Synchronization and Multiple Group Server Support for Kepler

In the last decade literally thousands of digital libraries have emerged but one of the biggest obstacles for dissemination of information to a user community is that many digital libraries use different, proprietary technologies that inhibit interoperability. Kepler framework addresses interoperability and gives publication control to individual publishers. In Kepler, OAI-PMH is used to support personal data providers or archivelets . . In our vision, individual publishers can be integrated with an institutional repository like Dspace by means of a Kepler Group Digital Library (GDL). The GDL aggregates metadata and full text from archivelets and can act as an OAI-compliant data provider for institutional repositories. The basic Kepler architecture and it working have been reported in earlier papers. In this paper we discuss the three main features that we have recently added to the Kepler framework: mobility support for users to switch transparently between traditional archivelet s to on-server archivelets, the ability of users to work with multiple GDLs, and flexibility to individual publishers to build an OAI-PMH compliant repository without getting attached to a GDL

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

Primary angiosarcoma of the lung and pleura

A 46 year old male smoker was admitted for severe continuing hemoptysis. Chest-X-rays and chest computed tomography revealed nodular infiltrates and bilateral hemothorax. Fiberoptic bronchoscopy resulted to non-diagnostic cytological and microbiological findings. Open lung and pleural biopsies after right thoracotomy revealed epithelioid angiosarcoma and further staging assessment showed secondary brain and liver foci. The patient received several courses of chemotherapy but he died one month later. The clinical, radiological, pathological, histochemical and therapeutic aspects of the disease are discussed. Angiosarcoma, a rare tumour with poor prognosis should be taken into consideration in the differential diagnosis of hemoptysis

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

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

Neuropathology in Mouse Models of Mucopolysaccharidosis Type I, IIIA and IIIB

Mucopolysaccharide diseases (MPS) are caused by deficiency of glycosaminoglycan (GAG) degrading enzymes, leading to GAG accumulation. Neurodegenerative MPS diseases exhibit cognitive decline, behavioural problems and shortened lifespan. We have characterised neuropathological changes in mouse models of MPSI, IIIA and IIIB to provide a better understanding of these events

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