Secondary metabolites in Gerbera hybrida

Plants produce a diversity of secondary metabolites, i.e., low-molecular-weight compounds that have primarily ecological functions in plants. The flavonoid pathway is one of the most studied biosynthetic pathways in plants. In order to understand biosynthetic pathways fully, it is necessary to isolate and purify the enzymes of the pathways to study individual steps and to study the regulatory genes of the pathways. Chalcone synthases are key enzymes in the formation of several groups of flavonoids, including anthocyanins. In this study, a new chalcone synthase enzyme (GCHS4), which may be one of the main contributors to flower colour, was characterised from the ornamental plant Gerbera hybrida. In addition, four chalcone synthase-like genes and enzymes (GCHS17, GCHS17b, GCHS26 and GCHS26b) were studied. Spatial expression of the polyketide synthase gene family in gerbera was also analysed with quantitative RT-PCR from 12 tissues, including several developmental stages and flower types. A previously identified MYB transcription factor from gerbera, GMYB10, which regulates the anthocyanin pathway, was transferred to gerbera and the phenotypes were analysed. Total anthocyanin content and anthocyanidin profiles of control and transgenic samples were compared spectrophotometrically and with HPLC. The overexpression of GMYB10 alone was able to change anthocyanin pigmentation: cyanidin pigmentation was induced and pelargonidin pigmentation was increased. The gerbera 9K cDNA microarray was used to compare the gene expression profiles of transgenic tissues against the corresponding control tissues to reveal putative target genes for GMYB10. GMYB10 overexpression affected the expression of both early and late biosynthetic genes in anthocyanin-accumulating transgenic tissues, including the newly isolated gene GCHS4. Two new MYB domain factors, named as GMYB11 and GMYB12, were also upregulated. Gene transfer is not only a powerful tool for basic research, but also for plant breeding. However, crop improvement by genetic modification (GM) remains controversial, at least in Europe. Many of the concerns relating to both human health and to ecological impacts relate to changes in the secondary metabolites of GM crops. In the second part of this study, qualitative and quantitative differences in cytotoxicity and metabolic fingerprints between 225 genetically modified Gerbera hybrida lines and 42 non-GM Gerbera varieties were compared. There was no evidence for any major qualitative and quantitative changes between the GM lines and non-GM varieties. The developed cell viability assays offer also a model scheme for cell-based cytotoxicity screening of a large variety of GM plants in standardized conditions.

Novel Molecular Mechanisms of Arabidopsis Disease Resistance

Plants are capable of recognizing phytopathogens through the perception of pathogen-derived molecules or plant cell-wall degradation products due to the activities of pathogen-secreted enzymes. Such elicitor recognition events trigger an array of inducible defense responses involving signal transduction networks and massive transcriptional re-programming. The outcome of a pathogen infection relies on the balance between different signaling pathways, which are integrated by regulatory proteins. This thesis characterized two key regulatory components: a damage control enzyme, chlorophyllase 1 (AtCHL1), and a transcription factor, WRKY70. Their roles in defense signaling were then investigated. The Erwinia-derived elicitors rapidly activated the expression of AtCLH1 and WRKY70 through different signaling pathways. The expression of the AtCHL1 gene was up-regulated by jasmonic acid (JA) but down-regulated by salicylic acid (SA), whereas WRKY70 was activated by SA and repressed by JA. In order to elucidate the functions of AtCLH1 and WRKY70 in plant defense, stable transgenic lines were produced where these genes were overexpressed or silenced. Additionally, independent knockout lines were also characterized. Bacterial and fungal pathogens were then used to assess the contribution of these genes to the Arabidopsis disease resistance. The transcriptional modulation of AtCLH1 by either the constitutive over-expression or RNAi silencing caused alterations in the chlorophyll-to-chlorophyllide ratio, supporting the claim that chlorophyllase 1 has a role in the chlorophyll degradation pathway. Silencing of this gene led to light-dependent over-accumulation of the reactive oxygen species (ROS) in response to infection by Erwinia carotovora subsp. carotovora SCC1. This was followed by an enhanced induction of SA-dependent defense genes and an increased resistance to this pathogen. Interestingly, little effect on the pathogen-induced SA accumulation at the early infection was observed, suggesting that action of ROS might potentiate SA signaling. In contrast, the pathogen-induced JA production was significantly reduced in the RNAi silenced plants. Moreover, JA signaling and resistance to Alternaria brassicicola were impaired. These observations provide support for the argument that the ROS generated in chloroplasts might have a negative impact on JA signaling. The over-expression of WRKY70 resulted in an enhanced resistance to E. carotovora subsp. carotovora SCC1, Pseudomonas syringae pv. tomato DC3000 and Erysiphe cichoracearum UCSC1, whilst an antisense suppression or an insertional inactivation of WRKY70 led to a compromised resistance to E. carotovora subsp. carotovora SCC1 and to E. cichoracearum UCSC1 but not to P. syringae pv. tomato DC3000. Gene expression analysis revealed that WRKY70 activated many known defense-related genes associated with the SAR response but suppressed a subset of the JA-responsive genes. In particular, I was able to show that both the basal and the induced expression of AtCLH1 was enhanced by the antisense silencing or the insertional inactivation of WRKY70, whereas a reduction in AtCLH1 expression was observed in the WRKY70 over-expressors following an MeJA application or an A. brassicicola infection. Moreover, the SA-induced suppression of AtCLH1 was relieved in wrky70 mutants. These results indicate that WRKY70 down-regulates AtCLH1. An epistasis analysis suggested that WRKY70 functions downstream of the NPR1 in an SA-dependent signaling pathway. When challenged with A. brassicicola, WRKY70 over-expressing plants exhibited a compromised disease resistance while wrky70 mutants had the opposite effect. These results confirmed the WRKY70-mediated inhibitory effects on JA signaling. Furthermore, the WRKY70-controlled suppression of A. brassicicola resistance was mainly through an NPR1-dependent mechanism. Taking all the data together, I suggest that the pathogen-responsive transcription factor WRKY70 is a common component in both SA- and JA-dependent pathways and plays a crucial role in the SA-mediated suppression of JA signaling.

Suppression of the zero-order term in off-axis digital holography through nonlinear filtering

We present experimental validation of a new reconstruction method for off-axis digital holographic microscopy (DHM). This method effectively suppresses the object autocorrelation,namely, the zero-order term,from holographic data,thereby improving the reconstruction bandwidth of complex wavefronts. The algorithm is based on nonlinear filtering and can be applied to standard DHM setups with realistic recording conditions.We study the robustness of the technique under different experimental configurations,and quantitatively demonstrate its enhancement capabilities on phase signals.

Induced higher-order aberrations after laser in situ keratomileusis (LASIK) performed with wavefront-guided IntraLase femtosecond laser in moderate to high astigmatism

Background Wavefront-guided Laser-assisted in situ keratomileusis (LASIK) is a widespread and effective surgical treatment for myopia and astigmatic correction but whether it induces higher-order aberrations remains controversial. The study was designed to evaluate the changes in higher-order aberrations after wavefront-guided ablation with IntraLase femtosecond laser in moderate to high astigmatism. Methods Twenty-three eyes of 15 patients with moderate to high astigmatism (mean cylinder, −3.22 ± 0.59 dioptres) aged between 19 and 35 years (mean age, 25.6 ± 4.9 years) were included in this prospective study. Subjects with cylinder ≥ 1.5 and ≤2.75 D were classified as moderate astigmatism while high astigmatism was ≥3.00 D. All patients underwent a femtosecond laser–enabled (150-kHz IntraLase iFS; Abbott Medical Optics Inc) wavefront-guided ablation. Uncorrected (UDVA), corrected (CDVA) distance visual acuity in logMAR, keratometry, central corneal thickness (CCT) and higher-order aberrations (HOAs) over a 6 mm pupil, were assessed before and 6 months, postoperatively. The relationship between postoperative change in HOA and preoperative mean spherical equivalent refraction, mean astigmatism, and postoperative CCT were tested. Results At the last follow-up, the mean UDVA was increased (P < 0.0001) but CDVA remained unchanged (P = 0.48) and no eyes lost ≥2 lines of CDVA. Mean spherical equivalent refraction was reduced (P < 0.0001) and was within ±0.50 D range in 61 % of eyes. The average corneal curvature was flatter by 4 D and CCT was reduced by 83 μm (P < 0.0001, for all), postoperatively. Coma aberrations remained unchanged (P = 0.07) while the change in trefoil (P = 0.047) postoperatively, was not clinically significant. The 4th order HOAs (spherical aberration and secondary astigmatism) and the HOA root mean square (RMS) increased from −0.18 ± 0.07 μm, 0.04 ± 0.03 μm and 0.47 ± 0.11 μm, preoperatively, to 0.33 ± 0.19 μm (P = 0.004), 0.21 ± 0.09 μm (P < 0.0001) and 0.77 ± 0.27 μm (P < 0.0001), six months postoperatively. The change in spherical aberration after the procedure increased with an increase in the degree of preoperative myopia. Conclusions Wavefront-guided IntraLASIK offers a safe and effective option for vision and visual function improvement in astigmatism. Although, reduction of HOA is possible in a few eyes, spherical-like aberrations are increased in majority of the treated eyes.

Neuromagnetic studies on cortical somatosensory functions in infants and children : Normal development and effect of early brain lesions

Until recently, objective investigation of the functional development of the human brain in vivo was challenged by the lack of noninvasive research methods. Consequently, fairly little is known about cortical processing of sensory information even in healthy infants and children. Furthermore, mechanisms by which early brain insults affect brain development and function are poorly understood. In this thesis, we used magnetoencephalography (MEG) to investigate development of cortical somatosensory functions in healthy infants, very premature infants at risk for neurological disorders, and adolescents with hemiplegic cerebral palsy (CP). In newborns, stimulation of the hand activated both the contralateral primary (SIc) and secondary somatosensory cortices (SIIc). The activation patterns differed from those of adults, however. Some of the earliest SIc responses, constantly present in adults, were completely lacking in newborns and the effect of sleep stage on SIIc responses differed. These discrepancies between newborns and adults reflect the still developmental stage of the newborns’ somatosensory system. Its further maturation was demonstrated by a systematic transformation of the SIc response pattern with age. The main early adult­like components were present by age two. In very preterm infants, at term age, the SIc and SIIc were activated at similar latencies as in healthy fullterm newborns, but the SIc activity was weaker in the preterm group. The SIIc response was absent in four out of the six infants with brain lesions of the underlying hemisphere. Determining the prognostic value of this finding remains a subject for future studies, however. In the CP adolescents with pure subcortical lesions, contrasting their unilateral symptoms, the SIc responses of both hemispheres differed from those of controls: For example the distance between SIc representation areas for digits II and V was shorter bilaterally. In four of the five CP patients with cortico­subcortical brain lesions, no normal early SIc responses were evoked by stimulation of the palsied hand. The varying differences in neuronal functions, underlying the common clinical symptoms, call for investigation of more precisely designed rehabilitation strategies resting on knowledge about individual functional alterations in the sensorimotor networks.

An investigation of first-order transition across charge ordered and ferromagnetic phases in Gd0.5Sr0.5MnO3 single crystals by magnetic and magnetotransport studies

Gadolinium strontium manganite single crystals of the composition Gd0.5Sr0.5MnO3 were grown using the optical float zone method. We report here the magnetic and magnetotransport properties of these crystals. A large magnetoresistance similar to 10(9)% was observed at 45 K under the application of a 110 kOe field. We have observed notable thermomagnetic anomalies such as open hysteresis loops across the broadened first-order transition between the charge order insulator and the ferromagnetic metallic phase while traversing the magnetic field-temperature (H-T) plane isothermally or isomagnetically. In order to discern the cause of these observed anomalies, the H-T phase diagram for Gd0.5Sr0.5MnO3 is formulated using the magnetization-field (M-H), magnetization-temperature (M-T) and resistance-temperature (R-T) measurements. The temperature dependence of the critical field (i.e. H-up, the field required for transformation to the ferromagnetic metallic phase) is non-monotonic. We note that the non-monotonic variation of the supercooling limit is anomalous according to the classical concepts of the first-order phase transition. Accordingly, H-up values below similar to 20 K are unsuitable to represent the supercooling limit. It is possible that the nature of the metastable states responsible for the observed open hysteresis loops is different from that of the supercooled ones.

IASDR 2015 Interplay Exhibition 2-5 NOV 2015

It has been said that we are living in a golden age of innovation. New products, systems and services aimed to enable a better future, have emerged from novel interconnections between design and design research with science, technology and the arts. These intersections are now, more than ever, catalysts that enrich daily activities for health and safety, education, personal computing, entertainment and sustainability, to name a few. Interactive functions made possible by new materials, technology, and emerging manufacturing solutions demonstrate an ongoing interplay between cross-disciplinary knowledge and research. Such interactive interplay bring up questions concerning: (i) how art and design provide a focus for developing design solutions and research in technology; (ii) how theories emerging from the interactions of cross-disciplinary knowledge inform both the practice and research of design and (iii) how research and design work together in a mutually beneficial way. The IASDR2015 INTERPLAY EXHIBITION provides some examples of these interconnections of design research with science, technology and the arts. This is done through the presentation of objects, artefacts and demonstrations that are contextualised into everyday activities across various areas including health, education, safety, furniture, fashion and wearable design. The exhibits provide a setting to explore the various ways in which design research interacts across discipline knowledge and approaches to stimulate innovation. In education, Designing South African Children’s Health Education as Generative Play (A Bennett, F Cassim, M van der Merwe, K van Zijil, and M Ribbens) presents a set of toolkits that resulted from design research entailing generative play. The toolkits are systems that engender pleasure and responsibility, and are aimed at cultivating South African’s youth awareness of nutrition, hygiene, disease awareness and prevention, and social health. In safety, AVAnav: Avalanche Rescue Helmet (Jason Germany) delivers an interactive system as a tool to contribute to reduce the time to locate buried avalanche victims. Helmet-mounted this system responds to the contextual needs of rescuers and has since led to further design research on the interface design of rescuing devices. In apparel design and manufacturing, Shrinking Violets: Fashion design for disassembly (Alice Payne) proposes a design for disassembly through the use of beautiful reversible mono-material garments that interactively responds to the challenges of garment construction in the fashion industry, capturing the metaphor for the interplay between technology and craft in the fashion manufacturing industry. Harvest: A biotextile future (Dean Brough and Alice Payne), explores the interplay of biotechnology, materiality and textile design in the creation of sustainable, biodegradable vegan textile through the process of a symbiotic culture of bacteria and yeast (SCOBY). SCOBY is a pellicle curd that can be harvested, machine washed, dried and cut into a variety of designs and texture combinations. The exploration of smart materials, wearable design and micro-electronics led to creative and aesthetically coherent stimulus-reactive jewellery; Symbiotic Microcosms: Crafting Digital Interaction (K Vones). This creation aims to bridge the gap between craft practitioner and scientific discovery, proposing a move towards the notion of a post-human body, where wearable design is seen as potential ground for new human-computer interactions, affording the development of visually engaging multifunctional enhancements. In furniture design, Smart Assistive chair for older adults (Chao Zhao) demonstrates how cross-disciplinary knowledge interacting with design strategies provide solution that employed new technological developments in older aged care, and the participation of multiple stakeholders: designers, health care system and community based health systems. In health, Molecular diagnosis system for newborns deafness genetic screening (Chao Zhao) presents an ambitious and complex project that includes a medical device aimed at resolving a number of challenges: technical feasibility for city and rural contexts, compatibility with standard laboratory and hospital systems, access to health system, and support the work of different hospital specialists. The interplay between cross-disciplines is evident in this work, demonstrating how design research moves forward through technology developments. These works exemplify the intersection between domains as a means to innovation. Novel design problems are identified as design intersects with the various areas. Research informs this process, and in different ways. We see the background investigation into the contextualising domain (e.g. on-snow studies, garment recycling, South African health concerns, the post human body) to identify gaps in the area and design criteria; the technologies and materials reviews (e.g. AR, biotextiles) to offer plausible technical means to solve these, as well as design criteria. Theoretical reviews can also inform the design (e.g. play, flow). These work together to equip the design practitioner with a robust set of ‘tools’ for design innovation – tools that are based in research. The process identifies innovative opportunity and criteria for design and this, in turn, provides a means for evaluating the success of the design outcomes. Such an approach has the potential to come full circle between research and design – where the design can function as an exemplar, evidencing how the research-articulated problems can be solved. Core to this, however, is the evaluation of the design outcome itself and identifying knowledge outcomes. In some cases, this is fairly straightforward that is, easily measurable. For example the efficacy of Jason Germany’s helmet can be determined by measuring the reduced response time in the rescuer. Similarly the improved ability to recycle Payne’s panel garments can be clearly determined by comparing it to those recycling processes (and her identified criteria of separating textile elements!); while the sustainability and durability of the Brough & Payne’s biotextile can be assessed by documenting the growth and decay processes, or comparative strength studies. There are however situations where knowledge outcomes and insights are not so easily determined. Many of the works here are open-ended in their nature, as they emphasise the holistic experience of one or more designs, in context: “the end result of the art activity that provides the health benefit or outcome but rather, the value lies in the delivery and experience of the activity” (Bennet et al.) Similarly, reconfiguring layers of laser cut silk in Payne’s Shrinking Violets constitutes a customisable, creative process of clothing oneself since it “could be layered to create multiple visual effects”. Symbiotic Microcosms also has room for facilitating experience, as the work is described to facilitate “serendipitous discovery”. These examples show the diverse emphasis of enquiry as on the experience versus the product. Open-ended experiences are ambiguous, multifaceted and differ from person to person and moment to moment (Eco 1962). Determining the success is not always clear or immediately discernible; it may also not be the most useful question to ask. Rather, research that seeks to understand the nature of the experience afforded by the artefact is most useful in these situations. It can inform the design practitioner by helping them with subsequent re-design as well as potentially being generalizable to other designers and design contexts. Bennett et. al exemplify how this may be approached from a theoretical perspective. This work is concerned with facilitating engaging experiences to educate and, ultimately impact on that community. The research is concerned with the nature of that experience as well, and in order to do so the authors have employed theoretical lenses – here these are of flow, pleasure, play. An alternative or complementary approach to using theory, is using qualitative studies such as interviews with users to ask them about what they experienced? Here the user insights become evidence for generalising across, potentially revealing insight into relevant concerns – such as the range of possible ‘playful’ or experiences that may be afforded, or the situation that preceded a ‘serendipitous discovery’. As shown, IASDR2015 INTERPLAY EXHIBITION provides a platform for exploration, discussion and interrogation around the interplay of design research across diverse domains. We look forward with excitement as IASDR continues to bring research and design together, and as our communities of practitioners continue to push the envelope of what is design and how this can be expanded and better understood with research to foster new work and ultimately, stimulate innovation.

Beyond fractional derivatives: local approximation of other convolution integrals

Dynamic systems involving convolution integrals with decaying kernels, of which fractionally damped systems form a special case, are non-local in time and hence infinite dimensional. Straightforward numerical solution of such systems up to time t needs O(t(2)) computations owing to the repeated evaluation of integrals over intervals that grow like t. Finite-dimensional and local approximations are thus desirable. We present here an approximation method which first rewrites the evolution equation as a coupled in finite-dimensional system with no convolution, and then uses Galerkin approximation with finite elements to obtain linear, finite-dimensional, constant coefficient approximations for the convolution. This paper is a broad generalization, based on a new insight, of our prior work with fractional order derivatives (Singh & Chatterjee 2006 Nonlinear Dyn. 45, 183-206). In particular, the decaying kernels we can address are now generalized to the Laplace transforms of known functions; of these, the power law kernel of fractional order differentiation is a special case. The approximation can be refined easily. The local nature of the approximation allows numerical solution up to time t with O(t) computations. Examples with several different kernels show excellent performance. A key feature of our approach is that the dynamic system in which the convolution integral appears is itself approximated using another system, as distinct from numerically approximating just the solution for the given initial values; this allows non-standard uses of the approximation, e. g. in stability analyses.

VIBRANTe 2.0

ARTIST STATEMENT VIBRANTe 2.0 was inspired by a research project for Parkinson’s disease patients aimed at developing a wearable device to collect relevant data for patients and medical health professionals. Vibrante is a Spanish word that translates to vibrant; literally meaning shaking or vibrations. Vibrante also has a dual meaning including vibrancy, energy, activity, and liveliness. Parkinson’s can be a debilitating disease, but it does not mean the person has to lose energy, activeness or vibrancy. As technology moves from being worn to becoming implantable and completely hidden within the body, the very notion of its physicality becomes difficult to grasp. While the human body hides implantable technology, VIBRANTe 2.0 intentionally hides the human body by making it invisible to reveal the technology stitched within. Wires become veins, delivering lifeblood to the technology inside, allowing it to pulsate and exist, while motherboards become networked hubs by which information is transferred through and within the body, performing functions that mirror and often surpass human performance capabilities. Ultimately, VIBRANTe 2.0 seeks to prompt the viewer to reflect on the potential ramifications of the complete immersion of technology into the human body. CONTEXT Technology is increasingly penetrating all aspects of our environment, and the rapid uptake of devices that live near, on or in our bodies is facilitating radical new ways of working, relating and socialising. Such technology, with its capacity to generate previously unimaginable levels of data, offers the potential to provide life-augmenting levels of interactivity. However, the absorption of technology into the very fabric of clothes, accessories and even bodies begins to dilute boundaries between physical, technological and social spheres, generating genuine ethical and privacy concerns and potentially having implications for human evolution. Embedding technology into the fabric of our clothes, accessories, and even the body enable the acquisition of and the connection to vast amounts of data about people and environments in order to provide life-augmenting levels of interactivity. Wearable sensors for example, offer the potential for significant benefits in the future management of our wellbeing. Fitness trackers such as ‘Fitbit’ and ‘Garmen’ provide wearers with the ability to monitor their personal fitness indicators while other wearables provide healthcare professionals with information that improves diagnosis and observation of medical conditions. This exhibition aimed to illustrate this shifting landscape through a selection of experimental wearable and interactive works by local, national and international artists and designers. The exhibition will also provide a platform for broader debate around wearable technology, our mediated future-selves and human interactions in this future landscape. EXHIBITION As part of Artisan’s Wearnext exhibition, the work was on public display from 25 July to 7 November 2015 and received the following media coverage: [Please refer to Additional URLs]

Recognition and alignment of homologous DNA sequences between minichromosomes and single-stranded DNA promoted by RecA protein

The incorporation of DNA into nucleosomes and higher-order forms of chromatin in vivo creates difficulties with respect to its accessibility for cellular functions such as transcription, replication, repair and recombination. To understand the role of chromatin structure in the process of homologous recombination, we have studied the interaction of nucleoprotein filaments, comprised of RecA protein and ssDNA, with minichromosomes. Using this paradigm, we have addressed how chromatin structure affects the search for homologous DNA sequences, and attempted to distinguish between two mutually exclusive models of DNA-DNA pairing mechanisms. Paradoxically, we found that the search for homologous sequences, as monitored by unwinding of homologous or heterologous duplex DNA, was facilitated by nucleosomes, with no discernible effect on homologous pairing. More importantly, unwinding of minichromosomes required the interaction of nucleoprotein filaments and led to the accumulation of circular duplex DNA sensitive to nuclease P1. Competition experiments indicated that chromatin templates and naked DNA served as equally efficient targets for homologous pairing. These and other findings suggest that nucleosomes do not impede but rather facilitate the search for homologous sequences and establish, in accordance with one proposed model, that unwinding of duplex DNA precedes alignment of homologous sequences at the level of chromatin. The potential application of this model to investigate the role of chromosomal proteins in the alignment of homologous sequences in the context of cellular recombination is considered.

Genetic background of bipolar disorder and related cognitive impairments

Bipolar disorder (BP) is a complex psychiatric disorder characterized by episodes of mania and depression. BP affects approximately 1% of the world’s population and shows no difference in lifetime prevalence between males and females. BP arises from complex interactions among genetic, developmental and environmental factors, and it is likely that several predisposing genes are involved in BP. The genetic background of BP is still poorly understood, although intensive and long-lasting research has identified several chromosomal regions and genes involved in susceptibility to BP. This thesis work aims to identify the genetic variants that influence bipolar disorder in the Finnish population by candidate gene and genome-wide linkage analyses in families with many BP cases. In addition to diagnosis-based phenotypes, neuropsychological traits that can be seen as potential endophenotypes or intermediate traits for BP were analyzed. In the first part of the thesis, we examined the role of the allelic variants of the TSNAX/DISC1 gene cluster to psychotic and bipolar spectrum disorders and found association of distinct allelic haplotypes with these two groups of disorders. The haplotype at the 5’ end of the Disrupted-in-Schizophrenia-1 gene (DISC1) was over-transmitted to males with psychotic disorder (p = 0.008; for an extended haplotype p = 0.0007 with both genders), whereas haplotypes at the 3’ end of DISC1 associated with bipolar spectrum disorder (p = 0.0002; for an extended haplotype p = 0.0001). The variants of these haplotypes also showed association with different cognitive traits. The haplotypes at the 5’ end associated with perseverations and auditory attention, while the variants at the 3’ end associated with several cognitive traits including verbal fluency and psychomotor processing speed. Second, in our complete set of BP families with 723 individuals we studied six functional candidate genes from three distinct signalling systems: serotonin-related genes (SLC6A4 and TPH2), BDNF -related genes (BDNF, CREB1 and NTRK2) and one gene related to the inflammation and cytokine system (P2RX7). We replicated association of the functional variant Val66Met of BDNF with BP and better performance in retention. The variants at the 5’ end of SLC6A4 also showed some evidence of association among males (p = 0.004), but the widely studied functional variants did not yield any significant results. A protective four-variant haplotype on P2RX7 showed evidence of association with BP and executive functions: semantic and phonemic fluency (p = 0.006 and p = 0.0003, respectively). Third, we analyzed 23 bipolar families originating from the North-Eastern region of Finland. A genome-wide scan was performed using the 6K single nucleotide polymorphism (SNP) array. We identified susceptibility loci at chromosomes 7q31 with a LOD score of 3.20 and at 9p13.1 with a LOD score of 4.02. We followed up both linkage findings in the complete set of 179 Finnish bipolar families. The finding on chromosome 9p13 was supported (maximum LOD score of 3.02), but the susceptibility gene itself remains unclarified. In the fourth part of the thesis, we wanted to test the role of the allelic variants that have associated with bipolar disorder in recent genome-wide association studies (GWAS). We could confirm findings for the DFNB31, SORCS2, SCL39A3, and DGKH genes. The best signal in this study comes from DFNB31, which remained significant after multiple testing corrections. Two variants of SORCS2 were allelic replications and presented the same signal as the haplotype analysis. However, no association was detected with the PALB2 gene, which was the most significantly associated region in the previous GWAS. Our results indicate that BP is heterogeneous and its genetic background may accordingly vary in different populations. In order to fully understand the allelic heterogeneity that underlies common diseases such as BP, complete genome sequencing for many individuals with and without the disease is required. Identification of the specific risk variants will help us better understand the pathophysiology underlying BP and will lead to the development of treatments with specific biochemical targets. In addition, it will further facilitate the identification of environmental factors that alter risk, which will potentially provide improved occupational, social and psychological advice for individuals with high risk of BP.

Supporting knowledge-intensive construction management tasks in BIM

The delivery of products and services for construction-based businesses is increasingly becoming knowledge-driven and information-intensive. The proliferation of building information modelling (BIM) has increased business opportunities as well as introduced new challenges for the architectural, engineering and construction and facilities management (AEC/FM) industry. As such, the effective use, sharing and exchange of building life cycle information and knowledge management in building design, construction, maintenance and operation assumes a position of paramount importance. This paper identifies a subset of construction management (CM) relevant knowledge for different design conditions of building components through a critical, comprehensive review of synthesized literature and other information gathering and knowledge acquisition techniques. It then explores how such domain knowledge can be formalized as ontologies and, subsequently, a query vocabulary in order to equip BIM users with the capacity to query digital models of a building for the retrieval of useful and relevant domain-specific information. The formalized construction knowledge is validated through interviews with domain experts in relation to four case study projects. Additionally, retrospective analyses of several design conditions are used to demonstrate the soundness (realism), completeness, and appeal of the knowledge base and query-based reasoning approach in relation to the state-of-the-art tools, Solibri Model Checker and Navisworks. The knowledge engineering process and the methods applied in this research for information representation and retrieval could provide useful mechanisms to leverage BIM in support of a number of knowledge intensive CM/FM tasks and functions.

Charge-order-driven multiferroic properties of Y1-xCaxMnO3

Dielectric measurements on the charge-ordered insulators, Y1-xCaxMnO3 (x = 0.4. 0.45 and 0.5), show maxima in the dielectric constant around the charge ordering transition temperature while magnetic measurements show the presence of weak ferromagnetic interactions at low temperatures. Besides the magnetic field dependence of the dielectric constant, these manganites also exhibit second harmonic generation. Thus, the charge-ordered Y1-xCaxMnO3 compositions are multiferroic and magnetoelectric, in accordance with theoretical predictions. Magnetoelectric properties are retained in small particles of Y0.5Ca0.5MnO3. (C) 2008 Elsevier Ltd. All rights reserved.