Proposal for a Performance Dashboard for the Monitoringof Water and Sewage Service Companies (WaSCs)

The water and sewage industry provides an essential service to the community, but it is characterized by natural monopoly tendencies of service suppliers. In this framework, it is very important to assist regulators with a small set of critical indicators (performance dashboard) for the evaluation and monitoring of the service provided by Water and Sewage Companies (WaSCs). The paper originates from the analysis of situation of Piemonte (Italy), where each regional and local body adopts a proprietary Performance Measurement System (PMS). In order to improve the coordination of information flow and to support the definition of common service standards, a methodology to merge existing PMSs and define a unique shared reference system is proposed. The Kaplan and Norton's Balanced Scorecard (BSC) is adopted as the reference model of this approach. BSC is widely recognized to be an exhaustive and balanced framework in describing the performances of an organization and ensures that all the operational aspects of WaSCs are adequately monitored. The output of the proposed procedure is a general performance dashboard for the monitoring of WaSCs. The dashboard is shown and some remarks about indicators properties are developed. In particular, this analysis highlights some common pitfalls originated by a ‘rushed' aggregation of several performance indicators. Description is supported by several example

Vortex Loop Phase Transitions in Liquid Helium, Cosmic Strings, and High-T_c Superconductors

The distribution of thermally excited vortex loops near a superfluid phase transition is calculated from a renormalized theory. The number density of loops with a given perimeter is found to change from exponential decay with increasing perimeter to algebraic decay as T_c is approached, in agreement with recent simulations of both cosmic strings and high-T_c superconductors. Predictions of the value of the exponent of the algebraic decay at T_c and of critical behavior in the vortex density are confirmed by the simulations, giving strong support to the vortex-folding model proposed by Shenoy.Comment: Version to appear in Phys. Rev. Lett, with a number of corrections and addition

Adapting “MOVE” to accelerate VMMC coverage for HIV prevention in priority populations:Implementation experiences from Uganda’s military settings

This paper describes the WHO’s Model of Optimizing Volumes and Efficiencies (MOVE), adapted by the University Research Council (URC) - Department of Defense HIV/AIDS Prevention Program (DHAPP) to rapidly scale up Voluntary Medical Male Circumcision (VMMC) within Uganda’s military health facilities. First, we examine the MOVE model and then present the URC-DHAPP adapted intervention package comprising of: a) a Command-driven approach, b) Mobile theatres c) Quality assurance d) Data strengthening and reflection. To expand VMMC, URC-DHAPP worked with army commanders to create awareness, mobilize their troops and surgeons were assigned daily targets. The mobile theatre involved regular visits to hard-to-reach outposts and placing several mobile camps at health facilities close to deployment sites. All stakeholders were briefed on performance trends of previous medical camps and the program was monitored through VMMC camp reports. URC-DHAPP registered an exponential increase in VMMC coverage from 13% performance at Q2 to over 140% in Q4. The integrated approach led to circumcision of over 22,000 men (15-49 years) in a record four months. Our approach also contributed to health system strengthening and national HIV preventiontargets. We conclude that the MOVE is cost-effective and can be successfully scaled up in resource-limited settings with a high HIV burden when implemented with cognizance of contextual specificities

An Approach to Conceptual and Embodiment Design within a New Product Development Lifecycle Framework

[EN] The design of new innovative products is the result of an accurate and precise management of knowledge sources all over its life cycle, such as technology, market, competitors and suppliers. The work contributes with a framework that shows how the knowledge sources influence in the state-of-the-art and market needs so that they become opportunities for innovating products addressing the whole product life cycle. It provides a systematic path from the early generation of ideas to the production of a new product proposal. Through a deep analysis of previous research works of new product innovation life cycle development frameworks and linking it with knowledge management, strategic planning and scorecards, we came out with a structured contribution. The result considers the concurrent activities and its relationships all the way through the product life cycle that can help in creativity and innovation, combined with a process management proposal. Managing the sources of knowledge in highly dynamic markets and technologies is one of the major difficulties involved in innovative products design and development. The emerging knowledge from external sources is confronted with organisation internal knowledge and experience in order to achieve the first product correct.This work was supported by the Spanish Government and the Universitat Jaume I of Castellon (Spain) through research [project number P11B2009-37], entitled 'Methodologies for Implementing Product lifecycle management tools for mechanical Small and Medium Enterprises'.Vila, C.; Albinana, JC. (2016). An Approach to Conceptual and Embodiment Design within a New Product Development Lifecycle Framework. International Journal of Production Research. 54(10):2856-2874. https://doi.org/10.1080/00207543.2015.1110632S28562874541

miR-143 Overexpression Impairs Growth of Human Colon Carcinoma Xenografts in Mice with Induction of Apoptosis and Inhibition of Proliferation

BACKGROUND: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and involved in the (dys)regulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s) II-nu/nu). METHODOLOGY/PRINCIPAL FINDINGS: HCT116 cells with stable miR-143 overexpression (Over-143) and control (Empty) cells were subcutaneously injected into the flanks of nude mice, and tumor growth was evaluated over time. Tumors arose ∼ 14 days after tumor cell implantation, and the experiment was ended at 40 days after implantation. miR-143 was confirmed to be significantly overexpressed in Over-143 versus Empty xenografts, by TaqMan® Real-time PCR (p<0.05). Importantly, Over-143 xenografts displayed slower tumor growth compared to Empty xenografts from 23 until 40 days in vivo (p<0.05), with final volumes of 928±338 and 2512±387 mm(3), respectively. Evaluation of apoptotic proteins showed that Over-143 versus Empty xenografts displayed reduced Bcl-2 levels, and increased caspase-3 activation and PARP cleavage (p<0.05). In addition, the incidence of apoptotic tumor cells, assessed by TUNEL, was increased in Over-143 versus Empty xenografts (p<0.01). Finally, Over-143 versus Empty xenografts displayed significantly reduced NF-κB activation and ERK5 levels and activation (p<0.05), as well as reduced proliferative index, evaluated by Ki-67 immunohistochemistry (p<0.01). CONCLUSIONS: Our results suggest that reduced tumor volume in Over-143 versus Empty xenografts may result from increased apoptosis and decreased proliferation induced by miR-143. This reinforces the relevance of miR-143 in colon cancer, indicating an important role in the control of in vivo tumor progression, and suggesting that miR-143 may constitute a putative novel therapeutic tool for colon cancer treatment that warrants further investigation

Nature of the Low Field Transition in the Mixed State of High Temperature Superconductors

We have numerically studied the statics and dynamics of a model three-dimensional vortex lattice at low magnetic fields. For the statics we use a frustrated 3D XY model on a stacked triangular lattice. We model the dynamics as a coupled network of overdamped resistively-shunted Josephson junctions with Langevin noise. At low fields, there is a weakly first-order phase transition, at which the vortex lattice melts into a line liquid. Phase coherence parallel to the field persists until a sharp crossover, conceivably a phase transition, near $T_{\ell} > T_m$ which develops at the same temperature as an infinite vortex tangle. The calculated flux flow resistivity in various geometries near $T=T_{\ell}$ closely resembles experiment. The local density of field induced vortices increases sharply near $T_\ell$, corresponding to the experimentally observed magnetization jump. We discuss the nature of a possible transition or crossover at $T_\ell$(B) which is distinct from flux lattice melting.Comment: Updated references. 46 pages including low quality 25 eps figures. Contact [email protected] or visit http://www.physics.ohio-state.edu:80/~ryu/ for better figures and additional movie files from simulations. To be published in Physical Review B1 01Jun9

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer

Background:MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC).Methods:Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association.Results:Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues.Conclusion:Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy. © 2009 Cancer Research UK.published_or_final_versio