LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS: The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS: The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.

The effects of inter-crop cultivation Between rows of citrus crop on spreading of Guignardia citricarpa Ascospores and in the citrus black spot occurrence

This study highlighted the effect of planting coast-cross grass and forage peanut cv. Amarilis between rows of Natal oranges on spreading of Guignardia citricarpa ascospores and consequent citrus black spot control. Treatments evaluated were: 1- conventional cultivation, free of fungicides; 2- conventional cultivation, using protective fungicides; 3- inter-crop cultivation of coast-cross grass between rows of citrus crops and; 4- inter-cropping cultivation of forage peanut between the rows of citrus crops. Quest Volumetric Spore SystemTM traps were set in order to determine the number of ascospores released. A total of 33 inspections were conducted weekly, from the end of August until early September the following year. A diagrammatic scale was used to determine the severity of the disease as well as the percentage of fruits having a commercial standard. The coast-cross grass was more effective in reducing the number of ascospores produced, whose average statistics were lower than in the conventional treatments, free-fungicides. The inter-crop and conventional cultivation method coupled with fungicide treatment was more effective in reducing the severity of citrus black spot symptoms, and differs statistically from the fungicide-free control method. These methods also resulted in a higher percentage of fruits of a commercial standard, ranging from the 89% through the 91% percentile, and the cultivation, free of fungicides, fell within the 73%.

Heterosis in papaya: inter and intragroup analysis

Papaya (Carica papaya L.) is a typical crop of tropical areas, and Brazil is one of the leading world producers. In recent decades, papaya culture has expanded to different regions of the country, but the number of cultivars available is still limited. In the present study, a complete diallel cross was carried out using eight accessions of papaya from the UENF/Caliman germplasm bank. Four genotypes belong to the Formosa heterotic group and four, to the Solo group. This study aimed to evaluate the occurrence and viability of exploring heterosis in heterotic intragroup hybrids. Fifty-six hybrid progenies were generated and evaluated. Among the Formosa intragroup hybrids, two hybrid combinations (MR x J4 and MR x SK) showed heterosis for all traits, as well as good average total fruit production. Among the Solo intragroup hybrids, three hybrid combinations (WM x GG, WM x SS and WM x SM) stand out for fruit production and high content of soluble solids. In Formosa x Solo hybrids, all hybrid combinations with the parent JS (JS x WM, JS x GG, JS x SS and JS x SM) showed high fruit quality and good average for fruit production. The heterotic profile of the hybrids tested allowed the identification of promising hybrids within Formosa and Solo heterotic groups. The analysis of the canonical variables also allowed the visualization of distinct groups of hybrids, depending on the provenance of the parents.

VARIABILIDAD GENÉTICA DE PARENTALES Y POBLACIONES F1 INTER E INTRAESPECÍFICAS DE Physalis peruviana L. Y P. floridana Rydb.

RESUMENLa uchuva, Physalis peruviana, es un frutal andino de importancia para la exportación; el principal limitante de su producción en Colombia es el marchitamiento vascular ocasionado por Fusarium oxysporum. En el presente trabajo se propuso generar poblaciones F1 entre parentales contrastantes por su respuesta a éste patógeno y evaluarlas molecularmente como apoyo al conocimiento y uso de los recursos genéticos de la especie. Para ello, cuatro genotipos de P. peruviana y uno de la especie relacionada P. floridana, fueron caracterizados a nivel morfo-agronómico empleando 34 variables cualitativas y 20 cuantitativas, y a nivel molecular con 328 marcadores tipoCOSII y 154 IRGs. Dichos genotipos se utilizaron como parentales para la generación y caracterización molecular de poblaciones F1. Las variables cuantitativas permitieron diferenciar las especies P. floridana y P. peruviana así como genotipos cultivados y silvestres dentro de P. peruviana. Se encontró un 100% de viabilidad en cruces F1 intraespecíficos y un 50% en interespecíficos, siendo viables aquellos donde P. floridana fue receptor de polen. A nivel molecular no se identificaron polimorfismos dentro de P. peruviana pero sí entre P. floridana y P. Peruviana. En una población F1 de 51 individuos generada entre las especies se encontró un total de 127 alelos con un promedio de 3,18 por locus, un PIC de 0,358 y altos valores de heterocigocidad (Ho: 0,737 y He: 0,449). Los análisis de PCA y agrupamiento permitieron discriminar la población F1 en tres grupos, en su mayoría con mayor similitud al parental P. floridana. Lo anterior se reflejó en una distorsión mendeliana del 75% favorecida por la presencia de un 63,75% de alelos maternos. El estudio aporta conocimiento sobre la cruzabilidad en uchuva y la variabilidad genética de genotipos parentales y poblaciones F1.

HIBRIDAÇÕES CONTROLADAS INTER E INTRAESPECÍFICAS PARA O MELHORAMENTO GENÉTICO DE PORTA-ENXERTOS DE PEREIRA

RESUMO O objetivo da pesquisa foi a averiguação da compatibilidade de pólen em pereira com marmeleiro (hibridações interespecíficas)e com cultivares de pereira (hibridações intraespecíficas). Foram usadas: ‘Packham’s Triumph’ (genitorfeminino) e ‘William’s’ e ‘Clapp’s Favorite’, ‘Maçã’ e ‘Portugal’ (genitores masculinos). Foi determinada frutificação efetiva (%) no campo aos 40 dias após as hibridações e a germinação in vivopor meio deatribuição de notas, seguindo escala de posição do tubo polínico no ovário. Obteve-se maior frutificaçãoefetiva entre as pereiras ‘Packham’s Triumph’ x ‘Clapp’s Favorite’. Nos cruzamentos interespecíficos, a maiorfrutificação efetiva foi obtida entre ‘Packham’s Triumph’ x ‘Portugal’. Na germinação in vivo, o estádio de desenvolvimento do tubo polínico apresentou variações significativas entre as combinações, porém não se obteve penetração de tubo polínico no óvulo. Como se observou frutificação em todos os cruzamentos, existe possível compatibilidade entre os genótipos estudados. Os resultados indicam que as cultivares doadoras de pólen da espécie P. communis são compatíveis com ‘Packham’s Triumph’. Outros estudos devem ser realizados com pólen de marmeleiro a fim de confirmar essa compatibilidade.

Inter-rater Reliability of Criteria-Based Content Analysis of Children's Statements of Abuse.

The evaluation of children's statements of sexual abuse cases in forensic cases is critically important and must and reliable. Criteria-based content analysis (CBCA) is the main component of the statement validity assessment (SVA), which is the most frequently used approach in this setting. This study investigated the inter-rater reliability (IRR) of CBCA in a forensic context. Three independent raters evaluated the transcripts of 95 statements of sexual abuse. IRR was calculated for each criterion, total score, and overall evaluation. The IRR was variable for the criteria, with several being unsatisfactory. But high IRR was found for the total CBCA scores (Kendall's W = 0.84) and for overall evaluation (Kendall's W = 0.65). Despite some shortcomings, SVA remains a robust method to be used in the comprehensive evaluation of children's statements of sexual abuse in the forensic setting. However, the low IRR of some CBCA criteria could justify some technical improvements.

Standardisation of elemental analytical techniques applied to provenance studies of archaeological ceramics: an inter laboratory calibration study

Chemical analysis is a well-established procedure for the provenancing of archaeological ceramics. Various analytical techniques are routinely used and large amounts of data have been accumulated so far in data banks. However, in order to exchange results obtained by different laboratories, the respective analytical procedures need to be tested in terms of their inter-comparability. In this study, the schemes of analysis used in four laboratories that are involved in archaeological pottery studies on a routine basis were compared. The techniques investigated were neutron activation analysis (NAA), X-ray fluorescence analysis (XRF), inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). For this comparison series of measurements on different geological standard reference materials (SRM) were carried out and the results were statistically evaluated. An attempt was also made towards the establishment of calibration factors between pairs of analytical setups in order to smooth the systematic differences among the results.

Communication challenges in virtual teams – a case study of implementing computer-mediated communication technologies in inter-organisational virtual teams

This thesis seeks to answer, if communication challenges in virtual teams can be overcome with the help of computer-mediated communication. Virtual teams are becoming more common work method in many global companies. In order for virtual teams to reach their maximum potential, effective asynchronous and synchronous methods for communication are needed. The thesis covers communication in virtual teams, as well as leadership and trust building in virtual environments with the help of CMC. First, the communication challenges in virtual teams are identified by using a framework of knowledge sharing barriers in virtual teams by Rosen et al. (2007) Secondly, the leadership and trust in virtual teams are defined in the context of CMC. The performance of virtual teams is evaluated in the case study by exploiting these three dimensions. With the help of a case study of two virtual teams, the practical issues related to selecting and implementing communication technologies as well as overcoming knowledge sharing barriers is being discussed. The case studies involve a complex inter-organisational setting, where four companies are working together in order to maintain a new IT system. The communication difficulties are related to inadequate communication technologies, lack of trust and the undefined relationships of the stakeholders and the team members. As a result, it is suggested that communication technologies are needed in order to improve the virtual team performance, but are not however solely capable of solving the communication challenges in virtual teams. In addition, suitable leadership and trust between team members are required in order to improve the knowledge sharing and communication in virtual teams.

A Dependency Parsing Approach to Biomedical Text Mining

Biomedical research is currently facing a new type of challenge: an excess of information, both in terms of raw data from experiments and in the number of scientific publications describing their results. Mirroring the focus on data mining techniques to address the issues of structured data, there has recently been great interest in the development and application of text mining techniques to make more effective use of the knowledge contained in biomedical scientific publications, accessible only in the form of natural human language. This thesis describes research done in the broader scope of projects aiming to develop methods, tools and techniques for text mining tasks in general and for the biomedical domain in particular. The work described here involves more specifically the goal of extracting information from statements concerning relations of biomedical entities, such as protein-protein interactions. The approach taken is one using full parsing—syntactic analysis of the entire structure of sentences—and machine learning, aiming to develop reliable methods that can further be generalized to apply also to other domains. The five papers at the core of this thesis describe research on a number of distinct but related topics in text mining. In the first of these studies, we assessed the applicability of two popular general English parsers to biomedical text mining and, finding their performance limited, identified several specific challenges to accurate parsing of domain text. In a follow-up study focusing on parsing issues related to specialized domain terminology, we evaluated three lexical adaptation methods. We found that the accurate resolution of unknown words can considerably improve parsing performance and introduced a domain-adapted parser that reduced the error rate of theoriginal by 10% while also roughly halving parsing time. To establish the relative merits of parsers that differ in the applied formalisms and the representation given to their syntactic analyses, we have also developed evaluation methodology, considering different approaches to establishing comparable dependency-based evaluation results. We introduced a methodology for creating highly accurate conversions between different parse representations, demonstrating the feasibility of unification of idiverse syntactic schemes under a shared, application-oriented representation. In addition to allowing formalism-neutral evaluation, we argue that such unification can also increase the value of parsers for domain text mining. As a further step in this direction, we analysed the characteristics of publicly available biomedical corpora annotated for protein-protein interactions and created tools for converting them into a shared form, thus contributing also to the unification of text mining resources. The introduced unified corpora allowed us to perform a task-oriented comparative evaluation of biomedical text mining corpora. This evaluation established clear limits on the comparability of results for text mining methods evaluated on different resources, prompting further efforts toward standardization. To support this and other research, we have also designed and annotated BioInfer, the first domain corpus of its size combining annotation of syntax and biomedical entities with a detailed annotation of their relationships. The corpus represents a major design and development effort of the research group, with manual annotation that identifies over 6000 entities, 2500 relationships and 28,000 syntactic dependencies in 1100 sentences. In addition to combining these key annotations for a single set of sentences, BioInfer was also the first domain resource to introduce a representation of entity relations that is supported by ontologies and able to capture complex, structured relationships. Part I of this thesis presents a summary of this research in the broader context of a text mining system, and Part II contains reprints of the five included publications.

Determinants of male fitness: disentangling intra- and inter-sexual selection.

Both intra- and inter-sexual selection may crucially determine a male's fitness. Their interplay, which has rarely been experimentally investigated, determines a male's optimal reproductive strategy and thus is of fundamental importance to the understanding of a male's behaviour. Here we investigated the relative importance of intra- and inter-sexual selection for male fitness in the common lizard. We investigated which male traits predict a male's access to reproduction allowing for both selective pressures and comparing it with a staged mating experiment excluding all types of intra-sexual selection. We found that qualitatively better males were more likely to reproduce and that sexual selection was two times stronger when allowing for both selective pressures, suggesting that inter- and intra-sexual selection determines male fitness and confirming the existence of multi-factorial sexual selection. Consequently, to optimize fitness, males should trade their investment between the traits, which are important for inter- and intra-sexual selection.

Trust in inter-organizational relationships

Trust in inter-organizational collaborative relationships has attracted substantial research interest among academics and practitioners. Previous studies have concentrated on the benefits of trust to business outcomes and economic performance, as it is considered to be a source of competitive advantage. Despite this increased level of interest, there is no consensus, much less overall agreement, about how it should be conceptualized or about the number of dimensions it incorporates. On the inter-organizational level there is an obvious challenge in defining both the trusting party and the objects of trust. Thus, the notion of trust as an under-theorized and poorly understood phenomenon still holds. Hence, the motivation of this study was fuelled by the need to increase our knowledge and understanding of the role and nature of trust in inter-organizational collaborative relationships. It is posited that there is a call for more understanding about its antecedents and consequences, as well as about the very concept in inter-organizational collaborative relationships. The study is divided into two parts. The first part gives a general overview, and the second part comprises four research publications. Both qualitative and quantitative research methodology is utilized. A multi-method research design was used because it provides different levels of data and different perspectives on the phenomenon. The results of this study reveal that trust incorporates three dimensions on both the individual and the organizational level: capability, goodwill, and self-reference. Trust develops from the reputation and behavior of the trusted party. It appears from this study that trust is clearly directed towards both individual boundary spanners and the counterpart company itself – i.e. not only to one or the other. The trusting party, on the other hand, is always an individual, and not the organization per se. Trust increases collaboration benefits and lowers collaboration drawbacks, thus having a positive effect on relationship performance. The major contribution of this study lies in uncovering the critical points and drawbacks in prior research and thereby in responding to the highlighted challenges. The way in which these challenges were addressed offers contributions to three major issues in the emerging theory of trust in the inter-organizational context: firstly, this study clarifies the trustor-trustee discussion; secondly, it conceptualizes trust as existing on both individual and organizational levels; and thirdly, it provides more information about the antecedents of trust and the ways in which it affects relationship performance.

Inter organizational learning within and by innovation networks

The thesis deals with the phenomenon of learning between organizations in innovation networks that develop new products, services or processes. Inter organizational learning is studied especially at the level of the network. The role of the network can be seen as twofold: either the network is a context for inter organizational learning, if the learner is something else than the network (organization, group, individual), or the network itself is the learner. Innovations are regarded as a primary source of competitiveness and renewal in organizations. Networking has become increasingly common particularly because of the possibility to extend the resource base of the organization through partnerships and to concentrate on core competencies. Especially in innovation activities, networks provide the possibility to answer the complex needs of the customers faster and to share the costs and risks of the development work. Networked innovation activities are often organized in practice as distributed virtual teams, either within one organization or as cross organizational co operation. The role of technology is considered in the research mainly as an enabling tool for collaboration and learning. Learning has been recognized as one important collaborative process in networks or as a motivation for networking. It is even more important in the innovation context as an enabler of renewal, since the essence of the innovation process is creating new knowledge, processes, products and services. The thesis aims at providing enhanced understanding about the inter organizational learning phenomenon in and by innovation networks, especially concentrating on the network level. The perspectives used in the research are the theoretical viewpoints and concepts, challenges, and solutions for learning. The methods used in the study are literature reviews and empirical research carried out with semi structured interviews analyzed with qualitative content analysis. The empirical research concentrates on two different areas, firstly on the theoretical approaches to learning that are relevant to innovation networks, secondly on learning in virtual innovation teams. As a result, the research identifies insights and implications for learning in innovation networks from several viewpoints on organizational learning. Using multiple perspectives allows drawing a many sided picture of the learning phenomenon that is valuable because of the versatility and complexity of situations and challenges of learning in the context of innovation and networks. The research results also show some of the challenges of learning and possible solutions for supporting especially network level learning.