Endospore abundance, microbial growth and necromass turnover in deep sub-seafloor sediment

Two decades of scientific ocean drilling have demonstrated widespread microbial life in deep sub-seafloor sediment, and surprisingly high microbial-cell numbers. Despite the ubiquity of life in the deep biosphere, the large community sizes and the low energy fluxes in this vast buried ecosystem are not yet understood. It is not known whether organisms of the deep biosphere are specifically adapted to extremely low energy fluxes or whether most of the observed cells are in a dormant, spore-like state. Here we apply a new approach--the D:L-amino-acid model--to quantify the distributions and turnover times of living microbial biomass, endospores and microbial necromass, as well as to determine their role in the sub-seafloor carbon budget. The approach combines sensitive analyses of unique bacterial markers (muramic acid and D-amino acids) and the bacterial endospore marker, dipicolinic acid, with racemization dynamics of stereo-isomeric amino acids. Endospores are as abundant as vegetative cells and microbial activity is extremely low, leading to microbial biomass turnover times of hundreds to thousands of years. We infer from model calculations that biomass production is sustained by organic carbon deposited from the surface photosynthetic world millions of years ago and that microbial necromass is recycled over timescales of hundreds of thousands of years.     

Activation of old carbon by erosion of coastal and subsea permafrost in Arctic Siberia

The future trajectory of greenhouse gas concentrations depends on interactions between climate and the biogeosphere. Thawing of Arctic permafrost could release significant amounts of carbon into the atmosphere in this century. Ancient Ice Complex deposits outcropping along the ~7,000-kilometre-long coastline of the East Siberian Arctic Shelf (ESAS), and associated shallow subsea permafrost, are two large pools of permafrost carbon, yet their vulnerabilities towards thawing and decomposition are largely unknown. Recent Arctic warming is stronger than has been predicted by several degrees, and is particularly pronounced over the coastal ESAS region. There is thus a pressing need to improve our understanding of the links between permafrost carbon and climate in this relatively inaccessible region. Here we show that extensive release of carbon from these Ice Complex deposits dominates (57?±?2 per cent) the sedimentary carbon budget of the ESAS, the world’s largest continental shelf, overwhelming the marine and topsoil terrestrial components. Inverse modelling of the dual-carbon isotope composition of organic carbon accumulating in ESAS surface sediments, using Monte Carlo simulations to account for uncertainties, suggests that 44?±?10 teragrams of old carbon is activated annually from Ice Complex permafrost, an order of magnitude more than has been suggested by previous studies. We estimate that about two-thirds (66?±?16 per cent) of this old carbon escapes to the atmosphere as carbon dioxide, with the remainder being re-buried in shelf sediments. Thermal collapse and erosion of these carbon-rich Pleistocene coastline and seafloor deposits may accelerate with Arctic amplification of climate warming.     

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.     

考虑估值不确定和搜索成本的预售决策研究

研究了预售环境下,存在消费者估值不确定和消费者搜索成本时,销售商的最优定价和配给决策.建立一个两阶段模型,考虑一个销售商出售单一新产品给若干具有战略行为的消费者,消费者根据自身效用最大化原则选择最佳购买时机,销售商则考虑消费者的战略行为,决策最优的两期价格和预售期配给量.研究结果表明,预售期的配给量取决于单位产品的采购成本.当且仅当单位产品的采购成本介于特定范围内时,销售商应采用预售策略,此时折扣预售策略总是销售商的最佳选择.否则销售商应采用正常销售策略.研究还表明,当消费者的风险成本系数较低时,消费者的搜索成本越高,销售商的预售价格和总利润越低.否则,消费者的搜索成本越高,销售商的预售价格和总利润越高.     

Improved Classification for Compositional Data Using the <Emphasis Type="Italic">α</Emphasis>-transformation

In compositional data analysis, an observation is a vector containing nonnegative values, only the relative sizes of which are considered to be of interest. Without loss of generality, a compositional vector can be taken to be a vector of proportions that sum to one. Data of this type arise in many areas including geology, archaeology, biology, economics and political science. In this paper we investigate methods for classification of compositional data. Our approach centers on the idea of using the α-transformation to transform the data and then to classify the transformed data via regularized discriminant analysis and the k-nearest neighbors algorithm. Using the α-transformation generalizes two rival approaches in compositional data analysis, one (when α=1) that treats the data as though they were Euclidean, ignoring the compositional constraint, and another (when α = 0) that employs Aitchison’s centered log-ratio transformation. A numerical study with several real datasets shows that whether using α = 1 or α = 0 gives better classification performance depends on the dataset, and moreover that using an intermediate value of α can sometimes give better performance than using either 1 or 0.     

Recognizing Treelike k-Dissimilarities

A k-dissimilarity D on a finite set X, |X|????k, is a map from the set of size k subsets of X to the real numbers. Such maps naturally arise from edgeweighted trees T with leaf-set X: Given a subset Y of X of size k, D(Y ) is defined to be the total length of the smallest subtree of T with leaf-set Y . In case k?=?2, it is well-known that 2-dissimilarities arising in this way can be characterized by the so-called ??4-point condition??. However, in case k?>?2 Pachter and Speyer (2004) recently posed the following question: Given an arbitrary k-dissimilarity, how do we test whether this map comes from a tree? In this paper, we provide an answer to this question, showing that for k????3 a k-dissimilarity on a set X arises from a tree if and only if its restriction to every 2?k-element subset of X arises from some tree, and that 2?k is the least possible subset size to ensure that this is the case. As a corollary, we show that there exists a polynomial-time algorithm to determine when a k-dissimilarity arises from a tree. We also give a 6-point condition for determining when a 3-dissimilarity arises from a tree, that is similar to the aforementioned 4-point condition.     

Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa.

The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11-13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology.     

Adriamycin-induced chromosome damage: elevated frequencies of isochromatid aberrations in G2 and S phases.

Analysis of chromosomes from cells treated with adriamycin during G2 and S phases showed a high frequency of isochromatid-type of breaks, in addition to the expected chromatid breaks. These are interpreted as independent breaks on sister chromatids because of preferential effects of the drug in specific chromosome regions. The break points are likely to be different, but morphologically such breaks would be indistinguishable from isochromatid or chromosome breaks.