Using Domain Features to Handle Feature Interactions

International audienceSoftware Product Lines in general and feature diagrams in particular support the modeling of software variability. Unfortunately, features may interact with each other, leading to feature interaction issues. Even if detected at the implementation level, interaction resolution choices are part of the business variability. In this paper, we propose to use a stepwise process to deal with feature interactions at the domain level: the way an interaction is resolved is considered as a variation point in the configuration process. This method and the associated implementation are applied onto a concrete case study (the jSeduite information system)

Current situation facing the needs of the scenarios from the deliverables I2.1.1 and I2.2.1

In this document we present the main issues that we have to face in order to define a Software Product Line (SPL) for Broadcasting Systems. These issues were identified through requirement analysis and refactoring of SEDUITE which are described in two internal deliverables: a) D.2.2.1: Introduces the requirements (functional and non-functional) of a Broadcasting System by using a case study based on large gatherings (e.g., concerts, competitions, parties, etc.). b) D.2.1.1: Explains the definition of SEDUITE as a SPL by identifying the different assets and products that make part of it. In particular, from each deliverable different questions were raised. We use these questions to identify the issues that we need to face and to guide the redaction of this document. We classify the questions according to three main topics: (i) user assistance (cf. Section 2), (ii) building and evolution of the SPL (cf. Section 3) and (iii) kinds of variability (cf. Section 4) The questions from the D.2.2.1 deliverable are identified with I.x and those from D.2.1.1 with Q.x. In both cases, the 'x' represents the number of the question in the deliverable. Additionally, we include the results of two questionnaires intended for consumers of information (i.e., professor and students) from broadcasting system in academic institutions

SPLEMMA: A Generic Framework for Controlled-Evolution of Software Product Lines

International audienceManaging in a generic way the evolution process of feature- oriented Software Product Lines (SPLs) is complex due to the number of elements that are impacted and the heterogeneity of the SPLs regarding artifacts used to define them. Existing work presents specific approaches to manage the evolution of SPLs in terms of such artifacts, i.e., assets, feature models and relation definitions. Moreover stakeholders do not necessarily master all the knowledge of the SPL making its evolution difficult and error-prone without a proper tool support. In order to deal with these issues, we introduce SPLEmma, a generic framework that follows a Model Driven Engineering approach to capture the evolution of a SPL independently of the kind of assets, technologies or feature models used for the product derivation. Authorized changes are described by the SPL maintainer and captured in a model used to generate tools that guide the evolution process and preserve the consistency of the whole SPL. We report on the application of our approach on two SPLs: YourCast for digital signage systems, and SALOON, which enables generation of configurations for cloud providers

Current situation facing the needs of the scenarios from the deliverables I2.1.1 and I2.2.1

In this document we present the main issues that we have to face in order to define a Software Product Line (SPL) for Broadcasting Systems. These issues were identified through requirement analysis and refactoring of SEDUITE which are described in two internal deliverables: a) D.2.2.1: Introduces the requirements (functional and non-functional) of a Broadcasting System by using a case study based on large gatherings (e.g., concerts, competitions, parties, etc.). b) D.2.1.1: Explains the definition of SEDUITE as a SPL by identifying the different assets and products that make part of it. In particular, from each deliverable different questions were raised. We use these questions to identify the issues that we need to face and to guide the redaction of this document. We classify the questions according to three main topics: (i) user assistance (cf. Section 2), (ii) building and evolution of the SPL (cf. Section 3) and (iii) kinds of variability (cf. Section 4) The questions from the D.2.2.1 deliverable are identified with I.x and those from D.2.1.1 with Q.x. In both cases, the 'x' represents the number of the question in the deliverable. Additionally, we include the results of two questionnaires intended for consumers of information (i.e., professor and students) from broadcasting system in academic institutions

CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner

Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011

Incidence and prognostic value of tumour cells detected by RT–PCR in peripheral blood stem cell collections from patients with Ewing tumour

To retrospectively evaluate the incidence of tumour cell contamination of peripheral blood stem cell (PBSC) collections and to correlate these data with the clinical outcome after high-dose chemotherapy (HDCT) with stem cell rescue in patients with a high-risk Ewing tumour. Peripheral blood stem cell collections obtained from 171 patients were analysed. Tumour contamination was assessed by reverse transcriptase–polymerase chain reaction (RT–PCR). The files of 88 patients who underwent HDCT followed by PBSC reinfusion were reviewed in detail, and their outcome compared to the PBSC RT–PCR results. Seven of 88 PBSC collections (8%) contained tumour cells as detected by RT–PCR. Peripheral blood stem cells were collected after a median of five cycles of chemotherapy. No clinical factor predictive of tumour cell contamination of PBSC harvest could be identified. Event-free survival (EFS) and overall survival (OS) of the whole study population were 45.3 % and 51.8 % at 3 years from the date of the graft, respectively. Forty-five patients relapsed with a median time of 15 months after graft, only four of whom had tumour cell contamination of the PBSC harvest. Tumour cell contamination of PBSC collection is rare and does not seem to be associated with a significantly poorer EFS or OS in this high-risk population

Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (padj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets

The BLLAST field experiment: Boundary-Layer late afternoon and sunset turbulence

Due to the major role of the sun in heating the earth's surface, the atmospheric planetary boundary layer over land is inherently marked by a diurnal cycle. The afternoon transition, the period of the day that connects the daytime dry convective boundary layer to the night-time stable boundary layer, still has a number of unanswered scientific questions. This phase of the diurnal cycle is challenging from both modelling and observational perspectives: it is transitory, most of the forcings are small or null and the turbulence regime changes from fully convective, close to homogeneous and isotropic, toward a more heterogeneous and intermittent state. These issues motivated the BLLAST (Boundary-Layer Late Afternoon and Sunset Turbulence) field campaign that was conducted from 14 June to 8 July 2011 in southern France, in an area of complex and heterogeneous terrain. A wide range of instrumented platforms including full-size aircraft, remotely piloted aircraft systems, remote-sensing instruments, radiosoundings, tethered balloons, surface flux stations and various meteorological towers were deployed over different surface types. The boundary layer, from the earth's surface to the free troposphere, was probed during the entire day, with a focus and intense observation periods that were conducted from midday until sunset. The BLLAST field campaign also provided an opportunity to test innovative measurement systems, such as new miniaturized sensors, and a new technique for frequent radiosoundings of the low troposphere. Twelve fair weather days displaying various meteorological conditions were extensively documented during the field experiment. The boundary-layer growth varied from one day to another depending on many contributions including stability, advection, subsidence, the state of the previous day's residual layer, as well as local, meso- or synoptic scale conditions. Ground-based measurements combined with tethered-balloon and airborne observations captured the turbulence decay from the surface throughout the whole boundary layer and documented the evolution of the turbulence characteristic length scales during the transition period. Closely integrated with the field experiment, numerical studies are now underway with a complete hierarchy of models to support the data interpretation and improve the model representations.publishedVersio