Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model

The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.     

Continuance of mHealth services at the bottom of the pyramid: the roles of service quality and trust

Continued usage of information systems (or, IS continuance) has proven to be a critical success parameter for ICT implementation at the top of the global economic pyramid. However, there are few studies which have explored continued IS usage at the bottom of the economic pyramid (BOP) though it represents the majority of the world’s population. To fill this knowledge gap, this study develops an mHealth continuance model at the BOP framing the impact of two post adoption expectation beliefs (i.e., perceived service quality and perceived trust). This study extends ECM (expectation confirmation model) perspective synthesizing the extant literature on continued IS usage, service quality and consumer trust. The proposed model was empirically tested within the context of mHealth (mobile health) services at the BOP, applying PLS (partial least squares) under a cross sectional study. The findings confirm that both perceived service quality and perceived trust have significant explanatory power under an integrated ECM providing superior prediction of continuance intentions. The study concludes by discussing conceptual contributions, practical implications, limitations and future research directions.     

Adaptive AMG with coarsening based on compatible weighted matching

We introduce a new composite adaptive Algebraic Multigrid (composite \(\alpha \) AMG) method to solve systems of linear equations without a-priori knowledge or assumption on characteristics of near-null components of the AMG preconditioned problem referred to as algebraic smoothness. Our version of \(\alpha \) AMG is a composite solver built through a bootstrap strategy aimed to obtain a desired convergence rate. The coarsening process employed to build each new solver component relies on a pairwise aggregation scheme based on weighted matching in a graph, successfully exploited for reordering algorithms in sparse direct methods to enhance diagonal dominance, and compatible relaxation. The proposed compatible matching process replaces the commonly used characterization of strength of connection in both the coarse space selection and in the interpolation scheme. The goal is to design a method leading to scalable AMG for a wide class of problems that go beyond the standard elliptic Partial Differential Equations (PDEs). In the present work, we introduce the method and demonstrate its potential when applied to symmetric positive definite linear systems arising from finite element discretization of highly anisotropic elliptic PDEs on structured and unstructured meshes. We also report on some preliminary tests for 2D and 3D elasticity problems as well as on problems from the University of Florida Sparse Matrix Collection.     

Enhancing non-task sociability of asynchronous CSCL environments

While from a technological perspective Computer Supported Collaborative Learning (CSCL) systems have been improved considerably, previous studies have shown that the social aspect of the CSCL is often neglected or assumed to happen automatically by simply creating such virtual learning environments. By distinguishing between students’ non-task social interactions from on-task interactions, and through a content analysis, this paper demonstrates that non-task interactions do occur frequently in CSCL environments. Furthermore, by conducting a self-reported survey, the present study operationalizes non-task sociability of CSCL environments and determines factors that affect them. The findings from the survey revealed that the sense of cohesion and awareness about others significantly impact the non-task sociability of CSCL. Furthermore, the study demonstrates that the perception of self-representation and perception of compatibility affect the sense of cohesion and awareness about others and indirectly contribute to the perceived non-pedagogical sociability of the environment. The findings of this paper can be used in future research for investigating the relationship between the non-task sociability of CSCL and other CSCL factors. The study also provides the CSCL lecturers and facilitators with a conceptual model by which sociability can be explicitly addressed in their course planning and delivery processes. And finally, this study develops and validates an instrument that guides required changes in current CSCL systems to improve the non-task social functionality of the environment.     

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario.     

Energy deprivation dynamics and regulatory reforms in Europe: Evidence from household panel data

The typical ingredients of energy reforms in the European Union (EU) in the 1990s were full or partial privatization, vertical disintegration and liberalization. This paper analyses the effects of energy reforms on the probability of households experiencing deprivation, defined as difficulty in paying the bills. We use two sets of micro-data. First, the European Community Household Panel (ECHP), a large EU survey, offers evidence on people who report having been unable to pay scheduled utility bills. We consider seven European countries: Denmark, Belgium, France, Ireland, Italy, the Netherlands and Spain, and eight ECHP waves (1994–2001), with around 28,000 observations. Second, we also use micro-data from the European Statistics on Income and Living Conditions survey (EU-SILC) 2004–2005, with around 84,000 observations. The countries included are Belgium, France, Ireland, Italy, Spain, Austria, Finland, Luxembourg, Norway and Sweden. As indicators of regulatory reforms in the same countries and years we use ECTR (formerly REGREF), a database provided by the OECD. In both samples we find evidence that privatization increases the probability of households experiencing deprivation. Vertical disintegration has a similar effect and also increases the persistence in the status of household deprivation. Liberalization has no statistically significant effect. We discuss possible interpretations of these findings.     

A comparison of numerical methods for solving diffusion-reaction equations in air quality models

In this paper we analyze the efficiency of some stiff ode solvers, applied to the coupled solution of vertical turbulent diffusion and chemical kinetics in Air Quality Models. We consider four general-purpose solvers, based on bdf or Rosenbrock methods, and two special-purpose solvers, developed for odes from atmospheric chemistry, and compare their performance on three test problems using different chemical models. The general-purpose solvers have been modified to take advantage of the sparsity of the Jacobian matrices arising in the application of implicit methods. The obtained results show that general-purpose solvers, provided with suitable sparse matrix techniques, perform generally better than special-purpose ones. Our analysis extends to the diffusion-reaction equations the recent work of other research groups, comparing ode solvers on atmospheric chemical kinetics equations. Received: 28 January 1998 / Accepted: 26 April 1999     

Towards freight transport system unification: reviewing and combining the advancements in the physical internet and synchromodal transport research

To achieve socio-economic and environmental sustainability, utilization of existing capacities and assets has become a key challenge for the transportation sector. This challenge has been recognised by many scholars, policy makers and practitioners leading to a substantial body of new concepts and models. The rather parallel evolution of the Physical Internet (PI) and synchromodal transport presents an opportunity to improve the current unsustainable freight transportation, by inducing a positive modal shift from roads to rails and inland waterways, and improving service levels by better connecting production research with freight movement. This paper thus examines the synchromodal and PI state-of-the-art models together with their designs, methodologies and findings proposed in the scientific literature. The main objective is to assess and explore the correlations between these two concepts in order to understand how they can reinforce each other. Despite the integrated vision of the Alliance for Logistics Innovation through Collaboration in Europe, the findings of this paper yield no well-established interconnections in the scientific literature between PI and synchromodality as they both merely coexist in parallel and address different dimensions, scales and levels of abstraction. This paper thus identifies potential synergies, future research directions and critical questions to be considered by modellers, developers and policy makers.     

Service quality of mHealth platforms: development and validation of a hierarchical model using PLS

Advancing research on service quality requires clarifying the theoretical conceptualizations and validating an integrated service quality model. The purpose of this study is to facilitate and elucidate practical issues and decisions related to the development of a hierarchical service quality model in mobile health (mHealth) services research. Conceptually, it extends theory by reframing service quality as a reflective, hierarchical construct and modeling its impact on satisfaction, intention to continue using and quality of life. Empirically, it confirms that PLS path modeling can be used to estimate the parameters of a higher order construct and its association with subsequent consequential latent variables in a nomological network. The findings of the study show that service quality is the third-order, reflective construct model with strong positive effects on satisfaction, continuance intentions and quality of life in the context of mHealth services. Finally, the study discusses the implications of hierarchical service quality modeling in electronic markets and highlights future research directions.     

Voltage control with on-load tap changers in medium voltage feeders in presence of distributed generation

This paper discusses voltage regulation on medium-voltage feeders with distributed generation (DG) using on-load tap changer (LTC) and line drop compensation (LDC). The analysis shows that LTC is robust against DG, whereas DG can affect the effectiveness of the voltage regulation provided by LDC. However, with proper coordination between DG and LDC, it is possible to ensure voltage regulation without unnecessarily restricting the integration of DG. It is shown that, while lowering the LTC setting can increase the DG integration limit, even higher increase can be obtained by activating the LDC feature, which is present in most LTCs, but often not used. LDC regulation is also compared with other alternatives such as using a DG unit with voltage control capability and installing a line voltage regulator.