Review of Immunoinformatic approaches to in-silico B-cell epitope prediction

In this paper, the current state of in-silico, B-cell epitope prediction is discussed. Recommendations for improving some of the approaches encountered are outlined, along with the presentation of an entirely novel technique, which uses molecular mechanics for epitope classification, evaluation and prediction

Human-centred computer architecture: redesigning the mobile datastore and sharing interface

This dissertation develops a material perspective on Information & Communication Technologies and combines this perspective with a Research through Design approach to interrogate current and develop new mobile sharing interfaces and datastores. through this approach I open up a line of inquiry that connects a material perspective of information with everyday sharing and communication practices as well as with the mobile and cloud architectures that increasingly mediate such practices. With this perspective, I uncover a shifting emphasis of how data is stored on mobile devices and how this data is made available to apps through sharing interfaces that prevent apps from obtaining a proper handle of data to support fundamentally human acts of sharing such as giving. I take these insights to articulate a much wider research agenda to implicate, beyond the sharing interface, the app model and mobile datastore, data exchange protocols, and the Cloud. I formalise the approach I take to bring technically and socially complex, multi-dimensional and changing ideas into correspondence and to openly document this process. I consider the history of the File abstraction and the fundamental grammars of action this abstraction supports (e.g. move, copy, & delete) and the mediating role this abstraction – and its graphical representation – plays in binding together the concerns of system architects, programmers, and users. Finding inspiration in the 30 year history of the file, I look beyond the Desktop to contemporary realms of computing on the mobile and in the Cloud to develop implications for reinvigorated file abstractions, representations, and grammars of actions. First and foremost, these need to have a social perspective on files. To develop and hone such a social perspective, and challenge the assumption that mobile phones are telephones – implying interaction at a distance – I give an interwoven account of the theoretical and practical work I undertook to derive and design a grammar of action – showing – tailored to co-present and co-located interactions. By documenting the process of developing prototypes that explore this design space, and returning to the material perspective I developed earlier, I explore how the grammars of show and gift are incongruent with the specific ways in which information is passed through the mobile’s sharing interface. This insight led me to prototype a mobile datastore – My Stuff – and design new file abstractions that foreground the social nature of the stuff we store and share on our mobiles. I study how that stuff is handled and shared in the Cloud by developing, documenting, and interrogating a cloud service to facilitate sharing, and implement grammars of actions to support and better align with human communication and sharing acts. I conclude with an outlook on the powerful generative metaphor of casting mobile media files as digital possessions to support and develop human-centred computer architecture that give people better awareness and control over the stuff that matters to them

In vivo, in vitro and in silico investigations on disc nucleus replacements in the sheep model

Bandscheibenbedingte Rückenschmerzen stellen eine Gesundheitsstörung von herausragender Bedeutung dar. Innovative Therapiekonzepte sind darauf ausgerichtet, schmerzhaft degenerierte Bandscheiben in ihren natürlichen Strukturen zu regenerieren. Allein durch den chirurgischen Eingriff zur Anwendung dieser Therapiekonzepte wird jedoch die mechanische Kompetenz der Bandscheibe empfindlich gestört. Derzeit ist nicht bekannt, ob neue Nukleusersatzmaterialien für Tissue engineering Strategien an der Bandscheibe diesen Verlust kompensieren können. Daher war es das Ziel der Dissertation in einem kombinierten experimentellen Versuchsansatz aus In-vivo-, Ex-vivo-, In-vitro- und In-silico- Untersuchungen, neu entwickelte Hydrogele als Nukleusersatz im Tiermodell Schaf zu untersuchen und das Schaf als Tiermodell im Bereich der Bandscheibenforschung näher zu charakterisieren. Um ein physiologisches Lastprotokoll für die In-vitro-Untersuchungen zu etablieren, wurde an drei Schafen der intradiskale Druck (IDP) über je 24 Stunden gemessen. Der gesamte Datenpool des ersten Schafes wurde in eine Aktivitäts- und Erholungsphase unterteilt und ex vivo aus den IDP-Durchschnittswerten beider Phasen die entsprechenden axialen Kompressionskräfte abgeleitet. In vitro wurde ein Kriech-Relaxations-Test an 36 ovinen lumbalen Bewegungssegmenten durchgeführt. Die Segmente wurden drei Belastungszyklen ausgesetzt, die jeweils aus einer 15-minütigen Belastungsphase (130 N) und einer 30-minütigen Erholungsphase (58 N) bestanden. IDP-Verlauf und Höhenverlust der Segmente wurden in sechs verschiedenen Versuchsgruppen untersucht: (i) INTAKT; (ii) DEF-AN: Eine schräge Anulusinzision. Der Defekt wurde durch Naht und Cyanoacrylatkleber verschlossen. (iii) DEF-NUKn+k: Nukleusgewebe wurde entfernt und anschließend reimplantiert. Der Anulusverschluss erfolgte wie in DEF-AN. (iv) DEF-NUKp: Entsprechend dem Vorgehen in Testgruppe DEF-NUKn+k wurde der Nukleus entfernt und reimplantiert. Um eine Volumenverdrängung reimplantierten Gewebes in den inneren Anulusdefekt zu vermeiden, erfolgte der Verschluss mittels eines Plugs. Abschließend wurden zwei Hydrogele als Nukleusersatz untersucht: (v) DDAHA und (vi) iGG-MA. Zur besseren Interpretation der In-vitro-Ergebnisse wurden Finite-Elemente-Analysen an einem Bandscheibenmodell durchgeführt. In vivo lag der Bandscheibendruck beim Schaf nahezu konstant höher als beim Menschen. Niedrigste Druckwerte wurden intraoperativ mit ~0,5 MPa ermittelt. Höchste Druckwerte wurden für Aufstehen oder Drehen mit 3,6 bzw. 2,6 MPa gemessen und waren damit ungefähr zwei- bis viermal höher in der ovinen Bandscheibe. Die IDP-Mittelwerte der Aktivitäts- und Erholungsphasen des ersten Schafes lagen bei ~0,75 bzw. ~0,5 MPa, welche axialen Kompressionskräften von 130 bzw. 58 N entsprachen. Im Kriech-Relaxations-Test hatte ein isolierter Anulusdefekt (DEF-AN) keinen Einfluss auf Höhenverlust und IDP der Segmente. DEF-NUKn+k, DEF-NUKp, DDAHA und iGG-MA hingegen steigerten den Höhenverlust und verringerten signifikant den IDP im Vergleich zu INTAKT. Die Modellvorhersagen belegten erhebliche Auswirkungen eines reduzierten Wassergehalts, Kompressionsmoduls und osmotischen Potentials des reimplantierten Gewebes auf den Höhenverlust und IDP des Segmentes. Die Lastübertragung innerhalb der Bandscheibe veränderte sich hierdurch deutlich und ging mit einer erhöhten Belastung des Anulus einher. Die vergleichsweise hohen Bandscheibendrücke des Schafes stehen der weit verbreiteten Meinung gegenüber, dass aufgrund der horizontal ausgerichteten Wirbelsäule des Vierbeiners, intradiskale Lasten geringer sein müssten als beim Menschen. In Kenntnis der vorliegenden Untersuchungen sollte die Rechtfertigung bzw. der Ausschluss des Schafes als Modell im Bereich der Wirbelsäule nicht auf Unterschieden im Gang begründet werden, sondern auf mechanischen Überlegungen bzgl. künftiger Einsatzgebiete. Die In-vitro-Ergebnisse zeigen, dass der Erfolg von Hydrogelen als Nukleusersatz nicht nur vom Ersatzmaterial selbst abhängt, sondern auch von der Wiederherstellung zerstörter Bandscheibenstrukturen, wie der Grenzflächen zwischen Nukleus und Umgebung sowie dem gesetzten Anulusdefekt. Die vorliegende Dissertation konnte die Bedeutung iatrogen induzierter struktureller Schädigungen der Bandscheibe für Nukleusersatzstrategien herausarbeiten und stellt somit wesentliche Anforderungskriterien an das zukünftige Designkonzept von Hydrogelen als Nukleusersatz für Tissue engineering Strategien an der Bandscheibe. Hydrogele, die allein das mechanische Verhalten des Nukleus imitieren, können ansonsten bei der Wiederherstellung der Mechanik des Gesamtsegmentes versagen.Discogenic low back pain represents a major health disorder in the musculoskeletal field. Innovative therapeutic approaches aim to regenerate the painfully degenerated disc by restoring its original structure. Surgical procedures like nucleotomy, however, which are necessary for the application of such therapeutic concepts, however, perturb the mechanical competence of the disc. It has not been fully clarified whether biomaterials for nucleus replacement are able to compensate for this. Therefore, a combined experimental approach of in vivo, ex vivo, in vitro and in silico studies was carried out to evaluate the efficiency of newly developed hydrogels for nucleus replacement in an ovine disc model and to characterize the sheep as an animal model in intervertebral disc research. To establish a physiological loading protocol for the in vitro studies, intradiscal pressure (IDP) was measured in three sheep over 24 hours. The total data set of the first sheep was divided into an activity phase and a recovery phase, and the resulting average pressures of both phases were calculated. Subsequently, the corresponding axial forces were derived ex vivo. In vitro, a creep and recovery test was performed on 36 ovine lumbar motion segments. Specimens were subjected to three loading cycles, each consisting of a loading period of 15 minutes at 130 N and a recovery period of 30 minutes at 58 N. IDP and segment height loss were investigated in six different test groups: (i) INTACT; (ii) DEF-ANN: A small oblique incision in the annulus. The defect was closed by suturing and with cyanoacrylate glue. (iii) DEF-NUCs+g: Nucleus tissue was removed and subsequently re-implanted. The annulus defect was closed as in DEF-ANN. (iv) DEF-NUCp: As in DEF-NUCs+g, the nucleus tissue was removed and re-implanted. To avoid squeezing of nucleus tissue into the inner annulus defect, sealant was applied using a plug. Finally, two hydrogels were investigated as nucleus replacements: (v) DDAHA and (vi) iGG-MA. To better interpret ambiguous results obtained in vitro, finite element analyses were conducted on a disc model. In vivo, ovine IDPs were almost consistently higher than the human. The lowest IDPs were measured intra-operatively with ~0.5 MPa. The highest IDPs were found for standing up or turning around, where IDPs were with 3.6 MPa and 2.6 MPa, respectively, approximately two to four times higher within the ovine disc in comparison to humans. In the creep and recovery test, an isolated annulus incision (DEF-ANN) did not affect segmental height-loss or fluid pressurization. DEF-NUCs+g, DEF-NUCp, DDAHA and iGG-MA increased the height loss and decreased the fluid pressurization compared with INTACT. Model predictions demonstrated substantial effects of reductions in replaced nucleus water content, bulk modulus and osmotic potential on disc height loss and pressure similar to the experimental measurements. For these events in the model, the compression load transfer in the disc was markedly altered by substantially increasing the load on the annulus when compared with the nucleus. The finding of comparably high ovine IDPs in vivo conflicts with the widespread belief that, due to the horizontally aligned spine of quadrupeds, intradiscal loads should be less than in the upright positioned spine of humans. Given the sometimes multiple higher load amplitudes within the ovine disc combined with comparably low axial external forces, current results suggest that the justification of using sheep for spinal research questions should not be primarily based on differences in gait, but rather on mechanical considerations regarding the scientific field of application. In vitro results reveal that the success of hydrogels for nucleus replacement is not only dependent on the implant material itself but also on the restoration of the environment perturbed during surgery. The importance of the interface between the nucleus and its surrounding structures and the relevance of an appropriate annulus closure to avoid a displacement of implant material into the inner annulus defect are clearly indicated. By emphasizing the importance of surgically induced structural damages to the intervertebral disc, the present PhD thesis prescribes essential requirements for future design concepts for hydrogels as nucleus replacements for tissue engineering strategies of the intervertebral disc. Hydrogels that mimic the mechanical behavior of the native nucleus alone may otherwise fail in restoring the mechanical competence of the disc

Orbital photogalvanic effects in quantum-confined structures

We report on the circular and linear photogalvanic effects caused by free-carrier absorption of terahertz radiation in electron channels on (001)-oriented and miscut silicon surfaces. The photocurrent behavior upon variation of the radiation polarization state, wavelength, gate voltage and temperature is studied. We present the microscopical and phenomenological theory of the photogalvanic effects, which describes well the experimental results. In particular, it is demonstrated that the circular (photon-helicity sensitive) photocurrent in silicon-based structures is of pure orbital nature originating from the quantum interference of different pathways contributing to the absorption of monochromatic radiation.Comment: 8 pages, 5 figures, two culumne

Analysis and comparison of British tabloid and serious press

Tato bakalářská práce se zabývá jazykovými, stylistickými a obsahovými charakteristikami britských seriózních a bulvárních novin se zaměřením na deníky The Guardian a The Sun, které reprezentují protichůdné politické ideologie. Analýzou a porovnáním těchto charakteristik se práce snaží pochopit různé novinářské přístupy a jejich možný vliv na vnímání zpráv čtenáři. Práce je rozdělena do pěti částí: úvod, teoretická část, metoda analýzy, praktická část a závěr. Zjištění zdůrazňují rozdíly ve stylu psaní, jazyce, tónu a podání informací mezi seriózními a bulvárními novinami.ObhájenoThis undergraduate thesis examines the linguistic, stylistic, and content-related characteristics of British serious and tabloid newspapers, with a particular focus on The Guardian and The Sun, which represent opposing political ideologies. By analyzing and contrasting these characteristics, the research seeks to comprehend the various journalistic approaches and how they may affect the perceptions of news by readers. The thesis is divided into five sections: introduction, theoretical background, method of analysis, practical part, and conclusion. The findings emphasize differences in writing style, language, tone, and information presentation between serious and tabloid newspapers

Designing Digital Storytelling for Rural African Communities

Chongilala – a long time ago – says Mama Rhoda of Adiedo, Kenya. She looks deeply into our eyes. We record her rhythms and rhymes as she sings and tells a story about her grandparents. She shows us the exact spot where her great-grandfathers and his friends used to sit and drink and how her grandmother used to dance. This thesis situates digital storytelling in rural African communities to enable rural people, like Mama Rhoda, to record and share their stories and to express their imaginations digitally. We explore the role of design, and the methods and perspectives designers need to take on to design across cultures and to understand the forms and meanings behind rural African interpretations of digital storytelling. These perspectives allow us to 'unconceal' how our Western storytelling traditions have influenced design methods and obscure the voices of ‘other’ cultures. By integrating ethnographic insights with previous experiences of designing mobile digital storytelling systems, we implement a method using cell-phones to localize storytelling and involve rural users in de- sign activities – probing ways to incorporate visual and audio media in storytelling. Products from this method help us to generate design ideas for our system, most notably flexibility. Leveraging this prototype as a probe and observing villagers using it in two villages in South Africa and Kenya, we report on situated use of our prototype and discuss, and relate to usage, the insights we gathered on our prototype, the users, their needs, and their context. We use these insights to uncover further implications for situating digital storytelling within those communities and reflect on the importance of spending time in-situ when designing across cultures. Deploying our prototype through an NGO, we stage first encounters with digital storytelling and show how key insiders can introduce the system to a wider community and make it accessible through their technical and social expertise. Our mobile digital storytelling system proved to be both useable and useful and its flexibility allowed users to form their own interpretations of digital storytelling and (re)appropriate our system to alternative ends. Results indicate that our system accommodates context and that storytelling activities around our system reflect identity. Our activities in communities across Africa also show that our system can be used as a digital voice that speaks to us, by allowing users to express themselves – through digital stories – in design