedated adult critical care patients Methods: Skin conductance variability, selected hemodynamic and respiratory parameters, Bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime in an adult ICU. 4h-Measurements were divided into 2 groups, based upon the sedation level of the patients: Group A – Ramsay Sedation Score 2–4 and Group B – Ramsay Sedation Score of 5–6. Selected recordings before and after pain stimulus were performed. The stimulus chosen was the pressure applied to nail bed for 10 sec, which was performed routinely during neurological examination. Patients’ demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed by 2 independent observers via Critical Care Pain Observation Tool (CPOT) and Adult Non Verbal Pain Score (ANVPS) Results: In both groups the rate of EDA changes was greater than other monitoring parameters: more in Group A than in Group B. Yet, the difference between groups was not statistically significant. Conclusion: EDA measurements are greater to pain stimuli, than cardiovascular, respiratory or even BIS monitoring. These encouraging results suggest that, further studies are needed to better define EDA role in ICU.
Cerebral Infarction in Young Marijuana Smokers – Case Reports
Authors: Šimůnek Libor , Krajina Antonín , Herzig Roman , Vališ Martin
Published: September 2018

Introduction: Causality of marijuana abuse with development of ischemic stroke has been indicated by numerous case reports and epidemiological studies. As a possible pathophysiological mechanism, the most common consideration is cardiac embolization during paroxysmal atrial fibrillation, systemic hypotension or multifocal intracerebral vasoconstriction. Case reports: We present three case reports of marijuana consumers who were admitted to our comprehensive stroke center due to ischemic stroke within 18-month period of our investigation. In one case, the cause of stroke was not related to the use of marijuana, it was a manifestation of antiphospholipid syndrome. In two cases the association with the abuse of this drug is probable but not certain. In both these cases, an isolated occlusion in vertebrobasilar arterial system was detected, without finding of a cerebral vessels stenosis. Although we did not register the atrial fibrillation, we consider cardiac embolization as probable etiological mechanism of stroke in both cases. In one case, paradoxical embolization due to the persistent foramen ovale represents another potential etiological mechanism. Conclusions: Cannabinoid use may cause ischemic stroke, especially in the younger age category. Therefore, in these patients we recommend focusing on the history of cannabinoid abuse and carry out toxicological urine tests.
The Case of "Rosa": Reflections on the Treatment of a Survivor of Relational Trauma
Authors: Vigoda Gonzalez Nicole
Published: September 2018

In this article, I respond to commentaries by Karen Riggs Skean (2018) and Shigeru Iwakabe (2018) on my presentation of the case of "Rosa," (Vigoda Gonzalez, 2018), a survivor of chronic relational trauma. In her insightful response, Riggs Skean (2018) elaborates on the interplay between language switching and the therapeutic frame, the suitability of Accelerated Experiential Dynamic Psychotherapy (AEDP; Fosha, 2000) for the treatment of trauma, and the short-term nature of the work with this particular client. Iwakabe (2018), an AEDP clinician and researcher, offers insights and reflections on the areas of language switching, emotional change process, and corrective emotional experiences, and poses evocative questions regarding the development of clinical skills relevant to affect-focused therapies. In the following response I consider these thoughtful commentaries and provide feedback with the hope to spur the dialogue regarding the flexible adaptation of treatment approaches to our clients’ psychological needs.
âˆ’174 G/C polymorphism of interleukin 6 gene is not significantly different in Turkish professional short and long distance runners
Authors: Arica Secil , Solgun Huseyin Avni , Demirel Dengi Ayse Seda , Bakmaz Enver , Akçay Teoman , Kapici Sezgin , Sercan Canan , Ulucan Korkut
Published: September 2018

Interleukin-6 (IL-6) is a kind of multifunctional cytokine and involved in mediating muscle repair metabolism, and therefore athletic capacity.  Muscular and circulating IL-6 levels increase in response to physical exercise. Responsible gene coding for IL-6 has a functional polymorphism in its promoter region, -174 G/C (rs1800795). We aimed to analyze the association of G allele and GG genotype in Turkish professional athletes and compare the allelic and genotypic difference between short distance and long distance runners. For this purpose, we enrolled 40 (24 short distance runners and 16 long distance runners) Turkish professional athletes to the study. Real time genotyping procedure was carried out to determine the -174 G/C polymorphism. G allele and GG genotype was more prevalent than the others in our cohort. We found no statistically significant difference between short and long distance runners in the terms of genotype (p=0.07). Our study suggests that-174 G/C polymorphism of IL-6 gene differs in athletes, G allele and GG genotype is higher than the other ones, at least in Turkish athletes, and therefore should be taken into consideration when determining genetic aspects of athletes. Further studies are necessary to confirm our results and show the effect of the given polymorphism in sports science.
MiR-33b inhibits osteosarcoma cell proliferation through suppression of glycolysis by targeting Lactate Dehydrogenase A (LDHA)
Authors: Zheng Xin-Min , Xu Chun-Wei , Wang Fei
Published: September 2018

Osteosarcoma (OS) is one of the most common types of malignant bone tumor in adolescent. MicroRNAs (miRNAs) are widely studied regulatory molecules which play important roles in tumor development, differentiation, growth, invasion, chemosensitivity and cellular metabolism. Recently, miR-33b has been reported to act as a tumor suppressor in osteosarcoma. However, the detailed mechanism of miR-33b in regulating osteosarcoma cell proliferation remains unclear. In this study, we detected miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. The decreased expressions of miR-33b were also found in multiple osteosarcoma cell lines, including MG63, Saos-2, U2OS and SOSP-9607 when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and anaerobic glycolysis. We identified Lactate dehydrogenase-A (LDHA) as a direct target of miR-33b in osteosarcoma tumors and cells by Western blot and luciferase assay. Moreover, inhibition of LDHA significantly suppressed glycolysis and cell proliferation of osteosarcoma cells. Restoration of LDHA in miR-33b-overexpressing osteosarcoma cells reversed the suppressive effect of miR-33b on cell proliferation. In addition, we report a significantly negative correlation between LDHA mRNA and miR-33b expression in osteosarcoma tumors: miR-33b is downregulated in OS tumors with high levels of LDHA (92.9%). Meanwhile, high miR-33b expressions were found majorly in OS tumors with low LDHA mRNA levels (82.4%). This study reveals that miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation through direct targeting LDHA. The miR-33b/glycolysis/LDHA axis may contribute to development of therapeutic anti-tumor agents for osteosarcoma.
Screening for novel peptides specifically binding to the surface of ectopic endometrium cells by phage display
Authors: Linzhi Yan , Dan Cao , Arhin Samuel Kofi , Ledan Wang , Wenju Li , Jieqiang Lv
Published: September 2018

A 7-mer phage display library was employed to isolate novel peptides that specifically bind to ectopic endometrium in vitro. Phage display technology with biopanning and rapid analysis of selective interactive ligands between ectopic and eutopic endometrium cells was utilized. After 5 rounds of biopanning, 50 phage clones were randomly selected and analyzed by enzyme-linked immunosorbent assay and DNA sequencing. A peptide-competitive inhibition assay was performed to identify the affinity of positive phages toward ectopic endometrium cells. The most enriched polypeptide RTRLHTR showed higher affinity toward ectopic endometrium cells.The polypeptide RTRLHTR screened by phage display technology may offer a new direction for early diagnosis and treatment of endometriosis.
Investigation of cochlear hair cells and the perception of ultrasound signals in guinea pigs
Authors: Wang Fu-Sen , Nie Guohui , Huang Cheng-Cheng , Li Qian , Li Tiegang , Zou Yuee , Zhang Shaoyan , Ceng Xinyu
Published: September 2018

We established a specific ultrasound frequency-dependent model of cochlear injury using bone conduction ultrasounds in the inner ear of guinea pigs at 50 kHz and 83 kHz, to explore the effects of bone conduction ultrasound in the cochlea. To establish a unilateral cochlear damage model, the unilateral cochlea was destroyed. The control group consisted of 50 kHz and 83 kHz bone conduction ultrasounds in unaltered guinea pigs. In each group, cerebral blood oxygenation level dependent (BOLD) effects were determined by functional magnetic resonance imaging (fMRI). The cochlear outer hair cell motor protein, Prestin, and the microfilament protein, F-Actin, were detected. We found that bone conduction ultrasound irradiation at 50 kHz and 83 kHz on the guinea pig inner ear for six hours leads to hair cell damage. Furthermore, low frequency bone conduction ultrasound induces major damage to outer hair cells, while high frequency ultrasound damages both internal and external hair cells. fMRI analysis of cerebral BLOD effects revealed an affected cerebral cortex region of interest (ROI) of 4 and 2, respectively, for the normal control group at 50 kHz or 83 kHz, and 2 for the 83 kHz bone conduction ultrasound cochlear injury group, while 50 kHz bone conduction ultrasound failed to induce the cortical ROI within injury model. Results reveal that the spatial location of guinea pig cochlear hair cells determines coding function for lower ultrasound frequencies, and high frequency bone conduction ultrasound may affect the cochlear spiral ganglion or cranial nerve nucleus in bone conduction ultrasound periphery perception.
Birleşik Krallık’ın Avrupa Birliği’nden Ayrılma Referandumu: Brexit Süreci ve Sonuçları
Authors: ARAS İlhan , GÜNAR Altuğ
Published: September 2018

United Kingdom which has an ongoing relationship with the European Union since 1973 has generallyhad problematic relations during the membership process. A country who does not play a part in theearly European integration process keeps wary eye to the process she joins lately. This turbulent anddetached relationship brings the membership process which mostly contains sharp discussions to anunexpected breakpoint. Brexit has been the most important milestone in the United Kingdom-theEuropean Union relations. Therefore, examining the process through Brexit, its reasons and resultswill help understand the issue better. Given this goal, therefore, this study aims to deal with the Brexitprocess in detail and contribute to the existing literature. Process beginning with the reform requestsby Conservative Party in relations with the European Union in 2013 resulted in a referendum with51.9% leaving decision on June 23, 2016. In the Brexit referendum which proceeds from the populistand unreal discourses, Conservative Party and United Kingdom Independence Party have been theactors managing the whole process. Even these two political parties conduct different campaigns onthe EU membership which they turn it into a domestic policy tool; they have eventually completedthe process. Thus, for the first time, a member state decided to enter leaving process in the EuropeanUnion’s history. In this framework, this study initially deals with the historical background of theUnited Kingdom-the European Union relations and causes of Brexit. Then, economic effects of Brexiton United Kingdom and roles of Conservative Party and United Kingdom Independence Party in thisprocess were mentioned. Lastly, leaving process was chronologically examined and the steps of leavingprocess and the progress were shown. The process which happens for the first time in the EU historyhas been shaped by the EU’s relevant institutions joint with the UK’s authorities. Similar to a candidatecountry’s membership process, the leaving negotiations have been going on between the EU and theUK. As a conclusion, it is indicated that Brexit has negative effects on politics and economy of UnitedKingdom. Economic-wise, the study shows that the UK economy has been affected negatively in theshort-run in addition the negative expectations in the long-run. Political-wise, on the other hand,Conservative Party and United Kingdom Independence Party that have taken place in every stage ofthe process have gone up in flames and led their leaders who conducted referendum campaigns toabandon politics. Consequently, after a referendum without an exact winner, it is also unclear whathappens after the Brexit process.
Rusya’nın Egemen Demokrasi Modelinin Orta Asya Devletleri Üzerindeki Etkisinin Analizi
Authors: KELKİTLİ Fatma Aslı
Published: September 2018

Russia appeared to be a country that did not eschew from resorting to hard power instruments suchas military intervention and economic sanctions in the post-Cold War period. Moscow fought a battleagainst Georgia over South Ossetia in August 2008. It also sent its military personnel to Crimea tocapture strategic points and to take control of the critical infrastructure in February 2014, shortlybefore the referendum which would decide whether the peninsula would merge with Russia. Russiaalso occasionally cut off natural gas supplies to Georgia and Ukraine in the middle of winter when thesetwo pro-Western states failed to pay their accumulated natural gas debt. Yet, Moscow starting from themid-2000s has been taking serious and systematic steps to strengthen and expand its soft power basein its immediate neighbourhood as well. These efforts speeded up in the wake of colour revolutionsin Georgia, Ukraine and Kyrgyzstan which resulted in the replacement of friendly governments thatpaid special attention to Russian concerns and sensitivities with new leaders and cadres that aimedto bring their countries closer to the West. This article will examine the Central Asian dimension ofRussia’s soft power policy by borrowing the soft power concept of Joseph Nye. Nye defines soft poweras the capacity to have an impact on or shape the preferences of others by relying upon intangibleassets such as political values, international institutions and culture. So, the study will start with theanalysis of the extent of recognition of Russia’s political values, especially its sovereign democracymodel which prioritizes the demands of the state over those of individuals, lays emphasis on theprinciples of independence, sovereignty and non-interference in internal affairs in the intercourse withother states and underlines the primacy of traditional and conservative values such as unity, solidarityand family over individualism, feminism and LGBT rights by the Central Asian political elites. Thearticle will then move on to explore the extent of Russia’s success in exporting the main tenets of thesovereign democracy model to Central Asia by examining some of the agreements, declarations,decisions and practices of the international institutions such as the Commonwealth of IndependentStates, the Collective Security Treaty Organization and the Shanghai Cooperation Organization whichplay significant role in the region. The study will end with the assessment of the cultural aspect of theRussian soft power in Central Asia by investigating the prevalence of Russian language, Russian highereducation institutions, Russian media and Russian mass entertainment in the region.
Turkish Foreign Policy Towards Balkans and Serbia Under Davutoğlu Administration
Authors: AREŽINA Sanja
Published: September 2018

Developments in geopolitics of the Eurasia emphasize the presence and the role of Turkey. Its positionhas substantially changed since the 1970s and 1980s and its influence has become far more visible. Asmultidimensionality becomes the characteristic of its foreign policy, Turkey is becoming more activeon the Eurasian geopolitical scene, trying to establish itself as (macro) regional power in the processof creating a multipolar world order. Serbia comes into focus of Turkey’s foreign policy as a key statein the Balkans that represents, in addition to the Middle East and the Caucasus, its primary sphere ofinfluence and a bridge to the West in which Turkey carries out visible political, economic and culturalimpact. This paper deals with modes of Turkey’s cooperation with Balkan states, primarily Serbia, andwith the influence that public opinion has on their bilateral relations.