Preparing DARIAH

In this paper, a preparatory project for an integrated European research infrastructure in the humanities is presented. This project, Preparing for the construction of the Digital Research Infrastructure for the Arts and Humanities - or Preparing DARIAH for short, is part of the ESFRI e-infrastructures programme and supports the emergence of a new collaborative framework in which researchers are able to maximise the impact of their work on the international stage and aims at providing the foundations for the timely construction of the infrastructure requisite for the arts, humanities and cultural heritage communities in the digital age. DARIAH uses an interdisciplinary approach and involves tackling a number of interrelated issues such as strategic, organisational, financial, technical and conceptual in order to facilitate long-term access to and use of all European humanities and cultural heritage information for the purposes of enhancing and expanding research, thereby increasing our knowledge and understanding of our histories, heritage, languages and cultures. The DARIAH network will act as a place where the incubation of new ideas and ways of working can be facilitated and developed, and then transitioned into established organisations thus ensuring long-term sustainability and stability and the integration of these methods and techniques into everyday research practice. DARIAH will support research practitioners at all stages in the research process, and at differing levels of sophistication, from beginners through to those employing advanced techniques and methodologies

XTraQue: traceability for product line systems

Product line engineering has been increasingly used to support the development and deployment of software systems that share a common set of features and are developed based on the reuse of core assets. The large number and heterogeneity of documents generated during the development of product line systems may cause difficulties to identify common and variable aspects among applications, and to reuse core assets that are available under the product line. In this paper, we present a traceability approach for product line systems. Traceability has been recognised as an important task in in software system development. Traceability relations can improve the quality of the product being developed and reduce development time and cost. We present a rule-based approach to support automatic generation of traceability relations between feature-based object-oriented documents. The traceability rules used in our work are classified into two groups namely (a) direct rules, which support the creation of traceability relations that do not depend on the existence of other relations, and (b) indirect rules, which require the existence of previously generated relations. The documents are represented in XML and the rules are represented in an extension of XQuery. A prototype tool called XTraQue has been implemented. This tool, together with a mobile phone product line case study, has been used to demonstrate and evaluate our work in various experiments. The results of these experiments are encouraging and comparable with other approaches that support automatic generation of traceability relations

The clinical significance of soluble E-cadherin in nonsmall cell lung cancer

Aim: Aberrant expression of the epithelial transmembrane adhesion molecule E-cadherin (E-cad) has been associated with many human malignancies. In the present study the clinical significance of serum levels of soluble E-cadherin (sE-cad) in newly diagnosed patients with non small cell lung cancer (NSCLC) was investigated. Material and Methods: An enzyme linked immunospecific assay (ELISA) to determine the circulating levels of sE-cad in 20 newly diagnosed patients with NSCLC as well as in 29 healthy volunteers (control group) was used. Results: NSCLC patients exerted increased circulating levels of sE-cad compared with individuals of the control group (p < 0.001). An association was also detected between serum sE-cad levels and the development of distant metastases. On the contrary, no statistically significant correlation could be established with histological type, gender and smoking habits. Patients with increased sE-cad levels at diagnosis had worser outcome, although multivariate analysis failed to demonstrate that sE-cad levels represent an independent prognostic factor of survival. Conclusion: Our data suggest that E-cad plays a role in the pathogenesis of NSCLC. sE-cad levels may be further studied as a potential prognostic biomarker.Цель: нарушения экспрессии трансмембранной молекулы адгезии эпителия Е-кадерина (Е-cad) ассоциированы со злокачеcтвенными новообразованиями у человека. Цель исследования — оценить клиническое значение содержания секретируемого Е-кадерина (sE-cad) в сыворотке крови больных с диагнозом немелкоклеточного рака легкого (НМКРЛ). Материалы и методы: для определения уровня циркулирующего sE-cad в сыворотке крови 20 больных с НМКРЛ и 29 здоровых доноров применили метод ELISA. Результаты: у больных с НМКРЛ выявлено значительное повышение содержания циркулирующего sE-cad в сыворотке крови по сравнению с таковым в контрольной группе (p < 0,001). Установлена связь между уровнем sE-cad в сыворотке крови и появлением периферических метастазов. Не выявлено статистически достоверной корреляции между гистологическим типом опухоли, полом больного и курением. У пациентов с повышенным содержанием sE-cad наблюдалась тенеденция к худшему исходу заболевания, хотя результаты статистического анализа не подтвердили прогностического значения sE-cad. Выводы: полученные данные позволили предположить, что E-cad участвует в патогенезе НМКРЛ. Оценка содержания sE-cad в качестве прогностического биомаркера нуждается в дальнейшем исследовании

Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks

International audienceIncreasing amounts of sequence data are becoming available for a wide range of non-model organisms. Investigating and modelling the metabolic behaviour of those organisms is highly relevant to understand their biology and ecology. As sequences are often incomplete and poorly annotated, draft networks of their metabolism largely suffer from incompleteness. Appropriate gap-filling methods to identify and add missing reactions are therefore required to address this issue. However, current tools rely on phenotypic or taxonomic information, or are very sensitive to the stoichiometric balance of metabolic reactions, especially concerning the co-factors. This type of information is often not available or at least prone to errors for newly-explored organisms. Here we introduce Meneco, a tool dedicated to the topological gap-filling of genome-scale draft metabolic networks. Meneco reformulates gap-filling as a qualitative combinatorial optimization problem, omitting constraints raised by the stoichiometry of a metabolic network considered in other methods, and solves this problem using Answer Set Programming. Run on several artificial test sets gathering 10,800 degraded Escherichia coli networks Meneco was able to efficiently identify essential reactions missing in networks at high degradation rates, outperforming the stoichiometry-based tools in scalability. To demonstrate the utility of Meneco we applied it to two case studies. Its application to recent metabolic networks reconstructed for the brown algal model Ectocarpus siliculosus and an associated bacterium Candidatus Phaeomarinobacter ectocarpi revealed several candidate metabolic pathways for algal-bacterial interactions. Then Meneco was used to reconstruct, from transcriptomic and metabolomic data, the first metabolic network for the microalga Euglena mutabilis. These two case studies show that Meneco is a versatile tool to complete draft genome-scale metabolic networks produced from heterogeneous data, and to suggest relevant reactions that explain the metabolic capacity of a biological system

As time goes by

A rather simple and non-technical exposition of our new approach to {\em Time, Quantum Physics, Black-Hole dynamics}, and {\em Cosmology}, based on non-critical string theory, is provided. A new fundamental principle, the {\em Procrustean Principle}, that catches the essence of our approach is postulated: the low-energy world is {\em unavoidably} an ``open" system due to the spontaneous truncation of the {\em delocalized, topological} string modes in continuous interaction with the low-lying-{\em localized} string modes. The origin of space-time, the expansion of the Universe, the entropy increase and accompanied irreversibility of time, as well as the collapse of the wavefunction are all very neatly tied together. Possible observable consequences include: quantum relaxation with time of the Universal, fundamental constants, like the velocity of light $c$ and the Planck constant $\hbar$ decreasing towards their asymptotic values, and the cosmological constant $\Lambda_C$ diminishing towards zero; possible violation of {\em CPT} invariance in the $K^0-\bar K^0$ system, possible apparent non-conservation of angular momentum, and possible loss of quantum coherence in SQUID-type experiments.Comment: CERN-TH.7260/94, 84 pages Latex (no figures

The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

BACKGROUND: The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. METHODS: We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. RESULTS: Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. CONCLUSION: Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found

Assessment of splenic function

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell–Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, 99mTc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed

Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells

Cytotoxicity and mutagenicity of tremolite, erionite and the man-made ceramic (RCF-1) fibre were studied using the human– hamster hybrid A L cells. Results from these fibres were compared with those of UICC Rhodesian chrysotile fibres. The A L cell mutation assay, based on the S1 gene marker located on human chromosome 11, the only human chromosome contained in the hybrid cell, has been shown to be more sensitive than conventional assays in detecting deletion mutations. Tremolite, erionite and RCF-1 fibres were significantly less cytotoxic to A L cells than chrysotile. Mutagenesis studies at the HPRT locus revealed no significant mutant yield with any of these fibres. In contrast, both erionite and tremolite induced dose-dependent S1− mutations in fibre-exposed cells, with the former inducing a significantly higher mutant yield than the latter fibre type. On the other hand, RCF-1 fibres were largely non-mutagenic. At equitoxic doses (cell survival at ∼ 0.7), erionite was found to be the most potent mutagen among the three fibres tested and at a level comparable to that of chrysotile fibres. These results indicate that RCF-1 fibres are non-genotoxic under the conditions used in the studies and suggest that the high mesothelioma incidence previously observed in hamster may either be a result of selective sensitivity of hamster pleura to fibre-induced chronic irritation or as a result of prolonged fibre treatment. Furthermore, the relatively high mutagenic potential for erionite is consistent with its documented carcinogenicity. © 1999 Cancer Research Campaig

Early Neurodegeneration Progresses Independently of Microglial Activation by Heparan Sulfate in the Brain of Mucopolysaccharidosis IIIB Mice

BACKGROUND: In mucopolysaccharidosis type IIIB, a lysosomal storage disease causing early onset mental retardation in children, the production of abnormal oligosaccharidic fragments of heparan sulfate is associated with severe neuropathology and chronic brain inflammation. We addressed causative links between the biochemical, pathological and inflammatory disorders in a mouse model of this disease. METHODOLOGY/PRINCIPAL FINDINGS: In cell culture, heparan sulfate oligosaccharides activated microglial cells by signaling through the Toll-like receptor 4 and the adaptor protein MyD88. CD11b positive microglial cells and three-fold increased expression of mRNAs coding for the chemokine MIP1alpha were observed at 10 days in the brain cortex of MPSIIIB mice, but not in MPSIIIB mice deleted for the expression of Toll-like receptor 4 or the adaptor protein MyD88, indicating early priming of microglial cells by heparan sulfate oligosaccharides in the MPSIIIB mouse brain. Whereas the onset of brain inflammation was delayed for several months in doubly mutant versus MPSIIIB mice, the onset of disease markers expression was unchanged, indicating similar progression of the neurodegenerative process in the absence of microglial cell priming by heparan sulfate oligosaccharides. In contrast to younger mice, inflammation in aged MPSIIIB mice was not affected by TLR4/MyD88 deficiency. CONCLUSIONS/SIGNIFICANCE: These results indicate priming of microglia by HS oligosaccharides through the TLR4/MyD88 pathway. Although intrinsic to the disease, this phenomenon is not a major determinant of the neurodegenerative process. Inflammation may still contribute to neurodegeneration in late stages of the disease, albeit independent of TLR4/MyD88. The results support the view that neurodegeneration is primarily cell autonomous in this pediatric disease