Radiant heat exchange in a space environment Scientific technical report, 1 Feb. - 31 Jul. 1969

Analytical methods development for predicting radiant heat transfer and temperature of engineering surfaces in space environmen

Naturally occurring sendai virus infection of athymic nude mice

Nude (nu/nu) mice, Balb/c derived, responded to a naturally occurring Sendai virus infection in a different manner than conventional mice. They developed a chronic debilitating disease and a persistent viral infection of the respiratory tract with intranuclear inclusion bodies in tracheal, bronchial and bronchiolar epithelial cells, laryngeal and tracheal glandular epithelium and in type I and II alveolar cells. The infection was identified by serologic and tissue culture studies, the mouse antibody production test and ultrastructural examination of pulmonary lesions. Phlebitis of pulmonary veins, suppurative rhinitis and otitis media accompanied the viral infection while some mice developed a secondary bronchopneumonia

Method to predict the minimum measurement and experiment durations needed to achieve converged and significant results in a wind energy field experiment

Experiments offer incredible value to science, but results must always come with an uncertainty quantification to be meaningful. This requires grappling with sources of uncertainty and how to reduce them. In wind energy, field experiments are sometimes conducted with a control and treatment. In this scenario uncertainty due to bias errors can often be neglected as they impact both control and treatment approximately equally. However, uncertainty due to random errors propagates such that the uncertainty in the difference between the control and treatment is always larger than the random uncertainty in the individual measurements if the sources are uncorrelated. As random uncertainties are usually reduced with additional measurements, there is a need to know the minimum duration of an experiment required to reach acceptable levels of uncertainty. We present a general method to simulate a proposed experiment, calculate uncertainties, and determine both the measurement duration and the experiment duration required to produce statistically significant and converged results. The method is then demonstrated as a case study with a virtual experiment that uses real-world wind resource data and several simulated tip extensions to parameterize results by the expected difference in power. With the method demonstrated herein, experiments can be better planned by accounting for specific details such as controller switching schedules, wind statistics, and postprocess binning procedures such that their impacts on uncertainty can be predicted and the measurement duration needed to achieve statistically significant and converged results can be determined before the experiment.</p

Conceptualising a Dynamic Technology Practice in Education Using Argyris and Schön's Theory of Action

Despite substantial national effort to integrate technology in education, it seems that practitioners in the education system are not working in line with the given policy. Evidence from large-scale studies of students’ technology practices at school over the last decade show disparities in student practices. The observed gap between the micro and the macro level call for a closer exploration. Research that explores the influence of social and organizational factors may be useful for understanding the processes behind such gaps. Argyris and Schön’s ‘Theory of Action’ (1978) is proposed as an example of an organizational theory that can be adopted in educational technology research to move towards understanding the complexities of technology practice. To encourage discourse and application of Argyris and Schön’s theory in the field of educational technology research, this paper introduces the theory, a review of its empirical application in research of teacher educations’ technology practice and relevant conceptual work. The paper presents a conceptual framework based on Argyris and Schön’s theory that has been developed through two recent studies, and invites its application in future research and development

Novel features of ARS selection in budding yeast Lachancea kluyveri

<p>Abstract</p> <p>Background</p> <p>The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined.</p> <p>Results</p> <p>In this study we have isolated and characterized autonomously replicating sequences (ARSs) in <it>Lachancea kluyveri </it>- a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that <it>L. kluyveri </it>ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in <it>Saccharomyces cerevisiae</it>. Moreover, compared with <it>S. cerevisiae </it>and <it>K. lactis</it>, the replication licensing machinery in <it>L. kluyveri </it>seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all <it>S. cerevisiae </it>ARSs tested and most <it>Kluyveromyces lactis </it>ARSs. In contrast, only about half of the <it>L. kluyveri </it>ARSs function in <it>S. cerevisiae </it>and less than 10% function in <it>K. lactis</it>.</p> <p>Conclusions</p> <p>Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.</p

Pediatric appendicitis rupture rate: a national indicator of disparities in healthcare access

BACKGROUND: The U.S. National Healthcare Disparities Report is a recent effort to measure and monitor racial and ethnic disparities in health and healthcare. The Report is a work in progress and includes few indicators specific to children. An indicator worthy of consideration is racial/ethnic differences in the rate of bad outcomes for pediatric acute appendicitis. Bad outcomes for this condition are indicative of poor access to healthcare, which is amenable to social and healthcare policy changes. METHODS: We analyzed the KID Inpatient Database, a nationally representative sample of pediatric hospitalization, to compare rates of appendicitis rupture between white, African American, Hispanic and Asian children. We ran weighted logistic regression models to obtain national estimates of relative odds of rupture rate for the four groups, adjusted for developmental, biological, socioeconomic, health services and hospital factors that might influence disease outcome. RESULTS: Rupture was a much more burdensome outcome than timely surgery and rupture avoidance. Rupture cases had 97% higher hospital charges and 175% longer hospital stays than non-rupture cases on average. These burdens disproportionately affected minority children, who had 24% – 38% higher odds of appendicitis rupture than white children, adjusting for age and gender. These differences were reduced, but remained significant after adjusting for other factors. CONCLUSION: The racial/ethnic disparities in pediatric appendicitis outcome are large and are preventable with timely diagnosis and surgery for all children. Furthermore, estimating this disparity using the KID survey is a relatively straightforward process. Therefore pediatric appendicitis rupture rate is a good candidate for inclusion in the National Healthcare Disparities Report. As with most other health and healthcare disparities, efforts to reduce disparities in income, wealth and access to care will most likely improve the odds of favorable outcome for this condition as well

A Test of Highly Optimized Tolerance Reveals Fragile Cell-Cycle Mechanisms Are Molecular Targets in Clinical Cancer Trials

Robustness, a long-recognized property of living systems, allows function in the face of uncertainty while fragility, i.e., extreme sensitivity, can potentially lead to catastrophic failure following seemingly innocuous perturbations. Carlson and Doyle hypothesized that highly-evolved networks, e.g., those involved in cell-cycle regulation, can be resistant to some perturbations while highly sensitive to others. The “robust yet fragile” duality of networks has been termed Highly Optimized Tolerance (HOT) and has been the basis of new lines of inquiry in computational and experimental biology. In this study, we tested the working hypothesis that cell-cycle control architectures obey the HOT paradigm. Three cell-cycle models were analyzed using monte-carlo sensitivity analysis. Overall state sensitivity coefficients, which quantify the robustness or fragility of a given mechanism, were calculated using a monte-carlo strategy with three different numerical techniques along with multiple parameter perturbation strategies to control for possible numerical and sampling artifacts. Approximately 65% of the mechanisms in the G1/S restriction point were responsible for 95% of the sensitivity, conversely, the G2-DNA damage checkpoint showed a much stronger dependence on a few mechanisms; ∼32% or 13 of 40 mechanisms accounted for 95% of the sensitivity. Our analysis predicted that CDC25 and cyclin E mechanisms were strongly implicated in G1/S malfunctions, while fragility in the G2/M checkpoint was predicted to be associated with the regulation of the cyclin B-CDK1 complex. Analysis of a third model containing both G1/S and G2/M checkpoint logic, predicted in addition to mechanisms already mentioned, that translation and programmed proteolysis were also key fragile subsystems. Comparison of the predicted fragile mechanisms with literature and current preclinical and clinical trials suggested a strong correlation between efficacy and fragility. Thus, when taken together, these results support the working hypothesis that cell-cycle control architectures are HOT networks and establish the mathematical estimation and subsequent therapeutic exploitation of fragile mechanisms as a novel strategy for anti-cancer lead generation

A Comprehensive Genome-Wide Map of Autonomously Replicating Sequences in a Naive Genome

Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins. The machinery that initiates DNA synthesis is highly conserved, but the sites where the replication initiation proteins bind have diverged significantly. Functional comparative genomics is an obvious approach to study the evolution of replication origins. However, to date, the Saccharomyces cerevisiae replication origin map is the only genome map available. Using an iterative approach that combines computational prediction and functional validation, we have generated a high-resolution genome-wide map of DNA replication origins in Kluyveromyces lactis. Unlike other yeasts or metazoans, K. lactis autonomously replicating sequences (KlARSs) contain a 50 bp consensus motif suggestive of a dimeric structure. This motif is necessary and largely sufficient for initiation and was used to dependably identify 145 of the up to 156 non-repetitive intergenic ARSs projected for the K. lactis genome. Though similar in genome sizes, K. lactis has half as many ARSs as its distant relative S. cerevisiae. Comparative genomic analysis shows that ARSs in K. lactis and S. cerevisiae preferentially localize to non-syntenic intergenic regions, linking ARSs with loci of accelerated evolutionary change

Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint