Electronic markets for home mortgages

Thesis (M.S.)--Massachusetts Institute of Technology, Sloan School of Management, 1992.Includes bibliographical references (leaves 56-58).by Christopher M. Hess.M.S

Concept development of a Mach 4 high-speed civil transport

A study was conducted to configure and analyze a 250 passenger, Mach 4 High Speed Civil Transport with a design range of 6500 n.mi. The design mission assumed an all-supersonic cruise segment and no community noise or sonic boom constraints. The study airplane was developed in order to examine the technology requirements for such a vehicle and to provide an unconstrained baseline from which to assess changes in technology levels, sonic boom limits, or community noise constraints in future studies. The propulsion, structure, and materials technologies utilized in the sizing of the study aircraft were assumed to represent a technology availability date of 2015. The study airplane was a derivative of a previously developed Mach 3 concept and utilized advanced afterburning turbojet engines and passive airframe thermal protection. Details of the configuration development, aerodynamic design, propulsion system, mass properties, and mission performance are presented. The study airplane was estimated to weigh approx. 866,000 lbs. Although an aircraft of this size is a marginally acceptable candidate to fit into the world airport infrastructure, it was concluded that the inclusion of community noise or sonic boom constraints would quickly cause the aircraft to grow beyond acceptable limits using the assumed technology levels

Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds

Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λmax) are evenly spaced across the light spectrum. In the course of avian evolution, the λmax of the most shortwave-sensitive cone, SWS1, has switched between violet (λmax > 400 nm) and ultraviolet (λmax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11',12'-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination

The use of standardized patients for mock oral board exams in neurology: a pilot study

BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. METHODS: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. RESULTS: Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. CONCLUSION: Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency

The apology mismatch: asymmetries between victim's need for apologies and perpetrator's willingness to apologize

Although previous research on apologies has shown that apologies can have many beneficial effects on victims’ responses, the dyadic nature of the apology process has largely been ignored. As a consequence, very little is known about the congruence between perpetrators’ willingness to apologize and victims’ willingness to receive an apology. In three experimental studies we showed that victims mainly want to receive an apology after an intentional transgression, whereas perpetrators want to offer an apology particularly after an unintentional transgression. As expected, these divergent apologetic needs among victims and perpetrators were mediated by unique emotions: guilt among perpetrators and anger among victims. These results suggest that an apology serves very different goals among victims and perpetrators, thus pointing at an apology mismatch

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females

The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1omat-/- mouse embryos born to Dnmt1Δ1o/Δ1o female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1Δ1o/Δ1o mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation. © 2013 McGraw et al