The top-performing linear poly(β-amino ester) (LPAE), poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (C32), has demonstrated gene transfection efficiency comparable to viral-mediated gene ...delivery. Herein, we report the synthesis of a series of highly branched poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (HC32) and explore how the branching structure influences the performance of C32 in gene transfection. HC32 were synthesized by an "A2 + B3 + C2" Michal addition strategy. Gaussia luciferase (Gluciferase) and green fluorescent protein (GFP) coding plasmid DNA were used as reporter genes and the gene transfection efficiency was evaluated in human cervical cancer cell line (HeLa) and human recessive dystrophic epidermolysis bullosa keratinocyte (RDEBK) cells. We found that the optimal branching structure led to a much higher gene transfection efficiency in comparison to its linear counterpart and commercial reagents, while preserving high cell viability in both cell types. The branching strategy affected DNA binding, proton buffering capacity and degradation of polymers as well as size, zeta potential, stability, and DNA release rate of polyplexes significantly. Polymer degradation and DNA release rate played pivotal parts in achieving the high gene transfection efficiency of HC32-103 polymers, providing new insights for the development of poly(β-amino ester)s-based gene delivery vectors.
This paper analyses the underlying dynamics of institutional change in economic governance in EMU. We show that the crisis revealed significant gaps between the intentions of the designers of EMU and ...the observed outcome. Building on the path dependence literature we use the framework of historical institutionalism to understand how policy-makers were constrained in their options for the containment and resolution of the sovereign debt crisis. We argue that the principle which prohibits the central bank from financing governments as enshrined in the Maastricht Treaty was a causal factor in fostering reform and deeper integration.
A small number of liver transplant candidates experience variceal bleeding that cannot be controlled by standard medical therapy. The objective of this study was to analyze the role of urgent liver ...transplantation for this subset of patients with acute, refractory, portal hypertensive bleeding.
Retrospective review of data from 416 patients undergoing 449 liver transplantations between March, 1988 and February, 1993 revealed seven patients (1.7%) with endstage liver disease who underwent transplantation for uncontrollable variceal bleeding. All patients failed therapy with intravenous pitressin, endoscopic sclerotherapy, balloon tamponade, and/or transjugular intrahepatic portosystemic shunt and continued to bleed. Patients ranged in age from 6 months to 56 years. All patients were Child's class C. Two patients were listed for transplantation with the United Network for Organ Sharing as status 3, and five patients were listed as status 4.
All patients underwent successful liver transplantation with immediate control of bleeding. One patient expired on the 26th postoperative day from multiple organ failure, and another patient expired with recurrent hepatocellular carcinoma on the 110th postoperative day. No patients experienced late rebleeding from varices after transplantation.
Urgent liver transplantation is effective and feasible for the small subset of patients with uncontrollable variceal bleeding and endstage liver disease. Prompt and complete evaluation of the potential recipient and availability of a donor organ are critical to the success of this approach.
484 State Aid and Urban Regeneration: A UK Perspective EStAL 3|2007 I. Introduction This article addresses the application of the State aid rules in the context of urban regeneration. Although not ...often addressed in the literature1, it is clear that compliance with the State aid rules is a key component of any publicly-funded urban regeneration project. Although the focus is on the UK experience, many of the same issues arise in other Member States. b
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