Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees

Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5-1.0 log(10) reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation

W-Lisp Sprachbeschreibung

W-Lisp [Wippennann 91] ist eine Sprache, die im Bereich der Implementierung höherer Programmiersprachen verwendet wird. Ihre Anwendung ist nicht auf diesen Bereich beschränkt. Gute Lesbarkeit der W-Lisp-Notation wird durch zahlreiche Anleihen aus dem Bereich der bekannten imperativen Sprachen erzielt. W-Lisp-Programme können im Rahmen eines Common Lisp-Systems ausgeführt werden. In der WLisp Notation können alle Lisp-Funktionen (inkl. MCS) verwendet werden, so daß die Mächtigkeit von Common-Lisp [Steele 90] in dieser Hinsicht auch in W-Lisp verfügbar ist

Tracing Variability from Implementation to Test Using Aspect-Oriented Programming

Abstract. Software product lines have proven to be a very promising approach to software reuse. One of the key concepts in product lines is variability that enables the adaptation of common core assets to varying requirements. Variability corresponding to functionality can be managed using well-established techniques like conditional compilation, inheritance, or parameterization. To manage variable cross-cutting concerns like security, transaction management, or error handling, aspect-oriented programming (AOP) provides a mechanism that has recently gained a lot of attention: socalled aspects allow to develop and maintain code fragments in a modular way that are then woven into (e.g., object-oriented designed) program code using automated tool support. This paper explores a way to combine two very popular tools in this context, AspectJ (being an AOP implementation for Java) and JUnit (being the most popular Java testing tool). It illustrates how the same aspects that encapsulate code for cross-cutting concerns in Java programs can also contain the code necessary to test these aspects. This allows to achieve traceability from the implementation of variable software product line parts to their tests.