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Search Results: 1 - 10 of 858 matches for " Nico Derichs "
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Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis
Nico Derichs
European Respiratory Review , 2013,
Abstract: Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.
Restructuring Logic
Joachim Derichs
Mathematics , 2014,
Abstract: The outline of a programme for restructuring mathematical logic. We explain what we mean by "restructuring" and carry out exemplary parts of the programme.
Constitutive versus Responsive Gene Expression Strategies for Growth in Changing Environments
Nico Geisel
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027033
Abstract: Microbes respond to changing environments by adjusting gene expression levels to the demand for the corresponding proteins. Adjusting protein levels is slow, consequently cells may reach the optimal protein level only by a time when the demand changed again. It is therefore not a priori clear whether expression “on demand” is always the optimal strategy. Indeed, many genes are constitutively expressed at intermediate levels, which represents a permanent cost but provides an immediate benefit when the protein is needed. Which are the conditions that select for a responsive or a constitutive expression strategy, what determines the optimal constitutive expression level in a changing environment, and how is the fitness of the two strategies affected by gene expression noise? Based on an established model of the lac- and gal-operon expression dynamics, we study the fitness of a constitutive and a responsive expression strategy in time-varying environments. We find that the optimal constitutive expression level differs from the average demand for the gene product and from the average optimal expression level; depending on the shape of the growth rate function, the optimal expression level either provides intermediate fitness in all environments, or maximizes fitness in only one of them. We find that constitutive expression can provide higher fitness than responsive expression even when regulatory machinery comes at no cost, and we determine the minimal response rate necessary for “expression on demand” to confer a benefit. Environmental and inter-cellular noise favor the responsive strategy while reducing fitness of the constitutive one. Our results show the interplay between the demand-frequency for a gene product, the genetic response rate, and the fitness, and address important questions on the evolution of gene regulation. Some of our predictions agree with recent yeast high throughput data, for others we propose the experiments that are needed to verify them.
Da desigualdade de classe à desigualdade de conhecimento
Stehr, Nico;
Revista Brasileira de Ciências Sociais , 2000, DOI: 10.1590/S0102-69092000000100007
Abstract: the discussion of knowledge as a crucial source of inequality is organized as follows. first, the author presents the general theoretical context within which the discussion of social inequality will be placed, namely the development of a theory of modern society as knowledge-based. secondly, he addresses some of the characteristics of contemporary social inquiry to inequality. he indicates that most of the theories and research into the structure of inequality are linked to the theory of modern society as an industrial society. thirdly the author seeks to show why knowledge, as a capacity for action, may be able to replace what have been for centuries, and continue to be for many observers in theory and for many others in practice, the invidious foundations of inequality of industrial society. using aggregate economic data, he points out that transformations in the material welfare of large numbers of individuals and households contribute to an uncoupling from the once rather tight linkage or dependence of individuals and households on the labor market. the material changes made room for new forms of social inequality; specifically, structures of inequality linked to knowledge. finally, the last section describes some of the ways in which knowledge has been employed to generate, reproduce and sustain inequalities.
Liberdade é filha do conhecimento?
Stehr, Nico;
Tempo Social , 2008, DOI: 10.1590/S0103-20702008000200011
Abstract: the theme explored in this paper concerns the multiple linkages between knowledge, civil society, governance and democracy. i could place this general set of questions within the context of whether or not they are co-determined by the enabling knowledgeability of modern actors and stress the growing possibilities for reflexive cooperation among civil society organizations and social movements, as well as the increasing influence of broad sectors of society in democratic regimes. however my specific objective is necessarily more modest. access to knowledge and its control are stratified. i shall explore three barriers and hurdles to the access to knowledge and ask: (1) can expertise and civil society be reconciled? (2) is it conceivable to reconcile civil society and knowledge as a form of private property? (3) and finally, are the social sciences and humanities a source for enabling knowledge?
Eddie Mabo e a Namíbia: reforma agrária e direitos pré-coloniais à posse da terra
Horn, Nico;
Sur. Revista Internacional de Direitos Humanos , 2005, DOI: 10.1590/S1806-64452005000200006
Abstract: what do the small murray islands, in the torres strait off the queensland coast have in common with namibia? unlike the bloody german/herero and nama wars, no shot was fired when her majesty's administration in queensland declared the murray islands a crown colony. yet, the two peoples had a common history of submission to a colonial power; and although allowed to remain on their ancestral lands, they were not informed that they'd been colonized. one of the oldest justifications for the occupation of inhabited land, the so-called terra nullius rule, was abandoned due to a lawsuit brought by the meriam people, the mabo case. the example of the mabo case provides an opportunity to approach the land reform program in namibia from a different perspective, at least in the central and southern regions of the country. the namibian constitution guarantees private property rights. however, the idea that more than one right can exist over a farm is not unknown to both common law and statutory law in the country. in this article the author proposes a process where several strategies are used to obtain the final goal: a just distribution of land to all the peoples of namibia in such a way that it contributes to peace, prosperity and stability.
Leadership in school-based management: a case study in selected schools
Nico Botha
South African Journal of Education , 2006,
Abstract: According to the literature on school-based management, there are two clear schools of thought on this issue. One school views school-based management as a positive and successful vehicle of school improvement. The other argues that it has been minimally successful in school improvement. The leadership role of the school principal is widely regarded as the primary factor contributing to a successful relationship between school-based management and school improvement and is therefore an essential dimension of successful school-based management. This article, derived from a qualitative case study undertaken among a number of divergent secondary schools in Gauteng province, is an attempt to conceptualise the important and pivotal leadership role of the school principal in ensuring school improvement via effective school-based management in South African schools South African Journal of Education Vol. 26(3) 2006: 341-353
Nico Pitrelli
S&F_scienzaefilosofia.it , 2009,
Developing a trust model for assisting management during change
Nico Martins
South African Journal of Industrial Psychology , 2000, DOI: 10.4102/sajip.v26i3.716
Abstract: This study investigates the relation of the "Big Five" personality dimensions and managerial practices to the dimension of trust relationships between managers and employees. The "Big Five" dimensions are conscientiousness, agreeableness, emotional stability, resourcefulness and extraversion. Managerial practices are credibility, team management, information sharing and work support. Results indicate that managerial practices have an influence on the trust relationships between managers and employees. For the "Big Five" personality dimensions, a weaker relationship with the dimension of trust was obtained. Although there appears to be a weaker relationship between the "Big Five" and the dimension of trust relationships, the relatively good fit of the model indicates that an overall implication of the model is that both managerial practices and the "Big Five" personality aspects of the manager might influence his/her subordinates indirectly. These findings have numerous implications for the relationships between managers and employees, especially in the selection, recruitment and appointment of managers and the role of managers during transformation. Opsomming Die studie ondersoek die verhouding tussen die Groot Vyf ("Big Five") persoonlikheidsdimensies en bestuurspraktyke en die dimensie van vertroue tussen bestuur en werknemers. Die Groot Vyf dimensies is konsensieusheid, eenstemmigheid, emosionele stabiliteit, vernuftigheid en ekstroversie. Die bestuurspraktyke is kredietwaardigheid, spanbestuur, die deel van inligting en werksondersteuning. Die resultate dui aan dat die bestuurspraktyke 'n invloed het op die verhouding tussen bestuur en werknemers. Wat die Groot Vyf dimensies aanbetref, is n swakker verhouding met die dimensie van vertroue bevind. Alhoewel dit skyn as of daar n swakker verhouding tussen die Groot Vyf en die dimensie van vertroue is, toon die relatiewe goeie passing van die model dat beide die bestuurspraktyke en die Groot Vyf persoonlikheidsaspekte van die bestuurder die verhouding tussen bestuur en werknemers mag beinvloed. Die resultate hou verskeie implikasies in vir die verhoudinge tussen bestuur en werknemers en spesifiek in die areas van keuring, werwing en aanstelling van bestuurders en die rol van bestuurders gedurende verandering.
An Arab printer in Surabaya in 1853
Nico Kaptein
Bijdragen tot de Taal-, Land- en Volkenkunde , 1993,
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