484 research outputs found
Modeling and managing tacit product line requirements knowledge
The success of very large product lines systems with
globally distributed stakeholders often builds significantly on the implicit knowledge of individuals. Final products are typically built by integrating numerous detailed specifications of subsystems. But how exactly all these parts can and need to be integrated to build valid end products is often left unspecified and to numerous discussions, reviews and the expertise of senior architects and product managers.
Building a high-level product line requirements model that explicitly and formally specifies common and variable requirements, their precise integration semantics and the constraints for selecting variable features helps significantly to manage this crucial and often tacit requirements knowledge. Based on an industrial exemplar we motivate and demonstrate such an approach and discuss our early ïŹndings regarding knowledge and rationale management in product line requirements engineering
Volcano remote sensing with ground-based spectroscopy
The chemical compositions and emission rates of volcanic gases carry important information about underground magmatic and hydrothermal conditions, with application in eruption forecasting. Volcanic plumes are also studied because of their impacts upon the atmosphere, climate and human health. Remote sensing techniques are being increasingly used in this field because they provide real-time data and can be applied at safe distances from the target, even throughout violent eruptive episodes. However, notwithstanding the many scientific insights into volcanic behaviour already achieved with these approaches, technological limitations have placed firm restrictions upon the utility of the acquired data. For instance, volcanic SO2 emission rate measurements are typically inaccurate (errors can be greater than 100%) and have poor time resolution (ca once per week). Volcanic gas geochemistry is currently being revolutionized by the recent implementation of a new generation of remote sensing tools, which are overcoming the above limitations and are providing degassing data of unprecedented quality. In this article, I review this field at this exciting point of transition, covering the techniques used and the insights thereby obtained, and I speculate upon the breakthroughs that are now tantalizingly close
Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case
IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP). We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy. Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD
Monitoring SO2 emission at the Soufriere Hills Volcano: implications for changes in erruptive conditions
FLWINinfo:eu-repo/semantics/publishe
Research on atmospheric volcanic emissions: An overview
The project Research on Atmospheric Volcanic Emissions is a unique effort by NASA and university scientists to investigate the detailed chemical nature of plumes from volcanic eruptions. The major goals of the project are to: 1) understand the impact major eruptions will have on atmospheric chemistry processes, 2) understand the importance of volcanic emissions in the atmospheric geochemical cycles of selected species, 3) use knowledge of the plume chemical composition to diagnose and predict magmatic processes. Project RAVE\u27S first mission used the NASA Lockheed Orion P-3 outfitted with equipment to measure concentrations of the gases SO2, OCS, H2S, CS2, NO, O3and trace elements in particles in Mt. St. Helens\u27 plume on September 22, 1980. Measurements of SO2 column densities in the plume permitted calculations of SO2 fluxes. This article is an overview of the first experimental design factors and performance of the initial RAVE experiment
SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness.
Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patientsÂŽ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically
SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness
Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patientsÂŽ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically
Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.
Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed
JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression
Oncogenic KRAS has been difficult to target and currently there is no KRASbased targeted therapy available for patients suffering from KRASdriven lung adenocarcinoma (AC). Alternatively, targeting KRASdownstream effectors, KRAScooperating signaling pathways or cancer hallmarks, such as tumorpromoting inflammation, has been shown to be a promising therapeutic strategy. Since the JAKSTAT pathway is considered to be a central player in inflammationmediated tumorigenesis, we investigated here the implication of JAKSTAT signaling and the therapeutic potential of JAK1/2 inhibition in KRASdriven lung AC. Our data showed that JAK1 and JAK2 are activated in human lung AC and that increased activation of JAKSTAT signaling correlated with disease progression and KRAS activity in human lung AC. Accordingly, administration of the JAK1/2 selective tyrosine kinase inhibitor ruxolitinib reduced proliferation of tumor cells and effectively reduced tumor progression in immunodeficient and immunocompetent mouse models of KRASdriven lung AC. Notably, JAK1/2 inhibition led to the establishment of an antitumorigenic tumor microenvironment, characterized by decreased levels of tumorpromoting chemokines and cytokines and reduced numbers of infiltrating myeloid derived suppressor cells, thereby impairing tumor growth. Taken together, we identified JAK1/2 inhibition as promising therapy for KRASdriven lung AC.(VLID)510233
Explosion dynamics of pyroclastic eruptions at Santiaguito Volcano
In Jan. 2003 we monitored explosions at Santiaguito Volcano (Guatemala) with thermal, infrasonic, and seismic sensors. Thermal data from 2 infrared thermometers allowed computation of plume rise speeds, which ranged from 8 to 20 m/s. Rise rates correlated with cumulative thermal radiance, indicating that faster rising plumes correspond to explosions with greater thermal flux. The relationship between rise speeds and elastic energy is less clear. Seismic radiation may not scale well with thermal output and/or rise speed because some of the thermal component may be associated with passive degassing, which does not induce significant seismicity. But non-impulsive gas release is still able to produce a high thermal flux, which is the primary control on buoyant rise speed
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