Otsing: 79998

The trafficking of membrane proteins between cellular compartments is regulated by their cytoplasmic signal sequences that are recognised by adaptor proteins. Adaptor proteins recruit membrane proteins into vesicles that traffic to a specific target organelle. The cation-dependent mannose 6-phosphate receptor (CD-MPR) is a membrane receptor that transports newly synthesised lysosomal enzymes from the trans-Golgi network to the lysosome and is continuously recycled. This work focused on two sorting signals that regulate the intracellular trafficking of the CD-MPR at different cellular locations. Palmitoylation is a post-translational modification that prevents missorting of the CD-MPR to lysosomes. GGA1 and AP-1 adaptor proteins bind to the cytoplasmic tail of the CD-MPR at a signal that overlaps with a phosphorylation site. This dissertation reveals novel aspects of these sorting signals and CD-MPR trafficking.

This book presents principles, rules, guidelines, and tips useful for designers and engineers when they design mechanical parts and assemblies. It contains descriptions and examples of real-world, practical ideas that come from successful design experience. Applying the book's ideas and methods during detail design will improve how designers develop products and will result in superior mechanical designs. The contents focus on mechanical design at the detailed level: how should parts and assemblies be configured for optimum performance. Methods are provided for synthesis and analysis in mechanical design. Basic design practices that will improve the strength, robustness, function, user handling, and manufacturability of parts and assemblies are described in depth. Guidelines for selecting plastic, rubber, and metal materials are presented. Finally, the book includes useful tips for selecting and designing components such as bolts, nuts, screws, springs, and adhesive joints. This book contains information that is in the past could only be accumulated after years of experience and interaction with other designers. It is of interest to mechanical design and project engineers, as well as to industrial designers and engineering managers.

"Blood-boiling…with quippy analysis…Taub proposes straightforward fixes and ways everyday people can get involved in taking white-collar criminals to task."-San Francisco ChronicleHow ordinary Americans suffer when the rich and powerful use tax dodges or break the law to get richer and more powerful-and how we can stop it.There is an elite crime spree happening in America, and the privileged perps are getting away with it. Selling loose cigarettes on a city sidewalk can lead to a choke-hold arrest, and death, if you are not among the top 1%. But if you're rich and commit mail, wire, or bank fraud, embezzle pension funds, lie in court, obstruct justice, bribe a public official, launder money, or cheat on your taxes, you're likely to get off scot-free (or even win an election). When caught and convicted, such as for bribing their kids' way into college, high-class criminals make brief stops in minimum security "Club Fed" camps. Operate the scam from the executive suite of a giant corporation, and you can prosper with impunity. Consider Wells Fargo & Co. Pressured by management, employees at the bank opened more than three million bank and credit card accounts without customer consent, and charged late fees and penalties to account holders. When CEO John Stumpf resigned in "shame," the board of directors granted him a $134 million golden parachute.This is not victimless crime. Big Dirty Money details the scandalously common and concrete ways that ordinary Americans suffer when the well-heeled use white collar crime to gain and sustain wealth, social status, and political influence. Profiteers caused the mortgage meltdown and the prescription opioid crisis, they've evaded taxes and deprived communities of public funds for education, public health, and infrastructure. Taub goes beyond the headlines (of which there is no shortage) to track how we got here (essentially a post-Enron failure of prosecutorial muscle, the growth of "too big to jail" syndrome, and a developing implicit immunity of the upper class) and pose solutions that can help catch and convict offenders.