Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing

Alternative splicing of pre-messenger RNAs diversifies gene products in eukaryotes and is guided by factors that enable spliceosomes to recognize particular splice sites. Here we report that alternative splicing of Saccharomyces cerevisiae SRC1 pre-mRNA is promoted by the conserved ubiquitin-like protein Hub1. Structural and biochemical data show that Hub1 binds non-covalently to a conserved element termed HIND, which is present in the spliceosomal protein Snu66 in yeast and mammals, and Prp38 in plants. Hub1 binding mildly alters spliceosomal protein interactions and barely affects general splicing in S. cerevisiae. However, spliceosomes that lack Hub1, or are defective in Hub1-HIND interaction, cannot use certain non-canonical 5' splice sites and are defective in alternative SRC1 splicing. Hub1 confers alternative splicing not only when bound to HIND, but also when experimentally fused to Snu66, Prp38, or even the core splicing factor Prp8. Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier.     

Multivariate Forecasting with BVARs and DSGE Models

In this paper I assess the ability of Bayesian vector autoregressions (BVARs) and dynamic stochastic general equilibrium (DSGE) models of different size to forecast comovements of major macroeconomic series in the euro area. Both approaches are compared to unrestricted VARs in terms of multivariate point and density forecast accuracy measures as well as event probabilities. The evidence suggests that BVARs and DSGE models produce accurate multivariate forecasts even for larger datasets. I also detect that BVARs are well calibrated for most events, while DSGE models are poorly calibrated for some. In sum, I conclude that both are useful tools to achieve parameter dimension reduction. Copyright © 2016 John Wiley & Sons, Ltd.     

A TWO-PHASE APPROACH TO FUZZY SYSTEM IDENTIFICATION

A two-phase approach to fuzzy system identification is proposed. The first phase produces a baseline design to identify a prototype fuzzy system for a target system from a collection of input-output data pairs. It uses two easily implemented clustering techniques: the subtractive clustering method and the fuzzy c-means (FCM) clustering algorithm. The second phase (fine tuning) is executed to adjust the parameters identified in the baseline design. This phase uses the steepest descent and recursive least-squares estimation methods. The proposed approach is validated by applying it to both a function approximation type of problem and a classification type of problem. An analysis of the learning behavior of the proposed approach for the two test problems is conducted for further confirmation.     

A Set of Conventions,a Model: An Application of Stafford Beer’s Viable Systems Model to the Strategic Planning Process

In contemplating better ways to manage, Stafford Beer says the big problem is that you are not determining absolute facts: you are establishing a set of conventions. Hence his view, that a model is neither true nor false: it is more or less useful. And while this paper suggests Beer’s Viable Systems Model (VSM) is overwhelmingly more, rather than less useful, that the VSM and its founding theories are virtually unknown at the level of everyday management begs the question, why? Over time we have learned about the usefulness of the VSM compared to other management theories, when used in the contest of the organisational strategic planning process. Thus through a sequence of diagrams based on Beer’s original drawings, we show how the VSM came to underpin a process for strategic planning in one organisation. The paper has three aims; to attach an everyday ‘common speak’ understanding to some of Beer’s work, to demonstrate how we have learned to appreciate the usefulness of the VSM and its associated diagrams and conventions and to suggest a link between the Action Research change methodology and Beer’s work.     

香港和深圳市铁路需求预测

亚洲的许多城市为解决城市交通问题,正关注铁路系统并允许进一步发展．对铁路系统的规划与设计必须有强有力的预测,同时对于有效路径选择效用方面的细微差别必须是敏感的．EMME／2中缺省的公交分配程序能生成出行费用矩阵,这些矩阵适用于战略模型,但是在用这个缺省的程序对铁路进行具体的预测时限制会增加．本文简述了基于logit模型的多路径公交EMME／2模型结构,它适用于低服务间隔的城市铁路网．该模型允许子模式（铁路或其他）的选择,车站和车站间路径的选择,并描述了所必需的网络编码和交通分配增加的自由选择等特征．     

High rates of photosynthesis in the desert shrub Chrysothamnus nauseosus ssp. albicaulis

  Basic aspects of photosynthesis were investigated in white rubber rabbitbrush ( Chrysothamnus nauseosus (Pallas) Britt. ssp. albicaulis ), a common C 3 deciduous shrub native to arid regions of the western U.S. Under favorable field conditions, net photosynthesis (P n ) ranged from 36 to 73 mgCO 2 · dm – 2 · hr – 1 , which is relatively high for a woody species. The leaves from the actively growing flowering shoots exhibited higher P n than those on the vegetative shoots. P n also varied according to the age of the leaves and the location of the plants. P n did not light saturate even at quantum flux densities (QFD) equivalent to full sunlight. The light compensation point was relatively high (ca 100 μ mol · m – 2 · S – 1 ), perhaps due to the presence of a tomentose vestiture on the leaf surface. At high QFD's, the stomatal conductance was high (ca 520 mmol · m – 2 · s – 1 ) for a woody species. RUBP - carboxylase content of the leaves ranged from 20 to 22 mg per gram F.W., which is similar to that found in most C 3 crop species. These results suggest that rabbitbrush is able to maintain high rates of P n , at least under nonstressed conditions.           

Prairie dog colony attributes and associated vertebrate species

A survey of colony attributes and associated vertebrates on black - tail ( Cynomys ludovicianus ), Gunnison's ( C. gunnisoni ), and white - tail ( C. leucurus ) prairie dogs was made. A belt transect 1.6 km wide and 13,334 km long from Hobbs, New Mexico, to the Utah - Wyoming state line was surveyed. There were 47 colonies located (4760 ha comprising 2.2 percent) in the belt. Intercolony distances varied significantly. Three black - tail towns averaged 33 ha in area (SD = 26, range 10 – 61), II Gunnison's averaged 46 ha (SD = 43, range 16 – 150), and 33 white - tail towns averaged 125 ha (SD = 200, range 0.2 – 958). Badger activity was positively and significantly correlated to colony size and number of burrow openings on Gunnison's and white - tail towns. There were 107 vertebrate species and subspecies (one amphibian, 25 reptiles, 51 birds, 30 mammals) observed on prairie dog colonies. Results of our surveys are compared with prairie dog studies elsewhere. The role of prairie dogs and relationships to some vertebrates species are discussed.     

Susceptibility variants for male-pattern baldness on chromosome 20p11

We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway.     

Immunogenicity of necrotic cell death

The mode of tumor cell death has significant effects on anti-tumor immunity. Although, previously it was thought that cell death is an inert effect, different investigators have clearly shown that dying tumors can attract, activate and mature professional antigen presenting cells and dendritic cells. In addition, others and we have shown that the type of tumor cell death not only controls the presence or absence of specific tumor antigens, but also can result in immunological responses ranging from immunosuppression to anti-tumor immunity. More importantly, it is possible to enhance anti-tumor immunity both in vitro and in vivo by targeting specific molecular mechanisms such as oligopeptidases and the proteasome. These studies not only extend our knowledge on basic immunological questions and the induction of anti-tumor immunity, but also have implications for all types of cancer treatments, in which rapid tumor cell death is induced. This review is a comprehensive summary of cell death and particularly necrosis and the pivotal role it plays in anti-tumor immunity.