Doctor of Philosophy

dissertationDrug-free macromolecular therapeutics are a new paradigm in polymer-based nanomedicines. Instead of carrying cytotoxic small molecular weight drugs, drug-free macromolecular therapeutics crosslink proteins in the cell membrane through hybridization of oligonucleotides to initiate apoptosis signaling. However, the mechanism of the nanomedicines was not fully understood. To study the mechanism and to better understand the interactions between the therapeutics and the cell membrane, super-resolution optical microscopy was used. Super-resolution imaging was performed on Raji B cells treated with the drug-free conjugates. The clustering of CD20 and lipid rafts was quantified. Lipid raft cluster size increased after treatment with drug-free conjugates. Drug-free conjugates induced apoptosis in a lipid raft-dependent mechanism where stable lipid rafts are needed for proper initiation of apoptosis. Direct stochastic optical reconstruction microscopy revealed nanoscale differences in membrane distribution of CD20 and lipid rafts. Pair-correlation analysis of super-resolution images showed lipid raft sizes of ~200 nm in cells treated with drug-free conjugates. General applicability of direct stochastic optical reconstruction microscopy to studying drug-delivery systems was also demonstrated. Two conceptually different polymer-based therapeutics were labeled with 4 different synthetic fluorophores, and three-dimensional (3D) direct stochastic optical reconstruction microscopy was conducted at different time points to track localization of the therapeutic components. An internalized polymer conjugate was localized in clusters at 4 h, but after 24 h, the polymer released into the cytosol a fluorophore attached via an enzymatically degradable peptide. Pair-correlation functions of the dye attached to the polymer and the released dye showed changes in their decay lengths between 4 h and 24 h. The pair-correlation function of the released dye showed random distribution after 24 h. Using reversible addition?fragmentation chain-transfer (RAFT) polymerization, branched and star polymers were synthesized to study the effect of architecture on apoptosis induction in Raji B cells. A new chain transfer monomer was synthesized in order to produce controlled branched polymers in RAFT polymerization. A degradable tetra-functional chain transfer agent was also synthesized. The star chain transfer agent produced degradable star polymers of high molecular weight (~170 kDa). Drug-free conjugates were synthesized to produce linear, branched, and star polymer-MORF2 conjugates. Apoptosis in Raji B cells was measured but the three different architectures induced the same levels of apoptosis as measure by annexin V and caspase 3

The Impact of Peculiar Velocities on the Estimation of the Hubble Constant from Gravitational Wave Standard Sirens

In this work we investigate the systematic uncertainties that arise from the calculation of the peculiar velocity when estimating the Hubble constant ($H_0$) from gravitational wave standard sirens. We study the GW170817 event and the estimation of the peculiar velocity of its host galaxy, NGC 4993, when using Gaussian smoothing over nearby galaxies. NGC 4993 being a relatively nearby galaxy, at $\sim 40 \ {\rm Mpc}$ away, is subject to a significant effect of peculiar velocities. We demonstrate a direct dependence of the estimated peculiar velocity value on the choice of smoothing scale. We show that when not accounting for this systematic, a bias of $\sim 200 \ {\rm km \ s ^{-1}}$ in the peculiar velocity incurs a bias of $\sim 4 \ {\rm km \ s ^{-1} \ Mpc^{-1}}$on the Hubble constant. We formulate a Bayesian model that accounts for the dependence of the peculiar velocity on the smoothing scale and by marginalising over this parameter we remove the need for a choice of smoothing scale. The proposed model yields$H_0 = 68.6 ^{+14.0}_{-8.5}~{\rm km\ s^{-1}\ Mpc^{-1}}$. We demonstrate that under this model a more robust unbiased estimate of the Hubble constant from nearby GW sources is obtained.Comment: 9 pages, 5 figure

Cheryl's Birthday

We present four logic puzzles and after that their solutions. Joseph Yeo designed 'Cheryl's Birthday'. Mike Hartley came up with a novel solution for 'One Hundred Prisoners and a Light Bulb'. Jonathan Welton designed 'A Blind Guess' and 'Abby's Birthday'. Hans van Ditmarsch and Barteld Kooi authored the puzzlebook 'One Hundred Prisoners and a Light Bulb' that contains other knowledge puzzles, and that can also be found on the webpage http://personal.us.es/hvd/lightbulb.html dedicated to the book.Comment: In Proceedings TARK 2017, arXiv:1707.0825

Do Pre-registration and Pre-analysis Plans Recue p-Hacking and Publication Bias? Evidence from 15,922 Tests Statistics and Suggestions for Improvement

Pre-registration is regarded as an important contributor to research credibility. We investigate this by analyzing the pattern of test statistics from the universe of randomized controlled trials (RCT) studies published in 15 leading economics journals. We draw two conclusions: (a) Pre-registration frequently does not involve a pre-analysis plan (PAP), or sufficient detail to constrain meaningfully the actions and decisions of researchers after data is collected. Consistent with this, we find no evidence that pre-registration in itself reduces p-hacking and publication bias. (b) When pre-registration is accompanied by a PAP we find evidence consistent with both reduced p-hacking and publication bias.<br/

Do Pre-registration and Pre-analysis Plans Recue p-Hacking and Publication Bias?:Evidence from 15,992 Test Statistics and Suggestions for Improvement

Pre-registration is regarded as an important contributor to research credibility. We investigate this by analyzing the pattern of test statistics from the universe of randomized controlled trials (RCT) studies published in 15 leading economics journals. We draw two conclusions: (a) Pre-registration frequently does not involve a pre-analysis plan (PAP), or sufficient detail to constrain meaningfully the actions and decisions of researchers after data is collected. Consistent with this, we find no evidence that pre-registration in itself reduces p-hacking and publication bias. (b) When pre-registration is accompanied by a PAP we find evidence consistent with both reduced p-hacking and publication bias.<br/

Presentation by the University of Nevada, Las Vegas: College of Fine Arts

Program listing performers and works performe

Characterization of Vertical Accelerations Experienced by Older People Attending an Aerobics Class Designed to Produce High Impacts

The purpose of this study was to establish the feasibility of using an aerobics class to produce potentially bone protective vertical impacts of ≥ 4g in older adults and to determine whether impacts can be predicted by physical function. Participants recruited from older adult exercise classes completed an SF-12 questionnaire, short physical performance battery, and an aerobics class with seven different components, performed at low and high intensity. Maximum g and jerk values were identified for each activity. Forty-one participants (mean 69 years) were included. Mean maximal values approached or exceeded the 4g threshold for four of the seven exercises. In multivariate analyses, age (–0.53; –0.77, –0.28) (standardized beta coefficient; 95% CI) and 4-m walk time (–0.39; –0.63, –0.16) were inversely related to maximum g. Aerobics classes can be used to produce relatively high vertical accelerations in older individuals, although the outcome is strongly dependent on age and physical function

The Physical Health of Caregivers of Children With Life-Limiting Conditions:A Systematic Review

CONTEXT: Parental caregiving for a child with a life-limiting condition (LLC) is complex physical and mental work. The impact of this caregiving on parents' physical health is unknown. OBJECTIVES: (1) To review existing evidence on the physical health of parents caring for a child with a LLC and (2) to determine how physical health of parents is measured. DATA SOURCES: Medline, Embase, PsycINFO, and Cumulative Index of Nursing and Allied Health Literature were searched. STUDY SELECTION: Peer-reviewed articles were included if they reported primary data on the physical health of a caregiver of a child with a LLC. Studies were excluded if they described only the caregiver's mental health or if the caregivers were bereaved at the time of data collection. DATA EXTRACTION: Of 69 335 unique citations, 81 studies were included in the review. RESULTS: Caregiver health was negatively impacted in 84% of studies. Pain and sleep disturbance were the most common problems. Ways of measuring the physical health of caregiver varied widely. We found an absence of in-depth explorations of the social and economic contexts, which could potentially mitigate the impact of caregiving. Furthermore, we find health interventions tailored to this group remain largely unexplored. LIMITATIONS: Studies were heterogenous in methodology, making comparisons of results across studies difficult. CONCLUSIONS: These findings support the need for improving access to interventions aimed at improving physical health in this population. The rate of health-seeking behaviors, preventive health care access and screening for health conditions is understudied and represent important directions for further research