bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying DEKOIS 2.0 in structure-based virtual screening to probe the impact of preparation procedures and score normalization
Authors: Ibrahim Tamer M , Bauer Matthias R , Boeckler Frank M 
Published: May 2015

Abstract

Background
Structure-based virtual screening techniques can help to identify new lead structures and complement other screening approaches in drug discovery. Prior to docking, the data (protein crystal structures and ligands) should be prepared with great attention to molecular and chemical details.

Results
Using a subset of 18 diverse targets from the recently introduced DEKOIS 2.0 benchmark set library, we found differences in the virtual screening performance of two popular docking tools (GOLD and Glide) when employing two different commercial packages (e.g. MOE and Maestro) for preparing input data. We systematically investigated the possible factors that can be responsible for the found differences in selected sets. For the Angiotensin-I-converting enzyme dataset, preparation of the bioactive molecules clearly exerted the highest influence on VS performance compared to preparation of the decoys or the target structure. The major contributing factors were different protonation states, molecular flexibility, and differences in the input conformation (particularly for cyclic moieties) of bioactives. In addition, score normalization strategies eliminated the biased docking scores shown by GOLD (ChemPLP) for the larger bioactives and produced a better performance. Generalizing these normalization strategies on the 18 DEKOIS 2.0 sets, improved the performances for the majority of GOLD (ChemPLP) docking, while it showed detrimental performances for the majority of Glide (SP) docking.

Conclusions
In conclusion, we exemplify herein possible issues particularly during the preparation stage of molecular data and demonstrate to which extent these issues can cause perturbations in the virtual screening performance. We provide insights into what problems can occur and should be avoided, when generating benchmarks to characterize the virtual screening performance. Particularly, careful selection of an appropriate molecular preparation setup for the bioactive set and the use of score normalization for docking with GOLD (ChemPLP) appear to have a great importance for the screening performance. For virtual screening campaigns, we recommend to invest time and effort into including alternative preparation workflows into the generation of the master library, even at the cost of including multiple representations of each molecule.
Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum
Authors: Haldipur Parthiv , Sivaprakasam Iswariya , Periasamy Vinod , Govindan Subashika , Mani Shyamala 
Published: May 2015

ABSTRACTThe plane of division of granule neuron progenitors (GNPs) was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of Sonic Hedgehog (Shh) signalling had an effect on plane of cell division. Asymmetric distribution of β-Catenin was shown to occur towards the source of a localized extracellular cue.
Endoglin potentiates nitric oxide synthesis to enhance definitive hematopoiesis
Authors: Nasrallah Rabab , Knezevic Kathy , Thai Thuan , Thomas Shane R. , Göttgens Berthold , Lacaud Georges , Kouskoff Valerie , Pimanda John E. 
Published: May 2015

ABSTRACTDuring embryonic development, hematopoietic cells develop by a process of endothelial-to hematopoietic transition of a specialized population of endothelial cells. These hemogenic endothelium (HE) cells in turn develop from a primitive population of FLK1+ mesodermal cells. Endoglin (ENG) is an accessory TGF-β receptor that is enriched on the surface of endothelial and hematopoietic stem cells and is also required for the normal development of hemogenic precursors. However, the functional role of ENG during the transition of FLK1+ mesoderm to hematopoietic cells is ill defined. To address this we used a murine embryonic stem cell model that has been shown to mirror the temporal emergence of these cells in the embryo. We noted that FLK1+ mesodermal cells expressing ENG generated fewer blast colony-forming cells but had increased hemogenic potential when compared with ENG non-expressing cells. TIE2+/CD117+ HE cells expressing ENG also showed increased hemogenic potential compared with non-expressing cells. To evaluate whether high ENG expression accelerates hematopoiesis, we generated an inducible ENG expressing ES cell line and forced expression in FLK1+ mesodermal or TIE2+/CD117+ HE cells. High ENG expression at both stages accelerated the emergence of CD45+ definitive hematopoietic cells. High ENG expression was associated with increased pSMAD2/eNOS expression and NO synthesis in hemogenic precursors. Inhibition of eNOS blunted the ENG induced increase in definitive hematopoiesis. Taken together, these data show that ENG potentiates the emergence of definitive hematopoietic cells by modulating TGF-β/pSMAD2 signalling and increasing eNOS/NO synthesis.
Saponin-permeabilization is not a viable alternative to isolated mitochondria for assessing oxidative metabolism in hibernation
Authors: Mathers Katherine E. , Staples James F. 
Published: May 2015

ABSTRACT
Saponin permeabilization of tissue slices is increasingly popular for characterizing mitochondrial function largely because it is fast, easy, requires little tissue and leaves much of the cell intact. This technique is well described for mammalian muscle and brain, but not for liver. We sought to evaluate how saponin permeabilization reflects aspects of liver energy metabolism typically assessed in isolated mitochondria. We studied the ground squirrel (Ictidomys tridecemlineatus Mitchell), a hibernating mammal that shows profound and acute whole-animal metabolic suppression in the transition from winter euthermia to torpor. This reversible metabolic suppression is also reflected in the metabolism of isolated liver mitochondria. In this study we compared euthermic and torpid animals using saponin permeabilized tissue and mitochondria isolated from the same livers. As previously demonstrated, isolated mitochondria have state 3 respiration rates, fueled by succinate, that are suppressed by 60-70% during torpor. This result holds whether respiration is standardized to mitochondrial protein, cytochrome a content or citrate synthase activity. In contrast, saponin-permeabilized liver tissue, show no such suppression in torpor. Neither citrate synthase activity nor VDAC content differ between torpor and euthermia, indicating that mitochondrial content remains constant in both permeabilized tissue and isolated mitochondria. In contrast succinate dehydrogenase activity is suppressed during torpor in isolated mitochondria, but not in permeabilized tissue. Mechanisms underlying metabolic suppression in torpor may have been reversed by the permeabilization process. As a result we cannot recommend saponin permeabilization for assessing liver mitochondrial function under conditions where acute changes in metabolism are known to occur.
The canonical eIF4E isoform ofC. elegansregulates growth, embryogenesis, and germline sex-determination
Authors: Mangio Richard S. , Votra SarahBeth , Pruyne David 
Published: May 2015

ABSTRACTeIF4E plays a conserved role in initiating protein synthesis, but with multiple eIF4E isoforms present in many organisms, these proteins also adopt specialized functions. Previous RNAi studies showed that ife-3, encoding the sole canonical eIF4E isoform of Caenorhabditis elegans, is essential for viability. Using ife-3 gene mutations, we show here that it is maternal ife-3 function that is essential for embryogenesis, but ife-3 null progeny of heterozygous animals are viable. We find that zygotic ife-3 function promotes body growth and regulates germline development in hermaphrodite worms. Specifically, the normal transition from spermatogenesis to oogenesis in the hermaphrodite germline fails in ife-3 mutants. This failure to switch is reversed by inhibiting expression of the key masculinizing gene, fem-3, suggesting ife-3 resembles a growing number of genes that promote the sperm/oocyte switch by acting genetically as upstream inhibitors of fem-3.
Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate,Ptychodera flava
Authors: Röttinger Eric , DuBuc Timothy Q. , Amiel Aldine R. , Martindale Mark Q. 
Published: May 2015

ABSTRACTNodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms.
Preanalytical Variables Affecting the Integrity of Human Biospecimens in Biobanking
Authors: Ellervik Christina , Vaught Jim 
Published: May 2015

AbstractBACKGROUNDMost errors in a clinical chemistry laboratory are due to preanalytical errors. Preanalytical variability of biospecimens can have significant effects on downstream analyses, and controlling such variables is therefore fundamental for the future use of biospecimens in personalized medicine for diagnostic or prognostic purposes.CONTENTThe focus of this review is to examine the preanalytical variables that affect human biospecimen integrity in biobanking, with a special focus on blood, saliva, and urine. Cost efficiency is discussed in relation to these issues.SUMMARYThe quality of a study will depend on the integrity of the biospecimens. Preanalytical preparations should be planned with consideration of the effect on downstream analyses. Currently such preanalytical variables are not routinely documented in the biospecimen research literature. Future studies using biobanked biospecimens should describe in detail the preanalytical handling of biospecimens and analyze and interpret the results with regard to the effects of these variables.
Foreign correspondents in Israel, and the Arab–Israeli conflict and peace process
Authors: Cohen Yoel 
Published: May 2015

Abstract
Foreign correspondents play a key role in the construction of foreign images about Israel. The overwhelming quantity of reporting about Israel is carried out by a relatively small number of persons. Reflecting the ongoing Arab-Israeli conflict and peace process, there has been a considerable growth in the number of foreign news organizations with representatives in Israel. Drawing on surveys of the foreign press corps by the author, the factors for the news interest are examined. Correspondents’ self-evaluations of their news interest found that War and Terrorism are overwhelmingly the major factors. Culturally proximate factors such as the Holyland, Israel-US ties and Israeli relations with Arab countries while existent have less significance than the military story. These were confirmed by separate questions measuring the frequency of contacts with news sources, where the Army Spokesman and the Foreign Ministry were found to be the major news sources. Structural factors such as military censorship; knowledge levels about Israel/Arab countries and Judaism/Islam; and advanced media technology were found to be lesser factors than the war and terrorism. This led to an overwhelming focus in foreign media coverage of Israel upon the conflict with little coverage of Israeli society itself.
Visualizing a society on the brink: Gaza and Hebron
Authors: Bratchford Gary 
Published: May 2015

Abstract
This article begins with Operation Protective Edge, the Israeli military operation against Gaza during the summer months of 2014. This article examines the Israeli use of language and the emphasis on terror, trauma and victimhood as vehicles upon which to mobilize and justify its multi-narrative, collective punishment of the Palestinian. I will identify how this use of language helps to frame Israel’s actions as democratic by acting in defence, a process articulated throughout previous military operations. Such a process is implicit within the dominant political imaginary that constitutes much of the popular discourse that shapes the Israeli relationship with the Palestinian. Thereafter, I will highlight how a number of documentary photographers have sought to challenge the political visibilities related to the Israeli Palestine conflict by attempting to visualize the ongoing ‘catastrophization of Gaza’ before switching my attention to Hebron and the work of the photography collective, Activestills.
The displacement effect of Internet use among Saudi students
Authors: Miliany Khulood 
Published: May 2015

Abstract
This study investigates the time Saudi students spend with different media and whether the time they spend with new mediums will cut into the time spent with other traditional media, particularly television. A time diary survey was administered to a sample of 200 university students to measure the way they spent their time during one 24-hour period. In general, the study has demonstrated that Saudi students shift to the Internet for social and entertainment purposes at the expense of the time they spend on TV viewing. However, there are gender differences in relation to which online activities emerge as the most powerful predictors of television watching.
A RAZÃO DIALÉTICA ENTRE O DIREITO E A CONDIÇÃO HUMANA: CONSCIÊNCIA, RECONHECIMENTO E EMANCIPAÇÃO
Authors: Da Silva Braz Luciano 
Published: May 2015

A proposta de Habermas que busca perquirir a legitimidade do Estado constitucional democrático com base nos direitos humanos visa a estabelecer uma conexão interna entre uma democracia efetiva – exercício político - e o direito. Para tanto, faz-se necessário a formulação de um conceito político de legitimação de ordens caracterizadas pela organização do poder estatal, que segue atrelado ao direito legitimamente instituído. Considerando que esse médium da potência estatal se constitui sob a forma do direito, as ordens políticas buscam, na legitimidade reivindicada do direito, seu vigor. O presente artigo tem como foco de pesquisa examinar o déficit teórico quanto as possibilidades de implementação do exercício democrático, o reconhecimento, bem como, analisar a relação de completitude entre a política e o direito. Dado às realidades dispares situadas no mundo da vida, questiona-se a própria validade do direito quando temas ligados aos direitos fundamentais do homem, sua dignidade e reconhecimento e, a compreensão do Estado Democrático de Direito se contradizem ante realidades que ainda apontam pessoas, grupos, e etnias esquecidas à margem da sociedade. Este esboço é suficiente para levantar o problema típico das sociedades modernas: como estabilizar, na perspectiva própria dos atores, a validade duma ordem social legitima do ponto de vista do direito? À vista de tal possibilidade, Habermas buscar envolver-se com o problema central que abarca as possibilidades de reprodução social, à luz das pretensões de validade.
LICENCIAMENTO AMBIENTAL: ENTRAVE OU REFERÊNCIA DE SUSTENTABILIDADE?
Authors: Costa Ramires Celso 
Published: May 2015

Para elaboração do presente artigo foi utilizado na fase de investigação o método indutivo, e como técnica de investigação a pesquisa bibliográfica. O objetivo geral é mostrar como o Direito Ambiental tornou-se importante instrumento de gestão para as empresas, para isso dividiu-se esta produção em três tópicos que têm por objetivos específicos apresentar as políticas públicas para a sustentabilidade, o licenciamento em seu aspecto legal, e o licenciamento ambiental enquanto política pública. Ao perceber sua existência no planeta ameaçada, o homem passou a mudar a maneira de se relacionar com a natureza. Questionar modelos de produção e consumo adotando atitudes sustentáveis, em busca do equilíbrio na relação com o meio ambiente, exigiu uma mudança de paradigma irreversível. O foco na produção, única e exclusivamente para a geração de riqueza, deu lugar ao foco no desenvolvimento sustentável. A adoção de políticas públicas a fim de estabelecer regras para o uso sustentável dos recursos naturais se pauta, então, na prevenção, que consiste na definição de instrumentos para a sustentabilidade. Nessa matéria, tem-se o licenciamento ambiental, processo que tem como uma das fases a análise prévia de impactos ambientais, que é o centro das atenções e das discussões. A análise prévia de impactos ambientais tem o intuito de orientar a concessão da licença, levando em conta que os aspectos ambientais precisam ser considerados em todas as fases da implementação do empreendimento. Todo este processo gera a controvérsia de que o licenciamento é mais uma imposição do Estado e menos a tomada de consciência do empreendedor. O licenciamento ambiental é referência de sustentabilidade quando evidencia o “esforço pela vida”. Mas, a morosidade na concessão das licenças devido a obstáculos burocráticos tanto pela falta de especialização de técnicos, para análise, como pela falta de interesse das consultorias em se engajarem no processo, faz com que ele seja visto como um entrave. Como afirmam os especialistas, as empresas tratam este instrumento de sustentabilidade como uma “simples formalidade”, o que sugere descaso com a questão ambiental. Nesta abordagem concluiu-se que o grande desafio do licenciamento ambiental é aumentar sua eficiência, ainda que nossa legislação ambiental venha se aprimorando cada vez mais.
The Structure of the Strength of Riveted Joints Determined in the Lap Joint Tensile Shear Test
Authors: Mucha Jacek , Witkowski Waldemar 
Published: May 2015

Abstract
The article presents the analysis of the structure of the load capacity of riveted joints. For the four joining systems the lap joint specimens were made and tested in the shearing test. The joints were prepared for the three combinations of the DC01 steel and EN AW- 5754 aluminium alloy sheets with the thickness of 2mm. On the basis of the obtained load-elongation diagram tensile shear test curves, the basic parameters defined in the ISO/DIS 12996 standard were determined. In the case of the conventional riveted joints the maximum load capacity of the joint is determined by the strength of the fastener. For the joints with aluminium-steel blind rivet , the load capacity of the joint was on the strength limit of the rivet tubular part and on the strength limit of the sheet material. The strength of the SSPR joint is determined by the mechanical properties of the material of the joined sheets. From all sheets and rivet specimens arrangements the highest load capacity of the joint was obtained for the DC01 sheet material joints, and the lowest load capacity of the joint was obtained for the EN AW-5754 sheet material joints.
Analysing the local geography of the relationship between residential property prices and its determinants
Authors: Dziauddin Mohd Faris , Ismail Kamarul , Othman Zainudin 
Published: May 2015

Abstract
This paper analyses the local geography of the relationship between residential property prices and its determinants. A semiparametric geographically weighted regression (S-GWR) technique is employed to explore this relationship. Selling prices, structural and locational attributes data were collected from the database of the Department of Valuation and Services of Malaysia, selected maps and reports. The outcome of this paper shows a strong geographically varying relationship between residential property prices and its determinants in which the residential property price determinants have a positive impact on prices in some areas but negative or no impact on the others. The magnitude of the effect is also found to be geographically varied; the capitalisation in residential property prices is found greater in some areas but less or with no effect in some other parts of the areas. The use of S-GWR technique makes it possible to reveal such geographically varying relationships, thus leading to a better understanding of the relationship between residential property prices and its determinants.
Role of green areas for space integration of Kraków’s Metropolitan Area
Authors: Hrehorowicz-Gaber Hanna 
Published: May 2015

Abstract
The Kraków Metropolitan Area (KOM) is a specific functional region comprising a big city that is the Kraków metropolis, together with its neighbouring complex of settlements with a variety of mutual interactions. The social and economic space requires multi-dimensional enhancement of its interrelations and partial rehabilitation of its developed areas; it constitutes, at the same time, a potential which strengthens the position of Kraków as a European city. A clear structure of the metropolitan area and its internal links through green seams provide the basis for functional and spatial integration of the metropolis. The greenery, comprised in larger natural structures such as river parks and green wedges, enhances the area’s polycentric concept. The shaping of the urban tissue of Kraków and its suburban zone by composing and building a network of open spaces is the basic criterion for developing a coherent metropolitan area with a sustainable structure. Many problems of the urban environment and its surroundings can be fully understood through their analyses in various scales. In order to better illustrate this complex system of interrelations, reference should be made in analyses to the macroregional scale then narrowing them to the regional scale, to ultimately go down to the metropolis. The issues covered in the paper concern open areas which should not be discussed without a broader spectrum because the notion of green areas is understood to mean primarily spaces which are networked and intertwined with the settlement structure. Some of them are clear, for instance the greenery which accompanies water courses, and easy to identify. Marshlands are mostly linearly continuous and this makes them coherent in their nature. Other green areas (apart from larger forest complexes) are not of essential significance for the integration of the metropolis. The example of Kraków shows that the KOM (1) has a big potential expressed through its natural environment in the form of green areas. The anthropopressure, however, is so high that open spaces are being absorbed by developments. It is riverside areas which have retained a clear structure of interrelations and they should be perceived as the future for the links in the metropolitan area.