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See detailResolving the Combinatorial Complexity of Smad Protein Complex Formation and Its Link to Gene Expression.
Lucarelli, Philippe UL; Schilling, Marcel; Kreutz, Clemens et al

in Cell Systems (2017)

Upon stimulation of cells with transforming growth factor beta (TGF-beta), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible ... [more ▼]

Upon stimulation of cells with transforming growth factor beta (TGF-beta), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. By combining quantitative mass spectrometry with a computational selection strategy, we predict and provide experimental evidence for the three most relevant Smad complexes in the mouse hepatoma cell line Hepa1-6. Utilizing dynamic pathway modeling, we specify the contribution of each Smad complex to the expression of representative Smad target genes, and show that these contributions are conserved in human hepatoma cell lines and primary hepatocytes. We predict, based on gene expression data of patient samples, increased amounts of Smad2/3/4 proteins and Smad2 phosphorylation as hallmarks of hepatocellular carcinoma and experimentally verify this prediction. Our findings demonstrate that modeling approaches can disentangle the complexity of transcription factor complex formation and its impact on gene expression. [less ▲]

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See detailMilitary Migrants. Luxembourgers in the Colonial Army of the Dutch East Indies
Bosma, Ulbe; Kolnberger, Thomas UL

in Itinerario (2017), 41(3), 555-580

Among the roughly 150,000 soldiers sent to the Dutch East Indies between 1815 and 1914, the Luxembourg contingent made up a tiny minority of just 1,075 men. Based upon extensive research into their ... [more ▼]

Among the roughly 150,000 soldiers sent to the Dutch East Indies between 1815 and 1914, the Luxembourg contingent made up a tiny minority of just 1,075 men. Based upon extensive research into their careers, data on these soldiers provide further clues to understanding what drove Europe’s young men to become colonial soldiers. The results of this national case study will be compared with earlier investigations by Bossenbroek and Bosma on recruits for the Dutch colonial army. Similar to the Dutch soldiers, their Luxembourg counterparts had a predominantly urban provenance. However, in contrast to the Dutch, they did not have a strong military background, and it appears that fewer Luxembourgers stayed behind in the Dutch East Indies after their tour of duty. They were more attracted by the payments that the recruiters doled out in advance, particularly at a time of economic crisis, than in a career in the tropics. [less ▲]

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See detailFirst Vertical Land Movement Estimates on South Georgia Island: An Impact Study on Sea Level Change from Tide Gauge and Altimetry Measurements
Teferle, Felix Norman UL; Hunegnaw, Addisu UL; Abraha, Kibrom Ebuy UL et al

Poster (2017, December 11)

South Georgia Island in the Southern Atlantic Ocean has been a key location for the seismic, geomagnetic and oceanic global monitoring networks. However, no permanent geodetic monitoring station had been ... [more ▼]

South Georgia Island in the Southern Atlantic Ocean has been a key location for the seismic, geomagnetic and oceanic global monitoring networks. However, no permanent geodetic monitoring station had been established there despite the lack of observations from this region within, for example, the International GNSS Service (IGS) network of Global Navigation Satellite System (GNSS) stations. Then, in 2013 the King Edward Point (KEP) Geodetic Observatory was established with a focus on sea level studies and in support of general geoscience applications. Currently, this observatory located roughly half-way along the main island and along its northern coastline, consists of two GNSS stations (KEPA and KRSA) with local benchmark networks, allowing the height determinations from the GNSS antennas to be transferred to the KEP tide gauge (GLOSS ID 187) and forming a height reference within the International Terrestrial Reference Frame. In late 2014, three additional GNSS stations (SG01, SG02 and SG03) were established, all on small islands at the perimeter of the main island. Together the stations provide the best possible opportunity to study various geophysical processes in the region. With the GNSS-derived position time series partly reaching over 4.5 years in length, it has become possible to provide first estimates of vertical land movements for the island and KEP with its surrounding area. Together with four precise levelling campaigns of the benchmark network in 2013, 2014 and two in 2017, it has also been possible to investigate the very local character of the vertical motions, ie. the stability of the jetty upon which the tide gauge is mounted. Our measurements show that while South Georgia Island and the area around KEP are rising, the jetty and tide gauge are subsiding. In this study, we will present the preliminary results from the GNSS and levelling measurements and will discuss their impact on the sea level record from the KEP tide gauge which is ideally situated in a mid-ocean location for satellite altimetry calibration over the Southern Atlantic and Southern Oceans. [less ▲]

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See detailContinuous Improvement of complex process flows by means of StreaM
Oberhausen, Christof UL; Minoufekr, Meysam UL; Plapper, Peter UL

Presentation (2017, December 11)

In numerous sectors and industries worldwide, there is a trend towards an intercompany and often international division of value creation and related work tasks. To overcome the challenges of complex ... [more ▼]

In numerous sectors and industries worldwide, there is a trend towards an intercompany and often international division of value creation and related work tasks. To overcome the challenges of complex cross-enterprise supply chain networks, innovative approaches to visualize, assess and enhance value streams are sought. The StreaM method, which is described in this paper, enables a comprehensive analysis, design and planning of cross-company product and information flows on different levels of value stream detail. At the same time, the entire methodology is based on a common understanding of key symbols, parameters and calculation procedures. In addition, the use of the developed StreaM method and the associated model in a case study proves its practical applicability in an industrial setting. In further validation projects, the transfer of the “Standardized cross-enterprise Value Stream Management Method” to other industry sectors is envisaged to continuously improve energy, trade or service processes. [less ▲]

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See detailDes hommes ordinaires
Scuto, Denis UL

Article for general public (2017)

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See detailDiscovery and pathogenicity assessment of neuropathology-associated gene variants
Neupert, Lisa-Marie; May, Patrick UL; Kobow, Katja et al

in Epilepsia (2017, December 08), 58(Suppl.5), 174

Germline and brain-specific somatic variants have been reported as an underlying cause in patients with epilepsy-associated neuropathologies, including focal cortical dysplasias (FCDs) and long-term ... [more ▼]

Germline and brain-specific somatic variants have been reported as an underlying cause in patients with epilepsy-associated neuropathologies, including focal cortical dysplasias (FCDs) and long-term epilepsy associated tumors (LEAT). However, evaluation of identified neuropathology associated variants in genetic screens is complex since not all observed variants contribute to the etiology of neuropathologies not even in genuinely disease-associated genes. Here, we critically reevaluated the pathogenicity of 12 previously published disease-related genes and of 79 neuropathology-associated missense variants listed in the PubMed and ClinVar databases. We (1) assessed the evolutionary gene constraint using the pLI and the missense z score, (2) used the latest American College of Medical Genetics and Genomics (ACMG) guidelines, and (3) performed bioinformatic variant pathogenicity prediction analyses using PolyPhen-2, CADD and GERP. Constraint analysis classified only seven out of 12 genes to be likely disease-associated. Furthermore, 78 (89%) of 88 neuropathology-associated missense variants were classified as being of unknown significance (VUS) and only 10 (11%) as being likely pathogenic (LPII). Pathogenicity prediction yielded a discrimination between LPII variants and a discrimination for VUS compared with rare variant scores from individuals present in the Genome Aggregation Database (gnomAD). In summary, our results demonstrate that interpretation of variants associated with neuropathologies is complex while the application of current ACMG guidelines including bioinformatic pathogenicity prediction can help improving variant evaluation. Furthermore, we will augment this set of literature-identified variants at the conference by results from our variant screen using self-generated deep sequencing data in >150 candidate genes in >50 patients not yet analyzed. [less ▲]

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See detailStatic and fatigue strength of a novel anatomically contoured implant compared to five current open-wedge high tibial osteotomy plates
Diffo Kaze, Arnaud UL; Maas, Stefan UL; Belsey, James et al

in Journal of Experimental Orthopaedics (2017), 4(39),

Abstract Background The purpose of the present study was to compare the mechanical static and fatigue strength of the size 2 osteotomy plate “Activmotion” with the following five other common implants for ... [more ▼]

Abstract Background The purpose of the present study was to compare the mechanical static and fatigue strength of the size 2 osteotomy plate “Activmotion” with the following five other common implants for the treatment of medial knee joint osteoarthritis: the TomoFix small stature, the TomoFix standard, the Contour Lock, the iBalance and the second generation PEEKPower. Methods Six fourth-generation tibial bone composites underwent a medial open-wedge high tibial osteotomy (HTO), according to standard techniques, using size 2 Activmotion osteotomy plates. All bone-implant constructs were subjected to static compression load to failure and load-controlled cyclic fatigue failure testing, according to a previously defined testing protocol. The mechanical stability was investigated by considering different criteria and parameters: maximum forces, the maximum number of loading cycles, stiffness, the permanent plastic deformation of the specimens during the cyclic fatigue tests, and the maximum displacement range in the hysteresis loops of the cyclic loading responses. Results In each test, all bone-implant constructs with the size 2 Activmotion plate failed with a fracture of the lateral cortex, like with the other five previously tested implants. For the static compression tests the failure occurred in each tested implant above the physiological loading of slow walking (> 2400 N). The load at failure for the Activmotion group was the highest (8200 N). In terms of maximum load and number of cycles performed prior to failure, the size 2 Activmotion plate showed higher results than all the other tested implants except the ContourLock plate. The iBalance implant offered the highest stiffness (3.1 kN/mm) for static loading on the lateral side, while the size 2 Activmotion showed the highest stiffness (4.8 kN/mm) in cyclic loading. Conclusions Overall, regarding all of the analysed strength parameters, the size 2 Activmotion plate provided equivalent or higher mechanical stability compared to the previously tested implant. Implants with a metaphyseal slope adapted to the tibia anatomy, and positioned more anteriorly on the proximal medial side of the tibia, should provide good mechanical stability. [less ▲]

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See detailL’enseignement du chinois standard en tant que 3ème ou 4ème langue étrangère dans une classe de seconde en Alsace : le rôle de la notion de compétence plurilingue et pluriculturelle
Chen, Yan-Zhen UL

Doctoral thesis (2017)

This thesis consists of a qualitative and ethnographic research. It aims to determinate the role played by the plurilingual and pluricultural competence of a teacher and her twenty-two full beginner ... [more ▼]

This thesis consists of a qualitative and ethnographic research. It aims to determinate the role played by the plurilingual and pluricultural competence of a teacher and her twenty-two full beginner students in the context of the teaching of Chinese as a foreign language. How does this teacher interpret this notion? How can this teacher take into account and make use of her students’ previously acquired languages, i.e. their plurilingual repertoire, to facilitate her teaching? This thesis concerns not only identifying the mechanisms and the frequency of the use of the plurilingual repertoire in the teaching of standard Chinese, but also interrogating the teacher and the students’ representation. This analysis intends to seize the causes of the gap between the official discourse and instructions on one hand and the empirical teaching and learning practices on the other hand. This thesis demonstrated two significant results: the “sloganization” of the notion of plurilingual and pluricultural competence in French educative language policies and the lack of awareness of the protagonists concerning their solicitation of the plurilingual and pluricultural competence in the classroom. [less ▲]

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See detailZugangsbarrieren im Gesundheitssystem - Ein Ländervergleich
Heinz, Andreas UL

Scientific Conference (2017, December 08)

In der international vergleichenden Forschung zu Gesundheitssystemen spielt der Zugang zu Gesundheitsleistungen eine zentrale Rolle. Entsprechende Typologien klassifizieren Gesundheitssysteme u.a. danach ... [more ▼]

In der international vergleichenden Forschung zu Gesundheitssystemen spielt der Zugang zu Gesundheitsleistungen eine zentrale Rolle. Entsprechende Typologien klassifizieren Gesundheitssysteme u.a. danach, ob Patienten Zuzahlungen leisten müssen, ob sie sich bei Hausärzten einschreiben müssen und nach welchen Regeln sie einen Facharzt konsultieren können (z.B. Reibling 2010, Wendt 2009, Böhm et al 2013). In der Typologie von Wendt gehört Österreich zum „Health service provision-oriented type“, der fast der gesamten Bevölkerung einen einfachen Zugang zu Gesundheitsleistungen bei geringen Zuzahlungen und freier Arztwahl ermöglicht (2009). Diese Typologien basieren jedoch auf den gesetzlichen Zugangsregeln in einem Land, nicht auf den subjektiven Erfahrungen der Bevölkerung mit Zugangsbarrieren. Im aktuellen European Social Survey (ESS) wurde nach diesen Barrieren gefragt: Haben Befragte medizinische Behandlungen nicht bekommen und was waren die Gründe (z.B. Kosten, Behandlung nicht erhältlich, Warteliste zu lang)? Der Vortrag stellt die Ergebnisse des ESS vor und geht auf folgende Fragen ein: • Wie häufig stoßen Kranke in Österreich und in anderen europäischen Ländern auf Zugangsbarrieren? • Welche Personen in Österreich sind besonders von Zugangsbarrieren betroffen? Die vorläufigen Ergebnisse deuten darauf hin, dass es durchaus nennenswerte Zugangsbarrieren im Gesundheitssystem Österreichs gibt und dass ohnehin benachteiligte Personen häufiger als andere auf Zugangsbarrieren stoßen. Für die wissenschaftliche Theorie stellt sich die Frage, ob die gängigen Typologien von Gesundheitssystemen um die subjektiven Erfahrungen ergänzt werden müssen. Für die Praxis stellt sich die Frage, wie schädlich Zugangsbarrieren sind und wie sie abgebaut werden können. [less ▲]

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See detailThe evolution of the macrophage-specific enhancer (Fms intronic regulatory element) within the CSF1R locus of vertebrates
Hume, David; Wollscheid-Lengeling, Evi UL; Rojo, Rocio et al

in Scientific Reports (2017), 7(17115),

The Csf1r locus encodes the receptor for macrophage colony-stimulating factor, which controls the proliferation, differentiation and survival of macrophages. The 300 bp Fms intronic regulatory element ... [more ▼]

The Csf1r locus encodes the receptor for macrophage colony-stimulating factor, which controls the proliferation, differentiation and survival of macrophages. The 300 bp Fms intronic regulatory element (FIRE), within the second intron of Csf1r, is necessary and sufficient to direct macrophage-specific transcription. We have analysed the conservation and divergence of the FIRE DNA sequence in vertebrates. FIRE is present in the same location in the Csf1r locus in reptile, avian and mammalian genomes. Nearest neighbor analysis based upon this element alone largely recapitulates phylogenies inferred from much larger genomic sequence datasets. One core element, containing binding sites for AP1 family and the macrophage-specific transcription factor, PU.1, is conserved from lizards to humans. Around this element, the FIRE sequence is conserved within clades with the most conserved elements containing motifs for known myeloid-expressed transcription factors. Conversely, there is little alignment between clades outside the AP1/PU.1 element. The analysis favours a hybrid between “enhanceosome” and “smorgasbord” models of enhancer function, in which elements cooperate to bind components of the available transcription factor milieu. [less ▲]

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See detailA finite element model of the lower limb during stance phase of gait cycle including the muscle forces
Diffo Kaze, Arnaud UL; Maas, Stefan UL; Arnoux, Pierre-Jean et al

in BioMedical Engineering OnLine (2017), 16(138),

Abstract Background Results of finite element (FE) analyses can give insight into musculoskeletal diseases if physiological boundary conditions, which include the muscle forces during specific activities ... [more ▼]

Abstract Background Results of finite element (FE) analyses can give insight into musculoskeletal diseases if physiological boundary conditions, which include the muscle forces during specific activities of daily life, are considered in the finite element modelling. So far, many simplifications of the boundary conditions are currently made. This study presents an approach for FE modelling of the lower limb for which muscle forces were included. Method The stance phase of normal gait was simulated. Muscle forces were calculated using a musculoskeletal rigid body (RB) model of the human body, and were subsequently applied to a FE model of the lower limb. It was shown that the inertial forces are negligible during the stance phase of normal gait. The contact surfaces between the parts within the knee were modelled as bonded. Weak springs were attached to the distal tibia for numerical reasons. Results Hip joint reaction forces from the RB model and those from the FE model were similar in magnitude with relative differences less than 16%. The forces of the weak spring were negligible compared to the applied muscle forces. The maximal strain was 0.23% in the proximal region of the femoral diaphysis and 1.7% in the contact zone between the tibia and the fibula. Conclusions The presented approach based on FE modelling by including muscle forces from inverse dynamic analysis of musculoskeletal RB model can be used to perform analyses of the lower limb with very realistic boundary conditions. In the present form, this model can be used to better understand the loading, stresses and strains of bones in the knee area and hence to analyse osteotomy fixation devices. [less ▲]

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See detailA multi-omic view of phage-host dynamics within a mixed microbial community
Martinez Arbas, Susana UL

Presentation (2017, December 07)

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See detailOn the non-stationary generalized Langevin Equation
Meyer, Hugues UL; Voigtmann, Thomas; Schilling, Tanja

in Journal of Chemical Physics (2017), 147(21), 214110

In molecular dynamics simulations and single molecule experiments, observables are usually measured along dynamic trajectories and then averaged over an ensemble (“bundle”) of trajectories. Under ... [more ▼]

In molecular dynamics simulations and single molecule experiments, observables are usually measured along dynamic trajectories and then averaged over an ensemble (“bundle”) of trajectories. Under stationary conditions, the time-evolution of such averages is described by the generalized Langevin equation. By contrast, if the dynamics is not stationary, it is not a priori clear which form the equation of motion for an averaged observable has. We employ the formalism of time-dependent projection operator techniques to derive the equation of motion for a non-equilibrium trajectory-averaged observable as well as for its non-stationary auto-correlation function. The equation is similar in structure to the generalized Langevin equation but exhibits a time-dependent memory kernel as well as a fluctuating force that implicitly depends on the initial conditions of the process. We also derive a relation between this memory kernel and the autocorrelation function of the fluctuating force that has a structure similar to a fluctuation-dissipation relation. In addition, we show how the choice of the projection operator allows us to relate the Taylor expansion of the memory kernel to data that are accessible in MD simulations and experiments, thus allowing us to construct the equation of motion. As a numerical example, the procedure is applied to Brownian motion initialized in non-equilibrium conditions and is shown to be consistent with direct measurements from simulations. [less ▲]

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See detailVSOC - A Virtual Security Operating Center
Falk, Eric UL; Fiz Pontiveros, Beltran UL; Repcek, Stefan et al

in Global Communications (2017)

Security in virtualised environments is becoming increasingly important for institutions, not only for a firm’s own on-site servers and network but also for data and sites that are hosted in the cloud ... [more ▼]

Security in virtualised environments is becoming increasingly important for institutions, not only for a firm’s own on-site servers and network but also for data and sites that are hosted in the cloud. Today, security is either handled globally by the cloud provider, or each customer needs to invest in its own security infrastructure. This paper proposes a Virtual Security Operation Center (VSOC) that allows to collect, analyse and visualize security related data from multiple sources. For instance, a user can forward log data from its firewalls, applications and routers in order to check for anomalies and other suspicious activities. The security analytics provided by the VSOC are comparable to those of commercial security incident and event management (SIEM) solutions, but are deployed as a cloud-based solution with the additional benefit of using big data processing tools to handle large volumes of data. This allows us to detect more complex attacks that cannot be detected with todays signature-based (i.e. rules) SIEM solutions. [less ▲]

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See detailComputational Systems Biology Approach for the Study of Rheumatoid Arthritis: From a Molecular Map to a Dynamical Model
Singh, Vidisha; Ostaszewski, Marek UL; Kalliolias, George D. et al

in Genomics and Computational Biology (2017)

In this work we present a systematic effort to summarize current biological pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a detailed molecular map based on exhaustive ... [more ▼]

In this work we present a systematic effort to summarize current biological pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a detailed molecular map based on exhaustive literature scanning, strict curation criteria, re-evaluation of previously published attempts and most importantly experts’ advice. The RA map will be web-published in the coming months in the form of an interactive map, using the MINERVA platform, allowing for easy access, navigation and search of all molecular pathways implicated in RA, serving thus, as an on line knowledgebase for the disease. Moreover the map could be used as a template for Omics data visualization offering a first insight about the pathways affected in different experimental datasets. The second goal of the project is a dynamical study focused on synovial fibroblasts’ behavior under different initial conditions specific to RA, as recent studies have shown that synovial fibroblasts play a crucial role in driving the persistent, destructive characteristics of the disease. Leaning on the RA knowledgebase and using the web platform Cell Collective, we are currently building a Boolean large scale dynamical model for the study of RA fibroblasts’ activation [less ▲]

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See detailDoing interdisciplinary research with an impact: the power of case studies
de Saint-Georges, Ingrid UL

Presentation (2017, December 05)

In this CALIDIE Colloquium, I will present ‘Nexus Analysis’ an interdisciplinary approach I have been using in different projects over the years. I will show how this approach is particularly useful for ... [more ▼]

In this CALIDIE Colloquium, I will present ‘Nexus Analysis’ an interdisciplinary approach I have been using in different projects over the years. I will show how this approach is particularly useful for doing research seeking to impact the situation one studies and often implies working in partnership with researchers and practitioners from different horizons. I will discuss two examples applying this framework. The first case study will concentrate on the study of reconversion of professionals to new lines of work. The second case study will investigate reflections towards making a multilingual Higher Education programme more inclusive. Both case study presentations will be an opportunity to reflect about the conditions under which case studies might be useful from a practical and a theoretical standpoint. In closing the presentation, I hope to engage the participants in a more interactive dialogue around issues linked with inter-disciplinarity and mixed-methods approaches, theorizing, and axiomatic stances regarding values in doing science [less ▲]

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See detailBlockchain Technology - Arsenal for a Shariah-Compliant Financial Ecosystem
Lacasse, Richard-Marc; Lambert, Berthe; Khan, Nida UL

in Journal of Business and Economics (2017, December 05)

The authors’ first challenge is to decipher the complexity of Islamic Finance despite the opacity of the sector. A second focal point is the agent’s agenda; in the Islamic Finance industry, contributors ... [more ▼]

The authors’ first challenge is to decipher the complexity of Islamic Finance despite the opacity of the sector. A second focal point is the agent’s agenda; in the Islamic Finance industry, contributors mandate intermediaries (agents) to transfer their contributions to social causes according to the Shariah; in principle, Islamic financial institutions must create value for their stakeholders by offering Shariah-compliant products and services. An underlying assumption of agency theory is that agents attempt to maximize their personal welfare and compensation, but such behaviour may not always be in the best interests of other stakeholders, and an analysis of the agent’s agenda can help explain how agents can fall off the pedestal of altruism. Relationships between Islamic banks and three key stakeholders (contributors, beneficiaries and regulators) are also explored via a complexity-aware monitoring process. Contributors provide funds to an Islamic bank (agent), and in return, the agent should be accountable to the contributors, but the form and degree of accountability can vary depending on the organization’s mission. There are many unanswered questions regarding the monitoring process. One objective of the article is to consider whether agents act in the best interests of the stakeholders. Finally, the authors explore the following question: Can blockchain technology and smart contracts support and enhance the transparency feature, which is the core underlying principle of all transactions in the Islamic Finance industry? A qualitative research framework was adopted because of the constraints of the enigmatic, secretive Islamic Finance culture. [less ▲]

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