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1.
My intention in this paper is to make sense of the relationship between Action Research (AR) and Critical Systems Thinking (CST). On the surface, the two strands of thinking do not seem to have much in common. There is hardly any common reference in texts written within each tradition. Deeper down, however, there may be common concerns. The point of departure is to focus on how professionals interact with real-world problems and to clarify the underlying values for professional practice. To facilitate a discussion on the relationship between AR and CST, a frame of reference is developed based on analyzing the meaning construction process. Based on this platform, the relationship among theory, practice, and people shapes the ground for the discussion. Within this discussion three questions are raised: (1) Is the theory understood by the people and based on their interests? (2) Are the research questions relevant for the people? and (3) Are people emancipated to act in their own interests? The relationship between AR and CST can be examined based on these three questions. In concluding, I argue for the potential of a mutual and fruitful dialogue between AR and CST.  相似文献   
2.
Pathogenic bacteria often use effector molecules to increase virulence. In most cases, the mode of action of effectors remains unknown. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA), a product of a mixed non-ribosomal peptide/polyketide synthetase, in planta. Here we identify SylA as a virulence factor because a SylA-negative mutant in Pss strain B728a obtained by gene disruption was markedly less virulent on its host, Phaseolus vulgaris (bean). We show that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors. The crystal structure of the yeast proteasome in complex with SylA revealed a novel mechanism of covalent binding to the catalytic subunits. Thus, SylA defines a new class of proteasome inhibitors that includes glidobactin A (GlbA), a structurally related compound from an unknown species of the order Burkholderiales, for which we demonstrate a similar proteasome inhibition mechanism. As proteasome inhibitors are a promising class of anti-tumour agents, the discovery of a novel family of inhibitory natural products, which we refer to as syrbactins, may also have implications for the development of anti-cancer drugs. Homologues of SylA and GlbA synthetase genes are found in some other pathogenic bacteria, including the human pathogen Burkholderia pseudomallei, the causative agent of melioidosis. It is thus possible that these bacteria are capable of producing proteasome inhibitors of the syrbactin class.  相似文献   
3.
Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD.  相似文献   
4.
At present, transgenes in Caenorhabditis elegans are generated by injecting DNA into the germline. The DNA assembles into a semistable extrachromosomal array composed of many copies of injected DNA. These transgenes are typically overexpressed in somatic cells and silenced in the germline. We have developed a method that inserts a single copy of a transgene into a defined site. Mobilization of a Mos1 transposon generates a double-strand break in noncoding DNA. The break is repaired by copying DNA from an extrachromosomal template into the chromosomal site. Homozygous single-copy insertions can be obtained in less than 2 weeks by injecting approximately 20 worms. We have successfully inserted transgenes as long as 9 kb and verified that single copies are inserted at the targeted site. Single-copy transgenes are expressed at endogenous levels and can be expressed in the female and male germlines.  相似文献   
5.
Basal-like breast cancer (BBC) is a subtype of breast cancer with poor prognosis. Inherited mutations of BRCA1, a cancer susceptibility gene involved in double-strand DNA break (DSB) repair, lead to breast cancers that are nearly always of the BBC subtype; however, the precise molecular lesions and oncogenic consequences of BRCA1 dysfunction are poorly understood. Here we show that heterozygous inactivation of the tumor suppressor gene Pten leads to the formation of basal-like mammary tumors in mice, and that loss of PTEN expression is significantly associated with the BBC subtype in human sporadic and BRCA1-associated hereditary breast cancers. In addition, we identify frequent gross PTEN mutations, involving intragenic chromosome breaks, inversions, deletions and micro copy number aberrations, specifically in BRCA1-deficient tumors. These data provide an example of a specific and recurrent oncogenic consequence of BRCA1-dependent dysfunction in DNA repair and provide insight into the pathogenesis of BBC with therapeutic implications. These findings also argue that obtaining an accurate census of genes mutated in cancer will require a systematic examination for gross gene rearrangements, particularly in tumors with deficient DSB repair.  相似文献   
6.
Lately, society has pressed for more direct societal relevance of social research. The argument of this special issue is that engaged research is an answer to the demand for a social science that matters. We define engaged research as a praxis where researchers actively engage in a social field in the pursuit of solving important local problems, while at the same time combining this with a scientific knowledge generation process. In other words, we discuss the conditions for research when researchers “go native” to solve problems and reflect along with participants. We have been able to find several sources of arguments supporting such a research strategy, but our search for methodological guidance on how to act as an engaged researcher has been in vain. What does it take for a researcher to do engaged research? The set of articles in this special issue all address certain aspects of this challenge. Some discuss the researcher’s path towards deep field engagement, whereas others discover various challenges and skills involved in engagement, and the task of developing scientific knowledge based on engaged research.  相似文献   
7.
During the late years there has been an ever-increasing focus on the possibilities to change the building process to raise quality on the final building products as well as the activities of actors involved in the building process. One reason for this interest is the new opportunities evolving due to introduction of advanced information and communication technology (ICT). The paper focuses on creative changes of the building process powered by user driven innovation activities. An overview of existing user driven innovation methodologies is given as well experiences from the ongoing Virtual Innovation in Construction (VIC) project. One important driving force for change is the opportunity for users to develop and articulate real needs concerning for example different functionalities of a building and its parts, but also on artifacts supporting the actual needs capture and requirements formulation during building design. A general methodological framework and meta ontology for Virtual Innovation in Construction is presented as well as findings from implementation of the method.  相似文献   
8.
The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material.  相似文献   
9.
Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.  相似文献   
10.
This paper sets focus on the relationship between knowledge production in universities and its application in everyday life. The point of departure is the linear model of knowledge production placing the university in the dominating role. This position is challenged by taking on a systems perspective where learning takes place across tradition boundaries. Universities, corporations, and governmental institutions integrate in the same knowledge production chain, blurring the whole concept of understanding universities as the linking pin in knowledge creation.  相似文献   
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