UPLC-TOF-MS for plant metabolomics: a sequential approach for wound marker analysis in Arabidopsis thaliana.

The model plant Arabidopsis thaliana was studied for the search of new metabolites involved in wound signalling. Diverse LC approaches were considered in terms of efficiency and analysis time and a 7-min gradient on a UPLC-TOF-MS system with a short column was chosen for metabolite fingerprinting. This screening step was designed to allow the comparison of a high number of samples over a wide range of time points after stress induction in positive and negative ionisation modes. Thanks to data treatment, clear discrimination was obtained, providing lists of potential stress-induced ions. In a second step, the fingerprinting conditions were transferred to longer column, providing a higher peak capacity able to demonstrate the presence of isomers among the highlighted compounds.

Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study.

BACKGROUND: Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. METHODS: We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. RESULTS: Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively. CONCLUSIONS: This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00817908.

Subjectively adapted high capacity lossless image data hiding based on prediction errors

This article reports on a lossless data hiding scheme for digital images where the data hiding capacity is either determined by minimum acceptable subjective quality or by the demanded capacity. In the proposed method data is hidden within the image prediction errors, where the most well-known prediction algorithms such as the median edge detector (MED), gradient adjacent prediction (GAP) and Jiang prediction are tested for this purpose. In this method, first the histogram of the prediction errors of images are computed and then based on the required capacity or desired image quality, the prediction error values of frequencies larger than this capacity are shifted. The empty space created by such a shift is used for embedding the data. Experimental results show distinct superiority of the image prediction error histogram over the conventional image histogram itself, due to much narrower spectrum of the former over the latter. We have also devised an adaptive method for hiding data, where subjective quality is traded for data hiding capacity. Here the positive and negative error values are chosen such that the sum of their frequencies on the histogram is just above the given capacity or above a certain quality.

Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid.

OBJECTIVE: We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE. METHODS: We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE. RESULTS: IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers. CONCLUSION: These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted.

The double-edged sword of social capital: Three essays on entrepreneurship in developing nations

ABSTRACT My study seeks to answer the main question: "how does entrepreneurs' social capital positively and negatively affect their resource mobilization efforts, and exploitation of entrepreneurial opportunity?" To answer this question, I develop a model for examining positive and negative effects of social capital on resource accumulation by entrepreneurs, and the subsequent effect of resource accumulation on the exploitation of entrepreneurial opportunity, and utilize data from Africa to ëmpirically test the relationships in this model. Developing nations are a suitable context because: a) They require entrepreneurship for economic development, b) They have received less attention in management and entrepreneurship research, c) Because of inadequately-developed institutions, entrepreneurs from developing nations face major resource mobilization challenges hence they often turn to their social ties for resources, and d) The communalistic and collectivistic nature of most developing nations -encouraging support and sharing of resources- may help us better understand how society's values and structures may contribute and also deduct firm resources. My study reveals that social capital contributes resources to entrepreneurs in developing nations at a cost that takes away resources, and that more resources but lower costs facilitate entrepreneurial opportunity exploitation. For entrepreneurs in developing nations, large networks, greater shared identity, and more trust are beneficial. To increase chances of raising more resources, entrepreneurs from communalistic societies should include network members from outside their communities. Besides providing financial support, policy-makers should develop training programs and advisory services on configuration of entrepreneurs' networks so as to achieve more resources at a low cost. My study insights can help improve entrepreneurs' resource accumulation efforts and the subsequent growth of their firms, leading to the overall economic growth of developing nations.

Interacting populations in heterogeneous environments

To optimally manage a metapopulation, managers and conservation biologists can favor a type of habitat spatial distribution (e.g. aggregated or random). However, the spatial distribution that provides the highest habitat occupancy remains ambiguous and numerous contradictory results exist. Habitat occupancy depends on the balance between local extinction and colonization. Thus, the issue becomes even more puzzling when various forms of relationships - positive or negative co-variation - between local extinction and colonization rate within habitat types exist. Using an analytical model we demonstrate first that the habitat occupancy of a metapopulation is significantly affected by the presence of habitat types that display different extinction-colonization dynamics, considering: (i) variation in extinction or colonization rate and (ii) positive and negative co-variation between the two processes within habitat types. We consequently examine, with a spatially explicit stochastic simulation model, how different degrees of habitat aggregation affect occupancy predictions under similar scenarios. An aggregated distribution of habitat types provides the highest habitat occupancy when local extinction risk is spatially heterogeneous and high in some places, while a random distribution of habitat provides the highest habitat occupancy when colonization rates are high. Because spatial variability in local extinction rates always favors aggregation of habitats, we only need to know about spatial variability in colonization rates to determine whether aggregating habitat types increases, or not, metapopulation occupancy. From a comparison of the results obtained with the analytical and with the spatial-explicit stochastic simulation model we determine the conditions under which a simple metapopulation model closely matches the results of a more complex spatial simulation model with explicit heterogeneity.

Identification of a Poor-Prognosis BRAF-Mutant-Like Population of Patients With Colon Cancer.

PURPOSE Our purpose was development and assessment of a BRAF-mutant gene expression signature for colon cancer (CC) and the study of its prognostic implications. Materials and METHODS A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type) and to construct a gene expression-based classifier for detecting BRAF mutant samples with high sensitivity. The classifier was validated in independent data sets, and survival rates were compared between classifier positive and negative tumors. Results A 64 gene-based classifier was developed with 96% sensitivity and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent samples. A subpopulation of BRAF wild-type patients (30% of KRAS mutants, 13% of double wild type) showed a gene expression pattern and had poor overall survival and survival after relapse, similar to those observed in BRAF-mutant patients. Thus they form a distinct prognostic subgroup within their mutation class. CONCLUSION A characteristic pattern of gene expression is associated with and accurately predicts BRAF mutation status and, in addition, identifies a population of BRAF mutated-like KRAS mutants and double wild-type patients with similarly poor prognosis. This suggests a common biology between these tumors and provides a novel classification tool for cancers, adding prognostic and biologic information that is not captured by the mutation status alone. These results may guide therapeutic strategies for this patient segment and may help in population stratification for clinical trials.

Euroopan yhteisen maksualueen (Single European payment area) vaikutukset maksuliikenteen tehokkuuteen case: Metso Oyj

Työn tavoitteena oli tutkia Euroopan yhteisen maksualueen (Single European Payment Area, SEPA) kehitystä ja selvittää mitä hyötyä siitä on Metso-konsernin maksuliikenteelle. Teoreettisessa osassa tarkastellaan mistä tehokas maksuliikenne koostuu ja esitetään SEPA:n kehitys peilaamalla sitä Berger et al.:n (1996) teoriasta muodostettuihin implikaatioihin. Empiirinen osuus sisältää kuvailevan Case-tutkimuksen, joka toteutettiin teemahaastatteluilla. Sitä täydennettiin kvantitatiivisella tilisiirtokustannusaineistolla (Metso-konserni). Tulosten mukaan SEPA-kehitys on sekä positiivista että negatiivista: 1) Jos kaikki maksuliikenteen osapuolet kokevat saavansa hyötyä uudistuksista, toteutuu sosiaalinen tehokkuus, jolloin kehitys nopeutuu ja kustannukset laskevat. Tämä on nähtävissä Metso-konsernin tilisiirtokustannusten kehityksestä. 2) SEPA lisää pankkien kustannuksia. 3) Järjestelmien kehitys vähentää maksuliikenneriskiä 4) Maksualuekehitys on vaarassa hidastua, jos alhaiseksi koetun riskin ehkäisemisestäei haluta maksaa.

Henkilökohtaiset suhteet teollisessa markkinoinnissa

Teollisessa markkinoinnissa myyjän suhde asiakkaaseen on erilainen kuin kuluttajamarkkinoinnissa. Asiakasyritys ja sen tarpeet täytyy ottaa tietoisemmin huomioon ja usein ostopäätökseen vaikuttavat aikaisemmat kokemukset tietystä kauppakumppanista. Myyntiä ja ostamista ei tapahdu ilman suhteita. Suhteisiin perustuva vaihdanta eroaa lyhyen kantaman transaktioluonteisesta vaihdannasta: kumppanit sitoutuvat ja luottavat toisiinsa vahvemmin, haluavat tavoitella päämääriään yhdessä ja ystävystyvät keskenään. Henkilökohtaisen sidosten muodostumista voidaan kiihdyttää ja suhdetta ylläpitää erilaisten toimintojen keinoin. Henkilökohtaisilla suhteilla on monenlaisia vaikutuksia, sekä positiivia että negatiivisia - useimmiten ne kuitenkin koetaan hyödyllisinä. Suhteet vaikuttavat muun muassa luottamukseen, vastavuoroisuuteen ja yksilöiden käyttäytymiseen. Nämä vaikutukset ja suhteiden merkitykset vaihtelevat eri maissa sekä kulttuureissa. Aina ei kuitenkaan voida luottaa henkilösuhteiden voimaan, vaan joskus on syytä keskittyä prosessien, tuotosten ja korkean laadun kehittämiseen.

Database Rights in Safe European Home: The Path to More Rigorous Protection of Information

1. Introduction "The one that has compiled ... a database, the collection, securing the validity or presentation of which has required an essential investment, has the sole right to control the content over the whole work or over either a qualitatively or quantitatively substantial part of the work both by means of reproduction and by making them available to the public", Finnish Copyright Act, section 49.1 These are the laconic words that implemented the much-awaited and hotly debated European Community Directive on the legal protection of databases,2 the EDD, into Finnish Copyright legislation in 1998. Now in the year 2005, after more than half a decade of the domestic implementation it is yet uncertain as to the proper meaning and construction of the convoluted qualitative criteria the current legislation employs as a prerequisite for the database protection both in Finland and within the European Union. Further, this opaque Pan-European instrument has the potential of bringing about a number of far-reaching economic and cultural ramifications, which have remained largely uncharted or unobserved. Thus the task of understanding this particular and currently peculiarly European new intellectual property regime is twofold: first, to understand the mechanics and functioning of the EDD and second, to realise the potential and risks inherent in the new legislation in economic, cultural and societal dimensions. 2. Subject-matter of the study: basic issues The first part of the task mentioned above is straightforward: questions such as what is meant by the key concepts triggering the functioning of the EDD such as presentation of independent information, what constitutes an essential investment in acquiring data and when the reproduction of a given database reaches either qualitatively or quantitatively the threshold of substantiality before the right-holder of a database can avail himself of the remedies provided by the statutory framework remain unclear and call for a careful analysis. As for second task, it is already obvious that the practical importance of the legal protection providedby the database right is in the rapid increase. The accelerating transformationof information into digital form is an existing fact, not merely a reflection of a shape of things to come in the future. To take a simple example, the digitisation of a map, traditionally in paper format and protected by copyright, can provide the consumer a markedly easier and faster access to the wanted material and the price can be, depending on the current state of the marketplace, cheaper than that of the traditional form or even free by means of public lending libraries providing access to the information online. This also renders it possible for authors and publishers to make available and sell their products to markedly larger, international markets while the production and distribution costs can be kept at minimum due to the new electronic production, marketing and distributionmechanisms to mention a few. The troublesome side is for authors and publishers the vastly enhanced potential for illegal copying by electronic means, producing numerous virtually identical copies at speed. The fear of illegal copying canlead to stark technical protection that in turn can dampen down the demand for information goods and services and furthermore, efficiently hamper the right of access to the materials available lawfully in electronic form and thus weaken the possibility of access to information, education and the cultural heritage of anation or nations, a condition precedent for a functioning democracy. 3. Particular issues in Digital Economy and Information Networks All what is said above applies a fortiori to the databases. As a result of the ubiquity of the Internet and the pending breakthrough of Mobile Internet, peer-to-peer Networks, Localand Wide Local Area Networks, a rapidly increasing amount of information not protected by traditional copyright, such as various lists, catalogues and tables,3previously protected partially by the old section 49 of the Finnish Copyright act are available free or for consideration in the Internet, and by the same token importantly, numerous databases are collected in order to enable the marketing, tendering and selling products and services in above mentioned networks. Databases and the information embedded therein constitutes a pivotal element in virtually any commercial operation including product and service development, scientific research and education. A poignant but not instantaneously an obvious example of this is a database consisting of physical coordinates of a certain selected group of customers for marketing purposes through cellular phones, laptops and several handheld or vehicle-based devices connected online. These practical needs call for answer to a plethora of questions already outlined above: Has thecollection and securing the validity of this information required an essential input? What qualifies as a quantitatively or qualitatively significant investment? According to the Directive, the database comprises works, information and other independent materials, which are arranged in systematic or methodical way andare individually accessible by electronic or other means. Under what circumstances then, are the materials regarded as arranged in systematic or methodical way? Only when the protected elements of a database are established, the question concerning the scope of protection becomes acute. In digital context, the traditional notions of reproduction and making available to the public of digital materials seem to fit ill or lead into interpretations that are at variance with analogous domain as regards the lawful and illegal uses of information. This may well interfere with or rework the way in which the commercial and other operators have to establish themselves and function in the existing value networks of information products and services. 4. International sphere After the expiry of the implementation period for the European Community Directive on legal protection of databases, the goals of the Directive must have been consolidated into the domestic legislations of the current twenty-five Member States within the European Union. On one hand, these fundamental questions readily imply that the problemsrelated to correct construction of the Directive underlying the domestic legislation transpire the national boundaries. On the other hand, the disputes arisingon account of the implementation and interpretation of the Directive on the European level attract significance domestically. Consequently, the guidelines on correct interpretation of the Directive importing the practical, business-oriented solutions may well have application on European level. This underlines the exigency for a thorough analysis on the implications of the meaning and potential scope of Database protection in Finland and the European Union. This position hasto be contrasted with the larger, international sphere, which in early 2005 does differ markedly from European Union stance, directly having a negative effect on international trade particularly in digital content. A particular case in point is the USA, a database producer primus inter pares, not at least yet having aSui Generis database regime or its kin, while both the political and academic discourse on the matter abounds. 5. The objectives of the study The above mentioned background with its several open issues calls for the detailed study of thefollowing questions: -What is a database-at-law and when is a database protected by intellectual property rights, particularly by the European database regime?What is the international situation? -How is a database protected and what is its relation with other intellectual property regimes, particularly in the Digital context? -The opportunities and threats provided by current protection to creators, users and the society as a whole, including the commercial and cultural implications? -The difficult question on relation of the Database protection and protection of factual information as such. 6. Dsiposition The Study, in purporting to analyse and cast light on the questions above, is divided into three mainparts. The first part has the purpose of introducing the political and rationalbackground and subsequent legislative evolution path of the European database protection, reflected against the international backdrop on the issue. An introduction to databases, originally a vehicle of modern computing and information andcommunication technology, is also incorporated. The second part sets out the chosen and existing two-tier model of the database protection, reviewing both itscopyright and Sui Generis right facets in detail together with the emergent application of the machinery in real-life societal and particularly commercial context. Furthermore, a general outline of copyright, relevant in context of copyright databases is provided. For purposes of further comparison, a chapter on the precursor of Sui Generi, database right, the Nordic catalogue rule also ensues. The third and final part analyses the positive and negative impact of the database protection system and attempts to scrutinize the implications further in the future with some caveats and tentative recommendations, in particular as regards the convoluted issue concerning the IPR protection of information per se, a new tenet in the domain of copyright and related rights.

Career engagement : Investigating intraindividual predictors of weekly fluctuations in proactive career behaviors

The present study applies a micro-level perspective on how within-individual differences in motivational and social-cognitive factors affect the weekly fluctuations of engagement in proactive career behaviors among a group of 67 German university students. Career self-efficacy beliefs, perceived career barriers, experienced social career support, positive and negative emotions, and career engagement were assessed weekly for 13 consecutive weeks. Hierarchical linear regression analyses showed that above-average levels of career engagement within individuals were predicted by higher than average perceived social support and positive emotions during a given week. Conversely, within-individual differences in self-efficacy, barriers, and negative emotions had no effect. The results suggest that career interventions should provide boosts in social support and positive emotions.

Spanish adaptation of the Expectancy Questionnaire (EQ) about alcohol effects in adolescents

Background: Alcohol-related expectancies are especially relevant in relation to alcohol consumption during adolescence. The main aim of this study was to adapt and translate into Spanish (Castilian) the Expectancy Questionnaire (EQ), and to study its psychometric properties in adolescents. Method: The sample was composed of 514 adolescents (57.20% female, mean age = 15.21; SD = .63) who completed the EQ and the alcohol consumption questionnaire AIS-UJI. Results: Confi rmatory factor analysis indicated that an eight-factor model, grouped into two general factors of positive and negative expectancies, had acceptable fi t indices. Cronbach’s alphas ranged from .75 to .96. Finally, the structural equation model showed that positive expectancies were positively related to alcohol use, whereas negative expectancies were negatively related to drinking. Conclusions: Results showed that the Spanish version of the EQ for adolescents is a valid and reliable questionnaire to measure expectancies about alcohol effects.

Western blotting as a tool for the serodiagnosis of farmer's lung disease: validation with Lichtheimia corymbifera protein extracts.

Electrosyneresis and double diffusion are immunoprecipitation techniques commonly used in the serological diagnosis of Farmer's lung disease (FLD). These techniques are reliable but lack standardization. The aim of this study was to evaluate Western blotting for the serodiagnosis of FLD. We carried out Western blotting with an antigenic extract of Lichtheimia corymbifera, an important aetiological agent of the disease. The membranes were probed with sera from 21 patients with FLD and 21 healthy exposed controls to examine the IgG antibody responses against purified somatic antigens. Given the low prevalence of the disease, 21 patients could be considered as a relevant series. Four bands were significantly more frequently represented in membranes probed with FLD sera (bands at 27.7, 40.5, 44.0 and 50.5 kDa) than those probed with control sera. We assessed the diagnostic value of different criteria alone or in combination. The diagnostic accuracy of the test was highest with the inclusion of at least two of the following criteria: at least five bands on the strip and the presence of one band at 40.5 or 44.0 kDa. Sensitivity, specificity and positive and negative predictive values were all 81%, and the odds ratio was 18.06. Inclusion of bands of high intensity diminished rather than improved the diagnostic value of the test. We concluded that Western blotting is a valuable technique for the serodiagnosis of FLD. The industrial production of ready-to-use membranes would enable the routine use of this technique in laboratories, and provide reliable and standardized diagnostic results within a few hours.

Luottamus sosiaalisen pääoman osana

Tutkielman tarkoituksena on tutkia luottamuksen ja toteutuneen sosiaalisen pääoman välistä suhdetta. Tavoitteena on tarkastella luottamuksen suhdetta sosiaalisen pääoman positiivisiin seurauksiin, kuten toisten tukemiseen, yhteistyöhön, luotettavuuteen sekä tehokkuuteen. Luottamus määritellään halukkuudeksi ottaa riski yhteistyösuhteessa. Luottamuksen perusta jakautuu kognitiiviseen eli järkiperäiseen ja affektiiviseen eli tunnepitoiseen luottamukseen ja näitä luottamuksen käsitteitä tarkastellaan yrityksen sisällä sekä horisontaalisesta (työntekijän luottamus toiseen työntekijään) että vertikaalisesta (työntekijän luottamus esimieheen ja ylimpään johtoon) näkökulmasta. Luottamuksen tasot kuvaavat osaltaan luottamuksen ja samalla koko yhteistyösuhteen kehittymistä. Työssä esitetään, että sosiaalinen pääoma on mielekästä jakaa potentiaaliseen ja toteutuneeseen sosiaaliseen pääomaan. Potentiaalisella sosiaalisella pääomalla tarkoitetaan sosiaalisia suhteita ja vastavuoroisuuden periaatteita, arvoja ja normeja sekä luottamusta. Toteutuneella pääomalla on sekä positiivisia että negatiivisia seurauksia. Tässä keskitytään lähinnä sosiaalisen pääoman positiivisiin seurauksiin.

Developing a theoretical framework using a nursing perspective to investigate perceived health in the "Sandwich Generation" group

Coexisting workloads from professional, household and family, and caregiving activities for frail parents expose middle-aged individuals, the so-called "Sandwich Generation", to potential health risks. Current trends suggest that this situation will continue or increase. Thus SG health promotion has become a nursing concern. Most existing research considers coexisting workloads a priori pathogenic. Most studies have examined the association of one, versus two, of these three activities with health. Few studies have used a nursing perspective. This article presents the development of a framework based on a nursing model. We integrated Siegrist's Effort-Reward Imbalance middle-range theory into "Neuman Systems Model". The latter was chosen for its salutogenic orientation, its attention to preventive nursing interventions and the opportunity it provides to simultaneously consider positive and negative perceptions of SG health and SG coexisting workloads. Finally, it facilitated a theoretical identification of health protective factors.