Saarland University

About: Saarland University is a education organization based out in Saarbrücken, Germany. It is known for research contribution in the topics: Population & Medicine. The organization has 19555 authors who have published 39678 publications receiving 1109295 citations. The organization is also known as: University of the Saarland & Universität des Saarlandes.

The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.

Abstract: BACKGROUND We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS We conducted a double-blind, randomized, placebo-controlled, multicenter, phase 3 trial. Patients received either placebo or eculizumab intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks, followed 1 week later by a 900-mg dose and then 900 mg every other week through week 26. The two primary end points were the stabilization of hemoglobin levels and the number of units of packed red cells transfused. Biochemical indicators of intravascular hemolysis and the patients' quality of life were also assessed. RESULTS Eighty-seven patients underwent randomization. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43) of the patients assigned to eculizumab and none (0 of 44) of those assigned to placebo (P<0.001). During the study, a median of 0 units of packed red cells was administered in the eculizumab group, as compared with 10 units in the placebo group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the 85.8% lower median area under the curve for lactate dehydrogenase plotted against time (in days) in the eculizumab group, as compared with the placebo group (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements were also found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo group had serious adverse events, none of which were considered to be treatment-related; all these patients recovered without sequelae. CONCLUSIONS Eculizumab is an effective therapy for PNH.

Glucosylation of Rho proteins by Clostridium difficile toxin B

Abstract: TOXIN A and B, the major virulence factors of Clostridium difficile, are the causative agents of antibiotic-associated pseudomembran-ous colitis. In cultured cell lines their potent cytotoxicity results from their ability to induce disaggregation of the microfilament cytoskeleton1,2. Toxin B acts on the low-molecular-mass GTPase Rho A3,4, which is involved in the regulation of the actin cytoskeleton. We report here that toxin B catalyses the incorporation of up to one mole of glucose per mole of RhoA at the amino acid thre-onine at position 37. The modification was identified and localized by tandem electrospray mass spectrometry. UDP-glucose selectively serves as cosubstrate for the monoglucosylation reaction catalysed by toxin B. Microinjection of RhoA previously glucosyl-ated by toxin B into monolayer cells caused disaggregation of actin filaments, indicating a dominant-negative activity of glucosylated RhoA.

Mining version histories to guide software changes

Abstract: We apply data mining to version histories in order to guide programmers along related changes: "Programmers who changed these functions also changed...." Given a set of existing changes, the mined association rules 1) suggest and predict likely further changes, 2) show up item coupling that is undetectable by program analysis, and 3) can prevent errors due to incomplete changes. After an initial change, our ROSE prototype can correctly predict further locations to be changed; the best predictive power is obtained for changes to existing software. In our evaluation based on the history of eight popular open source projects, ROSE's topmost three suggestions contained a correct location with a likelihood of more than 70 percent.

Simplifying and isolating failure-inducing input

Abstract: Given some test case, a program fails. Which circumstances of the test case are responsible for the particular failure? The delta debugging algorithm generalizes and simplifies the failing test case to a minimal test case that still produces the failure. It also isolates the difference between a passing and a failing test case. In a case study, the Mozilla Web browser crashed after 95 user actions. Our prototype implementation automatically simplified the input to three relevant user actions. Likewise, it simplified 896 lines of HTML to the single line that caused the failure. The case study required 139 automated test runs or 35 minutes on a 500 MHz PC.