Static Source Code Analysis using OCL

The majority of artifacts created during software development are representations of programs in textual syntax. Although graphical descriptions are becoming more widespread, source code is still indispensable. To obtain programs that behave correctly and adhere to given coding conventions, source code must be analyzed - preferably using automated tools. Building source code analyzers has a long tradition and various mature tools exist to check code written in conventional languages, such as Java or C. As new languages emerge (e.g., Domain Specific Languages) these tools can not be applied and building a tool for each language does not seem feasible either. This paper investigates how meta models for textual languages and the Object Constraint Language can enable generic static source code analysis for arbitrary languages. The presented approach is evaluated using three languages (Java, SQL and a DSL for state machines)

Designing Round-Trip Systems by Change Propagation and Model Partitioning

Software development processes incorporate a variety of different artifacts (e.g., source code, models, and documentation). For multiple reasons the data that is contained in these artifacts does expose some degree of redundancy. Ensuring global consistency across artifacts during all stages in the development of software systems is required, because inconsistent artifacts can yield to failures. Ensuring consistency can be either achieved by reducing the amount of redundancy or by synchronizing the information that is shared across multiple artifacts. The discipline of software engineering that addresses these problems is called Round-Trip Engineering (RTE). In this thesis we present a conceptual framework for the design RTE systems. This framework delivers precise definitions for essential terms in the context of RTE and a process that can be used to address new RTE applications. The main idea of the framework is to partition models into parts that require synchronization - skeletons - and parts that do not - clothings. Once such a partitioning is obtained, the relations between the elements of the skeletons determine whether a deterministic RTE system can be built. If not, manual decisions may be required by developers. Based on this conceptual framework, two concrete approaches to RTE are presented. The first one - Backpropagation-based RTE - employs change translation, traceability and synchronization fitness functions to allow for synchronization of artifacts that are connected by non-injective transformations. The second approach - Role-based Tool Integration - provides means to avoid redundancy. To do so, a novel tool design method that relies on role modeling is presented. Tool integration is then performed by the creation of role bindings between role models. In addition to the two concrete approaches to RTE, which form the main contributions of the thesis, we investigate the creation of bridges between technical spaces. We consider these bridges as an essential prerequisite for performing logical synchronization between artifacts. Also, the feasibility of semantic web technologies is a subject of the thesis, because the specification of synchronization rules was identified as a blocking factor during our problem analysis. The thesis is complemented by an evaluation of all presented RTE approaches in different scenarios. Based on this evaluation, the strengths and weaknesses of the approaches are identified. Also, the practical feasibility of our approaches is confirmed w.r.t. the presented RTE applications

Vergleich von Propofol MCT/LCT mit Propofol LCT unter besonderer Berücksichtigung des Fettsäurestoffwechsels

Propofol ist ein häufig verwendetes Hypnotikum in der Anästhesie. Da Propofol sehr wenig wasserlöslich ist, erhält man erst durch den Einsatz einer Fettemulsion ein Arzneimittel, das einen intravenösen Einsatz zuläßt. Hierbei wurde Disoprivan® 2 % (bestehend zu 99% aus langkettigen Fettsäuren der Länge C16 und C18; LCT-Präparation) und Propofol-® Lipuro 2 % (bestehend zu 45% aus mittelkettigen Fettsäuren der Länge C8 bis C10 sowie zu 54% aus langkettigen Fettsäuren der Länge C16 und C18; MCT/LCT - Präparation) in einer prospektiven, doppelblinden, kontrollierten und randomisierten Untersuchung verglichen. Hauptziel dieser Studie war es, festzustellen, ob eine günstigere Verstoffwechselung der MCT/LCT-Präparation in Bezug zum Fettstoffwechsel besteht und daher tödliche Komplikationen und Zwischenfälle minimiert werden können. Als Parameter des Fettsäurestoffwechsels wurde der Serum Triglycerid – Spiegel über die indirekte Meßmethode bestimmt. In diese Untersuchung wurden Patienten eingeschlossen, die sich einem herzchirurgischen Eingriff mit Hilfe der Herz-Lungen-Maschine unterziehen mußten und dabei mittels kontinuierlicher Propofol - Gabe mindestens 24 Stunden sediert wurden. Im Einzelnen wurden die Folgenden Fragestellungen bearbeitet: Vergleich der Verstoffwechselung der MCT/LCT-Präparation gegenüber der LCT- Präparation mit dem Serum Triglycerid-Spiegel als Zielparameter des Fettsäurestoffwechsels; Beeinflussung der Verstoffwechselung der beiden Präparationen bei Patienten mit Hypercholesterinämie und Diabetes Mellitus; Zusammenhang zwischen Propofol-Konzentration Propofol-Gesamtmenge in Hinblick auf die Triglycerid-Konzentrationen; Beeinflussung des Triglycerid-Spiegels durch die Immunantwort. Die Messzeitpunkte der Triglycerid-Konzentration waren: Baseline, vor EKZ, Ende EKZ, Ende OP, 12 Stunden und 24 Stunden nach OP-Beginn sowie 2-, 4-, 12- Stunden nach Sedierungsende. Von einem zuvor errechneten Patientenkollektiv von 56 Patienten wurden 50 Patienten ausgewertet. Die demographischen Daten und die Anamneseerhebung waren in beiden Gruppen gleich. Als anamnestische Risikofaktoren wurden Rauchen (13 von 56), arterielle Hypertonie (41 von 56), Diabetes mellitus (12 von 56) und Hypercholesterinämie (24 von 56) in der Studie untersucht. In Bezug auf die Triglycerid - Spiegel konnte nur zu den Zeitpunkten Ende OP, 24 Stunden nach OP - Beginn und 4 Stunden nach Sedierungsende ein signifikanter Unterschied zwischen den Propofol - Präparationen festgestellt werden. Hier zeigten sich geringere Triglycerid - Konzentrationen der Propofol MCT/LCT – Präparation, was auf eine günstigere Verstoffwechselung zurückgeführt werden kann, wobei jedoch die Triglycerid - Konzentrationen beider Präparationen immer unter dem pathologisch relevanten Bereich von 1,7 mmol/l lagen und keine Hypertriglyceridämien vorkamen. Die Triglycerid - Konzentration fiel unter Einsatz der Herz-Lungen-Maschine stark ab (vor EKZ:1,2 mmol/l (MCT/LCT) vs. 1,4 mmol/l (LCT); Ende EKZ: 0,6 mmol/l (MCT/LCT) vs. 0,6 mmol/l (LCT), was sowohl auf einen Verdünnungseffekt als auch auf den Einsatz von Heparin zurückzuführen ist. Danach stiegen die Triglycerid - Konzentrationen bis zum Messzeitpunkt 12 Stunden nach Start an (12 Stunden nach Start: 1,1 mmol/l (MCT/LCT) vs. 1,2 mmol/l (LCT), dass am ehesten auf einen verminderten Heparin - Effekt zurückzuführen ist. Ein Anstieg der Triglycerid - Konzentration durch eine kontinuierliche Propofol - Gabe wurde nicht beobachtet. Ab dem Messzeitpunkt 24 Stunden nach Start bis 4 Stunden nach Sedierungsende waren die Konzentrationen konstant (0,74 ± 0,01 mmol/l (MCT/LCT) vs. 0,93 ± 0,02 mmol/l (LCT). Auch bei Patienten, die an Hypercholesterinämie oder Diabetes mellitus erkrankt waren, wurden keine Hypertriglyceridämien festgestellt. Aber auch hier zeigte die MCT/LCT - Präparation eine günstigere Verstoffwechselung. Bei 6 Patienten, die zu Beginn der Untersuchung eine Triglycerid - Konzentration von über 1,7 mmol/l hatten, fielen die Triglycerid - Konzentration im Verlauf stetig ab. Sowohl die Propofol - Serumkonzentration (vor EKZ: 2,2 mg/l; Ende EKZ bis 24 Stunden nach Start: 1 ± 0,4 mg/l; nach Ende Sedierung Legende: EKZ = Herz-Lungen-Maschin

CoDaMine: Supporting Privacy and Trust Management in Ubiquitous Environments Through Communication Data Mining

In ubiquitous environments an increasing number of sensors capture information on users and at the same time an increasing number of actuators are available to present information to users. This vast capturing of information potentially enables the system to adapt to the users. At the same time the system might violate the users' privacy by capturing information that the users do not want to share, and the system might disrupt the users by being too obtrusive in its adaptation or information supply. In this paper we present CoDaMine - a novel approach for providing users with system - generated feedback and control in ubiquitous environments giving them the freedom they need while reducing their effort. Basically, CoDaMine captures and analyses the users' online communication to learn about their social relationships in order to provide them with recommendations for inter-personal privacy and trust management

A new and reliable culture system for superficial low-grade urothelial carcinoma of the bladder

Several bladder cancer culture systems have been developed in recent years. However, reports about successful primary cultures of superficial urothelial carcinomas (UC) are sparse. Based on the specific growth requirements of UC described previously, we developed a new and reliable culture system for superficial low-grade UC. Between November 2002 and April 2006, 64 primary cultures of bladder cancer specimens were performed. After incubating the specimens overnight in 0.1% ethylenediaminetetraacetic acid solution, tumour cells could easily be separated from the submucosal tissue. Subsequently, cells were seeded in a low-calcium culture medium supplemented with 1% serum, growth factors, non-essential amino acids and glycine. The malignant origin of the cultured cells was demonstrated by spectral karyotyping. Overall culture success rate leading to a homogenous tumour cell population without fibroblast contamination was 63%. Culture success could be remarkably enhanced by the addition of glycine to the culture medium. Interestingly, 86.4% of pTa tumours were cultured successfully compared to only 50% of the pT1 and 38% of advanced stage tumours, respectively. G1 and G2 tumours grew significantly better than G3 tumours (86, 73 and 41%, respectively). Up to three passages of low-grade UC primary cultures were possible. We describe a new and reliable culture system, which is highly successful for primary culture and passage of low-grade UC of the bladder. Therefore, this culture system can widely be used for functional experiments on early stage bladder cance

ФОРМУВАННЯ ГІДРОДИНАМІЧНОГО РЕЖИМУ В ЗОНІ ВПЛИВУ ВІДВАЛІВ ГІРСЬКИХ ПОРІД ТА ХВОСТОСХОВИЩ

За результатами моделювання з використанням тривимірної чисельної моделі, що комплексно відбиває планово-профільну фільтрацію в межах прони-кних і розділяючих шарів, встановлені закономірності геофільтрації у верхній частині породного масиву на ділянках розташування відвалів гірських порід і хвостосховищ. Виявлений характер впливу гідродинамічного режиму, що формується в умовах гравітаційно-навантаженого породного масиву, на гео-механічний стан прилеглої до об'єктів гірничого виробництва території. По результатам моделирования с использованием трехмерной численной модели, комплексно отражающей планово-профильную фильтрацию в пределах проницаемых и разделяющих слоев, установлены закономерности геофильтрации в верхней части породного массива на участках расположе-ния отвалов горных пород и хвостохранилищ. Определен характер влияния гидродинамического режима, формирующегося в условиях гравитационно-нагруженного породного массива, на геомеханическое состояние прилегаю-щей к объектам горного производства территории. The features of ground water flow have been determined for the top layers of the rock mass in dump tailing areas by numerical simulation using a model reproduc-ing 3D ground water flow within aquifers and confining layers. The impact of the hydrodynamic regime formed in the gravitationally loaded rock mass on geomechanical conditions of the territory affected by mining industry sites has been revealed

Impact of Extrinsic and Intrinsic Hypoxia on Catecholamine Biosynthesis in Absence or Presence of Hif2α in Pheochromocytoma Cells

Pheochromocytomas and paragangliomas (PPGLs) with activated pseudohypoxic pathways are associated with an immature catecholamine phenotype and carry a higher risk for metastasis. For improved understanding of the underlying mechanisms we investigated the impact of hypoxia and pseudohypoxia on catecholamine biosynthesis in pheochromocytoma cells naturally lacking Hif2α (MPC and MTT) or expressing both Hif1α and Hif2α (PC12). Cultivation under extrinsic hypoxia or in spheroid culture (intrinsic hypoxia) increased cellular dopamine and norepinephrine contents in all cell lines. To distinguish further between Hif1α- and Hif2α-driven effects we expressed Hif2α in MTT and MPC-mCherry cells (naturally lacking Hif2α). Presence of Hif2α resulted in similarly increased cellular dopamine and norepinephrine under hypoxia as in the control cells. Furthermore, hypoxia resulted in enhanced phosphorylation of tyrosine hydroxylase (TH). A specific knockdown of Hif1α in PC12 diminished these effects. Pseudohypoxic conditions, simulated by expression of Hif2α under normoxia resulted in increased TH phosphorylation, further stimulated by extrinsic hypoxia. Correlations with PPGL tissue data led us to conclude that catecholamine biosynthesis under hypoxia is mainly mediated through increased phosphorylation of TH, regulated as a short-term response (24-48 h) by HIF1α. Continuous activation of hypoxia-related genes under pseudohypoxia leads to a HIF2α-mediated phosphorylation of TH (permanent status).Funding: This research was funded by the Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio205/1 (project number: 314061271-TRR 205), Project No. B12 (N.B. and G.E.), Project No. B10 (S.R., J.P. and M.U.)and Project No. S01 (A.W., C.G. and M.P.) “The Adrenal: Central Relay in Health and Disease“, and by theParadi erence Foundation (N.B., I.P., S.R. and G.E.).S

Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin

IDH1R132H (isocitrate dehydrogenase 1) mutations play a key role in the development of low-grade gliomas. IDH1wt converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+), whereas IDH1R132H uses α-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). While the effects of 2-HG have been the subject of intense research, the 2-HG independent effects of IDH1R132H are still ambiguous. The present study demonstrates that IDH1R132H expression but not 2-HG alone leads to significantly decreased tricarboxylic acid (TCA) cycle metabolites, reduced proliferation, and enhanced sensitivity to irradiation in both glioblastoma cells and astrocytes in vitro. Glioblastoma cells, but not astrocytes, showed decreased NADPH and NAD+ levels upon IDH1R132H transduction. However, in astrocytes IDH1R132H led to elevated expression of the NAD-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT). These effects were not 2-HG mediated. This suggests that IDH1R132H cells utilize NAD+ to restore NADP pools, which only astrocytes could compensate via induction of NAMPT. We found that the expression of NAMPT is lower in patient-derived IDH1-mutant glioma cells and xenografts compared to IDH1-wildtype models. The Cancer Genome Atlas (TCGA) data analysis confirmed lower NAMPT expression in IDH1-mutant versus IDH1-wildtype gliomas. We show that the IDH1 mutation directly affects the energy homeostasis and redox state in a cell-type dependent manner. Targeting the impairments in metabolism and redox state might open up new avenues for treating IDH1-mutant gliomas.publishedVersio

Agroforestry : an appropriate and sustainable response to a changing climate in Southern Africa?

CITATION: Sheppard, Jonathan P. et al. 2020. Agroforestry : an appropriate and sustainable response to a changing climate in Southern Africa? Sustainability 12(17):6796, doi:10.3390/su12176796.The original publication is available at: https://www.mdpi.comENGLISH ABSTRACT: Agroforestry is often discussed as a strategy that can be used both for the adaptation to and the mitigation of climate change e ects. The climate of southern Africa is predicted to be severely a ected by such changes. With agriculture noted as the continent’s largest economic sector, issues such as food security and land degradation are in the forefront. In the light of such concerns we review the current literature to investigate if agroforestry systems (AFS) are a suitable response to the challenges besetting traditional agricultural caused by a changing climate. The benefits bestowed by AFS are multiple, o ering ecosystem services, influence over crop production and positive impacts on rural livelihoods through provisioning and income generation. Nevertheless, knowledge gaps remain. We identify outstanding questions requiring further investigation such as the interplay between trees and crops and their combination, with a discussion of potential benefits. Furthermore, we identify deficiencies in the institutional and policy frameworks that underlie the adoption and stimulus of AFS in the southern African region. We uphold the concept that AFS remains an appropriate and sustainable response for an increased resilience against a changing climate in southern Africa for the benefit of livelihoods and multiple environmental values.Publisher's versio