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21.
In several rural areas in Colombia there is a serious lack of water quality supply. Thereby the problematic situation is understood as complex one that involves stakeholders with pluralistic interests, multiple variables and requires the development of sustainable and suitable solutions. In order to address this issue, this paper proposes an integration of engineering design framework (CDIO) with a systemic approach. Particularly the approach emphasizes on systemic elements such as autonomy, systems within systems, cooperation between stakeholders and cause effect relations; it also proposes a previous observing phase for engineering design framework. Thus the proposed systemic framework aims to generate projects that improve living conditions in rural communities and promote the production of knowledge between the stakeholders to ensure sustainability in the long term. To illustrate the proposal, this work contains a case study that discusses a project carried out by a research team—Ingenieros Sin Fronteras Colombia—in a rural district near to Colombia’s capital. The experience, which involved and benefited 16 families in the community, provided strong evidence to support the proposed framework. The paper concludes with a discussion about the replication of this proposal in other contexts.  相似文献   
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An optical/infrared telescope of 20-100 m aperture located on the Moon would be able to observe objects 100 to 1,000 times fainter than the proposed next generation of space telescopes. The infrared region of the spectrum is particularly important for observations of objects at redshifts z > 7. The apparent simplicity and low mass of a liquid mirror telescope, compared with a traditional pointable glass mirror, suggest that the concept should be considered further. A previously proposed liquid mirror telescope, based upon a spinning liquid metallic alloy, is not appropriate for infrared applications, which will require a liquid below 130 K. Here we report the successful coating of an ionic liquid with silver. The surface is smooth and the silver coating is stable on a timescale of months. The underlying ionic liquid does not evaporate in a vacuum and remains liquid down to a temperature of 175 K. Given that there are approximately 10(6) simple and approximately 10(18) ternary ionic liquids, it should be possible to synthesize liquids with even lower melting temperatures.  相似文献   
24.
We undertook a quantitative trait locus (QTL) analysis in mice to identify modifier genes that might influence the severity of human iron disorders. We identified a strong QTL on mouse chromosome 9 that differentially affected macrophage iron burden in C57BL/10J and SWR/J mice. A C57BL/10J missense allele of an evolutionarily conserved gene, Mon1a, cosegregated with the QTL in congenic mouse lines. We present evidence that Mon1a is involved in trafficking of ferroportin, the major mammalian iron exporter, to the surface of iron-recycling macrophages. Differences in amounts of surface ferroportin correlate with differences in cellular iron content. Mon1a is also important for trafficking of cell-surface and secreted molecules unrelated to iron metabolism, suggesting that it has a fundamental role in the mammalian secretory apparatus.  相似文献   
25.
We report a population of the mussel the black sandshell ( Ligumia recta [Lamarck, 1819]) from the Carrot River in Saskatchewan, far north of the species’ known range in southern Manitoba and northwestern Ontario. Ligumia recta is reported to be declining substantially in its abundance and range, and this occurrence provides valuable information for the construction of a species status report in Canada.  相似文献   
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Scheduling is one of the most difficult issues in t he planning and operations of the aircraft services industry. In this paper, t he various scheduling problems in ground support operation of an aircraft mainte nance service company are addressed. The authors developed a set of vehicle rout ings to cover each schedule flights; the objectives pursued are the maximization of vehicle and manpower utilization and minimization of operation time. To obta in the goals, an integer-programming model with geneti...  相似文献   
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The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.  相似文献   
28.
CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.  相似文献   
29.
Ras proteins regulate cellular growth and differentiation, and are mutated in 30% of cancers. We have shown recently that Ras is activated on and transmits signals from the Golgi apparatus as well as the plasma membrane but the mechanism of compartmentalized signalling was not determined. Here we show that, in response to Src-dependent activation of phospholipase Cgamma1, the Ras guanine nucleotide exchange factor RasGRP1 translocated to the Golgi where it activated Ras. Whereas Ca(2+) positively regulated Ras on the Golgi apparatus through RasGRP1, the same second messenger negatively regulated Ras on the plasma membrane by means of the Ras GTPase-activating protein CAPRI. Ras activation after T-cell receptor stimulation in Jurkat cells, rich in RasGRP1, was limited to the Golgi apparatus through the action of CAPRI, demonstrating unambiguously a physiological role for Ras on Golgi. Activation of Ras on Golgi also induced differentiation of PC12 cells, transformed fibroblasts and mediated radioresistance. Thus, activation of Ras on Golgi has important biological consequences and proceeds through a pathway distinct from the one that activates Ras on the plasma membrane.  相似文献   
30.
Graded persistent activity in entorhinal cortex neurons   总被引:30,自引:0,他引:30  
Egorov AV  Hamam BN  Fransén E  Hasselmo ME  Alonso AA 《Nature》2002,420(6912):173-178
Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time. Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential. Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.  相似文献   
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