Attainability of the fractional Hardy constant with nonlocal mixed boundary conditions. Applications

The first goal of this paper is to study necessary and sufficient conditions to obtain the attainability of the \textit{fractional Hardy inequality } $$\Lambda_{N}\equiv\Lambda_{N}(\Omega):=\inf_{\{\phi\in \mathbb{E}^s(\Omega, D), \phi\neq 0\}} \dfrac{\frac{a_{d,s}}{2} \displaystyle\int_{\mathbb{R}^d} \int_{\mathbb{R}^d} \dfrac{|\phi(x)-\phi(y)|^2}{|x-y|^{d+2s}}dx dy} {\displaystyle\int_\Omega \frac{\phi^2}{|x|^{2s}}\,dx},$$ where $\Omega$ is a bounded domain of $\mathbb{R}^d$, $0<s<1$, $D\subset \mathbb{R}^d\setminus \Omega$ a nonempty open set and $$\mathbb{E}^{s}(\Omega,D)=\left\{ u \in H^s(\mathbb{R}^d):\, u=0 \text{ in } D\right\}.$$ The second aim of the paper is to study the \textit{mixed Dirichlet-Neumann boundary problem} associated to the minimization problem and related properties; precisely, to study semilinear elliptic problem for the \textit{fractional laplacian}, that is, $$P_{\lambda} \, \equiv \left\{ \begin{array}{rcll} (-\Delta)^s u &= & \lambda \dfrac{u}{|x|^{2s}} +u^p & {\text{ in }}\Omega, u & > & 0 &{\text{ in }} \Omega, \mathcal{B}_{s}u&:=&u\chi_{D}+\mathcal{N}_{s}u\chi_{N}=0 &{\text{ in }}\mathbb{R}^{d}\backslash \Omega, \\ \end{array}\right.$$ with $N$ and $D$ open sets in $\mathbb{R}^d\backslash\Omega$ such that $N \cap D=\emptyset$ and $\overline{N}\cup \overline{D}= \mathbb{R}^d \backslash\Omega$, $d>2s$, $\lambda> 0$ and $0<p\le 2_s^*-1$, $2_s^*=\frac{2d}{d-2s}$. We emphasize that the nonlinear term can be critical. The operators $(-\Delta)^s$, fractional laplacian, and $\mathcal{N}_{s}$, nonlocal Neumann condition, are defined below in (1.5) and (1.6) respectively

Business Model Innovation: A Review and Research Agenda

Purpose – The aim of this paper is to review and synthesise the recent advancements in the business model literature and explore how firms approach business model innovation. Design/methodology/approach – A systematic review of business model innovation literature was carried out by analysing 219 papers published between 2010 and 2016. Findings – Evidence reviewed suggests that rather than taking either an evolutionary process of continuous revision, adaptation and fine-tuning of the existing business model or a revolutionary process of replacing the existing business model, firms can explore alternative business models through experimentation, open and disruptive innovations. It was also found that changing business models encompasses modifying a single element, altering multiple elements simultaneously and/or changing the interactions between elements in four areas of innovation: value proposition, operational value, human capital and financial value. Research limitations/implications – Although this review highlights the different avenues to business model innovation, the mechanisms by which firms can change their business models and the external factors associated with such change remain unexplored. Practical implications – The business model innovation framework can be used by practitioners as a “navigation map” to determine where and how to change their existing business models. Originality/value – Because conflicting approaches exist in the literature on how firms change their business models, the review synthesises these approaches and provides a clear guidance as to the ways through which business model innovation can be undertaken

Analyse numérique de la convection forcée turbulente dans les tubes munis des chicanes transversales

International audienceOn présente une étude numérique du comportement dynamique et thermique d'un écoulement d'air turbulent dans un canal horizontal de section rectangulaire muni des chicanes transversales. Les équations gouvernantes, basées sur le modèle k-ε, sont résolues par la méthode des volumes finis à l'aide de l'algorithme SIMPLE. Les profils de vitesse axiale et les champs de vitesse et de température ainsi que la distribution du nombre de Nusselt sont présentés pour un cas d'exemple type

Adaptation and parameters studies of CS algorithm for flow shop scheduling problem

Scheduling concerns the allocation of limited resources overtime to perform tasks to fulfill certain criterion and optimize one or several objective functions. One of the most popular models in scheduling theory is that of the flow-shop scheduling. During the last 40 years, the permutation flow-shop sequencing problem with the objective of makespan minimization has held the attraction of many researchers. This problem characterized as Fm/prmu/Cmax in the notation of Graham, involves the determination of the order of processing of n jobs on m machines. In addition, there was evidence that m-machine permutation flow-shop scheduling problem (PFSP) is strongly NP-hard for m ≥3. Due to this NP-hardness, many heuristic approaches have been proposed, this work falls within the framework of the scientific research, whose purpose is to study Cuckoo search algorithm. Also, the objective of this study is to adapt the cuckoo algorithm to a generalized permutation flow-shop problem for minimizing the total completion time, so the problem is denoted as follow: Fm | | Cmax. Simulation results are judged by the total completion time and algorithm run time for each instance processed

Using Qualitative Study and GIS to Explore Road Accident Black Areas in Algeria

This work aims to explore black areas identification through a qualitative methodology based mainly on a series of questionnaires and interviews and by a development of a geographical information system on the road accidents in studied area. The road user, particularly the driver, is generally considered as the first person in charge in the case of accident, while his opinion is rarely joined into the establishment of the solutions to the problems of the road insecurity. Considering needs for the treatment of black areas, problems of the lack of data on the accidents, the different advantages that suggests the concept of participation and the feasibility integrating the road users into the analysis of the road safety. The Qualitative study aims at supplying with the accessibility for the users of the road to indicate the places of male performances of safety according to their feeling and of them the experience. The approach by the GIS aims at first to establish road accidents on the studied site by associating data of different nature and then to make a spatial analysis via ArcGis tool. The study area is a section of national road Highway RN6 of 38 Kms (from the PK00 to the PK38) which across the wilaya of Mascara. it is considered a potentially dangerous stretch in terms of road insafety. The results of this study show that the road users are the daily witnesses on the degree of the danger which presents their usual territory: the road. They can, therefore, to be the complementary information source for the localization of zones at high risk on the road network traveled daily

Business models innovation in investment banks: a resilience perspective

Firms frequently change their business models in order to respond to internal and external challenges. This study aims to explore how investments banks adjust their business models in response to internal and external challenges. Based on a qualitative data from ten major investment banks operating in the largest financial market in the Middle East, we show that investment banks can achieve resilience by adjusting their business models through continuous activity changes in response to internal and external challenges. Specifically, investment banks adjust their business models through deploying alternative combinations of activities from a broad repertoire of activities. Within the same bank, divisions that respond to external challenges tend to sustain their performance, whereas resilient divisions that respond to both internal and external challenges tend to bounce back or achieve substantial increase in performance levels. This study contributes to the literature by proposing resilience as an alternative approach to business model innovation and by providing insight into how firms adjust their business models by altering specific activities in response to both internal and external challenges

Tacrolimus pharmacodynamics and pharmacogenetics along the calcineurin pathway in human lymphocytes.

BACKGROUND: Although therapeutic drug monitoring has improved the clinical use of immunosuppressive drugs, there is still interpatient variability in efficacy and toxicity that pharmacodynamic monitoring may help to reduce. To select the best biomarkers of tacrolimus pharmacodynamics, we explored the strength and variability of signal transduction and the influence of polymorphisms along the calcineurin pathway. METHODS: Peripheral blood mononuclear cells from 35 healthy volunteers were incubated with tacrolimus (0.1-50 ng/mL) and stimulated ex vivo. Inhibition of NFAT1 (nuclear factor of activated T cells 1) translocation to the nucleus and intracellular expression of interleukin-2 in CD4(+) and CD8(+) T cells and the surface activation marker CD25 in CD3(+) cells were measured by flow cytometry. We sequenced the promoter regions of immunophilins and calcineurin subunits and characterized selected single nucleotide polymorphisms in the genes of the calcineurin pathway with allelic discrimination assays. RESULTS: All responses closely fitted an I/Imax sigmoid model. Large interindividual variability (n = 30) in I0 and IC50 was found for all biomarkers. Moreover, strong and statistically significant associations were found between tacrolimus pharmacodynamic parameters and polymorphisms in the genes coding cyclophilin A, the calcineurin catalytic subunit α isoenzyme, and CD25. CONCLUSIONS: This study demonstrates the consistency and large interindividual variability of signal transduction along the calcineurin pathway, as well as the strong influence of pharmacogenetic polymorphisms in the calcineurin cascade on both the physiological activity of this route and tacrolimus pharmacodynamics.Agencia Nacional de Investigación e InnovaciónUnidda de Biología Molecular, Facultad de Química, UdelarService de Coopération Sientífique et d´Action Culturelle de l´Ambassade de France en UruguayU1248 INSERM, IPPRITT (Individual Profiling and Preventions of Risks with Immunosuppressive Therapies and Transplantation) Université de Limoges, Franc

Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways.

BACKGROUND: Relatively few genes have been shown to directly affect the metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of proteins, incluing the Rho, Rac and Cdc42 subfamilies, are related to the small GTP binding protein Ras and regulated diverse biological processes including gene transcription, cytoskeletal organization, cell proliferation and transformation. The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible role for Rho proteins in cellular motility and metastasis; however, a formal analysis of the role of Rho proteins in breast cancer cellular growth and metastasis in vivo had not previously been performed. MATERIALS AND METHODS: We generated a panel of MTLn3 rat mammary adenocarcinoma cells that expressed similar levels of dominant inhibitory mutants of Cdc42-, Rac- and Rho-dependent signaling, to examine the contribution of these GTPases to cell spreading, guided chemotaxis, and metastasis in vivo. The ability of Rho proteins to regulate intravasation into the peripheral blood was determined by implanting MTLn3 cell stable dominant negative lines in nude mice and measuring the formation of breast cancer cell colonies grown from the peripheral blood. Serial sectioning of the lungs was performed to determine the presence of metastasis in mice in which mammary tumors expressing the dominant negative Rho family proteins had grown to a similar size. RESULTS: Cell spreading of MTLn3 cells was selectively abrogated by N17Rac1. N19RhoA and N17Cdc42 reduced the number of focal contacts (FCs) and disrupted the co-localization of vinculin with phosphotyrosine at FCs. While N17Rac1 and N17Cdc42 preferentially inhibited colony formation in soft agar, all three GTPases affected cell growth in vivo. To distinguish effects on tumorigenicity from intravasation into the bloodstream, implanted tumors were grown to the same size in nude mice. Each dominant inhibitory Rho protein reduced intravasation into the peripheral blood. Lung metastasis of MTLn3 cells was also abrogated by the dominant inhibitory Rho proteins, despite the presence of residual CFU. CONCLUSIONS: These studies demonstrate for the first time a critical role for the Rho GTPases involving independent signaling pathways to limit mammary tumor cellular growth and metastasis in vivo