Preparation and Comparison of Hydrolase-Coated Plastics

Polypropylene and polyethylene were coated with alpha-Chymotrypsin (a-CT) or subtilisin Carlsberg (SubC) or Burkholderia cepacia lipase (lipase BC) by different immobilization procedures, such as physical adsorption and covalent linking. This latter procedure was based on the chemical functionalization of the plastic surface by oxygen gas plasma treatment. Immobilization of the enzyme was carried out by using as cross-linking agent i) glutaraldehyde (GA) or ii) N’-diisopropylcarbodiimide (DIC) and N-hydroxysuccinimide (NHS). The effects of duration of the plasma treatment and the type of the immobilization procedure on the transesterification activity of the enzyme were investigated. In general polypropylene resulted a better support than polyethylene. Moreover, a-CT showed higher transesterification activity when immobilized with GA, while for SubC, DIC and NHS were better cross-linking agents than GA. No activity was observed with these enzymes when immobilization was carried out by physical adsorption. On the contrary, lipase BC immobilized by physical adsorption was even more active than the free enzyme. Concerning thermal stability, immobilized SubC was less stable than the free enzyme. Overall, these results show that plastics endowed with biocatalytic properties could be obtained by simple immobilization protocols and that optimal immobilization conditions depend on the type of starting plastic, plasma treatment, cross-linking method, and the nature of the enzyme

High-power test results of a 3 GHz single-cell cavity

Compact, reliable and little consuming accelerators are required for the treatment of tumours with ions. TERA proposes the "cyclinac", composed of a high-frequency, fast-cycling linac which boosts the energy of the particles previously accelerated in a cyclotron. The dimensions of the linac can be reduced if high gradients are used. TERA initiated a high-gradient test program to understand the operational limit of such structures. The program foresees the design, prototyping and high-power test of several high-gradient structures operating at 3 and 5.7 GHz. The high-power tests of the 3 GHz single-cell cavity were completed in Winter 2012. The maximum BDR threshold measured for Emax of 170 MV/m and RF pulses of 2.5 \mu s was 3 x 10-6 bpp/m

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

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

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

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