Parallel, distributed and GPU computing technologies in single-particle electron microscopy

An introduction to the current paradigm shift towards concurrency in software

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

Ligand-controlled Regioselective Cu-Catalyzed Trifluoromethylation to Generate Trifluoromethylallenes

“Cu–CF3” species have been used historically for a broad spectrum of nucleophilic trifluoromethylation reactions. Although recent advancements have employed ligands to stabilize and harness the reactivity of this key organometallic intermediate, the ability of a ligand to differentiate a regiochemical outcome of a Cu–CF3-mediated or -catalyzed reaction has not been previously reported. Herein, we report the first example of a Cu-catalyzed trifluoromethylation reaction in which a ligand controls the regiochemical outcome. More specifically, we demonstrate the ability of bipyridyl-derived ligands to control the regioselectivity of the Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles to generate trifluoromethylallenes. This method provides a variety of di-, tri- and tetra-substituted trifluoromethylallenes, which can be further modified to generate complex fluorinated substructures

Successful software product line development in a small organization. A case study

This report details the experience of a small company, Market Maker Software AG of Kaiserslautern, Germany, as they adopted and used the paradigm of software product lines to help their business grow successfully into a new market area. While software product lines are often associated with large, traditional software organizations, the experience of Market Maker and other small companies like it shows that software product lines represent an ideal development concept for companies of all sizes. This case study reports on the history of the company, how it came to adopt product lines as its prominent development strategy, the role of the key individuals involved, and how they met and overcame various technical challenges. The report concludes with a section analyzing the Market Maker approach

"Heidelberger Standarduntersuchung" - Erfahrungen von PJ-Studierenden mit Handbüchern und Lehrvideos zur Verbesserung der ärztlichen Kompetenz bei der Durchführung der körperlichen Untersuchung

Background: The physical examination (PE) of patients is a core competence in almost all medical disciplines. The teaching materials "Heidelberger Standard Examination", consisting of a handbook and accompanying videos, were developed with the objective of providing medical students with an innovative faculty-wide teaching and examination standard to sustainably advance students' PE competences during medical training.Methods: In a "mixed-method approach" comprising both quantitative and qualitative measures, our study examined Heidelberg University Hospital final year (FY) medical students' use and evaluation of the individual teaching material components. Therefore, 92 FY students completed quantitative evaluation measures and ten FY students took part in individual 30-minute semi-structured interviews.Results: Of the sample of n=77 students, who had completed the clinical part of their studies at Heidelberg University Hospital, 97.4% (n=75) had used the handbook and 35.0% (n=27) the accompanying videos. The teaching materials were evaluated via the common German six-point school grading system with an average mark of 1.35±0.5 for the handbook and a mark of 2.15±1.0 for the accompanying videos. Further, our results show that FY students especially valued the "Heidelberg Standard Examination" handbook as a guide and general reference work and felt the materials improved their self-perceived PE competence. Although FY students saw the accompanying video material as helpful, it was less frequently used, indicating further development potential. Overall, results reveal that FY students perceive the "Heidelberg Standard Examination" teaching program to contribute to the improvement of the quality of their PE training.Die körperliche Untersuchung (KU) von Patientinnen und Patienten ist in fast allen medizinischen Fachbereichen eine wichtige Kernkompetenz. Mit den Lehrmaterialien "Heidelberger Standarduntersuchung", bestehend aus einem Kitteltaschenbuch und Begleitvideos, wurde ein neuer Lehr-und Prüfungsstandard entwickelt, der Medizinstudierenden die Möglichkeit gibt, bereits während des Studiums eine hohe Kompetenz in der Durchführung der KU zu erlangen. In einer sowohl quantitativ als auch qualitativ angelegten Befragung nach dem "mixed-method approach" mit Studierenden im Praktischen Jahr (PJ) am Universitätsklinikum Heidelberg wurden Nutzungsverhalten und Bewertungen einzelner Komponenten der Lehrmaterialien untersucht. Der quantitative Teil der Untersuchung erfolgte dabei anhand eines Fragebogens, der von 92 PJ-Studierenden ausgefüllt wurde. Der qualitative Teil wurde in Form von halbstandardisierten Interviews mit zehn PJ-Studierenden durchgeführt. Von den n=77 Studierenden, die den klinischen Studienabschnitt am Standort absolviert hatten, hatten 97,4% (n=75) das Untersuchungsbuch und 35,0% (n=27) die Begleitvideos genutzt. Dabei wurde das Untersuchungsbuch mit einer Durchschnittsnote von 1,35±0,5 und die Begleitvideos mit einer Durchschnittsnote von 2,15±1,0 entsprechend dem Schulnotensystem bewertet. Unsere weiteren Ergebnisse zeigen, dass insbesondere das Kitteltaschenbuch als Leitfaden und Referenzwerk von den Studierenden sehr gut angenommen wurde und zu einer starken Verbesserung der selbstwahrgenommenen Kompetenz bei der KU beitragen konnte. Das Videomaterial wurde ebenfalls als sehr hilfreich bewertet, aber bisher noch weniger genutzt, sodass hier noch Entwicklungspotential zu sehen ist. Insgesamt zeigen unsere Ergebnisse, dass das Projekt "Heidelberger Standarduntersuchung" dazu beigetragen hat, die Qualität der studentischen Ausbildung in Bezug auf die KU aus Sicht der Studierenden nachhaltig zu verbessern