bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperbaric oxygen pretreatment benefits on decompression sickness in Bama pigs
Authors: Qing Long , Yi Hong-jie , Wang Ye-wei , Zhou Quan , Ariyadewa Dinesh K. , Xu Wei-gang
Published: December 2017

Decompression sickness (DCS) occurs when ambient pressure severely reduces during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been proven to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesize that HBO pretreatment will also reduce DCS via HSPs in swine models. In part 1, six swine were subjected to a session of HBO treatment. HSP 32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In part 2, another ten swine were randomly assigned into 2 groups, 5 in each. All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air. Five swine in the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second. The other 5 swine in the second group pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (P<0.05) with the greatest expression appearing at 18 h for HSP 32 and 70. HBO pretreatment reduced significantly all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.
Genetic bypass of essential RNA repair enzymes in budding yeast
Authors: Cherry Patrick D. , White Laura K. , York Kerri , Hesselberth Jay R.
Published: December 2017

RNA repair enzymes catalyze rejoining of an RNA molecule after cleavage of phosphodiester linkages. RNA repair in budding yeast is catalyzed by two separate enzymes that process tRNA exons during their splicing and HAC1 mRNA exons during activation of the unfolded protein response (UPR). The RNA ligase Trl1 joins 2′,3′-cyclic phosphate and 5′-hydroxyl RNA fragments, creating a phosphodiester linkage with a 2′-phosphate at the junction. The 2′-phosphate is removed by the 2′-phosphotransferase Tpt1. We bypassed the essential functions of TRL1 and TPT1 in budding yeast by expressing “prespliced,” intronless versions of the 10 normally intron-containing tRNAs, indicating this repair pathway does not have additional essential functions. Consistent with previous studies, expression of intronless tRNAs failed to rescue the growth of cells with deletions in components of the SEN complex, implying an additional essential role for the splicing endonuclease. The trl1Δ and tpt1Δ mutants accumulate tRNA and HAC1 splicing intermediates indicative of RNA repair defects and are hypersensitive to drugs that inhibit translation. Failure to induce the unfolded protein response in trl1Δ cells grown with tunicamycin is lethal owing to their inability to ligate HAC1 after its cleavage by Ire1. In contrast, tpt1Δ mutants grow in the presence of tunicamycin despite reduced accumulation of spliced HAC1 mRNA. We optimized a PCR-based method to detect RNA 2′-phosphate modifications and show they are present on ligated HAC1 mRNA. These RNA repair mutants enable new studies of the role of RNA repair in cellular physiology.
Lichens and allied fungi new for Latvia
Authors: Moisejevs Rolands
Published: December 2017

Six lichenized fungi (Calicium parvum, C. trabinellum, Carbonicola anthracophila, C. myrmecina, Peltigera extenuata, Pycnora sorophora), two lichenicolous (Clypeococcum hypocenomycis and Illosporium carneum), and two saprobic calicioid fungi (Chaenothecopsis savonica and Microcalicium arenarium) are reported as new for Latvia.
New records of lichens from the Zeysky Nature Reserve (Amur Region, Russia)
Authors: Kuznetsova Ekaterina S. , Dudov Sergey V.
Published: December 2017

The lichen biota of the Zeysky Nature Reserve (southern Russian Far East) was studied in the course of geobotanical expedition. In total 36 species of lichens and one lichenicolous fungus are reported for the first time for the reserve. Among them 19 are new to the Amur Region. Parmelia asiatica is reported for the first time for the southern Russian Far East, Cladonia norvegica – for the Asian part of Russia, Tuckermannopsis gilva – for Russia, Melanohalea laciniatula – for Asia. Four species are included in the Red Data Book of Russian Federation.
The first confirmed finding of Leptosporomyces mundus (Basidiomycota) in Russia
Authors: Khimich Yuliia R. , Zmitrovich Ivan V.
Published: December 2017

The first record of Leptosporomyces mundus in Russia is reported. The short note on distribution of this species in East Europe as well as main diagnostic features are presented. An detailed description of Russian material on the species is given and additional Transcarpatian (Ukraine) material is cited. It is supposed that the earlier record of L. mundus from Russia in literature is referred to the Ukrainian material of Parmasto.
The lichens of Bolshoy Tuters Island (Tytärsaari), Leningrad Region, Russia
Authors: Stepanchikova Irina S. , Andreev Mikhail P. , Himelbrant Dmitry E. , Motiejūnaitė Jurga , Schiefelbein Ulf , Konoreva Ludmila A. , Ahti Teuvo
Published: December 2017

The updated checklist of Tuters Island (Leningrad Region, Russia) is presented. Of 331 species of recognized biota, 314 species of lichens, 16 lichenicolous fungi and one non-lichenized saprobic fungus are reported from Tuters Island. Of them, 202 species are new to the study area. Aspicilia epiglypta, Fuscidea praeruptorum, Micarea byssacea and Sarcogyne hypophaeoides are reported for the first time for Russia, Roselliniella stereocaulorum – for European Russia, Aspicilia polychroma, Carbonea vorticosa, Cercidospora stereocaulorum, Cladonia ciliata f. flavicans, C. rangiformis, Parmelia ernstiae, Plectocarpon cf. encausticum and Roselliniella cladoniae – for North-Western European Russia; Bachmanniomyces uncialicola, Bacidina sulphurella, Micarea botryoides, Miriquidica griseoatra and Stereocaulon nanodes are new to the Leningrad Region.
Política externa e regionalismo em um ambiente internacional em transformação / Foreign policy and regionalism in a changing international system
Authors: Ramanzini Junior Haroldo
Published: December 2017

O texto analisa o tema do regionalismo na América Latina com foco nas posições do Brasil. Avalia que as transformações e indefinições no sistema internacional colocam para o país a pertinência de um engajamento regional propositivo e multidimensional.ABSTRACTThe paper analyzes the issue of regionalism in Latin America with focus on brazilian foreign policy positions. It considers that the transformations and uncertainties in the international system emphasize the pertinence of a multidimensional regional engagement.Palavras-chave: regionalismo, política externa brasileira, Mercosul, Unasul.Keywords: regionalism, brazilian foreign policy, Mercosur, Unasur.Recebido em 04 de Março de 2017 | Aceito em 26 de Setembro de 2017Received on March 4, 2017 | Accepted on September 26, 2017DOI: 10.12957/rmi.2016.27759
Processo Decisório e Política Externa nos Pequenos Estados da Periferia: Cabo Verde e Guiné-Bissau | Decision-Making Process and Foreign Policy in Small Peripheral States: Cape Verde and Guinea-Bissau
Authors: M'bunde Timóteo Saba
Published: December 2017

O texto questiona as perspectivas mais conservadoras do campo de Análise de Política Externa (APE), as quais se subsidiam de pressupostos teóricos do realismo para refutar a validade do uso de APE e processo decisório, como ferramentas cabíveis a estudar a política externa dos Estados da periferia do sistema internacional. O texto busca identificar o processo decisório de política externa em Cabo Verde e Guiné-Bissau e apresentar pistas pelas quais é possível lançar mão de APE para estudar a política externa desses dois países luso-africanos. O trabalho também apresenta alguns aspectos dos modelos políticos e constitucionais de Cabo Verde e Guiné-Bissau e a influência que os respectivos contextos políticos exercem sobre a formulação de política externa, caracterizando o tipo de processo decisório que tende a se predominar em cada um dos dois contextos.ABSTRACTThe paper question the most conservatives outlook of Foreign Policy Analysis (FPA) field, that subsidize from theoretical realism assumptions to refute the validity of the use of FPA and decision-making process as appropriate tools to study the foreign policy of international system peripheral states. The paper seeks to identify the decision-making process of foreign policy in Cape Verde and Guinea-Bissau and provides clues by which it’s possible to make use of FPA to study and understand the foreign policy of both luso-africans countries. The work also presents some aspects of Guinea-Bissau and Cape Verde political and constitutional models and the influence that the respective political contexts have on foreign policy formulation, characterizing the kind of decision-making that tends to predominate in each of the two contexts.Palavras-chave: processo decisório; política externa; Estados da periferia.Keywords: decision-making; foreign policy; peripheral States.Recebido em 14 de Agosto de 2017 | Aceito em 29 de Novembro de 2017.Received on August 14, 2017 | Accepted on November 29, 2017. DOI: 10.12957/rmi.2016.29990
The local Cauchy problem for a generalized fifth-order Camassa-Holm equation
Authors: Montes Alex M. , Molina Wilmer L. , Tobar Jaime
Published: December 2017

In this paper we show local well-posedness for a generalized Camassa-Holm
equation of fifth-order.
Efektivitas Juru Bahasa Isyarat Khutbah di Masjid UIN Sunan Kalijaga
Authors: Mustarjudin Mustarjudin
Published: December 2017

The center for Disability Services at UIN Sunan Kalijaga in collaboration with UIN Sunan Kalijaga Mosque provides sign interpreter service for the Deaf worshipers during the Friday sermon. This study aims to assess the effectiveness of sign language interpreters. Based on the analysis of three approaches and five measures of effectiveness, research shows that the Friday sermon interpretation program has not been effective. This is due to several factors, namely: the sitting position of the Deaf which determines the quality of visualization of sign language interpretation of khutbah material, the lack of language capability of sign language interpreters, the coordination is not done between the PLD and mosque management, the absence of material publications that facilitate the sign interpreter understand the material, lack of religious understanding of Deaf so that they ar less able to understand the sermon topic.[Pusat Layanan Difabel UIN Sunan Kalijaga Yogyakarta bekerja sama dengan Laboratorium Agama Masjid UIN Sunan Kalijaga Yogyakarta menyediakan layanan juru bahasa isyarat untuk jamaah Tuli pada saat khutbah Jumat. Penelitian ini bertujuan untuk menilai efektifitas juru bahasa isyarat. Berdasarkan analisis tiga pendekatan dan lima ukuran efektivitas, penelitian menunjukkan bahwa program juru bahasa isyarat khutbah Jumat belum dapat dikatakan efektif. Hal tersebut disebabkan beberapa faktor, yaitu: posisi duduk Tuli yang menentukan kualitas visualisasi juru bahasa isyarat materi khutbah, minimnya kemampuan bahasa juru bahasa isyarat, koordinasi yang tidak dilakukan antara pihak PLD dan pengurus masjid, tidak adanya publikasi materi yang memudahkan juru bahasa isyarat memahami materi, minimnya pemahaman keagamaan Tuli sehingga kurang dapat memahami materi khutbah.]
Judging Constitutions: Aristotle’s Critique of Plato’s Republic and Sparta
Authors: Lockwood Thornton
Published: December 2017

Although the second book of Aristotle’s
Complete signal peptide of Tk1884, an α-amylase from Thermococcus kodakarensis, is not necessary for extracellular secretion of the enzyme by Escherichia coli
Authors: Muhammad Majida A. , Falak Samia , Rashid Naeem , Ahmed Nasir , Gardner Qurra-Tul-Ann A. , Tariq Anam , Akhtar Muhammad
Published: December 2017

In order to elucidate if Escherichia coli secretion system recognizes the N-terminally truncated signal sequence of an archaeal α-amylase from Thermococcus kodakarensis (Tk1884) and secretes the recombinant protein to the extracellular medium, we have cloned Tk1884 with the deletion of the sixteen N-terminal amino acids and produced the recombinant protein Tk1884Δ16 in E. coli. Analysis of the intracellular, membranous and extracellular fractions demonstrated the presence of Tk1884Δ16 in all the three fractions. The intracellular α-amylase activity, similar to the membranous fraction, increased with the passage of time till 8 h of induction and then decreased. In contrast, the extracellular α-amylase activity slowly increased with the passage of time after induction. The extracellular amylase activity was purified and determination of the molecular mass by electrospray ionization mass spectrometry demonstrated that Tk1884Δ16 was secreted to the extracellular medium without cleavage of the signal peptide. To the best of our knowledge, this is the first report on recognition of N-terminally truncated signal peptide of archaeal origin by E. coli.
Ḫatti and Ḫattuša
Authors: Kryszeń Adam
Published: December 2017

The article addresses long-standing but still pertinent questions regarding the two most frequent toponyms in Hittite texts:

In order to deal with these issues, all attestations of both toponyms have been collected and analyzed statistically, taking various criteria into consideration: the dating and language of the texts mentioning
Judgement on camels- or fiction?
Authors: Syrkou Angeliki
Published: December 2017

The evidence strongly suggests that the text presented here is a report of court proceedings about camels. However, two peculiarities might point in a different direction: ( 1 ) the personal name Adikran which is mentioned only in Herodotus 4.159 as a king of the Libyans; (2) the phrase ταυ δέ μετρίου φροντίζων, which recalls a rhetorical context. Could this be a description of a court scene in a novel?
Catalogue des textes magiques coptes
Authors: Sarrazin Roxanne Belanger
Published: December 2017

This article presents an up-to-date checklist of Coptic magical texts. It deals with methodological issues, such as the criteria used for the selection of the texts and their classification into three categories (certain, probable and possible magical texts), and with the main characteristics of the texts included in the corpus: their geographical and chronological distribution, language and dialects, materials and purposes, and how they compare to Greek magical texts. A list with all items follows, including the basic characteristics for each of them
The Cost of Basic Income: Back-of-the-Envelope Calculations
Authors: Widerquist Karl
Published: December 2017

This article shows how the cost of Universal Basic Income (UBI) is often misunderstood and greatly exaggerated. It then presents simple, “back-of-the-envelope” estimates of the net cost of a UBI set at about the official poverty line: $12,000 per adult and $6,000 per child with a 50 % “marginal tax rate.” These back-of-the-envelope calculations present a greatly simplified UBI scheme meant not as a practical proposal but as a method to obtain a ballpark estimate of the cost of UBI in isolation. Even with simplifying assumptions, these figures are several times more accurate than many common but exaggerated estimates. Key findings of this study include the following. The net cost — the real cost — of this UBI scheme is $539 billion per year: about one-sixth its often-mentioned but not-very-meaningful gross cost of about $3.415 trillion. The net cost of this UBI scheme is less than 25 % of the cost of current U.S. entitlement spending, less than 15 % of overall federal spending, and about 2.95 % of Gross Domestic Product (GDP). The average net beneficiary is a family of about two people making about $27,000 per year in market income. The family’s net benefit from the UBI would be nearly $9,000, raising their income to almost $36,000.
A Black Swan in clinical laboratory practice: the analytical error due to interferences in immunoassay methods
Authors: Clerico Aldo , Belloni Lucia , Carrozza Cinzia , Correale Mario , Dittadi Ruggero , Dotti Claudio , Fortunato Antonio , Vignati Giulio , Zucchelli Gian Carlo , Migliardi Marco
Published: December 2017

It is well known that the results of immunoassay methods can be affected by specific or non-specific interferences, ranging from 0.4% to 4.0%. The presence of interference may greatly compromise the accuracy of immunoassay analyses causing an error in the measurement, producing false-positive or false-negative results. From a clinical point of view, these analytical errors may have serious implications for patient care because they can cause misdiagnosis or inappropriate treatment. Unfortunately, it is a very difficult task to identify the irregular analytical errors related to immunoassay methods because they are not detectable by normal laboratory quality control procedures, are reproducible within the test system, may be clinically plausible and are relatively rare. The first line of defense against erroneous results is to use in laboratory practice only immunoassay systems with the highest level of robustness against interference. The second line of defense is always taking into account the possibility of interference in immunoassay results. A correct approach should be addressed on identification of samples at high risk of interference. The attainment of this goal requires a critical review of the test result in relation to patient’s clinical conditions and literature data, taking into account the analytical characteristics of the immunoassay system. The experts in immunoassay systems should make every effort to find some specific and reliable quality indicators for irregular analytical errors in order to better detect and monitor erroneous immunoassay results due to specific or non-specific interferences.
Pitting corpus-based classification models against each other: a case study for predicting constructional choice in written Estonian
Authors: Klavan Jane
Published: December 2017

In the context of constructional alternatives, we may assume that speakers’ choice between alternative forms is influenced by a multitude of factors. At the moment, multivariate statistical classification modelling seems to be the best tool available to capture this knowledge quantitatively. There is a vast array of techniques available. In this paper, two distinct modelling techniques are applied – logistic regression and naïve discriminative learning – to predict the choice between two constructional alternatives in written Estonian. One of the central questions in statistical modelling concerns the evaluation of model fit. It is proposed that for linguistic analysis, the performance of alternative corpus-based models can be evaluated by, first, pitting them against each other and second, pitting them against experimental data. Previous work on modelling constructional and lexical choice has focused on one of the two aspects. The present paper takes this line of analysis further by combining the two approaches.
Scale dependence of biotic homogenisation by urbanisation: a comparison of urban bird communities between central Argentina and northern Finland
Authors: Leveau Lucas M. , Jokimäki Jukka , Kaisanlahti-Jokimäki Marja-Liisa
Published: December 2017

Recent studies showed contrasting results about the homogenising force of urbanisation on bird community composition at large and regional scales. We studied whether urbanisation promotes the homogenisation of wintering bird communities and if this varies when comparing towns located within a specific region and towns located in two different biomes of two countries. We used both similarity indices based on the presence/absence data and the abundance data in comparing communities. Processes governing bird community dissimilarity between urbanisation levels were examined with the partitioning of Sörensen index in species turnover and nestedness. We made bird surveys in town centres and suburban habitats of three cities located in the Pampean region of Argentina and in the boreal region of Finland using a single-visit study plot method. Rarefacted species richness did not differ amongst the town centres between the countries, but it was higher in the suburban areas of Argentina than in Finland. At the country-level comparison, we found a higher similarity amongst the town centres than amongst the suburban areas; whereas at the regional comparison, similarity between town centres was comparable to the similarity between suburban areas. The use of an abundance-based index produced a higher similarity between town centre communities of both countries than when using a presence-based index. The dissimilarity between habitats in Argentina was related to nestedness and to species turnover in Finland. Our results indicate that urban-based biotic homogenisation of bird communities is dependent on the scale used, being more evident when comparing cities of different biomes where the same and abundant bird species, such as sparrows and doves, dominate. At the regional scale, quite a high beta-diversity can still be found within urban habitats. Processes of community dissimilarity between urban habitats may differ according to the regional pool of species, being more related to nestedness toward the tropics.
Trends in High Nature Value farmland studies: A systematic review
Authors: Benedetti Yanina
Published: December 2017

Background. Since the High Nature Value (HNV) concept was defined in the early 1990s, several studies on HNV farmland has been increasing over the past 30 years in Europe, highlighting the interest by scientific community of HNV farming systems supporting biodiversity conservation. The aim of this study was to evaluate the trends and main gaps on HNV farmland peer-reviewed publications in order to contribute to the effectiveness of future research in this field. Methods. Searches were conducted using the databases Web of SciencesTM and Scopus in order to identify only peer-reviewed articles on HNV farmland, published prior to July 2017. The inclusion and exclusion criteria were developed a priori. Data as year, country, type of document, subject area, taxa studied and biodiversity metrics assessed were extracted and explored in order to analyse the spatial and temporal distribution of the concept, including the main topics addressed in HNV farmland literature. Results. After screening 308 original articles, 90 were selected for this review. HNV farmland studies involved several disciplines, mainly biodiversity and conservation and environmental sciences and ecology. Most peer-reviewed articles focused on HNV farming were conducted in Spain, Italy, Ireland and Portugal. The main studied taxa were plants and birds. Taxonomic diversity was the biodiversity metric more often used to assess the biodiversity status on HNV farmland areas. A positive correlation was found between HNV farmland area and HNV farmland studies conducted in respective countries. Discussion. The HNV farmland research subject is a relative novel approach, and this systematic review provides a comprehensive overview about the main topics in the HNV farmland peer-reviewed literature contributing to highlight the main gaps and provide some considerations in order to assist the performance of HNV farming systems and conservation policies, addressed to sustain high levels of biodiversity.
Simulated Cell Division Processes of the Xenopus Cell Cycle Pathway by Genomic Object Net
Authors: Matsui Mika , Fujita Sachie , Suzuki Shunichi , Matsuno Hiroshi , Miyano Satoru
Published: December 2017

Matsuno et al.[1] modeled and simulated that multicellular patterning by the Drosophila Delta-Notch signaling pathway by using the software “Genomic Object Net” which was developed based on hybrid functional Petri net (HFPN) architecture. In this model, cellular formation is fixed throughout the simulation. This paper constructs an HFPN model of the Xenopus cell cycle pathway, which includes the mechanism for cell division control as well as checkpoint processes. This model simulates dynamic cell division processes of the early Xenopus embryo, including the changes in cell division cycles from synchronous to asynchronous.
A Multi-Scale Modeling Concept and Computational Tools for the Integrative Analysis of Stationary Metabolic Data
Authors: Lieres Eric von , Petersen Sören , Wiechert Wolfgang
Published: December 2017

Metabolic Engineering aims at the systematic analysis and targeted manipulation of the metabolism in biotechnologically utilized microorganisms [1,2]. Recently, consistent stationary in vivo data sets of intracellular metabolite concentrations, fluxes and specific enzyme activities have become available for this purpose [3,4]. For the integrative analysis of the metabolic data at hand, a novel multi-scale modeling concept, computeralgebraic methods and efficient numerical algorithms are proposed. The available metabolic data are typically afflicted with comparatively large measurement errors. Therefore, reliable comprehensive error estimations are essential for the reasonable interpretation of consecutive outcomes, such as simulation results.

The concepts, methods and algorithms are first presented as universal methods and subsequently applied to the anaplerotic regulation in lysine-producing Corynebacterium glutamicum. A multi-scale model is set up, fitted to the available experimental data and validated by the prediction of further experiments. This model is capable of forecasting the quantitative effect of changes in the specific activity of anaplerotic enzymes, namely phosphoenolpyruvate carboxylase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase, on lysine productivity and yield.
Integration of Data in Pathogenomics: Three Layers of cellular complexity and an XML-based Framework
Authors: Dünßer M. , Lampidis R. , Schmidt S. , Seipel D. , Dandekar T.
Published: December 2017

Integration of data in pathogenomics is achieved here considering three different levels of cellular complexity: (i) genome and comparative genomics, (ii) enzyme cascades and pathway analysis, (iii) networks including metabolic network analysis.

After direct sequence annotation exploiting tools for protein domain annotation (e.g. AnDOM) and analysis of regulatory elements (e.g. the RNA analyzer tool) the analysis results from extensive comparative genomics are integrated for the first level, pathway alignment adds data for the pathway level, elementary mode analysis and metabolite databanks add to the third level of cellular complexity.

For efficient data integration of all data the XML based platform myBSMLStudio2003 is discussed and developed here. It integrates XQuery capabilities, automatic scripting updates for sequence annotation and a JESS expert system shell for functional annotation. In the context of genome annotation platforms in place (GenDB, PEDANT) these different tools and approaches presented here allow improved functional genome annotation as well as data integration in pathogenomics.
Searching for ncRNAs in eukaryotic genomes: Maximizing biological input with RNAmotif
Authors: Collins Lesley J. , Macke Thomas J. , Penny David
Published: December 2017

Non-coding RNAs (ncRNAs) contain both characteristic secondary-structure and short sequence motifs. However, “complex” ncRNAs (RNA bound to proteins in ribonucleoprotein complexes) can be hard to identify in genomic sequence data. Programs able to search for ncRNAs were previously limited to ncRNA molecules that either align very well or have highly conserved secondary-structure. The RNAmotif program uses additional information to find ncRNA gene candidates through the design of an appropriate “descriptor” to model sequence motifs, secondary-structure and protein/RNA binding information. This enables searches of those ncRNAs that contain variable secondary-structure and limited sequence motif information. Applying the biologically-based concept of “positive and negative controls” to the RNAmotif search technique, we can now go beyond the testing phase to successfully search real genomes, complete with their background noise and related molecules. Descriptors are designed for two “complex” ncRNAs, the U5snRNA (from the spliceosome) and RNaseP RNA, which successfully uncover these sequences from some eukaryotic genomes. We include explanations about the construction of the input “descriptors” from known biological information, to allow searches for other ncRNAs. RNAmotif maximizes the input of biological knowledge into a search for an ncRNA gene and now allows the investigation of some of the hardest-to-find, yet important, genes in some very interesting eukaryotic organisms.
Matching of PDB chain sequences to information in public databases as a prerequisite for 3D functional site visualization
Authors: Dieterich Guido , Heinz Dirk W. , Reichelt Joachim
Published: December 2017

The 3D structures of biomacromolecules stored in the Protein Data Bank [1] were correlated with different external, biological information from public databases. We have matched the feature table of SWISS-PROT [2] entries as well InterPro [3] domains and function sites with the corresponding 3D-structures. OMIM [4] (Online Mendelian Inheritance in Man) records, containing information of genetic disorders, were extracted and linked to the structures. The exhaustive all-against-all 3D structure comparison of protein structures stored in DALI [5] was condensed into single files for each PDB entry. Results are stored in XML format facilitating its incorporation into related software. The resulting annotation of the protein structures allows functional sites to be identified upon visualization.
Using gene networks to drug target identification
Authors: Jiang Zhenran , Zhou Yanhong
Published: December 2017

The complete genome sequences have provided a plethora of potential drug targets. Gene network technique holds the promise of providing a conceptual framework for analysis of the profusion of biological data being generated on potential drug targets and providing insights to understand the biological regulatory mechanisms in diseases, which are playing an increasingly important role in searching for novel drug targets from the information contained in genomics. In this paper, we discuss some of the network-based approaches for identifying drug targets, with the emphasis on the gene network strategy. In addition, some of the relevant data resources and computational tools are given.
Identification of embryo specific human isoforms using a database of predicted alternative splice forms
Authors: Pospisil Heike
Published: December 2017

Alternative splicing is one of the most important mechanisms to generate a large number of mRNA and protein isoforms from a small number of genes. Its study became one of the hot topics in computational genome analysis. The repository EASED (Extended Alternatively Spliced EST Database, http://eased.bioinf.mdc-berlin.de/) stores a large collection of splice variants predicted from comparing the human genome against EST databases. It enables finding new unpublished splice forms that could be interesting candidate genes for stage specific, diseases specific or tissue specific splicing. The main idea behind selecting specific splice forms is to compare the number and the origin of ESTs confirming one isoform with the number and the origin of ESTs confirming the opposite isoform. A measure asDcs is introduced to take into account the unequal distribution of ESTs per splice site on one hand, and the possible uncertainties due to the relatively low quality of EST data on the other hand. First, the number of ESTs per splice site is scaled with a modified Hill function. The measure asDcs computes in the second step the distance of each pair of ESTs from equipartition. Equipartition exists if for every number of adult ESTs the same number of embryonic ESTs. The effect of several input parameters for the scaling of true EST values is analysed and can be reproduced on http://cardigan.zbh.uni-hamburg.de/asDcs. Some of the obtained best scoring hits for selected parameters (transcription factor P65, drebrin, and fetuin) have been already described in literature as been involved in embryonic development. This result shows the plausibility of this approach and looks promising for the identification of unplublished embryo specific alternative splice sites in human.
A structural keystone for drug design
Authors: Rother Kristian , Dunkel Mathias , Michalsky Elke , Trissl Silke , Goede Andrean , Leser Ulf , Preissner Robert
Published: December 2017

3D-structures of proteins and potential ligands are the cornerstones of rational drug design. The first brick to build upon is selecting a protein target and finding out whether biologically active compounds are known. Both tasks require more information than the structures themselves provide. For this purpose we have built a web resource bridging protein and ligand databases. It consists of three parts: i) A data warehouse on annotation of protein structures that integrates many well-known databases such as Swiss-Prot, SCOP, ENZYME and others. ii) A conformational library of structures of approved drugs. iii) A conformational library of ligands from the PDB, linking the realms of proteins and small molecules.

The data collection contains structures of 30,000 proteins, 5,000 different ligands from 70,000 ligand-protein complexes, and 2,500 known drugs. Sets of protein structures can be refined by criteria like protein fold, family, metabolic pathway, resolution and textual annotation. The structures of organic compounds (drugs and ligands) can be searched considering chemical formula, trivial and trade names as well as medical classification codes for drugs (ATC). Retrieving structures by 2D-similarity has been implemented for all small molecules using Tanimoto coefficients. For the drug structures, 110,000 structural conformers have been calculated to account for structural flexibility. Two substances can be compared online by 3D-superimposition, where the pair of conformers that fits best is detected. Together, these web-accessible resources can be used to identify promising drug candidates. They have been used in-house to find alternatives to substances with a known binding activity but adverse side effects.
Network integration of data and analysis of oncology interest
Authors: Romano P. , Bertolini G. , De Paoli F. , Fattore M. , Marra D. , Mauri G. , Merelli E. , Porro I. , Scaglione S. , Milanesi L.
Published: December 2017

The Human Genome Project has deeply transformed biology and the field has since then expanded to the management, processing, analysis and visualization of large quantities of data from genomics, proteomics, medicinal chemistry and drug screening. This huge amount of data and the heterogeneity of software tools that are used implies the adoption on a very large scale of new, flexible tools that can enable researchers to integrate data and analysis on the network. ICT technology standards and tools, like Web Services and related languages, and workflow management systems, can support the creation and deployment of such systems. While a number of Web Services are appearing and personal workflow management systems are also being more and more offered to researchers, a reference portal enabling the vast majority of unskilled researchers to take profit from these new technologies is still lacking. In this paper, we introduce the rationale for the creation of such a portal and present the architecture and some preliminary results for the development of a portal for the enactment of workflows of interest in oncology.
Noise in Genetic Toggle Switch Models
Authors: Andrecut M. , Kauffman S. A.
Published: December 2017

In this paper we study the intrinsic noise effect on the switching behavior of a simple genetic circuit corresponding to the genetic toggle switch model. The numerical results obtained from a noisy mean-field model are compared to those obtained from the stochastic Gillespie simulation of the corresponding system of chemical reactions. Our results show that by using a two step reaction approach for modeling the transcription and translation processes one can make the system to lock in one of the steady states for exponentially long times.
The implications for Bioinformatics of integration across physical scales
Authors: Hodgman T.C. , Ugartechea-Chirino Y. , Tansley G. , Dryden I.
Published: December 2017

Bioinformatics blossomed with research developments in molecular biology. But as the focus of research moves back up the physical scale to the biology of whole multicellular organisms, there are new integration challenges. Data integration is a perennial theme that will not be explored here. Rather, we outline a survey of the types of data generated in whole organisms, putting particular emphasis on complex image capture, management and analysis, bio-systems modelling techniques at this higher scale, and approaches to integrating models across these physical scales. This change in biological focus raises certain challenges, one of which may be the need to retrain bioinformaticians in sciences pertaining to whole plants and animals.
Targeted Projection Pursuit Tool for Gene Expression Visualisation
Authors: Faith Joe , Brockway Michael
Published: December 2017

A tool is introduced that uses a novel technique to enable users to explore two-dimensional views of high dimensional gene expression data sets. Unlike other such tools, the interface is intuitive and efficient, allowing the user to easily select views that meet their requirements. The tool is tested on publicly available gene expression data sets and demonstrated to find views that show the seperation of gene expression data sets into classes more effectively than standard dimension-reduction methods.
The BioRSTM Integration and Retrieval System: An open system for distributed data integration
Authors: Kaps Andreas , Dyshlevoi Konstantin , Heumann Klaus , Jost Ralf , Kontodinas Ioannis , Wolff Martin , Hani Jean
Published: December 2017

Modern academic and industrial research in life sciences generates huge amounts of data and information. To extract knowledge from this information space, optimized integration and retrieval software tools are essential. In the last years, a number of academic as well as commercial systems have been developed to solve this problem. However, as scientific projects are distributed at different locations (e.g., subsidiaries of companies, academic partnerships), data exchange and availability must be realized in a way that avoids data replication.

In this article, we describe a global solution for integrating distributed information by applying the BioRSTM Integration and Retrieval System and its inter-BioRS communication capability that goes beyond the standard issue of local data integration. Each site integrates and maintains locally generated data using a local copy of the BioRS software. Applying the inter-BioRS communication, all available BioRS instances can communicate with each other realizing a global network of integrated databanks. All databanks integrated in this network can be accessed from any site without any data replication. This open system allows the addition of new information and sites dynamically. However, access privileges for certain databanks can be maintained on a per user and databank level ensuring data security when required.
Identifying Transcription Regulatory Elements in the Human and Mouse Genomes Using Tissue-specific Gene Expression Profiles
Authors: Karmaker Amitava , Yoon Kihoon , Doderer Mark , Kruzelock Russell , Kwek Stephen
Published: December 2017

Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.
Defining Mapping Mashups with BioXMash
Authors: Hunt Ela , Jakubowska Joanna , Bösinger Caroline , Norrie Moira C.
Published: December 2017

We present a novel approach to XML data integration which allows a biologist to select data from a large XML file repository, add it to a genome map, and produce a mapping mashup showing integrated data in map context. This approach can be used to produce contextual views of arbitrary XML data which relates to objects shown on a map. A biologist using BioXMash searches in XML tags, and is guided by XML path data availability, shown as the number of values reachable via a path, in both global, genome-wide, and local, per-gene, context. Then she examines sample values in an area of interest on the map. If required, the resulting data is dumped to files, for subsequent analysis.

This is a lightweight integration approach, and differs significantly from other known methods. It assumes that data integration can be performed on a lab computer with limited memory, with no database installation or programming knowledge. It is different from BioMarts which predefine possible data selections, in that arbitrary data sources related to map items can be used. BioXMash offers full textual search in XML paths, shows path statistics, and supports visual verification of data values. Repeated scanning of all XML files at query time is avoided by the use of a high level indexing technique. Our prototype demonstrates this new approach. It efficiently supports data browsing on 2 GB od data from GeneCards with an index size of 40 MB.
Stochastic effects in a compartmental model for mitotic checkpoint regulation
Authors: Ibrahim Bashar , Dittrich Peter , Diekmann Stephan , Schmitt Eberhard
Published: December 2017

The proper segregation of sister chromatids at onset of anaphase is surveyed by the mitotic spindle assembly checkpoint. The concentration dynamics of the complexes APC:Cdc20 and MCC:APC determine exit from metaphase to anaphase. We have developed a model based on 14 proteins and complexes to describe concentration dynamics by ordinary differential equations in three compartments coupled by diffusion. One kinetochore in each compartment determines the attachment status to the spindle pole. Here, we focus on the role of noise in the segregation surveillance process. The deterministic differential equations are enriched by a stochastic term adding white noise of different amplitudes. Obviously, for the known physiological parameter ranges, noise does not disturb the checkpoint function. On the other hand, there is a connection between diffusion and noise, that could become important when considering a larger number of chromosomes.
Data Linkage Graph: computation, querying and knowledge discovery of life science database networks
Authors: Lange Matthias , Himmelbach Axel , Schweizer Patrick , Scholz Uwe
Published: December 2017

To support the interpretation of measured molecular facts, like gene expression experiments or EST sequencing, the functional or the system biological context has to be considered. Doing so, the relationship to existing biological knowledge has to be discovered. In general, biological knowledge is worldwide represented in a network of databases. In this paper we present a method for knowledge extraction in life science databases, which prevents the scientists from screen scraping and web clicking approaches.

We developed a method for extraction of knowledge networks from distributed, heterogeneous life science databases. To meet the requirement of the very large data volume, the method used is based on the concept of data linkage graphs (DLG).We present an efficient software which enables the joining of millions of data points over hundreds of databases. In order to motivate possible applications, we computed networks of protein knowledge, which interconnect metabolic, disease, enzyme and gene function data.

The computed networks enabled a holistic relationship among measured experimental facts and the combined biological knowledge. This was successfully applied for a high throughput functional classification of barley EST and gene expression experiments with the perspective of an automated pipeline for the provisioning of controlled annotation of plant gene arrays and chips.

Availability: The data linkage graphs (XML or TGF format), the schema integrated database schema (GML or GRAPH-ML) and the graph computation software may be downloaded from the following URL: http://pgrc.ipk-gatersleben.de/dlg/
Community-based Linking of Biological Network Resources: Databases, Formats and Tools
Authors: Telgkamp Michael , Koschützki Dirk , Schwöbbermeyer Henning , Schreiber Falk
Published: December 2017

The analysis of biological networks is increasingly important in the life sciences and in particular in systems biology. Computer-based analysis tools are exploited for the investigation of these networks. However, to find relevant data sources can be a time-consuming task, access to information changes, frequently it is not obvious to a user which tools can be used in combination with specific data sources, and network data is often not available in a format directly usable by analysis tools.

To assist in collecting information about biological network data sources, and to help in investigating possible combinations of data sources and analysis software, we created BiNCo-wiki. BiNCo-wiki is a wiki system that stores information related to biological networks and allows all users to add or modify this information in an easy way. The collaborative character of a wiki system supports easy sharing of information and allows the community-based extension of the information already stored in BiNCo-wiki. We describe the general structure and functionality of the system and its initial content. BiNCo-wiki is accessible, free of charge, at http://pgrc.ipk-gatersleben.de/BiNCO-wiki.