Sitosterolemia: Twenty Years of Discovery of the Function of \u3ci\u3eABCG5ABCG8\u3c/i\u3e

Sitosterolemia is a lipid disorder characterized by the accumulation of dietary xenosterols in plasma and tissues caused by mutations in either ABCG5 or ABCG8. ABCG5 ABCG8 encodes a pair of ABC half transporters that form a heterodimer (G5G8), which then traffics to the surface of hepatocytes and enterocytes and promotes the secretion of cholesterol and xenosterols into the bile and the intestinal lumen. We review the literature from the initial description of the disease, the discovery of its genetic basis, current therapy, and what has been learned from animal, cellular, and molecular investigations of the transporter in the twenty years since its discovery. The genomic era has revealed that there are far more carriers of loss of function mutations and likely pathogenic variants of ABCG5 ABCG8 than previously thought. The impact of these variants on G5G8 structure and activity are largely unknown. We propose a classification system for ABCG5 ABCG8 mutants based on previously published systems for diseases caused by defects in ABC transporters. This system establishes a framework for the comprehensive analysis of disease-associated variants and their impact on G5G8 structure–function

Optimization of kitting operations for an automated microelectronics assembly process

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering; and, (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; in conjunction with the Leaders for Manufacturing Program at MIT, 2006.Includes bibliographical references (p. [73]).Raytheon's Solid-State Microwave (SSM) manufacturing area produces a low-volume, high mix assortment of Microwave Integrated Circuits (MIC) for airborne radars. The current kitting process for pick-and-place assembly is manually-intensive with significant die handling, resulting in multiple opportunities for damage and loss as well as accidental switching of near-identical components. These defects are difficult to detect and are often not discovered until the completed MICs are tested, by which time significant value has been added. The core of this project was to reduce kitting defects, total process cycle time and overall cost through reduction of "touch" labor and kit screenings. The establishment of customized die packaging requirements will result in the optimization of die packaging before the material is received into the storeroom. These new packaging requirements, in combination with the implementation of a point-of-use store for residual materials on the factory floor, enables in large part the elimination of the kitting process, resulting in significant reduction in handling and correlated reductions in lost or damaged parts and "wrong part" defects.(cont.) This initiative was piloted on a single MIC line, but the solution was designed to be portable to other areas of SSM/SCM kitting operations. This thesis documents the process by which the new process was developed and piloted at Raytheon, as well as the organizational issues and barriers that made the project implementation challenging. In particular, successful implementation of the new processes will require a major shift in organizational thinking towards Total Cost of Ownership and greater cooperation across the boundary between the Solid-State Microwave and Supply Chain Management organizations.by Gregory A. Williams.M.B.A.S.M

Practice in Child Phonological Disorders: Tackling some Common Clinical Problems

Goal of presentation is to identify areas of child phonology that clinicans have difficulty with

Non-invasive neurosensory testing used to diagnose and confirm successful surgical management of lower extremity deep distal posterior compartment syndrome

<p>Abstract</p> <p>Background</p> <p>Chronic exertional compartment syndrome (CECS) is characterized by elevated pressures within a closed space of an extremity muscular compartment, causing pain and/or disability by impairing the neuromuscular function of the involved compartment. The diagnosis of CECS is primarily made on careful history and physical exam. The gold standard test to confirm the diagnosis of CECS is invasive intra-compartmental pressure measurements. Sensory nerve function is often diminished during symptomatic periods of CECS. Sensory nerve function can be documented with the use of non-painful, non-invasive neurosensory testing.</p> <p>Methods</p> <p>Non-painful neurosensory testing of the myelinated large sensory nerve fibers of the lower extremity were obtained with the Pressure Specified Sensory Device™ in a 25 year old male with history and invasive compartment pressures consistent with CECS both before and after running on a tread mill. After the patient's first operation to release the deep distal posterior compartment, the patient failed to improve. Repeat sensory testing revealed continued change in his function with exercise. He was returned to the operating room where a repeat procedure revealed that the deep posterior compartment was not completely released due to an unusual anatomic variant, and therefore complete release was accomplished.</p> <p>Results</p> <p>The patient's symptoms numbness in the plantar foot and pain in the distal calf improved after this procedure and his repeat sensory testing performed before and after running on the treadmill documented this improvement.</p> <p>Conclusion</p> <p>This case report illustrates the principal that non-invasive neurosensory testing can detect reversible changes in sensory nerve function after a provocative test and may be a helpful non-invasive technique to managing difficult cases of persistent lower extremity symptoms after failed decompressive fasciotomies for CECS. It can easily be performed before and after exercise and be repeated at multiple intervals without patient dissatisfaction. It is especially helpful when other traditional testing has failed.</p

Development of Nutrition Curriculum for Adults with I/DD: Part of a Mentoring Program to Improve Nutrition Knowledge and Self-Efficacy

poster presentation undergraduate - Gregory Lon

Potential converter for laser-power beaming

Future space missions, such as those associated with the Space Exploration Initiative (SEI), will require large amounts of power for operation of bases, rovers, and orbit transfer vehicles. One method for supplying this power is to beam power from a spaced based or Earth based laser power station to a receiver where laser photons can be converted to electricity. Previous research has described such laser power stations orbiting the Moon and beaming power to a receiver on the surface of the Moon by using arrays of diode lasers. Photovoltaic converters that can be efficiently used with these diode lasers are described

Design & manufacture of a high-performance bicycle crank by additive manufacturing

A new practical workflow for the laser Powder Bed Fusion (PBF) process, incorporating topological design, mechanical simulation, manufacture, and validation by computed tomography is presented, uniquely applied to a consumer product (crank for a high-performance racing bicycle), an approach that is tangible and adoptable by industry. The lightweight crank design was realised using topology optimisation software, developing an optimal design iteratively from a simple primitive within a design space and with the addition of load boundary conditions (obtained from prior biomechanical crank force–angle models) and constraints. Parametric design modification was necessary to meet the Design for Additive Manufacturing (DfAM)considerations for PBF to reduce build time, material usage, and post-processing labour. Static testing proved performance close to current market leaders with the PBF manufactured crank found to be stiffer than the benchmark design (static load deflection of 7.0±0.5 mm c.f. 7.67mm for a Shimano crank at a competitive mass (155g vs. 175g). Dynamic mechanical performance proved inadequate, with failure at 2495±125cycles; the failure mechanism was consistent in both its form and location. This research is valuable and novel as it demonstrates a complete work flow from design, manufacture, post-treatment, and validation of a highly loaded PBF manufactured consumer component, offering practitioners a validated approach to the application of PBF for components with application outside of the accepted sectors (aerospace, biomedical, autosports, space, and power generation)

On the nature of the z=0 X-ray absorbers: I. Clues from an external group

Absorption lines of OVII at redshift zero are observed in high quality Chandra spectra of extragalactic sightlines. The location of the absorber producing these lines, whether from the corona of the Galaxy or from the Local Group or even larger scale structure, has been a matter of debate. Here we study another poor group like our Local Group to understand the distribution of column density from galaxy to group scales. We show that we cannot yet rule out the group origin of z=0 systems. We further argue that the debate over Galactic vs. extragalactic origin of z=0 systems is premature as they likely contain both components and predict that future higher resolution observations will resolve the z=0 systems into multiple components.Comment: Submitted to ApJ

Resilience mediates the relationship between household dysfunction in childhood and postpartum depression in adolescent mothers in Peru

National Institute of Mental HealthRevisión por pare