Medicine and Health Sciences Commons^™

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Forecasting Covid-19 With Temporal Hierarchies And Ensemble Methods, Li Shandross

Masters Theses

Infectious disease forecasting efforts underwent rapid growth during the COVID-19 pandemic, providing guidance for pandemic response and about potential future trends. Yet despite their importance, short-term forecasting models often struggled to produce accurate real-time predictions of this complex and rapidly changing system. This gap in accuracy persisted into the pandemic and warrants the exploration and testing of new methods to glean fresh insights.

In this work, we examined the application of the temporal hierarchical forecasting (THieF) methodology to probabilistic forecasts of COVID-19 incident hospital admissions in the United States. THieF is an innovative forecasting technique that aggregates time-series data into …

Differential Toxicity Of Pm2.5 Components And Modified Health Effects Modeling: A Case Study In Nepal, Jeremy Brownholtz

Masters Theses

During the latter part of the 20^th century, a transition away from coal as a major energy source in developed countries was accompanied by a notable decrease in air pollution-related deaths in those countries. Currently the same phenomenon is being observed in developing nations like China and India. However, many areas that do still rely on coal for their energy production or industrial needs also reflect a gap in research on the effects of those specific processes on local populations. Located in Nepal at the foot of the Himalayan Plateau, Kathmandu represents one such location. The local economy of …

Unobtrusive Assessment Of Upper-Limb Motor Impairment Using Wearable Inertial Sensors, Brandon R. Oubre

Doctoral Dissertations

Many neurological diseases cause motor impairments that limit autonomy and reduce health-related quality of life. Upper-limb motor impairments, in particular, significantly hamper the performance of essential activities of daily living, such as eating, bathing, and changing clothing. Assessment of impairment is necessary for tracking disease progression, measuring the efficacy of interventions, and informing clinical decision making. Impairment is currently assessed by trained clinicians using semi-quantitative rating scales that are limited by their reliance on subjective, visual assessments. Furthermore, existing scales are often burdensome to administer and do not capture patients' motor performance in home and community settings, resulting in a …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Three Dimensional Spatio-Temporal Cluster Analysis Of Sars-Cov-2 Infections, Keith W. Allison

Masters Theses

The COVID-19 pandemic has heightened the need for fine-scale analysis of the clustering of cases of infectious disease in order to better understand and prevent the localized spread of infection. The students living on the University of Massachusetts, Amherst campus provided a unique opportunity to do so, due to frequent mandatory testing during the 2020-2021 academic year, and dense living conditions. The South-West dormitory area is of particular interest due to its extremely high population density, housing around half of students living on campus during normal conditions. Using data gathered by the Public Health Promotion Center (PHPC), we analyzed the …

Deciphering Protein Higher-Order Structure And Interactions Via Diethylpyrocarbonate Labeling-Mass Spectrometry, Xiao Pan

Doctoral Dissertations

The study of protein higher-order structures is vital because it is closely related to the investigation of protein folding, aggregation, interaction and protein therapeutics. Consequently, numerous biochemical and biophysical tools have been developed to study protein higher-order structures in many different situations. The combination of covalent labeling (CL) and mass spectrometry (MS) has emerged as a powerful tool for studying protein structures and offers many advantages over other traditional techniques, such as better structural coverage, high throughput, high sensitivity, and the ability to study proteins in mixtures. This dissertation focuses on diethylpyrocarbonate (DEPC) as an effective CL reagent that can …

Decision-Analytic Models Using Reinforcement Learning To Inform Dynamic Sequential Decisions In Public Policy, Seyedeh Nazanin Khatami

Doctoral Dissertations

We developed decision-analytic models specifically suited for long-term sequential decision-making in the context of large-scale dynamic stochastic systems, focusing on public policy investment decisions. We found that while machine learning and artificial intelligence algorithms provide the most suitable frameworks for such analyses, multiple challenges arise in its successful adaptation. We address three specific challenges in two public sectors, public health and climate policy, through the following three essays. In Essay I, we developed a reinforcement learning (RL) model to identify optimal sequence of testing and retention-in-care interventions to inform the national strategic plan “Ending the HIV Epidemic in the US”. …

High-Dimensional Feature Selection And Multi-Level Causal Mediation Analysis With Applications To Human Aging And Cluster-Based Intervention Studies, Hachem Saddiki

Doctoral Dissertations

Many questions in public health and medicine are fundamentally causal in that our objective is to learn the effect of some exposure, randomized or not, on an outcome of interest. As a result, causal inference frameworks and methodologies have gained interest as a promising tool to reliably answer scientific questions. However, the tasks of identifying and efficiently estimating causal effects from observed data still pose significant challenges under complex data generating scenarios. We focus on (1) high-dimensional settings where the number of variables is orders of magnitude higher than the number of observations; and (2) multi-level settings, where study participants …

Design Of Resposive Oligomeric And Polymeric Interfaces For Sensing And Controlled Release Applications, . Manisha

Doctoral Dissertations

Nature has designed magnificent responsive systems by constructing several interacting molecular level networks for the recognition and propagation of chemical and biochemical information. One of the eminent characteristics of these systems is their capability to quickly transduce molecular scale recognition events into macroscopic or visually observable responses. Inspired by these systems present in nature, we became interested in developing artificial responsive systems with similar capabilities. This dissertation will feature four such systems that employ amphiphilic oligomers and polymers which were chosen as the scaffolds because of their high thermodynamic stability, low critical aggregation concentrations, convenient handles to incorporate functional group …

Evaluating Public Masking Mandates On Covid-19 Growth Rates In U.S. States, Angus K. Wong

Masters Theses

U.S. state governments have implemented numerous policies to help mitigate the spread of COVID-19. While there is strong biological evidence supporting the wearing of face masks or coverings in public spaces, the impact of public masking policies remains unclear. We aimed to evaluate how early versus delayed implementation of state-level public masking orders impacted subsequent COVID-19 growth rates. We defined “early” implementation as having a state-level mandate in place before September 1, 2020, the approximate start of the school-year. We defined COVID-19 growth rates as the relative increase in confirmed cases 7, 14, 21, 30, 45, 60-days after September 1. …

The Role Of Vegetative Cover In Enhancing Resilience To Climate Change And Improving Public Health, Anastasia D. Ivanova

Masters Theses

Changing temperature and precipitation patterns are causing degraded soil, water, and air quality which is negatively affecting the safety and health of people, and the productivity of urban and rural communities. However, research shows that implementing urban forests and cover crops into urban and rural landscapes, respectively, can mitigate these effects by providing ecosystem services. As extreme precipitation and heat events continue to intensify, there is a need for comprehensively assessing these ecosystem services under changing climates and for this information to be easily accessible by communities for rapid land-use decision making. Therefore, I investigated the role of urban forests …

Raising Dielectric Permittivity Mitigates Dopant-Induced Disorder In Conjugated Polymers, Meenakshi Upadhyaya, Michael Lu-Díaz, Subhayan Samanta, Muhammad Abdullah, Keith Dusoe, Kevin R. Kittilstved, Dhandapani Venkataraman, Zlatan Akšamija

Electrical and Computer Engineering Faculty Publication Series

Conjugated polymers need to be doped to increase charge carrier density and reach the electrical conductivity necessary for electronic and energy applications. While doping increases carrier density, Coulomb interactions between the dopant molecules and the localized carriers are poorly screened, causing broadening and a heavy tail in the electronic density-of-states (DOS). The authors examine the effects of dopant-induced disorder on two complimentary charge transport properties of semiconducting polymers, the Seebeck coefficient and electrical conductivity, and demonstrate a way to mitigate them. Their simulations, based on a modified Gaussian disorder model with Miller-Abrahams hopping rates, show that dopant-induced broadening of the …

Evaluating Epidemic Forecasts In An Interval Format, Johannes Bracher, Evan L. Ray, Tilmann Gneiting, Nicholas G. Reich

Biostatistics and Epidemiology Faculty Publications Series

For practical reasons, many forecasts of case, hospitalization, and death counts in the context of the current Coronavirus Disease 2019 (COVID-19) pandemic are issued in the form of central predictive intervals at various levels. This is also the case for the forecasts collected in the COVID-19 Forecast Hub (https://covid19forecasthub.org/). Forecast evaluation metrics like the logarithmic score, which has been applied in several infectious disease forecasting challenges, are then not available as they require full predictive distributions. This article provides an overview of how established methods for the evaluation of quantile and interval forecasts can be applied to epidemic forecasts in …

Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati

Doctoral Dissertations

Using mass spectrometry (MS) to obtain information about a higher order structure of protein requires that a protein’s structural properties are encoded into the mass of that protein. Covalent labeling (CL) with reagents that can irreversibly modify solvent accessible amino acid side chains is an effective way to encode structural information into the mass of a protein, as this information can be read-out in a straightforward manner using standard MS-based proteomics techniques. The differential reactivity of proteins under two or more conditions can be used to distinguish protein topologies, conformations, and/or binding sites. CL-MS methods have been effectively used for …

Protein Detection And Structural Characterization By Mass Spectrometry Using Supramolecular Assemblies And Small Molecules, Bo Zhao

Doctoral Dissertations

Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pK_a on host-guest interactions …

Game-Assisted Rehabilitation For Post-Stroke Survivors, Hee-Tae Jung

Doctoral Dissertations

Stroke is a leading cause of permanent impairments among its survivors. Although patients need to go through intensive, longitudinal rehabilitation to regain function before the stroke, patients show poor engagement and adherence to rehabilitation therapies which hampers their recovery. As a means to enhance stroke survivors' motivation, engagement, and adherence to intensive and longitudinal rehabilitation, the use of games in stroke rehabilitation has received attention from research and clinical communities. In order to realize this, it is important to take a holistic, end-to-end research approach that encompasses 1) the development of game technologies that are not only entertaining but also …

Real-Time Dengue Forecasting In Thailand: A Comparison Of Penalized Regression Approaches Using Internet Search Data, Caroline Kusiak

Masters Theses

Dengue fever affects over 390 million people annually worldwide and is of particu- lar concern in Southeast Asia where it is one of the leading causes of hospitalization. Modeling trends in dengue occurrence can provide valuable information to Public Health officials, however many challenges arise depending on the data available. In Thailand, reporting of dengue cases is often delayed by more than 6 weeks, and a small fraction of cases may not be reported until over 11 months after they occurred. This study shows that incorporating data on Google Search trends can improve dis- ease predictions in settings with severely …

Microtransplantation Of Rat Brain Neurolemma Into Xenopus Laevis Oocytes To Study The Effect Of Environmental Toxicants On Endogenous Voltage-Sensitive Ion Channels, Edwin Murenzi

Masters Theses

Microtransplantation of mammalian neurolemma into Xenopus laevis oocytes has been used to study ion channels in terms of their structure and function in the central nervous system. Use of microtransplanted neurolemma is advantageous in that tissue can be obtained from various sources, ion channels and receptors are present in their native configuration and they can be used to evaluate numerous channelpathies caused by environmental toxicants. Here we show that Xenopus oocytes injected with fragments of rat brain neurolemma successfully express functional native ion channels that are assembled in their own plasma membrane. Using a high throughput two electrode voltage clamp …

Superhero Robotics, Frank Sup, Brian Umberger, Nick Sawyer

Science and Engineering Saturday Seminars

No abstract provided.

A Comparison Of Techniques For Handling Missing Data In Longitudinal Studies, Alexander R. Bogdan

Masters Theses

Missing data are a common problem in virtually all epidemiological research, especially when conducting longitudinal studies. In these settings, clinicians may collect biological samples to analyze changes in biomarkers, which often do not conform to parametric distributions and may be censored due to limits of detection. Using complete data from the BioCycle Study (2005-2007), which followed 259 premenopausal women over two menstrual cycles, we compared four techniques for handling missing biomarker data with non-Normal distributions. We imposed increasing degrees of missing data on two non-Normally distributed biomarkers under conditions of missing completely at random, missing at random, and missing not …

Sleep Patterns, Urinary Levels Of Melatonin And Subsequent Weight Change In The Women’S Health Initiative Observational Study, Nicole M. Barron

Masters Theses

Results from prospective studies examining associations between sleep duration and weight gain have been mixed. Melatonin has been hypothesized to mediate the association between sleep duration and weight/body composition. In cross-sectional studies, aMT6s has been shown to be inversely associated with weight/body fat percentage. We examined associations between baseline sleep duration, insomnia status, aMT6s levels with weight/body fat percentage through 6 years, utilizing a subset 690 women who participated in a breast cancer case-control study nested within the WHI-OS. Multi-variable and mixed-effects regression was used to calculate beta-coefficients and 95% confidence intervals. Cross-sectional analyses showed urinary aMT6s levels were inversely …

A Comparative Sustainability Study For Treatment Of Domestic Wastewater: Conventional Concrete And Steel Technology Vs. Vegetated Sand Beds (Vsb’S) And Their Relative Differences In Co2 Production, Alicia M. Milch

Masters Theses

Conventional wastewater treatment in the U.S. is an energy dependent and carbon dioxide emitting process. Typical mechanical systems consume copious amounts of energy, which is most commonly produced from fossil fuel combustion that results in the production of CO₂. The associated organic load is also metabolized by microorganisms into CO₂ and H₂O. As the desire to reduce CO₂ output becomes more prominent, it is logical to assess the costs of conventional treatment methods and to compare them to alternative, more sustainable technology. Vegetated Sand Bed (VSB) and Reed Bed (RB) systems are green technologies …

Thermo-Responsive Poly(N-Isopropylacrylamide) And Its Critical Solution Temperature Type Behavior In Presence Of Hydrophilic Ionic Liquids, Purnendu K. Nayak

Masters Theses

Thermo-responsive homopolymer poly(N-isopropylacrylamide), is a widely studied and used polymer. Our recent observations on thermal behavior of aqueous solutions of this polymer requires a short overview of existing results in order to understand the formation of different phases, both stable and unstable with the addition of hydrophilic Ionic liquids (ILs) 1-Butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF₄]), 1-Butyl-3-methylimidazolium acetate ([BMIM][OAc]) and 1-Butyl-3-methylimidazolium thiocyanate ([BMIM][SCN]) to the system. PNIPAM is soluble in cold water due to its inter- and intramolecular hydrogen bonding but phase separates upon heating at T > 32 , which is its lower critical solution temperature (LCST). PNIPAM exists in an …

Model-Based Guidance For Human-Intensive Processes, Stefan Christov

Doctoral Dissertations

Human-intensive processes (HIPs), such as medical processes involving coordination among doctors, nurses, and other medical staff, often play a critical role in society. Despite considerable work and progress in error reduction, human errors are still a major concern for many HIPs. To address this problem of human errors in HIPs, this thesis investigates two approaches for online process guidance, i.e., for guiding process performers while a process is being executed. Both approaches rely on monitoring a process execution and base the guidance they provide on a detailed formal process model that captures the recommended ways to perform the corresponding HIP. …

Ozone, Uv, And Nanoparticles, Morton Sternheim, Jennifer Welborn

Nanotechnology Teacher Summer Institutes

•Ultraviolet light causes skin damage and cancer •Ozone in the stratosphere blocks UV •Sunscreen blocks UV, partly •Nanoparticles in sunscreen improve blocking Sunscreen PowerPoint and activities based on NanoSense web site:

http://nanosense.sri.com/activities/clearsunscreen/index.html

Nanomedicine, Mark Tuominen

Nanotechnology Teacher Summer Institutes

An overview of nanomedicine. The end goal of nanomedicine is improved diagnostics, treatment and prevention of disease. Nanotechnology holds key to a number of recent and future breakthroughs in medicine.

Evaluating Predictors Of An Individual’S Dietary Intake Latent Value Under Different Mixed Models, Shuli Yu

Doctoral Dissertations

The accurate estimation of an individual’s usual dietary intake is important since the estimates are essential to uncover the diet-disease relationships. This study explores a more accurate method to estimate an individual’s latent value of usual dietary intake when it is repeatedly measured using a 24-hour dietary recall (24HR) and seven day dietary recall (7DDR), accounting for random measurement error and bias. The performance of the (empirical) predictor of subject’s latent value obtained under the finite population mixed model (FPMM) framework is compared with those obtained under the usual mixed model and the measurement error model through a simulation study. …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

In Silico Surveillance: Evaluating Outbreak Detection With Simulation Models, Bryan Lewis, Stephen Eubank, Allyson M. Abrams, Ken Kleinman

Public Health Department Faculty Publication Series

Background

Detecting outbreaks is a crucial task for public health officials, yet gaps remain in the systematic evaluation of outbreak detection protocols. The authors’ objectives were to design, implement, and test a flexible methodology for generating detailed synthetic surveillance data that provides realistic geographical and temporal clustering of cases and use to evaluate outbreak detection protocols.

Methods

A detailed representation of the Boston area was constructed, based on data about individuals, locations, and activity patterns. Influenza-like illness (ILI) transmission was simulated, producing 100 years ofin silico ILI data. Six different surveillance systems were designed and developed using gathered cases …