Systems and organizations: Distal and proximal thinking

The paper introduces the contributions to this special issue ofSystems Practice on Systems and Organizations: New Directions in terms ofdistal andproximal thinking. Distal thinking refers to ready-made concepts, to the finished effects and outcomes of thought and action; proximal thinking, to process and event, to the continuous and unfinished. The papers presented here deal with various aspects of the distal/proximal distinction in social systems and organizations, and especially draw out the implications of recent work in information technology, sociology of technology, accounting theory, and organization studies for a proximal conception of systems and organizations.     

A massive phytoplankton bloom induced by an ecosystem-scale iron fertilization experiment in the equatorial Pacific Ocean

The seeding of an expanse of surface waters in the equatorial Pacific Ocean with low concentrations of dissolved iron triggered a massive phytoplankton bloom which consumed large quantities of carbon dioxide and nitrate that these microscopic plants cannot fully utilize under natural conditions. These and other observations provide unequivocal support for the hypothesis that phytoplankton growth in this oceanic region is limited by iron bioavailability.     

管材超声检测中导波模式及频厚积的选择

用轴向功率流分布来选择检测自由管状结构的最佳导波模式及其最佳频厚积 ,并将混合边界元法应用于管状结构 ,对其结果的有效性进行了验证 .结果表明 :对于自由管材 ,用超声纵向L(0 ,1)模式检测时 ,频厚积在 0 .15MHz·mm以下时较为灵敏 ;用L(0 ,2 )模式检测时 ,在 1.4～ 1.8MHz·mm之间对检测管壁中央的缺陷较灵敏 ;用L(0 ,3)模式检测时 ,在 2 .0MHz·mm以下对管内外表面上的缺陷都较灵敏 .轴向功率流分布能有效地选择检测的最佳导波模式及其频厚积 .     

肌肉自发振动过程中结合几率与化学反应速率的变化

定量分析肌球蛋白与肌动蛋白丝的结合几率及相关化学反应的速率常数,对于准确掌握肌肉收缩的内在机制具有非常重要的意义.以肌肉自发振动的实验结果为依据,从振动过程所满足的动力学方程出发,推导出结合几率与肌丝滑行速度及肌节长度之间的定量关系,并求得化学反应速率随肌肉收缩的速度变化而改变的数学规律.结果显示,结合几率的基准值由溶液中主要化学成分的浓度决定;结合几率的变化值与肌肉收缩的速度成正比,与肌节长度成反比;而化学反应速率随收缩速度按指数规律变化.上述结果与实验值基本一致.     

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Systematic assessment of copy number variant detection via genome-wide SNP genotyping

SNP genotyping has emerged as a technology to incorporate copy number variants (CNVs) into genetic analyses of human traits. However, the extent to which SNP platforms accurately capture CNVs remains unclear. Using independent, sequence-based CNV maps, we find that commonly used SNP platforms have limited or no probe coverage for a large fraction of CNVs. Despite this, in 9 samples we inferred 368 CNVs using Illumina SNP genotyping data and experimentally validated over two-thirds of these. We also developed a method (SNP-Conditional Mixture Modeling, SCIMM) to robustly genotype deletions using as few as two SNP probes. We find that HapMap SNPs are strongly correlated with 82% of common deletions, but the newest SNP platforms effectively tag about 50%. We conclude that currently available genome-wide SNP assays can capture CNVs accurately, but improvements in array designs, particularly in duplicated sequences, are necessary to facilitate more comprehensive analyses of genomic variation.     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.