节理边坡渗流离散元模拟及边坡可靠性分析

采用定性研究和定量分析相结合的方法，对地下水对节理边坡稳定性的影响进行了较为全面的研究。首先采用离散元方法进行了节理边坡地下水流动的数值模拟；其次用不确定性方法——模糊点估计方法对有水和无水作用两种情况下的边坡稳定性进行了模糊随机可靠性对比分析。研究表明，地下水的存在使边坡的破坏面积增大，破坏概率剧增，边坡可靠性指标极大地降低，因此地下水对节理边坡稳定性具有不可忽视的作用。     

A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis

A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies.     

Pilus chaperones represent a new type of protein-folding catalyst

Adhesive type 1 pili from uropathogenic Escherichia coli strains have a crucial role during infection by mediating the attachment to and potentially the invasion of host tissue. These filamentous, highly oligomeric protein complexes are assembled by the 'chaperone-usher' pathway, in which the individual pilus subunits fold in the bacterial periplasm and form stoichiometric complexes with a periplasmic chaperone molecule that is essential for pilus assembly. The chaperone subsequently delivers the subunits to an assembly platform (usher) in the outer membrane, which mediates subunit assembly and translocation to the cell surface. Here we show that the periplasmic type 1 pilus chaperone FimC binds non-native pilus subunits and accelerates folding of the subunit FimG by 100-fold. Moreover, we find that the FimC-FimG complex is formed quantitatively and very rapidly when folding of FimG is initiated in the presence of both FimC and the assembly-competent subunit FimF, even though the FimC-FimG complex is thermodynamically less stable than the FimF-FimG complex. FimC thus represents a previously unknown type of protein-folding catalyst, and simultaneously acts as a kinetic trap preventing spontaneous subunit assembly in the periplasm.     

Degree of methylation of transgenes is dependent on gamete of origin

Data derived from both pronuclear transplantation experiments and classical genetic experiments indicate that the maternal and paternal genetic contributions to the mammalian zygote nucleus do not function equivalently during subsequent development. These observations have been interpreted as resulting from differential 'genome imprinting' during male and female gametogenesis. The molecular mechanism responsible for genome imprinting is unknown, but data gathered to date require that the mechanism fulfill at least four criteria: (1) the imprint must be physically linked to the pronucleus; (2) the imprint must persist through DNA replication and cell division; (3) the mechanism must be capable of affecting gene expression; and (4) the mechanism must be capable of switching the identity of the imprint from one sex to the other in successive generations. One molecular mechanism which could satisfy the first three criteria is differential DNA methylation during gametogenesis itself, or before formation of the zygote nucleus during embryogenesis. We present data indicating that the methylation patterns of exogenous DNA sequences in transgenic mice can be changed by switching their gamete of origin in successive generations. These data suggest that DNA methylation can also satisfy the fourth criterion for an imprinting mechanism.     

Abductive Reasoning as a Way of Worldmaking

The author deals with the operational core oflogic, i.e. its diverse procedures ofinference, in order to show that logicallyfalse inferences may in fact be right because –in contrast to logical rationality – theyactually enlarge our knowledge of the world.This does not only mean that logically trueinferences say nothing about the world, butalso that all our inferences are inventedhypotheses the adequacy of which cannot beproved within logic but only pragmatically. Inconclusion the author demonstrates, through therelationship between rule-following andrationality, that it is most irrational to wantto exclude the irrational: it may, at times, bemost rational to think and infer irrationally.Focussing on the operational aspects of knowingas inferring does away with the hiatus betweenlogic and life, cognition and the world(reality) – or whatever other dualism one wantsto invoke –: knowing means inferring, inferringmeans rule-governed interpreting, interpretingis a constructive, synthetic act, and aconstruction that proves adequate (viable) inthe ``world of experience', in life, in thepraxis of living, is, to the constructivistmind, knowledge. It is the practice of livingwhich provides the orienting standards forconstructivist thinking and its judgments ofviability. The question of truth is replaced bythe question of viability, and viabilitydepends on the (right) kind of experiential fit.     

Proteome survey reveals modularity of the yeast cell machinery

Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. Through systematic tagging of open reading frames (ORFs), the majority of complexes were purified several times, suggesting screen saturation. The richness of the data set enabled a de novo characterization of the composition and organization of the cellular machinery. The ensemble of cellular proteins partitions into 491 complexes, of which 257 are novel, that differentially combine with additional attachment proteins or protein modules to enable a diversification of potential functions. Support for this modular organization of the proteome comes from integration with available data on expression, localization, function, evolutionary conservation, protein structure and binary interactions. This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling.     

An integrated view of the chemistry and mineralogy of martian soils

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.     

Voluntarism and Citizenship: A Response to Lena Dominelli

This article responds to Dominelli’s contribution by mapping three lines of discussion. The first relates to the issue of how to understand voluntary work with regard to the realization of citizenship. The authors argue that this understanding depends on the way citizenship is conceived. Whereas a rights-based conception of citizenship focuses on issues of equal access to voluntary work, a duty-oriented notion of citizenship tends to see voluntarism as embedded in an educational strategy, alongside professionalized social work. The authors plead for an alternative understanding of voluntary work and social work as joined partners in practices of ‘learning democracy’. The second line of discussion revolves around the relation between social and political dimensions of citizenship. With Dominelli, the authors point out how the obscuring of the political dimension risks to nurture societal discourses that put pressure on the welfare state. The third point relates to the difficulties in positioning voluntary work with regard to professional social work. One of these difficulties is the tendency to over-romanticize voluntary work as warm, informal, generous, while giving an exclusively technical reading of social work professionalization.