Salivaproteomik – Optimierung, Etablierung und Realisierung von proteomischen Strategien zur Untersuchung von pathologie-assoziierten Proteinsignaturen in humaner Saliva aus populationsbasierten Studien

Die vorliegende Arbeit adressiert die Nutzbarkeit des humanen Speichelproteoms als diagnostisches Instrument im Kontext einer oralen Mukositis bei Kopf- und Halskarzinoms. Als häufigste Nebenwirkung einer Radio(chemo)therapie kann die Mukositis therapielimitierend sein und hat für betroffene Patienten meist eine Einschränkung ihrer Lebensqualität zur Folge. Trotz der guten Verfügbarkeit von Speichel existieren wenige Studien, welche zeigen, dass das Speichelproteom für die Diagnostik einer Krankheit oder zur Therapieentscheidung nutzbar ist. Das hat unter anderem seinen Grund in der Komplexität der massenspektrometrischen Methode. Die erste Veröffentlichung (Golatowski et al. 2013) erarbeitete deshalb einen Standard in der Probengewinnung von Speichel. Als Ergebnis steht die Empfehlung zur Nutzung eines Paraffin-Kaugummis, aufgrund des hohen Speichelvolumens und der guten Vergleichbarkeit mit der nichtstimulierten Salivation beim identifizierten Proteom. In einer zweiten Veröffentlichung (Jehmlich & Golatowski et al. 2014) wurden C18 Mikrosäulen verschiedener Hersteller bezüglich ihres Einflusses auf die Proteinidentifizierung verglichen. Die Säulen sind notwendig für die Entsalzung und Aufreinigung eines Peptidgemisches. Mit allen verwendeten Säulen konnten ähnliche Ergebnisse erzielt werden, wobei die ZipTip® µC18 sowie C18 Systeme der OASIS® HLB μElution 96er Well Platte und TopTip® C18 Pipettenspitzen leicht überlegen sind. In der letzten Arbeit (Jehmlich et al. 2015) wurden die gewonnenen Erkenntnisse genutzt, um die Speichelproben von Patienten mit Kopf- und Halskarzinom zu untersuchen. Insgesamt zeigten wir die Möglichkeit, alterierte Proteine zwischen zwei Patientengruppen massenspektrometrisch zu detektieren. Mit den gefundenen Daten konnte demonstrieren werden, dass massenspektrometrische Techniken geeignet sind, um schon vor Behandlungsbeginn Patienten zu identifizieren, die für die Entwicklung einer oralen Mukositis prädisponiert sind. Es ist hierbei die Proteinklasse der Metalloproteinasen hervorzuheben, da diese für einen therapeutischen Ansatz gegen Mukositis interessant sind. In Zukunft werden jedoch größere und voraussichtlich multizentrische Studien erforderlich sein, um ausreichend große Patientenkohorten zusammenzustellen und die Klassifikation speziell für Patienten ohne Mukositisrisiko sensitiver zu gestalten.This work addresses the usability of the human saliva proteome for diagnostics of oral mucositis in head and neck cancer. Being a common side-effect of radio(chemo)therapy, a mucositis can limit treatment and causes restrictions in quality of life. Whereas saliva is widely accessible, there are only a few studies demonstrating the usability of the salivary proteome for diagnostics or for therapeutic decisions. One reason is that mass-spectrometric methods are very complex. The first publication (Golatowski et al. 2013) establishes a standard for obtaining human saliva. As a result, we recommend using paraffine gum yielding high sample volume and high overlap of the proteome compared to unstimulated salivation. A second publication (Jehmlich & Golatowski et al. 2014) compares different C18-microcolumns concerning their influence for protein identifications. Those microcolumns are necessary for desalting of peptide mixtures. All tested columns yielded comparable results while ZipTip® µC18 and C18 Systems are slightly superior to OASIS® HLB μElution 96er Well plate and TopTip® C18 pipette tips. The last publication (Jehmlich et al. 2015) applies obtained knowledge for analysis of human saliva of patients with head and neck cancer. We demonstrated the possibility to identify altered proteins via mass-spectrometry in two patient groups. With the obtained data we could show the possible use of mass-spectrometric supported analyses for identifying patients who are prone to develop a mucositis during treatment even in advance of the treatment. Here, the protein class of metalloproteinases should be emphasized, being of use for a therapeutic approach. However, in the future larger, likely multicenter studies will be required to include sufficiently large patient cohorts that might allow even better classification, especially for patients without risk of developing an oral mucositis

QoS Challenges and Opportunities in Wireless Sensor/Actuator Networks

A wireless sensor/actuator network (WSAN) is a group of sensors and actuators that are geographically distributed and interconnected by wireless networks. Sensors gather information about the state of physical world. Actuators react to this information by performing appropriate actions. WSANs thus enable cyber systems to monitor and manipulate the behavior of the physical world. WSANs are growing at a tremendous pace, just like the exploding evolution of Internet. Supporting quality of service (QoS) will be of critical importance for pervasive WSANs that serve as the network infrastructure of diverse applications. To spark new research and development interests in this field, this paper examines and discusses the requirements, critical challenges, and open research issues on QoS management in WSANs. A brief overview of recent progress is given.Comment: 12 pages, 1 figure; revie

A Lightweight SOAP over CoAP Transport Binding for Resource Constraint Networks

Abstract—A huge momentum towards IP enabled Wire-less Sensor Networks (WSN) appeared through the emerging 6LoWPAN protocols (i.e. IPv6 over Low power Wireless Personal Area Networks). By using existing cross domain open standards in contrast of proprietary solutions, technologies and deployments are not tailored too tight for specific applications. Nevertheless, 6LoWPAN is only the first step. Still efforts on higher layers on top of 6LoWPAN are an urgent need to provide the seamless connectivity and interaction of highly re-source constrained devices with higher valued applications and services. This paper describes a new approach to bind SOAP to the emerging Constrained Application Protocol (CoAP) protocol. Thereby, CoAP provides a lightweight but reliable transport binding for SOAP. Compared to the widespread TCP based HTTP binding, round trip times can be reduced by 43% in an exemplary scenario because of the omitted expensive bidirectional TCP handshake mechanisms. Combined with dedicated XML compressors like EXI, SOAP based protocols become also applicable in WSNs

SIRENA - Service Infrastructure for Real-time Embedded Networked Devices: A service oriented framework for different domains

The SIRENA project started in 2003 to leverage Service Oriented Architectures (SOA) to seamlessly interconnect (embedded) devices inside and between four distinct domains- the industrial, telecommunication, automotive and home automation domain. A framework was developed to achieve this aim as well as to assure interoperability with existing devices and extensibility of networks based on SIRENA technology. The core of the framework is the Devices Profile for Web Services (DPWS) which will play an important role in the upcoming Microsoft Windows Vista platform. The first DPWS stack worldwide for embedded devices developed by the SIRENA consortium is described and its operation evidenced in several demonstrators. This paper presents the results of the SIRENA project, provides insight into the technologies used and presents tools, components and services for advanced development, deployment and maintenance of devices. 1