The C-terminal head domain of Burkholderia pseudomallei BpaC has a striking hydrophilic core with an extensive solvent network

Gram-negative pathogens like Burkholderia pseudomallei use trimeric autotransporter adhesins such as BpaC as key molecules in their pathogenicity. Our 1.4 angstrom crystal structure of the membrane-proximal part of the BpaC head domain shows that the domain is exclusively made of left-handed parallel beta-roll repeats. This, the largest such structure solved, has two unique features. First, the core, rather than being composed of the canonical hydrophobic Ile and Val, is made up primarily of the hydrophilic Thr and Asn, with two different solvent channels. Second, comparing BpaC to all other left-handed parallel beta-roll structures showed that the position of the head domain in the protein correlates with the number and type of charged residues. In BpaC, only negatively charged residues face the solvent-in stark contrast to the primarily positive surface charge of the left-handed parallel beta-roll "type" protein, YadA. We propose extending the definitions of these head domains to include the BpaC-like head domain as a separate subtype, based on its unusual sequence, position, and charge. We speculate that the function of left-handed parallel beta-roll structures may differ depending on their position in the structure.Peer reviewe

Development and Integration of DOPS as Formative Tests in Head and Neck Ultrasound Education : Proof of Concept Study for Exploration of Perceptions

In Germany, progress assessments in head and neck ultrasonography training have been carried out mainly theoretically and lack standardisation. Thus, quality assurance and comparisons between certified courses from various course providers are difficult. This study aimed to develop and integrate a direct observation of procedural skills (DOPS) in head and neck ultrasound education and explore the perceptions of both participants and examiners. Five DOPS tests oriented towards assessing basic skills were developed for certified head and neck ultrasound courses on national standards. DOPS tests were completed by 76 participants from basic and advanced ultrasound courses (n = 168 documented DOPS tests) and evaluated using a 7-point Likert scale. Ten examiners performed and evaluated the DOPS after detailed training. The variables of “general aspects” (6.0 Scale Points (SP) vs. 5.9 SP; p = 0.71), “test atmosphere” (6.3 SP vs. 6.4 SP; p = 0.92), and “test task setting” (6.2 SP vs. 5.9 SP; p = 0.12) were positively evaluated by all participants and examiners. There were no significant differences between a basic and advanced course in relation to the overall results of DOPS tests (p = 0.81). Regardless of the courses, there were significant differences in the total number of points achieved between individual DOPS tests. DOPS tests are accepted by participants and examiners as an assessment tool in head and neck ultrasound education. In view of the trend toward “competence-based” teaching, this type of test format should be applied and validated in the future

Cloud-Based Secure Logger for Medical Devices

A logger in the cloud capable of keeping a secure, time-synchronized and tamper-evident log of medical device and patient information allows efficient forensic analysis in cases of adverse events or attacks on interoperable medical devices. A secure logger as such must meet requirements of confidentiality and integrity of message logs and provide tamper-detection and tamper-evidence. In this paper, we propose a design for such a cloud-based secure logger using the Intel Software Guard Extensions (SGX) and the Trusted Platform Module (TPM). The proposed logger receives medical device information from a dongle attached to a medical device. The logger relies on SGX, TPM and standard encryption to maintain a secure communication channel even on an untrusted network and operating system. We also show that the logger is resilient against different kinds of attacks such as Replay attacks, Injection attacks and Eavesdropping attacks

A blended learning approach for teaching thoracic radiology to medical students: a proof-of-concept study

IntroductionThe best way to impart knowledge to medical students is still unclear. Therefore, we designed a blended learning course in thoracic radiology including both “traditional” in-class time as well as online learning modules. The aims were (1) to investigate students’ attitudes toward this blended learning approach; and (2) to test whether it improved their knowledge about thoracic radiology.MethodsA prospective study was conducted at the local medical center; 156 fourth-year medical students completed this study. Before and after the course, students had to complete (1) questionnaires to investigate their attitudes (7-point Likert scale); and (2) an objective test to assess their knowledge (multiple-choice/free text questions; results as % of correct answers).ResultsRegarding (1), the course led to an improvement in all items compared to baseline, exemplary: interest in thoracic radiology (precourse 4.2 vs. 5.4 postcourse) and the fulfillment of students’ expressed requirements regarding the teaching content (4.5 precourse vs. 6.2 postcourse). Furthermore, the great majority (88%) of our participants wished for more online learning offerings in the future. Regarding (2), the course led to improved knowledge on the objective test (precourse: 40% vs. postcourse: 63% correct answers).ConclusionThis feasibility study showed the successful design and implementation of a blended learning approach in thoracic radiology. Furthermore, it revealed medical students’ positive attitudes toward this approach and showed an increased knowledge in thoracic radiology. Thus, such approaches might be used to enrich the teaching armamentarium in medical education and to further enhance interest and knowledge in thoracic diseases among medical students

ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids

Chemotherapy resistance is a major challenge in ovarian cancer (OvCa). Thus, novel treatment combinations are highly warranted. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. For this reason, we analyzed our drug combination not only in monolayers but also in three-dimensional (3D) tumor spheroids. One potential therapeutic target for OvCa is A disintegrin and metalloprotease 17 (ADAM17). ADAM17 can be activated by chemotherapeutics, which leads to enhanced tumor growth due to concomitant substrate cleavage. Therefore, blocking ADAM17 during chemotherapy may overcome resistance. Here, we tested the effect of the ADAM17 inhibitor GW280264X in combination with cisplatin on ovarian cancer cells in 2D and 3D. In 2D, the effect on five cell lines was analyzed with two readouts. Three of these cell lines formed dense aggregates or spheroids (HEY, SKOV-3, and OVCAR-8) in 3D and the treatment effect was analyzed with a multicontent readout (cytotoxicity, viability, and caspase3/7 activation). We tested the combined therapy on tumor spheroids derived from primary patient cells. In 2D, we found a significant reduction in the half minimal (50%) inhibitory concentration (IC50) value of the combined treatment (GW280264X plus cisplatin) in comparison with cisplatin monotherapy in all five cell lines with both 2D readout assays (viability and caspase activation). In contrast, the combined treatment only showed an IC50 reduction in HEY and OVCAR-8 3D tumor spheroid models using caspase3/7 activity or CelltoxTM Green as the readout. Finally, we found an improved effect of GW280264X with cisplatin in tumor spheroids derived from patient samples. In summary, we demonstrate that ADAM17 inhibition is a promising treatment strategy in ovarian cancer

Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development

Einfluss von Saattermin und Sortentyp auf die frühe Ertragsbildung von Winterraps (Brassica napus) an drei Standorten in Süddeutschland

In der Praxis stellt sich immer häufiger die Frage, in wie weit der Aussaattermin verschoben werden kann und ob es hinsichtlich der Sortentypen Unterschiede bei verschiedenen Saatterminen gibt. Darum wurde 2007/08 ein Versuch durchgeführt, der den Einfluss von Saattermin und Sortentyp auf die Ertragsbildung von Winterraps an drei Standorten in Süddeutschland untersuchte. Die Versuchsflächen waren in Biberach a. d. Riss einem Versuchsfeld der BayWa Vertriebsgruppe Biberach, auf dem Lehr- und Versuchsbetrieb der Hochschule für Wirtschaft und Umwelt Nürtingen – Geislingen in Tachenhausen und in Gründl einer Versuchsstation der BayWa München. In Biberach und Tachenhausen wurden 3, in Gründl 2 verschiedene Saattermine ausgesät. Die drei Saattermine waren in Früh-, Normal- und Spätsaaten untergliedert. Diese Saattermine wurden zwischen dem 18.08.07 und dem 14.09.07 ausgesät. Bei den verschiedenen Sortentypen waren Linien- Hybrid- und Halbzwerghybridsorten vorhanden. Über die Vegetationszeit wurden die Parameter Feldaufgang, Vegetationskegelhöhe, Wurzelhalsdicke, Bestandesdichte nach dem Winter, Blattanzahl je Pflanze und die Pflanzenlänge erhoben. Aufgrund der Ergebnisse konnte nicht eindeutig festgestellt werden, ob sich der „optimale“ Aussaattermin an diesen Standorten verschoben hat. Aber die Saattermine bis zum 3. September konnten in diesem Versuchsjahr immer noch die gewünschte Vorwinterentwicklung erreiche

Using Cellular Automata with Evolutionary Learned Rules to Solve the Online Partitioning Problem

In recent computer science research highly robust and scalable sets that are composed of autonomous individuals have become more and more important. The Online Partitioning Problem (OPP) deals with the distribution of huge sets of agents onto different targets in consideration of several objectives. The agents can only interact locally and there is no central instance or global knowledge. In this paper we work on this problem field by modifying ideas from the area of cellular automata (CA). We expand the well known Majority /Density Classification Task for one-dimensional CAs to two-dimensional CAs. The transition rules for the CA will be learned by using a genetic algorithm (GA). Each individual in the GA is a set of transition rules with additional distance information. This approach shows very good behaviour compared to other strategies for the OPP and is very fast once an appropriate set of rules is learned by the GA

Self-Repairing Programs (Dagstuhl Seminar 11062)

Dagstuhl seminar 11062 ``Self-Repairing Programs\u27\u27 included 23 participants and organizers from research and industrial communities. Self-Repairing Programs are a new and emerging area, and many participants reported that they initially felt their first research home to be in another area, such as testing, program synthesis, debugging, self-healing systems, or security. Over the course of the seminar, the participants found common ground in discussions of concerns, challenges, and the state of the art

Abstract

This paper contains the description of a self-reconfigurable module robot and a proposal for an emergent distributed control of such robots. The proposed control system is inspired by biological archetypes as well as by research in the field of peer-to-peer systems. The main design paradigm for this control system is robustness in relation to communication failures, incomplete information, fluctuations in the number of modules and defects of single modules. This robustness is achieved by the use of information pieces (memes) and communication to build and maintain the structure of the robot.