Erythrocyte Oxidative Stress, Salivary Cortisol, and Oxygen Consumption with Low-Intensity Blood Flow Restricted Resistance Exercise Before and After Training.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017

Space shuttle electromagnetic environment experiment. Phase A: Definition study

A program is discussed which develops a concept for measuring the electromagnetic environment on earth with equipment on board an orbiting space shuttle. Earlier work on spaceborne measuring experiments is reviewed, and emissions to be expected are estimated using, in part, previously gathered data. General relations among system parameters are presented, followed by a proposal on spatial and frequency scanning concepts. The methods proposed include a nadir looking measurement with small lateral scan and a circularly scanned measurement looking tangent to the earth's surface at the horizon. Antenna requirements are given, assuming frequency coverage from 400 MHz to 40 GHz. For the low frequency range, 400-1000 MHz, a processed, thinned array is proposed which will be more fully analyzed in the next phase of the program. Preliminary hardware and data processing requirements are presented

Asymptotic information leakage under one-try attacks

We study the asymptotic behaviour of (a) information leakage and (b) adversary’s error probability in information hiding systems modelled as noisy channels. Specifically, we assume the attacker can make a single guess after observing n independent executions of the system, throughout which the secret information is kept fixed. We show that the asymptotic behaviour of quantities (a) and (b) can be determined in a simple way from the channel matrix. Moreover, simple and tight bounds on them as functions of n show that the convergence is exponential. We also discuss feasible methods to evaluate the rate of convergence. Our results cover both the Bayesian case, where a prior probability distribution on the secrets is assumed known to the attacker, and the maximum-likelihood case, where the attacker does not know such distribution. In the Bayesian case, we identify the distributions that maximize the leakage. We consider both the min-entropy setting studied by Smith and the additive form recently proposed by Braun et al., and show the two forms do agree asymptotically. Next, we extend these results to a more sophisticated eavesdropping scenario, where the attacker can perform a (noisy) observation at each state of the computation and the systems are modelled as hidden Markov models

Reviews

Unfinished Tales of Numenor and Middle-earth. J. R. R. Tolkien. Ed. by Christopher Tolkien. Reviewed by Paul H. Kocher. The Achievement of C.S. Lewis. Thomas Howard. Reviewed by Nancy-Lou Patterson. The Silmarillion. J.R.R. Tolkien. Ed. by Christopher Tolkien. Reviewed by Thomas M. Egan

J.R.R. Tolkien and George MacDonald

Traces moral, religious, and creative parallels between MacDonald and Tolkien. Finds that Christianity gives Tolkien’s work “a firm structure and objectivity” as opposed to the “fervent but rather formless spirituality” due to MacDonald’s romanticism

Targeting FGFR signaling to disrupt cellular cross-talk in pancreatic cancer

PhD Thesi

Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer.

BACKGROUND: The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we aimed to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations. METHODS: We followed 3 patients with resectable disease and 4 patients with unresectable disease, including 4 patients with ≥ 3 serial follow-up samples, of whom 2 were rare long survivors (> 5 years). We performed whole exome sequencing of tumour gDNA and plasma ctDNA (n = 20) collected over a ~ 2-year period from diagnosis through treatment to death or final follow-up. Plasma from 3 chronic pancreatitis cases was used as a comparison for analysis of ctDNA mutations. RESULTS: We detected > 55% concordance between somatic mutations in tumour tissues and matched serial plasma. Mutations in ctDNA were detected within known PDAC driver genes (KRAS, TP53, SMAD4, CDKN2A), in addition to patient-specific variants within alternative cancer drivers (NRAS, HRAS, MTOR, ERBB2, EGFR, PBRM1), with a trend towards higher overall mutation loads in advanced disease. ctDNA alterations with potential for therapeutic actionability were identified in all 7 patients, including DNA damage response (DDR) variants co-occurring with hypermutation signatures predictive of response to platinum chemotherapy. Longitudinal tracking in 4 patients with follow-up > 2 years demonstrated that ctDNA mutant allele fractions and clonal trends were consistent with CA19-9 measurements and/or clinically reported disease burden. The estimated prevalence of 'stem clones' was highest in an unresectable patient where changes in ctDNA dynamics preceded CA19-9 levels. Longitudinal evolutionary trajectories revealed ongoing subclonal evolution following chemotherapy. CONCLUSION: These results provide proof-of-concept for the use of exome sequencing of serial plasma to characterise patient-specific ctDNA profiles, and demonstrate the sensitivity of ctDNA in monitoring disease burden in PDAC even in unresectable cases without matched tumour genotyping. They reveal the value of tracking clonal evolution in serial ctDNA to monitor treatment response, establishing the potential of applied precision medicine to guide stratified care by identifying and evaluating actionable opportunities for intervention aimed at optimising patient outcomes for an otherwise intractable disease

A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma-Toward a Better Mimicry of the in vivo Tumor Microenvironment

With a very low survival rate, pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. This has been primarily attributed to (i) its late diagnosis and (ii) its high resistance to current treatment methods. The latter specifically requires the development of robust, realistic in vitro models of PDAC, capable of accurately mimicking the in vivo tumor niche. Advancements in the field of tissue engineering (TE) have helped the development of such models for PDAC. Herein, we report for the first time a novel hybrid, polyurethane (PU) scaffold-based, long-term, multicellular (tri-culture) model of pancreatic cancer involving cancer cells, endothelial cells, and stellate cells. Recognizing the importance of ECM proteins for optimal growth of different cell types, the model consists of two different zones/compartments: an inner tumor compartment consisting of cancer cells [fibronectin (FN)-coated] and a surrounding stromal compartment consisting of stellate and endothelial cells [collagen I (COL)-coated]. Our developed novel hybrid, tri-culture model supports the proliferation of all different cell types for 35 days (5 weeks), which is the longest reported timeframe in vitro. Furthermore, the hybrid model showed extensive COL production by the cells, mimicking desmoplasia, one of PDAC's hallmark features. Fibril alignment of the stellate cells was observed, which attested to their activated state. All three cell types expressed various cell-specific markers within the scaffolds, throughout the culture period and showed cellular migration between the two zones of the hybrid scaffold. Our novel model has great potential as a low-cost tool for in vitro studies of PDAC, as well as for treatment screening

Spectroscopic factors for bound s-wave states derived from neutron scattering lengths

A simple and model-independent method is described to derive neutron single-particle spectroscopic factors of bound s-wave states in $^{A+1}Z = ^{A}Z \otimes n$ nuclei from neutron scattering lengths. Spectroscopic factors for the nuclei ^{13}C, ^{14}C, ^{16}N, ^{17}O, ^{19}O, ^{23}Ne, ^{37}Ar, and ^{41}Ar are compared to results derived from transfer experiments using the well-known DWBA analysis and to shell model calculations. The scattering length of ^{14}C is calculated from the ^{15}C_{g.s.} spectroscopic factor.Comment: 9 pages (uses revtex), no figures, accepted for publication in PRC, uuencoded tex-files and postscript-files available at ftp://is1.kph.tuwien.ac.at/pub/ohu/Thermal.u