Hermetically sealed encasements for historic document display and preservation

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 191-194).The goal of this thesis was to develop designs and methods for the preservation and display of historic documents. The results were applied via the design, manufacture, and installation of five hermetic display encasements for the original Massachusetts Constitution (1780), a Goddard broadside of the Declaration of Independence (1777), an original copy of the Bill of Rights (1789), the 1629 Charter of Massachusetts Bay, and the 1692 Charter of the Province of Massachusetts Bay. In addition to meeting the aesthetic requirements for a permanent exhibit, the encasements had to have leak rates that would maintain less than 0.5 % oxygen content over 20 years and preserve 40 % relative humidity at 70 'F. Furthermore, the encasement portion of the project had a 300,000 USD total budget, approximately one tenth the budget allocated for the "Charters of Freedom" project at the National Archives. The encasements designed for this project incorporated a novel seal arrangement that "floats" the glass and allows for helium leak testingat any time, without disturbing the document. These design choices were motivated by developing a model for permeation of gases through a network of polymer seals. Preparing the preservation environment also required the design and fabrication of the "Moisturematic", a device that allows for controlled filling of a vessel with precisely humidified gas. Continuous monitoring of the atmosphere inside the encasements was made possible by the development of specialized instrumentation. In January 2009, these historic documents were put on permanent display in the Treasures Gallery at The Massachusetts Archives. Initial leak testing indicates that all encasement have preservation quality environments exceeding 20 years. In addition to design rules for developing high quality, relatively low cost environments for preservation, this thesis presents a roadmap for design of more generalized hermetic sealing and conditioned environments.by Keith Vaughn Durand.Ph.D

A Two-Pressure Humidity Generator

A device for precisely humidifying a process gas is presented, with particular application to document preservation. The machine is designed to minimize the risk of damage from overpressure by incorporating multiple safety mechanisms and a simple user interface. The design theory is presented, discussed, and verified. This device is capable of generating humidified gases with relative humidities between 7 and 96 to high accuracy. At conditions suitable for document preservation, the machine is accurate to within 3.5 %, generating a relative humidity of (40 1.4)

Design of an energy efficient and economical actuator for automobile windows

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references.This thesis describes the design and analysis of an efficient, yet low cost, drum driven window actuation system for an automotive power window. The design uses a novel approach that involves using cables to both actuate and constrain the window. Test units were constructed and cycled well beyond the typical life expectancy of a window actuator, demonstrating that this technology is robust enough to be considered as a replacement for current mechanisms. Variations on the design that may produce either better longevity or higher efficiency are also presented, along with the tradeoffs that must be considered.by Keith V. Durand.S.M

Design of a chain driven limited slip differential and rear driveline package for Formula SAE applications

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005.Includes bibliographical references (leaf 52).by Keith Durand.S.B

A novel cardioport for beating-heart, image-guided intracardiac surgery

Objective Intracardiac beating-heart procedures require the introduction and exchange of complex instruments and devices. To prevent potential complications such as air embolism and bleeding, a universal cardioport was designed and tested. Methods The design consists of a port body and a series of interchangeable sleeves. The port uses a fluid purging system to remove air from the instrument before insertion into the heart, and a valve system minimizes blood loss during instrument changes. Results The cardioport was tested ex vivo and in vivo in pigs (n = 5). Beating-heart procedures, such as septal defect closure and mitral valve repair, were modeled. Ex vivo trials (n = 150) were performed, and no air emboli were introduced using the port. In comparison, air emboli were detected in 40% to 85% of the cases without the use of the port-based purging system. Port operation revealed excellent ergonomics and minimal blood loss. Conclusions A novel cardioport system designed to prevent air entry and blood loss from transcardiac instrument introduction was shown to be an enabling platform for intracardiac beating-heart surgery. The port system improves safety and facilitates further development of complex instruments and devices for transcardiac beating-heart surgery.Center for Integration of Medicine and Innovative Technology (Award 07-026)National Institutes of Health (U.S.) (National Heart, Lung, and Blood Institute Award 5R01HL073647)Massachusetts Technology Transfer Cente

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A first update on mapping the human genetic architecture of COVID-19

peer reviewe