Enabling a direct path from end-user specifications to executable protocols in a biology laboratory environment

Biomedical analyses are becoming increasingly complex, with respect to both the type of the data to be produced and the procedures to be executed. This trend is expected to continue in the future. The development of information and protocol management systems that can sustain this challenge is therefore becoming an essential enabling factor for all actors in the field. The use of custom-built solutions that require the biology domain expert to acquire or procure software engineering expertise in the development of the laboratory infrastructure is not fully satisfactory because it incurs undesirable mutual knowledge dependencies between the two camps. We propose instead an infrastructure concept that enables the domain experts to express laboratory protocols using proper domain knowledge, free from the incidence and mediation of the software implementation artefacts. In the system that we propose this is made possible by basing the modelling language on an authoritative domain specific ontology and then using modern model-driven architecture technology to transform the user models in software artefacts ready for execution in a multi-agent based execution platform specialized for biomedical laboratories.

On the path of Exploratory Search Users - A Semantic Web tool

L’Exploratory Search, paradigma di ricerca basato sulle attività di scoperta e d’apprendimento, è stato per diverso tempo ignorato dai motori di ricerca tradizionali. Invece, è spesso dalle ricerche esplorative che nascono le idee più innovative. Le recenti tecnologie del Semantic Web forniscono le soluzioni che permettono d’implementare dei motori di ricerca capaci di accompagnare gli utenti impegnati in tale tipo di ricerca. Aemoo, motore di ricerca sul quale s’appoggia questa tesi ne è un esempio efficace. A partire da quest’ultimo e sempre con l’aiuto delle tecnologie del Web of Data, questo lavoro si propone di fornire una metodologia che permette di prendere in considerazione la singolarità del profilo di ciascun utente al fine di guidarlo nella sua ricerca esplorativa in modo personalizzato. Il criterio di personalizzazione che abbiamo scelto è comportamentale, ovvero basato sulle decisioni che l’utente prende ad ogni tappa che ritma il processo di ricerca. Implementando un prototipo, abbiamo potuto testare la validità di quest’approccio permettendo quindi all’utente di non essere più solo nel lungo e tortuoso cammino che porta alla conoscenza.

Hard x-ray photoelectron spectroscopy of bulk and thin films of Heusler compounds

X-ray photoemission spectroscopy (XPS) is one of the most universal and powerful tools for investigation of chemical states and electronic structures of materials. The application of hard x-rays increases the inelastic mean free path of the emitted electrons within the solid and thus makes hard x-ray photoelectron spectroscopy (HAXPES) a bulk sensitive probe for solid state research and especially a very effective nondestructive technique to study buried layers.rnThis thesis focuses on the investigation of multilayer structures, used in magnetic tunnel junctions (MTJs), by a number of techniques applying HAXPES. MTJs are the most important components of novel nanoscale devices employed in spintronics. rnThe investigation and deep understanding of the mechanisms responsible for the high performance of such devices and properties of employed magnetic materials that are, in turn, defined by their electronic structure becomes feasible applying HAXPES. Thus the process of B diffusion in CoFeB-based MTJs was investigated with respect to the annealing temperature and its influence on the changes in the electronic structure of CoFeB electrodes that clarify the behaviour and huge TMR ratio values obtained in such devices. These results are presented in chapter 6. The results of investigation of the changes in the valence states of buried off-stoichiometric Co2MnSi electrodes were investigated with respect to the Mn content α and its influence on the observed TMR ratio are described in chapter 7.rnrnMagnetoelectronic properties such as exchange splitting in ferromagnetic materials as well as the macroscopic magnetic ordering can be studied by magnetic circular dichroism in photoemission (MCDAD). It is characterized by the appearance of an asymmetry in the photoemission spectra taken either from the magnetized sample with the reversal of the photon helicity or by reversal of magnetization direction of the sample when the photon helicity direction is fixed. Though recently it has been widely applied for the characterization of surfaces using low energy photons, the bulk properties have stayed inaccessible. Therefore in this work this method was integrated to HAXPES to provide an access to exploration of magnetic phenomena in the buried layers of the complex multilayer structures. Chapter 8 contains the results of the MCDAD measurements employing hard x-rays for exploration of magnetic properties of the common CoFe-based band-ferromagnets as well as half-metallic ferromagnet Co2FeAl-based MTJs.rnrnInasmuch as the magnetoresistive characteristics in spintronic devices are fully defined by the electron spins of ferromagnetic materials their direct measurements always attracted much attention but up to date have been limited by the surface sensitivity of the developed techniques. Chapter 9 presents the results on the successfully performed spin-resolved HAXPES experiment using a spin polarimeter of the SPLEED-type on a buried Co2FeAl0.5Si0.5 magnetic layer. The measurements prove that a spin polarization of about 50 % is retained during the transmission of the photoelectrons emitted from the Fe 2p3/2 state through a 3-nm-thick oxide capping layer.rn

On arc-routing problems

Das Basisproblem von Arc-Routing Problemen mit mehreren Fahrzeugen ist das Capacitated Arc-Routing Problem (CARP). Praktische Anwendungen des CARP sind z.B. in den Bereichen Müllabfuhr und Briefzustellung zu finden. Das Ziel ist es, einen kostenminimalen Tourenplan zu berechnen, bei dem alle erforderlichen Kanten bedient werden und gleichzeitig die Fahrzeugkapazität eingehalten wird. In der vorliegenden Arbeit wird ein Cut-First Branch-and-Price Second Verfahren entwickelt. In der ersten Phase werden Schnittebenen generiert, die dem Master Problem in der zweiten Phase hinzugefügt werden. Das Subproblem ist ein kürzeste Wege Problem mit Ressourcen und wird gelöst um neue Spalten für das Master Problem zu liefern. Ganzzahlige CARP Lösungen werden durch ein neues hierarchisches Branching-Schema garantiert. Umfassende Rechenstudien zeigen die Effektivität dieses Algorithmus. Kombinierte Standort- und Arc-Routing Probleme ermöglichen eine realistischere Modellierung von Zustellvarianten bei der Briefzustellung. In dieser Arbeit werden jeweils zwei mathematische Modelle für Park and Loop und Park and Loop with Curbline vorgestellt. Die Modelle für das jeweilige Problem unterscheiden sich darin, wie zulässige Transfer Routen modelliert werden. Während der erste Modelltyp Subtour-Eliminationsbedingungen verwendet, werden bei dem zweiten Modelltyp Flussvariablen und Flusserhaltungsbedingungen eingesetzt. Die Rechenstudie zeigt, dass ein MIP-Solver den zweiten Modelltyp oft in kürzerer Rechenzeit lösen kann oder bei Erreichen des Zeitlimits bessere Zielfunktionswerte liefert.

Laparoscopic incisional hernia repair is feasible and safe after liver transplantation

Incisional hernia is a common complication after liver transplantation. The current study evaluated incidence and risk factors for incisional hernia and compared laparoscopic and open hernia repair in terms of feasibility and outcome.

Real-time polymerase chain-reaction detection of pathogens is feasible to supplement the diagnostic sequence for urinary tract infections

To evaluate, in a prospective pilot study, the feasibility of identifying pathogens in urine using real-time polymerase chain reaction (PCR), and to compare the results with the conventional urine culture-based procedures.

GSR deposition along the bullet path in contact shots to composite models

In contact shots, all the materials emerging from the muzzle (combustion gases, soot, powder grains, and metals from the primer) will be driven into the depth of the entrance wound and the following sections of the bullet track. The so-called "pocket" ("powder cavity") under the skin containing soot and gunpowder particles is regarded as a significant indicator of a contact entrance wound since one would expect that the quantity of GSR deposited along the bullet's path rapidly declines towards the exit hole. Nevertheless, experience has shown that soot, powder particles, and carboxyhemoglobin may be found not only in the initial part of the wound channel, but also far away from the entrance and even at the exit. In order to investigate the propagation of GSRs under standardized conditions, contact test shots were fired against composite models of pig skin and 25-cm-long gelatin blocks using 9-mm Luger pistol cartridges with two different primers (Sinoxid® and Sintox®). Subsequently, 1-cm-thick layers of the gelatin blocks were examined as to their primer element contents (lead, barium, and antimony as discharge residues of Sinoxid® as well as zinc and titanium from Sintox®) by means of X-ray fluorescence spectroscopy. As expected, the highest element concentrations were found in the initial parts of the bullet tracks, but also the distal sections contained detectable amounts of the respective primer elements. The same was true for amorphous soot and unburned/partly burned powder particles, which could be demonstrated even at the exit site. With the help of a high-speed motion camera it was shown that for a short time the temporary cavitation extends from the entrance to the exit thus facilitating the unlimited spread of discharge residues along the whole bullet path.

First clinical evidence that imaging with somatostatin receptor antagonists is feasible

Preclinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In this study, we evaluated whether imaging with sst antagonists was feasible in patients.

Webinar Training: an acceptable, feasible and effective approach for multi-site medical record abstraction: the BOWII experience

Background Abstractor training is a key element in creating valid and reliable data collection procedures. The choice between in-person vs. remote or simultaneous vs. sequential abstractor training has considerable consequences for time and resource utilization. We conducted a web-based (webinar) abstractor training session to standardize training across six individual Cancer Research Network (CRN) sites for a study of breast cancer treatment effects in older women (BOWII). The goals of this manuscript are to describe the training session, its participants and participants' evaluation of webinar technology for abstraction training. Findings A webinar was held for all six sites with the primary purpose of simultaneously training staff and ensuring consistent abstraction across sites. The training session involved sequential review of over 600 data elements outlined in the coding manual in conjunction with the display of data entry fields in the study's electronic data collection system. Post-training evaluation was conducted via Survey Monkey©. Inter-rater reliability measures for abstractors within each site were conducted three months after the commencement of data collection. Ten of the 16 people who participated in the training completed the online survey. Almost all (90%) of the 10 trainees had previous medical record abstraction experience and nearly two-thirds reported over 10 years of experience. Half of the respondents had previously participated in a webinar, among which three had participated in a webinar for training purposes. All rated the knowledge and information delivered through the webinar as useful and reported it adequately prepared them for data collection. Moreover, all participants would recommend this platform for multi-site abstraction training. Consistent with participant-reported training effectiveness, results of data collection inter-rater agreement within sites ranged from 89 to 98%, with a weighted average of 95% agreement across sites. Conclusions Conducting training via web-based technology was an acceptable and effective approach to standardizing medical record review across multiple sites for this group of experienced abstractors. Given the substantial time and cost savings achieved with the webinar, coupled with participants' positive evaluation of the training session, researchers should consider this instructional method as part of training efforts to ensure high quality data collection in multi-site studies.

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Maternal mental health in the first 3-week postpartum: the impact of caregiver support and the subjective experience of childbirth - a longitudinal path model

Acute stress reactions (ASR) and postpartum depressive symptoms (PDS) are frequent after childbirth. The present study addresses the change and overlap of ASR and PDS from the 1- to 3-week postpartum and examines the interplay of caregiver support and subjective birth experience with regard to the development of ASR/PDS within a longitudinal path model.

ON THE MERITS OF VOXEL-BASED MORPHOMETRIC PATH-ANALYSIS FOR INVESTIGATING VOLUMETRIC MEDIATION OF A TOXICANT'S INFLUENCE ON COGNITIVE FUNCTION

We previously showed that lifetime cumulative lead dose, measured as lead concentration in the tibia bone by X-ray fluorescence, was associated with persistent and progressive declines in cognitive function and with decreases in MRI-based brain volumes in former lead workers. Moreover, larger region-specific brain volumes were associated with better cognitive function. These findings motivated us to explore a novel application of path analysis to evaluate effect mediation. Voxel-wise path analysis, at face value, represents the natural evolution of voxel-based morphometry methods to answer questions of mediation. Application of these methods to the former lead worker data demonstrated potential limitations in this approach where there was a tendency for results to be strongly biased towards the null hypothesis (lack of mediation). Moreover, a complimentary analysis using anatomically-derived regions of interest volumes yielded opposing results, suggesting evidence of mediation. Specifically, in the ROI-based approach, there was evidence that the association of tibia lead with function in three cognitive domains was mediated through the volumes of total brain, frontal gray matter, and/or possibly cingulate. A simulation study was conducted to investigate whether the voxel-wise results arose from an absence of localized mediation, or more subtle defects in the methodology. The simulation results showed the same null bias evidenced as seen in the lead workers data. Both the lead worker data results and the simulation study suggest that a null-bias in voxel-wise path analysis limits its inferential utility for producing confirmatory results.