Zebraflsh z-otu, a novel Otu and Tudor domain-containing gene, is expressed in early stages of oogenesis and embryogenesis

Several studies have suggested that Otu domain had de-ubiquitinating activity and Tudor domain was important for the formation of germ cells. Here, we reported a novel zebrafish ovary-specific gene containing Otu and Tudor domain, z-otu, which was expressed at stages I-III oocytes and embryonic stages from zygotes to early blastula during embryonic cells maintained their totipotency. Therefore, z-otu might link the ubiquitin signaling pathway to early oogenesis and maintaining the totipotency of embryonic cell. (c) 2005 Elsevier B.V. All rights reserved.

Expression of the tudor-related gene Tdrd5 during development of the male germline in mice

Homologues of Drosophila germ cell determinant genes such as vasa, nanos and tudor have recently been implicated in development of the male germline in mice. In the present study, the mouse gene encoding Tudor domain containing protein 5 (TDRD5) was isolated from a 12.5-13.5 days post coitum (dpc) male-enriched subtracted cDNA library. Whole-mount in situ hybridization analysis of Tdrd5 expression in the mouse embryonic gonad indicated that this gene is upregulated in the developing testis from 12.5 dpc, with expression levels remaining higher in testis than ovary throughout embryogenesis. Expression of Tdrd5 was absent in testes isolated from W-e/W-e embryos, which lack germ cells. In situ hybridization (ISH) on cryosectioned 13.5 dpc testes suggests that expression of Tdrd5, like that of Oct4, is restricted to germ cells. Northern hybridization analysis of expression in adult tissues indicated that Tdrd5 is expressed in the testis only, implying that expression of this gene is restricted to the male germline throughout development to adulthood. (C) 2004 Elsevier B.V. All rights reserved.

Targeting the Transposase Domain of the DNA Repair Component Metnase to Enhance Chemotherapy

Previous studies have shown that the DNA repair component Metnase (SETMAR) mediates resistance to DNA damaging cancer chemotherapy. Metnase has a nuclease domain that shares homology with the Transposase family. We therefore virtually screened the tertiary Metnase structure against the 550,000 compound ChemDiv library to identify small molecules that might dock in the active site of the transposase nuclease domain of Metnase. We identified eight compounds as possible Metnase inhibitors. Interestingly, among these candidate inhibitors were quinolone antibiotics and HIV integrase inhibitors, which share common structural features. Previous reports have described possible activity of quinolones as antineoplastic agents. Therefore, we chose the quinolone ciprofloxacin for further study, based on its wide clinical availability and low toxicity. We found that ciprofloxacin inhibits the ability of Metnase to cleave DNA and inhibits Metnase-dependent DNA repair. Ciprofloxacin on its own did not induce DNA damage, but it did reduce repair of chemotherapy-induced DNA damage. Ciprofloxacin increased the sensitivity of cancer cell lines and a xenograft tumor model to clinically relevant chemotherapy. These studies provide a mechanism for the previously postulated antineoplastic activity of quinolones, and suggest that ciprofloxacin might be a simple yet effective adjunct to cancer chemotherapy. Cancer Res; 72(23); 6200-8. (C) 2012 AACR.

Domain-Specific Program Checking

Lint-like program checkers are popular tools that ensure code quality by verifying compliance with best practices for a particular programming language. The proliferation of internal domain-specific languages and models, however, poses new challenges for such tools. Traditional program checkers produce many false positives and fail to accurately check constraints, best practices, common errors, possible optimizations and portability issues particular to domain-specific languages. We advocate the use of dedicated rules to check domain-specific practices. We demonstrate the implementation of domain-specific rules, the automatic fixing of violations, and their application to two case-studies: (1) Seaside defines several internal DSLs through a creative use of the syntax of the host language; and (2) Magritte adds meta-descriptions to existing code by means of special methods. Our empirical validation demonstrates that domain-specific program checking significantly improves code quality when compared with general purpose program checking.

The Moldable Inspector: a framework for domain-specific object inspection

Answering run-time questions in object-oriented systems involves reasoning about and exploring connections between multiple objects. Developer questions exercise various aspects of an object and require multiple kinds of interactions depending on the relationships between objects, the application domain and the differing developer needs. Nevertheless, traditional object inspectors, the essential tools often used to reason about objects, favor a generic view that focuses on the low-level details of the state of individual objects. This leads to an inefficient effort, increasing the time spent in the inspector. To improve the inspection process, we propose the Moldable Inspector, a novel approach for an extensible object inspector. The Moldable Inspector allows developers to look at objects using multiple interchangeable presentations and supports a workflow in which multiple levels of connecting objects can be seen together. Both these aspects can be tailored to the domain of the objects and the question at hand. We further exemplify how the proposed solution improves the inspection process, introduce a prototype implementation and discuss new directions for extending the Moldable Inspector.

The Moldable Debugger: A Framework for Developing Domain-Specific Debuggers

Debuggers are crucial tools for developing object-oriented software systems as they give developers direct access to the running systems. Nevertheless, traditional debuggers rely on generic mechanisms to explore and exhibit the execution stack and system state, while developers reason about and formulate domain-specific questions using concepts and abstractions from their application domains. This creates an abstraction gap between the debugging needs and the debugging support leading to an inefficient and error-prone debugging effort. To reduce this gap, we propose a framework for developing domain-specific debuggers called the Moldable Debugger. The Moldable Debugger is adapted to a domain by creating and combining domain-specific debugging operations with domain-specific debugging views, and adapts itself to a domain by selecting, at run time, appropriate debugging operations and views. We motivate the need for domain-specific debugging, identify a set of key requirements and show how our approach improves debugging by adapting the debugger to several domains.

GTInspector: A Moldable Domain-Aware Object Inspector

Understanding the run-time behaviour of object-oriented applications entails the comprehension of run-time objects. Traditional object inspectors favor generic views that focus on the low-level details of the state of single objects. While universally applicable, this generic approach does not take into account the varying needs of developers that could benefit from tailored views and exploration possibilities. GTInspector is a novel moldable object inspector that provides different high-level ways to visualize and explore objects, adapted to both the object and the current developer need.

Practical domain-specific debuggers using the Moldable Debugger framework

Understanding the run-time behavior of software systems can be a challenging activity. Debuggers are an essential category of tools used for this purpose as they give developers direct access to the running systems. Nevertheless, traditional debuggers rely on generic mechanisms to introspect and interact with the running systems, while developers reason about and formulate domain-specific questions using concepts and abstractions from their application domains. This mismatch creates an abstraction gap between the debugging needs and the debugging support leading to an inefficient and error-prone debugging effort, as developers need to recover concrete domain concepts using generic mechanisms. To reduce this gap, and increase the efficiency of the debugging process, we propose a framework for developing domain-specific debuggers, called the Moldable Debugger, that enables debugging at the level of the application domain. The Moldable Debugger is adapted to a domain by creating and combining domain-specific debugging operations with domain-specific debugging views, and adapts itself to a domain by selecting, at run time, appropriate debugging operations and views. To ensure the proposed model has practical applicability (i.e., can be used in practice to build real debuggers), we discuss, from both a performance and usability point of view, three implementation strategies. We further motivate the need for domain-specific debugging, identify a set of key requirements and show how our approach improves debugging by adapting the debugger to several domains.

Histoire d'Angleterre contenant la Maison de Tudor /

Mode of access: Internet.

Histoire d'Angleterre contenant la Maison de Tudor /

Mode of access: Internet.

Histoire d'Angleterre contenant la Maison de Tudor /

Mode of access: Internet.

Histoire d'anglaterre contenant la Maison de Tudor /

Contiene: t. 1, t. 2, t. 3, t. 4, t. 5, t. 6.

Histoire d'Angleterre contenant la Maison de Tudor /

Mode of access: Internet.