Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Development of Monolithic DC -Dc Converters

146 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.The mathematical analysis is supported by several experiments. The experiments demonstrate full integration of the monolithic dc-dc converters. The experimental results confirm the feasibility of the proposed concepts and suggest a few future areas of research.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Development of Monolithic DC -Dc Converters

146 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.The mathematical analysis is supported by several experiments. The experiments demonstrate full integration of the monolithic dc-dc converters. The experimental results confirm the feasibility of the proposed concepts and suggest a few future areas of research.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

An investigation into the effect of rockmass properties on mean fragmentation

Desired rock fragmentation is the need of the hour, which influences the entire mining cycle. Thus, most engineering segments pay attention to rock fragmentation and neglect by-products like ground vibration and fly rock. Structural and mechanical properties of rock mass like joint spacing, joint angle, and compressive strength of rock pose a puzzling impact on both fragmentation and ground vibration. About 80% of explosive energy that gets wasted in producing ill effects can be positively optimised, with a new set of blast design parameters upon identifying the behaviour of rock mass properties. In this connection, this research aims to investigate the influence of joint spacing, joint angle, and compressive strength of rock on fragmentation and induced ground vibration. To accomplish this task, research was carried out at an opencast coal mine. It was discovered from this research that compressive strength, joint spacing, and joint angle have a significant effect on the mean fragmentation size (MFS) and peak particle velocity (PPV). With the increase in compressive strength, MFS explicit both increase and decrease trends whilst PPV increased with a specific increase in compressive strength of the rock. An increase in joint spacing triggers both increase and decrease trends in both MFS and PPV. While there is an increase in joint angle, MFS and PPV decrease

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia▿ †

Hospital-acquired bacterial pneumonia is a common and serious complication of modern medical care. Many aspects of such infections remain unclear, including the mechanisms by which invading pathogens resist clearance by the innate immune response and the tendency of the infections to be polymicrobial. Here, we used a mouse model of infection to show that Pseudomonas aeruginosa, a leading cause of hospital-acquired pneumonia, interferes with the ability of recruited phagocytic cells to eradicate bacteria from the lung. Early in infection, phagocytic cells, predominantly neutrophils, are recruited to the lungs but are incapacitated when they enter the airways by the P. aeruginosa toxin ExoU. The resulting paucity of functioning phagocytes allows P. aeruginosa to persist within the lungs and results in local immunosuppression that facilitates superinfection with less-pathogenic bacteria. Together, our results provide explanations for previous reports linking ExoU-secreting P. aeruginosa with more severe pulmonary infections and for the tendency of hospital-acquired pneumonia to be polymicrobial