51 research outputs found
Comparative genetic analysis: the utility of mouse genetic systems for studying human monogenic disease
One of the long-term goals of mutagenesis programs in the mouse has been to generate mutant lines to facilitate the functional study of every mammalian gene. With a combination of complementary genetic approaches and advances in technology, this aim is slowly becoming a reality. One of the most important features of this strategy is the ability to identify and compare a number of mutations in the same gene, an allelic series. With the advent of gene-driven screening of mutant archives, the search for a specific series of interest is now a practical option. This review focuses on the analysis of multiple mutations from chemical mutagenesis projects in a wide variety of genes and the valuable functional information that has been obtained from these studies. Although gene knockouts and transgenics will continue to be an important resource to ascertain gene function, with a significant proportion of human diseases caused by point mutations, identifying an allelic series is becoming an equally efficient route to generating clinically relevant and functionally important mouse models
Steering the future. The emergence of âWesternâ futures research and its production of expertise, 1950s to early 1970s
The BRICS component model: A model-based development paradigm for complex robotics software systems
Because robotic systems get more complex all the time, developers around the world have, during the last decade, created component-based software frameworks (Orocos, Open-RTM, ROS, OPRoS, SmartSoft) to support the development and reuse of "large grained" pieces of robotics software. This paper introduces the BRICS Component Model (BCM) to provide robotics developers with a set of guidelines, metamodels and tools for structuring as much as possible the development of, both, individual components and component-based architectures, using one or more of the aforementioned software frameworks at the same time, without introducing any framework-or application-specific details. The BCM is built upon two complementary paradigms: the "5Cs" (separation of concerns between the development aspects of Computation, Communication, Coordination, Configuration and Composition) and the meta-modeling approach from Model-Driven Engineering. Copyright 2013 ACM.status: publishe
Evidence that endogenous SST inhibits ACTH and ghrelin expression by independent pathways
RecombinationâBased Assay (RBA) for Screening Bacteriophage Lambda Libraries
The recombinationâbased assay represents a convenient way to screen a complex library constructed in bacteriophage l for homology to a given sequence cloned into a specially designed plasmid. The technique serves to screen a bacteriophage library rapidly and efficiently with a sequence cloned into a plasmid; counterselection then yields the gene product of interest with its plasmid carrier deleted. Because 106 to 107 plaqueâforming units (pfu) may be screened using several petri dishes, and the homology for crossingâover need only be greater than 25 bp, the RBA represents an efficient way to screen complex l libraries rapidly for homology to a given sequence. In this procedure, a l library is screened using a specially designed plasmid carrying the desired target sequence. Recombinants arising from crossâover events between the plasmid and a bacteriophage carrying a corresponding region of homology are selected by their ability to grow on strain DM21. Growth of l on DM21 requires the presence of an allele encoded on the plasmid to suppress an amber mutation in the host strain that prevents l propagation. Recovery of the original phage carrying the target sequence requires a reversal of the homologous recombination event. This reversal occurs spontaneously, and is detected by PCR amplification using primers that flank the cloning site in the l vector.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153261/1/cpmb0612.pd
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