A Study of the Interaction of Peroxidic Tumor Promoters With Mitochondria.

When micromolar concentrations of benzoyl peroxide (BPO) are added to rat liver mitochondria, inhibition of mitochondrial NADH-oxidase and succinoxidase is observed. The addition of a classical uncoupler of oxidative phosphorylation results in only partial release of this inhibition, suggesting that BPO inhibits both electron- and energy-transfer in mitochondria. Difference spectroscopy and artificial electron donor results indicate that BPO interacts at coupling site II between cytochromes b and c\sb1. BPO only yields radicals in mitochondria via inhibition of electron transport, which results in the formation of superoxide radicals. BPO also induces rapid, large-amplitude swelling of mitochondria; the swelling is dependent on the presence of monovalent cations but is independent of the presence of calcium, oxygen and respiratory substrate. BPO-induced swelling appears to be disassociated from radical production and lipid peroxidation. When isolated rat liver mitochondria are treated with millimolar concentrations of tert-butyl hydroperoxide (TBHP), methyl, tert-butoxyl and tert-butylperoxyl radicals are detected using the ESR spin- trapping technique. The addition of respiratory substrate results in a significant increase in methyl radical production, no change in the concentration of tert-butoxyl radicals, and complete loss of tert-butylperoxyl radicals. One-electron reduction of TBHP by the electron transport chain results in the formation of tert-butoxyl radicals, which subsequently undergo beta-scission to form methyl radicals. The site of interception of electrons by TBHP is shown to be cytochrome c\sb 1 by the use of classical chain inhibitors and depletion of mitochondrial cytochrome c. TBHP also appears to interact with a tightly-liganded metal in non-respiring mitochondria, as metal chelators have no effect on TBHP-induced radical production while sodium cyanide inhibits this process. TBHP induces lipid peroxidation in both respiring- and non-respiring mitochondria, as measured by the thiobarbituric acid test, although the degree of peroxidation is less in respiring mitochondria. Radical production is also observed when either cumene hydroperoxide or linoleic acid hydroperoxide is added to mitochondria in the presence of spin trap. The mechanisms of TBHP-induced radical production in both respiring- and non-respiring mitochondria are discussed

Doubly Robust Causal Inference With Complex Parameters

Semiparametric doubly robust methods for causal inference help protect against bias due to model misspecification, while also reducing sensitivity to the curse of dimensionality (e.g., when high-dimensional covariate adjustment is necessary). However, doubly robust methods have not yet been developed in numerous important settings. In particular, standard semiparametric theory mostly only considers independent and identically distributed samples and smooth parameters that can be estimated at classical root-n rates. In this dissertation we extend this theory and develop novel methodology for three settings outside these bounds: (1) matched cohort studies, (2) nonparametric dose-response estimation, and (3) complex high-dimensional effects with continuous instrumental variables. After giving an introduction in Chapter 1, we show in Chapter 2 that, for matched cohort studies, efficient and doubly robust estimators of effects on the treated are computationally equivalent to standard estimators that ignore the non-standard sampling. We also show that matched cohort studies are often more efficient than random sampling for estimating effects on the treated, and derive the optimal number of matches for given matching variables. We apply our methods in a study of the effect of hysterectomy on the risk of cardiovascular disease. In Chapter 3 we develop a novel approach for causal dose-response curve estimation that is doubly robust without requiring any parametric assumptions, and which naturally incorporates general off-the-shelf machine learning. We derive asymptotic properties for a kernel-based version of our approach and propose a data-driven method for bandwidth selection. The methods are used to study the effect of hospital nurse staffing on excess readmissions penalties. In Chapter 4 we develop novel estimators of the local instrumental variable curve, which represents the treatment effect among compliers who would take treatment when the instrument passes some threshold. Our methods do not require parametric assumptions, allow for flexible data-adaptive estimation of effect modification, and are doubly robust. We derive asymptotic properties under weak conditions, and use the methods to study infant mortality effects of neonatal intensive care units with high versus low technical capacity, using travel time as an instrument

Art. IX.—On the views of niemeyer regarding phthisis

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Application of neural networks and sensitivity analysis to improved prediction of trauma survival

Application of neural networks and sensitivity analysis to improved prediction of trauma surviva

Another Poem to Beloved Pastor and Friend

Another poem to Beloved Pastor and Friend. Apparently another class of the teacher was not to be outdone by the class which sent the teacher a poem on 17 October. This poem is much longer although part of the document is damaged and the beginning of the lines of the first three stanzas are missing. There is a clue that the teacher is Dr. Albertus C. Van Raalte for the first line in stanza five reads: May He spare you for family and for flock. If the flock is the Pillar Church congregation (First Reformed Church), then the teacher is Van Raalte and the students may be members of his catechism class. There are thirty-four students in the class. Their names are: Willem E. van Herwijnen, Amos Wevers, C. Schilleman, J. Mulder, J. Westveer, A. Pauels, C. de Fijter, D. B. Meengs, W.P. Klaver, E. Smits, H. Elferdink, P. Boot, J. Vaupell, J. te Roller, L. Schoon, H. van Rij, C. Verschure, L. T. Kanters, H. Westveer, O. J. Pauels, H. Te Roller, C. Vaupell, A. De Fijter, P. Te Spelder, J. Vande Veen, J. C. Post, J. A. Smits, Henry M. Ferry, A. Pfanstiehl, G. J. Heering, H. Bottenberg, W. Kieft, M. Kanters, and P. Thibout.https://digitalcommons.hope.edu/vrp_1860s/1191/thumbnail.jp

Exploring heritage through time and space : Supporting community reflection on the highland clearances

On the two hundredth anniversary of the Kildonan clearances, when people were forcibly removed from their homes, the Timespan Heritage centre has created a program of community centred work aimed at challenging pre conceptions and encouraging reflection on this important historical process. This paper explores the innovative ways in which virtual world technology has facilitated community engagement, enhanced visualisation and encouraged reflection as part of this program. An installation where users navigate through a reconstruction of pre clearance Caen township is controlled through natural gestures and presented on a 300 inch six megapixel screen. This environment allows users to experience the past in new ways. The platform has value as an effective way for an educator, artist or hobbyist to create large scale virtual environments using off the shelf hardware and open source software. The result is an exhibit that also serves as a platform for experimentation into innovative ways of community co-creation and co-curation.Postprin

Water Handling And Hygiene Practices On The Transmission Of Diarrhoeal Diseases And Soil Transmitted Helminthic Infections In Communities In Rural Ghana

In Ghana, diarrhoeal diseases have been identified as the second commonest health problem treated in outpatient clinics. In this study, the relevance of water handling and hygienic practices on the transmission of diarrhoeal diseases and soil-transmitted helminthic infections in three communities in Ghana was evaluated. Specifically, the research looked at physico-chemical qualities of household water, the incidence of diarrhoeal diseases and soil-transmitted helminthic infections. Thirty households were selected by the systematic random sampling technique from the three communities namely Mayera, Ashongman village and Tetegu. Within each household, domestic water was collected and transported to the laboratory for physico-chemical testing. Standardized questionnaires were also administered. The questionnaires addressed issues such as water storage, treatment and hygienic practices among households. The incidence of diarrhoeal diseases and soil transmitted helminthic (STH) infections among households were also assessed. The commonest water sources included pipe-borne water, borehole, rainwater and water from rivers. Most households in the three communities did not treat their water before use. The commonest water storage containers included barrels without lids, pots and plastic containers. There was no significant correlation between STH and diarrhoeal diseases at both Mayera and the Ashongman communities (R=0.279, p=0.136 for Mayera; R=0.311, p=0.094 for Ashongman). However, there existed a weak significantly positive correlation between the incidences of diarrhoeal diseases and the incidence of STH at the Tetegu community (R=0.384, p=0.036). Health education in the aspect of proper hand washing with soap under running water should be intensified in the three communities. Keywords: diarrhoeal disease, water handling, hygiene, soil transmitted helminth, water qualit

Towards the 3D Web with Open Simulator

Continuing advances and reduced costs in computational power, graphics processors and network bandwidth have led to 3D immersive multi-user virtual worlds becoming increasingly accessible while offering an improved and engaging Quality of Experience. At the same time the functionality of the World Wide Web continues to expand alongside the computing infrastructure it runs on and pages can now routinely accommodate many forms of interactive multimedia components as standard features - streaming video for example. Inevitably there is an emerging expectation that the Web will expand further to incorporate immersive 3D environments. This is exciting because humans are well adapted to operating in 3D environments and it is challenging because existing software and skill sets are focused around competencies in 2D Web applications. Open Simulator (OpenSim) is a freely available open source tool-kit that empowers users to create and deploy their own 3D environments in the same way that anyone can create and deploy a Web site. Its characteristics can be seen as a set of references as to how the 3D Web could be instantiated. This paper describes experiments carried out with OpenSim to better understand network and system issues, and presents experience in using OpenSim to develop and deliver applications for education and cultural heritage. Evaluation is based upon observations of these applications in use and measurements of systems both in the lab and in the wild.Postprin

Letter from Albertus C. Van Raalte to Lieve Kinderen (His Children)

A letter of Rev. Albertus C. Van Raalte to Lieve Kinderen, his children about the letters to the Dames, or the sisters of Rev. and Mrs. John Vleck in New Jersey to whom Van Raalte had sold some lots. The letter is puzzling and it is difficult for the reader just what the problems were that needed to be solved.https://digitalcommons.hope.edu/vrp_1850s/1021/thumbnail.jp