A model driven approach for software systems reliability

The reliability assurance of software systems from design to deployment level through transformation techniques and model driven approach, is described. Once the reliability mechanisms provided by current component-based development architectures (CBDA) are designed in a platform-independent way, platform-based design and implementation models must be extended. Current CBDAs, such as Enterprise Java Beans, address a considerable range of features to support system reliability. The evaluation aims to test maturity of the approach, its applicability, and the effectiveness of reliability models. The techniques such as process algebras are generally considered time consuming, in regard to software development

Sensitivity Analysis for a Scenario-Based Reliability Prediction Model

As a popular means for capturing behavioural requirements, scenariosshow how components interact to provide system-level functionality.If component reliability information is available, scenarioscan be used to perform early system reliability assessment. Inprevious work we presented an automated approach for predictingsoftware system reliability that extends a scenario specificationto model (1) the probability of component failure, and (2) scenariotransition probabilities. Probabilistic behaviour models ofthe system are then synthesized from the extended scenario specification.From the system behaviour model, reliability predictioncan be computed. This paper complements our previous work andpresents a sensitivity analysis that supports reasoning about howcomponent reliability and usage profiles impact on the overall systemreliability. For this purpose, we present how the system reliabilityvaries as a function of the components reliabilities and thescenario transition probabilities. Taking into account the concurrentnature of component-based software systems, we also analysethe effect of implied scenarios prevention into the sensitivity analysisof our reliability prediction technique

Engaging the articulators enhances perception of concordant visible speech movements

PURPOSE This study aimed to test whether (and how) somatosensory feedback signals from the vocal tract affect concurrent unimodal visual speech perception. METHOD Participants discriminated pairs of silent visual utterances of vowels under 3 experimental conditions: (a) normal (baseline) and while holding either (b) a bite block or (c) a lip tube in their mouths. To test the specificity of somatosensory-visual interactions during perception, we assessed discrimination of vowel contrasts optically distinguished based on their mandibular (English /ɛ/-/æ/) or labial (English /u/-French /u/) postures. In addition, we assessed perception of each contrast using dynamically articulating videos and static (single-frame) images of each gesture (at vowel midpoint). RESULTS Engaging the jaw selectively facilitated perception of the dynamic gestures optically distinct in terms of jaw height, whereas engaging the lips selectively facilitated perception of the dynamic gestures optically distinct in terms of their degree of lip compression and protrusion. Thus, participants perceived visible speech movements in relation to the configuration and shape of their own vocal tract (and possibly their ability to produce covert vowel production-like movements). In contrast, engaging the articulators had no effect when the speaking faces did not move, suggesting that the somatosensory inputs affected perception of time-varying kinematic information rather than changes in target (movement end point) mouth shapes. CONCLUSIONS These findings suggest that orofacial somatosensory inputs associated with speech production prime premotor and somatosensory brain regions involved in the sensorimotor control of speech, thereby facilitating perception of concordant visible speech movements. SUPPLEMENTAL MATERIAL https://doi.org/10.23641/asha.9911846R01 DC002852 - NIDCD NIH HHSAccepted manuscrip

Response to Nauenberg's "Critique of Quantum Enigma: Physics Encounters Consciousness"

Nauenberg's extended critique of Quantum Enigma rests on fundamental misunderstandings.Comment: To be published in Foundations of Physic

Metformin as a Therapeutic Target in Endometrial Cancers.

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation of surrounding stromal cells to produce energy-rich catabolites, fueling the growth, and survival of cancer cells. Such mechanisms raise the prospect of the metabolic microenvironment itself as a viable target for treatment of malignancies. Metformin is a biguanide drug that is a first-line treatment for type 2 diabetes that has beneficial effects on various markers of the metabolic syndrome. Many studies suggest that metformin shows potential as an adjuvant treatment for uterine and other cancers. Here, we review the evidence for metformin as a treatment for cancers of the endometrium. We discuss the available clinical data and the molecular mechanisms by which it may exert its effects, with a focus on how it may alter the tumor microenvironment. The pleiotropic effects of metformin on cellular energy production and usage as well as intercellular and hormone-based interactions make it a promising candidate for reprogramming of the cancer ecosystem. This, along with other treatments aimed at targeting tumor metabolic pathways, may lead to novel treatment strategies for endometrial cancer

Fabrication of minority-carrier-limited n-Si/insulator/metal diodes

A photoelectrochemical anodization technique has been used to fabricate n-Si/insulator/metal (MIS) diodes with improved electrical properties. MIS structures fabricated with Au have provided the first experimental observation of a solid-state n-Si surface barrier device whose open circuit voltage Voc is controlled by minority-carrier bulk diffusion/recombination processes. For these diodes, variation of the minority-carrier diffusion length and majority-carrier dopant density produced changes in Voc that were in accord with bulk diffusion/recombination theory. Additionally, the variation in Voc in response to changes in the work function of the metal overlayer indicated that these MIS devices were not subject to the Fermi level pinning restrictions observed for n-Si Schottky structures. X-ray photoelectron spectroscopic characterization of the anodically grown insulator indicated 8.2±0.9 Å of a strained SiO2 layer as the interfacial insulator resulting from the photoanodization process

HDAC inhibition potentiates immunotherapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) represents a more aggressive and difficult subtype of breast cancer where responses to chemotherapy occur, but toxicity is significant and resistance often follows. Immunotherapy has shown promising results in various types of cancer, including breast cancer. Here, we investigated a new combination strategy where histone deacetylase inhibitors (HDACi) are applied with immune checkpoint inhibitors to improve immunotherapy responses in TNBC. Testing different epigenetic modifiers, we focused on the mechanisms underlying HDACi as priming modulators of immunotherapy. Tumor cells were co-cultured with human peripheral blood mononuclear cells (PBMCs) and flow cytometric immunophenotyping was performed to define the role of epigenetic priming in promoting tumor antigen presentation and immune cell activation. We found that HDACi up-regulate PD-L1 mRNA and protein expression in a time-dependent manner in TNBC cells, but not in hormone responsive cells. Focusing on TNBC, HDACi up-regulated PD-L1 and HLA-DR on tumor cells when co-cultured with PBMCs and down-regulated CD4+ Foxp3+ Treg in vitro. HDACi significantly enhanced the in vivo response to PD-1/CTLA-4 blockade in the triple-negative 4T1 breast cancer mouse model, the only currently available experimental system with functional resemblance to human TNBC. This resulted in a significant decrease in tumor growth and increased survival, associated with increased T cell tumor infiltration and a reduction in CD4+ Foxp3+ T cells in the tumor microenvironment. Overall, our results suggest a novel role for HDAC inhibition in combination with immune checkpoint inhibitors and identify a promising therapeutic strategy, supporting its further clinical evaluation for TNBC treatment

Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8+ and CD4+ effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity

Measuring Information Transfer

An information theoretic measure is derived that quantifies the statistical coherence between systems evolving in time. The standard time delayed mutual information fails to distinguish information that is actually exchanged from shared information due to common history and input signals. In our new approach, these influences are excluded by appropriate conditioning of transition probabilities. The resulting transfer entropy is able to distinguish driving and responding elements and to detect asymmetry in the coupling of subsystems.Comment: 4 pages, 4 Figures, Revte

Asymptotically stable phase synchronization revealed by autoregressive circle maps

A new type of nonlinear time series analysis is introduced, based on phases, which are defined as polar angles in spaces spanned by a finite number of delayed coordinates. A canonical choice of the polar axis and a related implicit estimation scheme for the potentially underlying auto-regressive circle map (next phase map) guarantee the invertibility of reconstructed phase space trajectories to the original coordinates. The resulting Fourier approximated, Invertibility enforcing Phase Space map (FIPS map) is well suited to detect conditional asymptotic stability of coupled phases. This rather general synchronization criterion unites two existing generalisations of the old concept and can successfully be applied e.g. to phases obtained from ECG and airflow recordings characterizing cardio-respiratory interaction.Comment: PDF file, 232 KB, 24 pages, 3 figures; cheduled for Phys. Rev. E (Nov) 200