Surface Response-based Behavioral Modeling of Accurate Digitizers: a Case Study on a Fast Digital Integrator at CERN

A statistical approach to behavioral modeling for assessing dynamic metrological performance during the concept design of accurate digitizers is proposed. A surface-response approach based on statistical experiment design is exploited for avoiding unrealistic hypothesis of linearity, optimizing simulation, exploring operating conditions systematically, as well as verifying identification and validation uncertainty. An actual case study on the dynamic metrological characterization of a Fast Digital Integrator for high-performance magnetic measurements at the European Organization for Nuclear Research (CERN) is presented

Capturing the facets of evolvability in a mechanistic framework

‘Evolvability’ – the ability to undergo adaptive evolution – is a key concept for understanding and predicting the response of biological systems to environmental change. Evolvability has various facets and is applied in many ways, easily leading to misunderstandings among researchers. To clarify matters, we first categorize the mechanisms and organismal features underlying evolvability into determinants providing variation, determinants shaping the effect of variation on fitness, and determinants shaping the selection process. Second, we stress the importance of timescale when studying evolvability. Third, we distinguish between evolvability determinants with a broad and a narrow scope. Finally, we highlight two contrasting perspectives on evolvability: general evolvability and specific evolvability. We hope that this framework facilitates communication and guides future research

A RESEARCH ON EMISSION ALLOWANCE TRADING SYSTEM IN CHINA

随着环境问题的日益严重，各国政府开始将价格、税收、财政、信贷、收费、保险等经济手段运用到环境管理之中，推行一系列环境经济政策，排污权交易就是其中之一。排污权交易有着深厚的经济学基础，即环境纳污能力的商品化、市场化和外部不经济的内在化。排污权交易制度的实施可以在社会总污染治理成本最小化的前提下促进企业的减排以及治污技术的革新，且通过这种手段政府对环境质量的调控更加灵活。污染企业在排污权交易制度安排的激励下，不仅将治污减排视为企业的技术和合规管理，还可以通过对排污权市场价格的预测，对企业排污治污成本的精确核算，对减排行为进行经济评估，将排污管理融入到财务管理中。本文在总结分析比较美国、欧洲、日本的...Along with the increasingly serious environmental problems, governments try to apply economics principles, like price, tax, finance, credit, charge, insurance, to environmental policy. The emission allowance trade system is one of them. This policy can promote the enterprise to reduce the emission and improve the emission-reducing technology with minimizing the social pollution control cost, and t...学位：管理学硕士院系专业：管理学院会计系_会计学学号：1752006115128

Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors

The development of functional peripheral ganglia requires a balance of specification of both neuronal and glial components. In the developing dorsal root ganglia (DRGs), these compo- nents form from partially-restricted bipotent neuroglial precursors derived from the neural crest. Work in mouse and chick has identified several factors, including Delta/Notch signal- ing, required for specification of a balance of these components. We have previously shown in zebrafish that the Sry-related HMG domain transcription factor, Sox10, plays an unex- pected, but crucial, role in sensory neuron fate specification in vivo. In the same study we described a novel Sox10 mutant allele, sox10baz1, in which sensory neuron numbers are elevated above those of wild-types. Here we investigate the origin of this neurogenic pheno- type. We demonstrate that the supernumerary neurons are sensory neurons, and that enteric and sympathetic neurons are almost absent just as in classical sox10 null alleles; peripheral glial development is also severely abrogated in a manner similar to other sox10 mutant alleles. Examination of proliferation and apoptosis in the developing DRG reveals very low levels of both processes in wild-type and sox10baz1, excluding changes in the bal- ance of these as an explanation for the overproduction of sensory neurons. Using chemical inhibition of Delta-Notch-Notch signaling we demonstrate that in embryonic zebrafish, as in mouse and chick, lateral inhibition during the phase of trunk DRG development is required to achieve a balance between glial and neuronal numbers. Importantly, however, we show that this mechanism is insufficient to explain quantitative aspects of the baz1 phenotype. The Sox10(baz1) protein shows a single amino acid substitution in the DNA binding HMG domain; structural analysis indicates that this change is likely to result in reduced flexibility in the HMG domain, consistent with sequence-specific modification of Sox10 binding to DNA. Unlike other Sox10 mutant proteins, Sox10(baz1) retains an ability to drive neurogenin1 transcription. We show that overexpression of neurogenin1 is sufficient to produce supernu- merary DRG sensory neurons in a wild-type background, and can rescue the sensory neu- ron phenotype of sox10 morphants in a manner closely resembling the baz1 phenotype. We conclude that an imbalance of neuronal and glial fate specification results from the Sox10 (baz1) protein\u2019s unique ability to drive sensory neuron specification whilst failing to drive glial development. The sox10baz1 phenotype reveals for the first time that a Notch-dependent lat- eral inhibition mechanism is not sufficient to fully explain the balance of neurons and glia in the developing DRGs, and that a second Sox10-dependent mechanism is necessary. Sox10 is thus a key transcription factor in achieving the balance of sensory neuronal and glial fates

miR-7 Controls the Dopaminergic/Oligodendroglial Fate through Wnt/\u3b2-catenin Signaling Regulation

During the development of the central nervous system, the proliferation of neural progenitors and differentiation of neurons and glia are tightly regulated by different transcription factors and signaling cascades, such as the Wnt and Shh pathways. This process takes place in cooperation with several microRNAs, some of which evolutionarily conserved in vertebrates, from teleosts to mammals. We focused our attention on miR-7, as its role in the regulation of cell signaling during neural development is still unclear. Specifically, we used human stem cell cultures and whole zebrafish embryos to study, in vitro and in vivo, the role of miR-7 in the development of dopaminergic (DA) neurons, a cell type primarily affected in Parkinson's disease. We demonstrated that the zebrafish homologue of miR-7 (miR-7a) is expressed in the forebrain during the development of DA neurons. Moreover, we identified 143 target genes downregulated by miR-7, including the neural fate markers TCF4 and TCF12, as well as the Wnt pathway effector TCF7L2. We then demonstrated that miR-7 negatively regulates the proliferation of DA-progenitors by inhibiting Wnt/\u3b2-catenin signaling in zebrafish embryos. In parallel, miR-7 positively regulates Shh signaling, thus controlling the balance between oligodendroglial and DA neuronal cell fates. In summary, this study identifies a new molecular cross-talk between Wnt and Shh signaling pathways during the development of DA-neurons. Being mediated by a microRNA, this mechanism represents a promising target in cell differentiation therapies for Parkinson's disease

Understanding 'non-genetic' inheritance : insights from molecular-evolutionary crosstalk

The idea for this paper was initially proposed by I.A.-K. and was further developed by all authors in a workshop generously funded by grant No 789240 from the European Research Council (ERC) to F.J.W. S.E.S. acknowledges support from Wesleyan University and The John Templeton Foundation.Understanding the evolutionary and ecological roles of 'non-genetic' inheritance (NGI) is daunting due to the complexity and diversity of epigenetic mechanisms. We draw on insights from molecular and evolutionary biology perspectives to identify three general features of 'non-genetic' inheritance systems: (i) they are functionally interdependent with, rather than separate from, DNA sequence; (ii) precise mechanisms vary phylogenetically and operationally; and (iii) epigenetic elements are probabilistic, interactive regulatory factors and not deterministic 'epialleles' with defined genomic locations and effects. We discuss each of these features and offer recommendations for future empirical and theoretical research that implements a unifying inherited gene regulation (IGR) approach to studies of 'non-genetic' inheritance.Publisher PDFPeer reviewe