Protein kinases have emerged as one of the most successful families of drug targets. To date, most selective kinase inhibitors have been discovered serendipitously either through broad selectivity ...screening or through the discovery of unique binding modes. Here we discuss design strategies that could lead to a broader coverage of the kinome with selective inhibitors and to a more rational approach for developing them.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
This conceptual paper aims to identify, present, and analyze potential knowledge risks organizations might face. With the growing complexity of organizational environments and the plethora of new ...knowledge risks emerging, this critical but under-researched field of knowledge management (KM) deserves closer attention. The study is based on a critical analysis of the extant literature devoted to knowledge risks, discusses potential outcomes of these risks and proposes a concept map of knowledge risks. The map shows a number of knowledge risks organizations should be aware of. Knowledge risks can be assigned to three categories: human, technological and operational. The research is the first systematic and comprehensive review of knowledge risks at the organizational level. By aggregating and consolidating the knowledge risks covered, the study does not only provide a knowledge risk taxonomy but also promising directions for future research. The study also contributes to a more comprehensive understanding of KM.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The detection of mRNAs undergoing transcription or decay is challenging, because both processes are fast. However, the relative proportion of an mRNA in synthesis or decay increases with mRNA size ...and decreases with mRNA half-life. Based on this rationale, I have exploited a 22 200 nucleotide-long, short-lived endogenous mRNA as a reporter for mRNA metabolism in trypanosomes. The extreme 5΄ and 3΄ ends were labeled with red- and green-fluorescent Affymetrix® single mRNA FISH probes, respectively. In the resulting fluorescence images, yellow spots represent intact mRNAs; red spots are mRNAs in transcription or 3΄-5΄ decay, and green spots are mRNAs in 5΄-3΄ degradation. Most red spots were nuclear and insensitive to transcriptional inhibition and thus likely transcription intermediates. Most green spots were cytoplasmic, confirming that the majority of cytoplasmic decay in trypanosomes is 5΄-3΄. The system showed the expected changes at inhibition of transcription or translation and RNAi depletion of the trypanosome homologue to the 5΄-3΄ exoribonuclease Xrn1. The method allows to monitor changes in mRNA metabolism both on cellular and on population/tissue wide levels, but also to study the subcellular localization of mRNA transcription and decay pathways. I show that the system is applicable to mammalian cells.
Globalization in rural areas is commonly described in terms of both challenges and opportunities. Opportunities include increased communication and reduced distance. These factors, however, are also ...favorable for illicit activities such as increased opportunities for marketing drugs on the Internet and reduced barriers for transporting drugs. The drug industry is global and involves cross-site processes, but the drug problem is very local. This article discusses how drug activities infiltrate the work of professionals in rural places and the way this affects rural people and their living environment. In local communities, the police have the authority to counteract the spread and use of drugs, an authority that is described as geographically thinned. That is, police as well as other professionals combating the effects of drug abuse are affected as local cooperation, which is often encouraged by short distances, dense networks, and local knowledge, is weakened. Using a qualitative interview approach, this study argues that local practices related to prevention of drug-related crime are poorly equipped to deal with the speed and range of the contemporary drug trade.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Longitudinal research holds great promise for researching change and continuity. Qualitative and quantitative longitudinal research can be combined within a mixed methods framework, which enables ...gaining complementary insights that are more nuanced and more valid. However, longitudinal research generally entails more practical challenges than cross-sectional research. Further, combining qualitative and quantitative strategies in mixed methods longitudinal research (MMLR) multiplies these challenges. In this publication, I start by conceptualizing qualitative and quantitative longitudinal research and highlighting their respective strengths and challenges. I subsequently outline design options and implications of mixed methods longitudinal projects. Hereby, I distinguish traditional dimensions of mixed methods and longitudinal research designs, such as time and timing, priority, purpose, sampling, data collection, analysis and interpretation, and reporting. In MMLR these dimensions have an extended time dimension because these design decisions have to be made or revisited in each wave. With this contribution, I aim to advance conceptual thinking in an area of research that is certainly underdeveloped, but has great potential.
► We examined the results of 5 different Fish Sexual Development Tests with zebrafish. ► We developed the maturity index for the quantification of gonad maturation in fish. ► VTG induction and ...maturity index were excellently correlating for all 5 substances. ► The maturity index is a useful tool for the interpretation of EDC-related effects.
In July 2011, the Fish Sexual Development Test (FSDT) has officially been adopted as OECD test guideline 234 for the detection of endocrine disrupting chemicals (EDCs). Sex ratio and vitellogenin (VTG) induction are the mandatory endocrine endpoints within this test, whereas gonad staging is only included as an option. In the present study, five FSDTs with zebrafish (Danio rerio) were conducted with EDCs with different modes of action (17α-ethinylestradiol, dihydrotestosterone, 17β-trenbolone, prochloraz and 4-tert-pentylphenol). Results document that not only sex ratio and VTG production of the exposed fish were massively affected, but also gonad maturation. As a novel approach for the quantification of gonad maturation in zebrafish, the maturity index was developed to allow not only an improved assessment of dose-dependent EDC-related effects on gonad maturation, but also statistical analysis of histological data. VTG induction and maturity index showed an excellent correlation for all five EDCs tested. Most importantly, the maturity index often helped to find appropriate interpretations for results that seemed contradictory at first sight. Results show that histological analyses and their predictive power for population fitness are currently underestimated and should become a standard component in the evaluation of potential EDCs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
How (wo)men rebel Schaftenaar, Susanne
Journal of peace research,
11/2017, Volume:
54, Issue:
6
Journal Article
Peer reviewed
Previous studies find a strong relationship between armed conflict and gender equality, but only compare armed conflict to no armed conflict onset. However, opposition movements use different means ...to challenge governments, such as nonviolent or armed strategies. This study explores this variation and poses the question: How does the level of gender equality affect the onset of nonviolent campaigns and armed conflicts? It makes two contributions. First, I quantitatively test the impact of gender equality on different forms of conflict onset, and second, I propose a comprehensive gendered mobilization argument based on strategic choice theory. Nonviolent campaigns rely on mass participation, and the nonviolent conflict literature claims that they are open to a wider array of participants, including women, compared to armed conflicts. I argue that gender norms affect movements’ expectations of mobilization (mass or limited) as well as conflict norms (nonviolent or violent) in society, and subsequently, the choice of conflict strategy. I hypothesize that higher levels of gender equality, measured by fertility rate and female-to-male primary school enrolment ratio, increase the likelihood of nonviolent campaign onset, compared to both armed and no campaign onset. This study analyses country-year data from the UCDP and NAVCO datasets between 1961 and 2006 and finds that increases in gender equality are, on average, associated with an increased likelihood of nonviolent conflict onset.
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BFBNIB, INZLJ, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK, ZRSKP
The branched reduction system at the Heidenschmiede described here is hitherto exceptional for the Middle Paleolithic of the Swabian Jura. By means of refits and supporting objects, we are able to ...describe a superordinate reduction system that combines several individual reduction concepts, such as Levallois and blade production, within one volume. In the Middle Paleolithic of the Swabian Jura, blade technology has thus far played a rather minor role. On the one hand, it is possible to split a selected volume (nodule) into three parts, which are reduced separately according to individual concepts. On the other hand, it is also possible to reduce parts of a volume with one concept first and then with another. The hypothetical reduction system can be branched or linear, thus emphasizing the technological flexibility in core reduction, which requires a high degree of cognitive skills of three-dimensional imagination.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic alongside other environmental and social crises have raised questions around the role of government, governance and the notion of tourism value. The aim of this paper, ...therefore, was to develop a conceptual framework that makes sense of the tourism value discussion within the wider context of the New Zealand Department of Conservation's aspiration of Papatūānuku Thrives (Mother Earth Thrives). Drawing on critical studies, current New Zealand tourism strategies, stakeholder input and discussions with government employees, a values-based tourism framework has been developed. The "tourism tree" integrates aspects of a regenerative tourism paradigm and cultural values from Te Ao Māori (the world of Māori) and recognises the importance of healthy roots for tourism to contribute positively to multiple wellbeings and give back to place. Whilst only a stepping-stone towards transformative blending of paradigms, the framework will help the Department in their policy and operational decisions, with a view towards achieving intergenerational positive outcomes from tourism.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
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