TINA as a virtual market place for telecommunication and information services: the VITAL experiment

The VITAL (Validation of Integrated Telecommunication Architectures for the Long-Term) project has defined, implemented and demonstrated an open distributed telecommunication architecture (ODTA) for deploying, managing and using a set of heterogeneous multimedia, multi-party, and mobility services. The architecture was based on the latest specifications released by TINA-C. The architecture was challenged in a set of trials by means of a heterogeneous set of applications. Some of the applications were developed within the project from scratch, while some others focused on integrating commercially available applications. The applications were selected in such a way as to assure full coverage of the architecture implementation and reflect a realistic use of it. The VITAL experience of refining and implementing TINA specifications and challenging the resulting platform by a heterogeneous set of services has proven the openness, flexibility and reusability of TINA. This paper describes the VITAL approach when choosing the different services and how they challenge and interact with the architecture, focusing especially on the service architecture and the Ret reference point definitions. The VITAL adjustments and enhancements to the TINA architecture are described. This paper contributes to proving that the TINA-based VITAL ODTA allows for easy and cost-effective development and deployment of advanced end-user and operator services, and can indeed act as the basis for a virtual market place for telecommunications service

Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila.

The Drosophila lymph gland is a haematopoietic organ in which progenitor cells, which are most akin to the common myeloid progenitor in mammals, proliferate and differentiate into three types of mature cell--plasmatocytes, crystal cells and lamellocytes--the functions of which are reminiscent of mammalian myeloid cells. During the first and early second instars of larval development, the lymph gland contains only progenitors, whereas in the third instar, a medial region of the primary lobe of the lymph gland called the medullary zone contains these progenitors, and maturing blood cells are found juxtaposed in a peripheral region designated the cortical zone. A third group of cells referred to as the posterior signalling centre functions as a haematopoietic niche. Similarly to mammalian myeloid cells, Drosophila blood cells respond to multiple stresses including hypoxia, infection and oxidative stress. However, how systemic signals are sensed by myeloid progenitors to regulate cell-fate determination has not been well described. Here, we show that the haematopoietic progenitors of Drosophila are direct targets of systemic (insulin) and nutritional (essential amino acid) signals, and that these systemic signals maintain the progenitors by promoting Wingless (WNT in mammals) signalling. We expect that this study will promote investigation of such possible direct signal sensing mechanisms by mammalian myeloid progenitors

Testing real-time systems using TINA

The paper presents a technique for model-based black-box conformance testing of real-time systems using the Time Petri Net Analyzer TINA. Such test suites are derived from a prioritized time Petri net composed of two concurrent sub-nets specifying respectively the expected behaviour of the system under test and its environment.We describe how the toolbox TINA has been extended to support automatic generation of time-optimal test suites. The result is optimal in the sense that the set of test cases in the test suite have the shortest possible accumulated time to be executed. Input/output conformance serves as the notion of implementation correctness, essentially timed trace inclusion taking environment assumptions into account. Test cases selection is based either on using manually formulated test purposes or automatically from various coverage criteria specifying structural criteria of the model to be fulfilled by the test suite. We discuss how test purposes and coverage criterion are specified in the linear temporal logic SE-LTL, derive test sequences, and assign verdicts

Optimal design of parallel triplex forming oligonucleotides containing Twisted Intercalating Nucleic Acids—TINA

Twisted intercalating nucleic acid (TINA) is a novel intercalator and stabilizer of Hoogsteen type parallel triplex formations (PT). Specific design rules for position of TINA in triplex forming oligonucleotides (TFOs) have not previously been presented. We describe a complete collection of easy and robust design rules based upon more than 2500 melting points (Tm) determined by FRET. To increase the sensitivity of PT, multiple TINAs should be placed with at least 3 nt in-between or preferable one TINA for each half helixturn and/or whole helixturn. We find that ΔTm of base mismatches on PT is remarkably high (between 7.4 and 15.2°C) compared to antiparallel duplexes (between 3.8 and 9.4°C). The specificity of PT by ΔTm increases when shorter TFOs and higher pH are chosen. To increase ΔTms, base mismatches should be placed in the center of the TFO and when feasible, A, C or T to G base mismatches should be avoided. Base mismatches can be neutralized by intercalation of a TINA on each side of the base mismatch and masked by a TINA intercalating direct 3′ (preferable) or 5′ of it. We predict that TINA stabilized PT will improve the sensitivity and specificity of DNA based clinical diagnostic assays

Die Expression und Rolle des Immuncheckpoint Regulators PD-L1 in der Tumor-Stroma Interaktion des duktalen Pankreasadenokarzinoms

Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries. This high mortality is associated with the late stage of disease at diagnosis due to the lack of specific symptoms and poor specificity of tumor markers. Immune checkpoint inhibitors (ICI), e.g., targeting programmed cell death protein 1-ligand 1 (PD-L1) or its receptor PD-1, have markedly improved therapy of many cancers but so far failed in PDAC. Macrophages represent one of the most abundant immune cell populations within the tumor microenvironment (TME) of PDAC being able to either support or restrain tumor progression. To better understand treatment failure of PD-L1/PD-1 inhibitors in PDAC, this thesis examined PD-L1 expression in the context of a dynamic TME in PDAC with a particular focus on the impact of macrophages. Immunohistochemical analyses revealed that PD-L1 is mainly expressed by stroma cells, including macrophages and not PDAC cells in primary PDAC tissues and corresponding liver metastases. Notably, a high local abundance of macrophages and strong PD-L1 staining were commonly found at invasion fronts of tumoral lesions between CD8+ T cells and tumor cells. In a 3D spheroid model comprising PDAC cells and different ratios of in vitro differentiated primary M1- or M2-like macrophages, high PD-L1 expression was observed in macrophages. The effector phenotype of co-cultured CD8+ T cells was rather enhanced by PDAC macrophage spheroids. However, this was not associated with enhanced PDAC cell death. ICI treatment with either Durvalumab or Pembrolizumab alone or in combination with Gemcitabine hardly affected the effector phenotype of CD8+ T cells along with PDAC cell death. Thus, despite strong PD-L1 expression in macrophages, ICI treatment did not result in an enhanced cytotoxic phenotype of CD8+ T cells, suggesting that PD-1/PD-L1 axis is not the main immunosuppressive mechanism in PDAC

A Construct-Modeling Approach to Develop a Learning Progression of how Students Understand the Structure of Matter

This paper builds on the current literature base about learning progressions in science to address the question, “What is the nature of the learning progression in the content domain of the structure of matter?” We introduce a learning progression in response to that question and illustrate a methodology, the Construct Modeling (Wilson, 2005) approach, for investigating the progression through a developmentally based iterative process. This study puts forth a progression of how students understand the structure of matter by empirically inter-relating constructs of different levels of sophistication using a sample of 1,087 middle grade students from a large diverse public school district in the western part of the United States. The study also shows that student thinking can be more complex than hypothesized as in the case of our discovery of a substructure of understanding in a single construct within the larger progression. Data were analyzed using a multidimensional Rasch model. Implications for teaching and learning are discussed—we suggest that the teacher’s choice of instructional approach needs to be fashioned in terms of a model, grounded in evidence, of the paths through which learning might best proceed, working toward the desired targets by a pedagogy which also cultivates students’ development as effective learners. This research sheds light on the need for assessment methods to be used as guides for formative work and as tools to ensure the learning goals have been achieved at the end of the learning period. The development and investigation of a learning progression of how students understand the structure of matter using the Construct Modeling approach makes an important contribution to the research on learning progressions and serves as a guide to the planning and implementation in the teaching of this topic. # 2017 Wiley Periodicals, Inc. J Res Sci Teach 54: 1024–1048, 201

Microwave Background Anisotropies from Alfven waves

We investigate microwave background anisotropies in the presence of primordial magnetic fields. We show that a homogeneous field with fixed direction can amplify vector perturbations. We calculate the correlations of $\delta T/T$ explicitly and show that a large scale coherent field induces correlations between $a_{\ell-1,m}$ and $a_{\ell+1,m}$. We discuss constraints on amplitude and spectrum of a primordial magnetic field imposed by observations of CMB anisotropies.Comment: 18 page LaTeX file, 4 postscript figs. included, submitted to PR