An assessment of evaluation methods applied in decision support systems for sustainable urban mobility planning

The objective of this paper is to discuss procedures for assessing the impacts of different evaluation methods used in systems designed to sustainable urban mobility planning and management. The case studied shows a comparison of the points of view assumed by a small group of experts when using two particular systems. The evaluation methods used in those systems are: Pair-wise Comparisons and Scale of Points. The evaluation was conducted for groups of indicators devised for urban mobility monitoring, which were called Themes. The twenty Themes were also grouped in the following five general Categories: Transport and Environment, Transport Management, Transport Infrastructure, Transport Planning, and Socioeconomic Aspects of Transport. The main conclusions drawn from the application of non-parametric statistical methods for comparing the results of the evaluations suggest that the method Scale of Points could be the most indicated for evaluations with community members in general (experts or non-experts).GRICES (Office for International Relations in Science and Higher Education of the Portuguese Ministry of Science).CNPq (Brazilian National Council for Scientific and Technological Development).FAPESP (Foundation for the Promotion of Science of the State of São Paulo).CAPES (Post-Graduate Federal Agency)

Comparative evaluation and optimization of off-the-shelf cationic polymers for gene delivery purposes

Cationic polymers are amongst the most utilized non-viral vectors for gene transfer owing to their ability to condense and protect the genetic material within polyplexes and to ferry it into cells. Quite a number of parameters, both related to the features of the vectors themselves (e.g. degree of branching, molecular weight, polydispersity) and to polyplexes (e.g. nitrogen to phosphate ratio (N/P), dose of complexes delivered, complexation buffer, etc.), are known to affect transfection behaviour. Consequently, some substantial discrepancy found in raw materials and in-home protocols across laboratories account for some disagreement and conflicting data about their performance. Hereinafter we provide a thorough chemical-physical and in vitro biochemical characterization, comparison, and optimization of the most widely used, commercially sourced polymers used in transfection, namely linear polyethylenimines (lPEIs), branched PEIs (bPEIs), linear poly-L-lysines (lPLLs), and polyamidoamine dendrimers (dPAMAMs). By means of a stepwise approach, we pinpointed the most effective molecular weight and complexation conditions specific to each of them and correlated the physicochemical features of polyplexes with their transfection effectiveness. Besides, taking separately into account the effects on transfection of the plasmid dose delivered to cells, the cell seeding density and the volume of the culture medium, we highlited a range of optimal conditions roughly specific to each studied polymer. Finally, we coped with the effect of the variation of these three parameters at once on the transfection effectiveness of lPEI and bPEI and pinpointed an array of settings specifically optimized to attain truly superior performances

Ehrlich ascites tumor-bearing mice treated with aqueous ethanol plant extract from Euphorbia tirucalli showed signs of systemic toxicity

Purpose: To evaluate the antitumor effect of a latex extract from Euphorbia tirucalli Linn. (Euphorbiaceae) and its toxicity.Methods: Aqueous ethanol and petroleum ether extracts were obtained through maceration. .Maximum tolerated dose was determined in healthy mice. Antitumor activity was measured in Ehrlich ascites tumor-bearing mice treated with the extract through intraperitoneal injection (62.5, 125 or 250 mg/kg) every 48 h (four doses). Efficacy was assessed by weight gain, abdominal circumference, volume of ascitic fluid and packed tumor cells, tumor cell viability and survival. Toxicity indicators were serum glucose, triglycerides, total proteins, activity of alanine and aspartate aminotransferases and mass of heart, spleen, kidney and liver. A hemolysis assay was also performed.Results: Doses of 62.5 and 125 mg/kg caused no antitumor activity, while 250 mg/kg dose reduced weight gain (3-fold), abdominal circumference and volume of ascitic fluid (> 50 %) and packed cells (50 %), but lowered tumor cell viability (40 %). However, mice treated with the extract survived for a shorter time than control mice. Furthermore, the 250 mg/kg dose caused cardiac atrophy, splenomegaly and fasting hyperglycemia. The extract caused hemolysis, and the half-maximal effective concentration (EC50) was 1.6 (0.9 – 2.7) mg/mL.Conclusion: Euphorbia tirucalli extract inhibits Ehrlich ascites tumor in mice, but the therapeutic dose is also harmful to non-tumor tissues.Keywords: Euphorbia tirucalli, Ehrlich ascites tumor-bearing mice, Antitumor, Toxicity, Cardiac atrophy, Splenomegal

A CITY THAT NEVER EXISTED: XIAO BAI'S LITERARY REMAKING OF 1931 SHANGHAI

This article provides an account of the literary recreation of the semi-colonial Shanghai of 1931, carried out by the Chinese contemporary author Xiao Bai in his 2011 novel Zujie. It also includes the features and implications of such an operation. Critically praised as a turning point in contemporary Chinese fiction about old Shanghai, the novel appears to transcend genre categories, and was welcomed as a heterogeneous "third type" crossing the boundaries between genre fiction and pure literature. Inspired by historical facts and supported by painstaking archival research, Zujie originally incorporates a variety of literary models, narrative techniques, sources, genres, themes, and perspectives. The heterogeneity at play in the novel can be essentially scrutinised at three levels. Such levels are: the debate on the genre as it emerges from a number of paratextual sources; the treatment of historical factuality and its relationship with fictional creation; the use of polyphonic devices, with reference to the portrayal of hybrid characters, deliberately disorienting narrative techniques, and a re-elaboration of imported and domestic sources and literary models that plays havoc with the very notions of foreignness and identity. Xiao Bai's original representation of 1930s Shanghai is analysed and commented upon with respect to such factors. Finally, the significance of this multi-layered literary operation and its implications for the reader are highlighted

A Dialogue between the Hypoxia-Inducible Factor and the Tumor Microenvironment

The hypoxia-inducible factor is the key protein responsible for the cellular adaptation to low oxygen tension. This transcription factor becomes activated as a result of a drop in the partial pressure of oxygen, to hypoxic levels below 5% oxygen, and targets a panel of genes involved in maintenance of oxygen homeostasis. Hypoxia is a common characteristic of the microenvironment of solid tumors and, through activation of the hypoxia-inducible factor, is at the center of the growth dynamics of tumor cells. Not only does the microenvironment impact on the hypoxia-inducible factor but this factor impacts on microenvironmental features, such as pH, nutrient availability, metabolism and the extracellular matrix. In this review we discuss the influence the tumor environment has on the hypoxia-inducible factor and outline the role of this factor as a modulator of the microenvironment and as a powerful actor in tumor remodeling. From a fundamental research point of view the hypoxia-inducible factor is at the center of a signaling pathway that must be deciphered to fully understand the dynamics of the tumor microenvironment. From a translational and pharmacological research point of view the hypoxia-inducible factor and its induced downstream gene products may provide information on patient prognosis and offer promising targets that open perspectives for novel “anti-microenvironment” directed therapies

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system

Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature