Gene Discovery in Nonsyndromic Cleft Lip with or without Cleft Palate

Nonsyndromic cleft lip with or without cleft palate (NSCLP), a common, complex orofacial birth defect that affects approximately 4,000 newborns each year in the United States, is caused by both genetic and environmental factors. Orofacial clefts affect the mouth and nose, causing severe deformity of the face, which require medical, dental and speech therapies. Despite having substantial genetic liability, less than 25% of the genetic contribute to NSCLP has been identified. The studies described in this thesis were performed to identify genes that contribute to NSCLP and to demonstrate the role of these genes in normal craniofacial development. Using genome scan and candidate gene approaches, novel associations with NSCLP were identified. These include MYH9 (7 SNPs, 0.009≤p<0.05), Wnt3A (4 SNPs, 0.001≤p≤0.005), Wnt11 (2 SNPs, 0.001≤p≤0.01) and CRISPLD2 (4 SNPs, 0.001≤p<0.05). The most interesting findings were for CRISPLD2. This gene is expressed in the fused mouse palate at E17.5. In zebrafish, crispld2 localized to the craniofacial region by one day post fertilization. Morpholino knockdown of crispld2 resulted in a lower survival rates and altered neural crest cell (NCC) clustering. Because NCCs form the tissues that populate the craniofacies, this NCC abnormality resulted in cartilage abnormalities of the jaw including fewer ceratobranchial cartilages forming the lower jaw (three pairs compared to five) and broader craniofacies compared to wild-type zebrafish. These findings suggest that the CRISPLD2 gene plays an important role in normal craniofacial development and perturbation of this gene in humans contributes to orofacial clefting. Overall, these results are important because they contribute to our understanding of normal craniofacial development and orofacial clefting etiology, information that can be used to develop better methods to diagnose, counsel and potentially treat NSCLP patients.

Knowledge transfer in software-maintenance offshore outsourcing

Software-maintenance offshore outsourcing (SMOO) projects have been plagued by tedious knowledge transfer during the service transition to the vendor. Vendor engineers risk being over-strained by the high amounts of novel information, resulting in extra costs that may erode the business case behind offshoring. Although stakeholders may desire to avoid these extra costs by implementing appropriate knowledge transfer practices, little is known on how effective knowledge transfer can be designed and managed in light of the high cognitive loads in SMOO transitions. The dissertation at hand addresses this research gap by presenting and integrating four studies. The studies draw on cognitive load theory, attributional theory, and control theory and they apply qualitative, quantitative, and simulation methods to qualitative data from eight in-depth longitudinal cases. The results suggest that the choice of appropriate learning tasks may be more central to knowledge transfer than the amount of information shared with vendor engineers. Moreover, because vendor staff may not be able to and not dare to effectively self-manage learn-ing tasks during early transition, client-driven controls may be initially required and subsequently faded out. Collectively, the results call for people-based rather than codification-based knowledge management strategies in at least moderately specific and complex software environments.

Managing Knowledge Transfer in Software-Maintenance Outsourcing Transitions: A System-Dynamics Perspective

The existing literature suggests that transitions in software-maintenance offshore outsourcing projects are prone to knowledge transfer blockades, i.e. situations in which the activities that would yield effective knowledge transfer do not occur, and that client management involvement is central to overcome them. However, the theoretical understanding of the knowledge transfer blockade is limited, and the reactive management behavior reported in case studies suggests that practitioners may frequently be astonished by the dynamics that may give rise to the blockade. Drawing on recent research from offshore sourcing and reference theories, this study proposes a system dynamics framework that may explain why knowledge transfer blockades emerge and how and why client management can overcome the blockade. The results suggest that blockades may emerge from a vicious circle of weak learning due to cognitive overload of vendor staff and resulting negative ability attributions that result in reduced helping behavior and thus aggravate cognitive load. Client management may avoid these vicious circles by selecting vendor staff with strong prior related experience. Longer phases of coexistence of vendor staff and subject matter experts and high formal and clan controls may also mitigate vicious circles.

Ethics in science: enhancing the democratisation of knowledge production in transdisciplinary research partnerships for sustainable development

Better access to knowledge and knowledge production has to be reconsidered as key to successful individual and social mitigation and adaptation strategies for global change. Indeed, concepts of sustainable development imply a transformation of science towards fostering democratisation of knowledge production and the development of knowledge societies as a strategic goal. This means to open the process of scientific knowledge production while simultaneously empowering people to implement their own visions for sustainable development. Advocates of sustainability science support this transformation. In transdisciplinary practice, they advance equity and accountability in the access to and production of knowledge at the science–society interface. UNESCO points to advancements, yet Northern dominance persists in knowledge production as well as in technology design and transfer. Further, transdisciplinary practice remains experimental and hampered by inadequate and asymmetrically equipped institutions in the North and South and related epistemological and operational obscurity. To help identify clear, practicable transdisciplinary approaches, I recommend examining the institutional route – i.e., the learning and adaptation process – followed in concrete cases. The transdisciplinary Eastern and Southern Africa Partnership Programme (1998–2013) is a case ripe for such examination. Understanding transdisciplinarity as an integrative approach, I highlight ESAPP’s three key principles for a more democratised knowledge production for sustainable development: (1) integration of scientific and “non-scientific” knowledge systems; (2) integration of social actors and institutions; and (3) integrative learning processes. The analysis reveals ESAPP’s achievements in contributing to more democratic knowledge production and South ownership in the realm of sustainable development.

Knowledge as a resource: enhancing the democratisation of knowledge production in transdisciplinary research partnerships for sustainable development

Better access to knowledge and knowledge production has to be reconsidered as key to successful individual and social mitigation and adaptation strategies for global change. Indeed, concepts of sustainable development imply a transformation of science (Lubchenco 1998; WBGU 2011 and 2012) towards fostering democratisation of knowledge production as a contribution to the development of knowledge societies as a strategic goal (UNESCO 2005). This means to open the process of scientific knowledge production while simultaneously empowering people to implement their own visions for sustainable development. Advocates of sustainability science support this transformation. In transdisciplinary practice, they advance equity and accountability in the access to and production of knowledge at the science–society interface (Hirsch Hadorn et al 2006; Hirsch Hadorn et al 2008; Jäger 2009; Adger and Jordan 2009; KFPE 2012). UNESCO (2010) points to advancements, yet Northern dominance persists in knowledge production as well as in technology design and transfer (Standing and Taylor 2007; Zingerli 2010). Further, transdisciplinary practice remains experimental and hampered by inadequate and asymmetrically equipped institutions in the North and South and related epistemological and operational obscurity (Wiesmann et al 2011). To help identify clear, practicable transdisciplinary approaches, I recommend examining the institutional route (Mukhopadhyay et al 2006) – i.e., the learning and adaptation process – followed in concrete cases. The transdisciplinary Eastern and Southern Africa Partnership Programme (1998–2013) is a case ripe for such examination. Understanding transdisciplinarity as an integrative approach (Pohl et al 2008; Stock and Burton 2011), I highlight ESAPP’s three key principles for a more democratised knowledge production for sustainable development: (1) integration of scientific and “non-scientific” knowledge systems; (2) integration of social actors and institutions; and (3) integrative learning processes. The analysis reveals ESAPP’s achievements in contributing to more democratic knowledge production and South ownership in the realm of sustainable development.

Fuzzy knowledge representation in cognitive cities

This paper gives an insight into cognitive computing for smart cities, resulting in cognitive cities. Cognitive cities and cognitive computing research with the underlying concepts of knowledge graphs and fuzzy cognitive maps are presented and supported by existing tools (i.e., IBM Watson and Google Now) and intended tools (meta-app). The paper illustrates FCM as a suiting instrument to represent information/knowledge in a city environment driven by human-technology interaction, enforcing the concept of cognitive cities. A proposed paper prototype combines the findings of the paper and shows the next step in the implementation of the proposed meta-app.

Test anxiety, self-control, and knowledge retrieval in secondary school students

Es wurde kürzlich gezeigt, dass die Stärke des Zusammenhangs zwischen Angst und Leistung von der momentan vorhandenen Selbstkontrollkraft abhängt. Wir untersuchten an einer Stichprobe aus Wirtschaftsschülern (N = 136), ob dieser Befund auf den Abruf von Wissen generalisierbar ist. Die Leistungsängstlichkeit der Teilnehmenden wurde erfasst und deren Selbstkontrollkraft experimentell manipuliert, woraufhin sie einen standardisierten Wortschatztest bearbeiteten. Während das Wissen nicht von der Leistungsängstlichkeit oder der Selbstkontrollkraft abhing, sagte die Interaktion aus beiden Variablen das gezeigte Wissen vorher. Übereinstimmend mit früheren Studien fiel die Leistung von Schülern mit niedriger Selbstkontrollkraft umso geringer aus, je leistungsängstlicher sie waren. Bei Schülern mit hoher Selbstkontrollkraft hingen die Leistungsängstlichkeit und die Wortschatzleistung hingegen nicht zusammen. Wir interpretieren dieses Muster dergestalt, dass Leistungsängstlichkeit den Wissensabruf nur dann behindert, wenn Selbstkontrolle nicht zur Kompensierung angstbezogener Aufmerksamkeitsdefizite herangezogen werden kann. Die Befunde implizieren, dass gründliche Vorbereitung keine guten Testnoten garantiert.

(Table 3) Sedimentation rates of stage 1 and last glacial maximum from different Holes during cruises of RRS Discovery in 1984-1985 and 1987-1988, and RRS James Clark Ross in 1992-1993

Within the Scotia Sea, the axis of the Antarctic Circumpolar Current (ACC) is geographically confined, and sediments therefore contain a record of palaeo-flow speed uncomplicated by ACC axis migration. We outline Holocene and Last Glacial Maximum (LGM) current-controlled sedimentation using data from 3.5-kHz profiles, cores and current meter moorings. Geophysical surveys show areas of erosion and deposition controlled by Neogene basement topography. Deposition occurs in mounded sediment drifts or flatter areas, where 500-1000 m of sediment overlies acoustic basement. 3.5-kHz profiles show parallel, continuous sub-bottom reflectors with highest sedimentation rates in the centre of the drifts, and reflectors converging towards marginal zones of non-deposition. Locally, on the flanks of continental blocks (e.g. South Georgia), downslope processes are dominant. The absence of mudwaves on the sediment drifts may result from the unsteadiness of ACC flow. A core transect from the ACC axis south to the boundary with the Weddell Gyre shows a southward decrease in biogenic content, controlled by the Polar Front and the spring sea-ice edge. Both these features lay farther north at LGM. The cores have been dated by relative abundance of the radiolarian Cycladophora davisiana, and by changes in the biogenic Ba content, a palaeoproductivity indicator. Sedimentation rates range from 3 to 17 cm/ka. The grain size of Holocene sediments shows a coarsening trend from south to north, consistent with strongest bottom-current flow near the ACC axis, though interpretation is complicated by the presence of biogenic grains. Year-long current meter records indicate mean speeds from 7 cm/s in the south to 12 cm/s in the north, with benthic storm frequency increasing northwards. LGM sediments are predominantly terrigenous and show a clearer northward-coarsening trend, with well-sorted silts in the northern Scotia Sea. Assuming a constant terrigenous source, this implies stronger ACC flow at the LGM, contrasting with weaker Weddell Gyre flow deduced from earlier work.

Knowledge spillover in Indian automobile industry : the process and the coverage

In India, as the production of passenger cars increased, many local small and medium enterprises (SMEs) entered the parts and components manufacturing sector. The sources of knowledge for large enterprises and SMEs are different. Naturally, spillover effects among large enterprises and between large enterprises and SMEs are different. This paper focuses on knowledge spillover among large enterprises and from large enterprises to SMEs. Subcontractor can absorb relation-specific skills through repeated interaction with parent company. The results of field survey emphasizes that relation-specific skills are a determinant factor of spillover effects from assemblers and large auto component manufacturers to SMEs. Econometric analysis shows that spillover effects among medium and large automobile units and from medium and large automobile units to small units went beyond boundary of cluster.

Knowledge pipeline in freight pipeline industry: competence- based model for open innovation

There is growing concern over the challenges for innovation in Freight Pipeline industry. Since the early works of Chesbrough a decade ago, we have learned a lot about the content, context and process of open innovation. However, much more research is needed in Freight Pipeline Industry. The reality is that few corporations have institutionalized open innovation practices in ways that have enabled substantial growth or industry leadership. Based on this, we pursue the following question: How does a firm’s integration into knowledge networks depend on its ability to manage knowledge? A competence-based model for freight pipeline organizations is analysed, this model should be understood by any organization in order to be successful in motivating professionals who carry out innovations and play a main role in collaborative knowledge creation processes. This paper aims to explain how can open innovation achieve its potential in most Freight Pipeline Industries.