VictorJuiz/thesis huggingface dataset:
Simvastatin Prevents and Reverses Chronic Pulmonary Hypertension in Newborn Rats via Pleiotropic Inhibition of RhoA Signaling
Keywords: Echocardiography
Newborn
Pleiotropic
Pulmonary Hypertension
ROCK/RhoA
Statins

Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but with side effects including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoids that may limit activity of RhoA, which signals ROCK. We examined the preventive and rescue effects of simvastatin on chronic hypoxia-mediated chronic PHT. Newborn rats were exposed to normoxia (room air) or moderate hypoxia (13% O2) from postnatal day 1 and received simvastatin (2 mg/kg/day i.p.) from postnatal days 1-14 (prevention) or from postnatal days 14-21 (rescue). Simvastatin decreased RhoA/ROCK signaling in the hypoxiaexposed lung. Treatment of chronic hypoxia-exposed animals with simvastatin decreased pulmonary vascular resistance, right ventricular hypertrophy, and pulmonary arterial remodeling. We conclude that simvastatin limits RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus ameliorating hemodynamic and structural markers of chronic PHT, without causing adverse systemic effects.
Effects of Concurrent Exposure of Diesel Exhaust Particles and House Dust Mite on the Development of Allergen-Induced Airways Inflammation
Keywords: allergen
asthma
particulate matter
pollution

Chronic air pollution exposure is associated with accelerated lung function decline and increased prevalence and exacerbations of chronic inflammatory lung diseases, such as asthma. However, its pathological effects have not been studied extensively. Therefore we assessed the physiological and immune responses induced by chronic exposure to low concentrations of diesel particles (freshly-generated particles [DEP] or diesel standard reference material [SRM]) in both healthy mice and those with house dust mite (HDM)-induced allergic airways inflammation (reflective of asthma). We found that SRM exposure led to subtle neutrophilic inflammation in healthy mice, and that DEP increased central airway reactivity without affecting resultant airway constriction to methacholine in the asthma model. Results suggest that chronic exposure leads to immune changes in mice representing healthy individuals that may enhance the adverse effects of future allergen encounter; the low dose of particulate matter exposure has no effect in asthmatic background.
The Influence of Selective Attention on Auditory Localization in Younger and Older Adults
Keywords: aging
Auditory localization
cognition
perception
Selective attention
spatial perception

Auditory localization, the ability to locate sounds, declines with age due to changes in peripheral and central auditory processing. As selective attention is typically preserved in older adults, drawing their attention towards the stimulus before it occurs may improve auditory localization. This study evaluated this hypothesis by precueing younger and older participants towards a likely location of the upcoming target (a broadband noise) with a visual attentional cue. The attentional cues either provided a) correct information about the upcoming target location (valid) b) incorrect information about the upcoming target location (invalid), or c) no information about the upcoming target location (neutral). Participants estimated the targetâ s location on a schematic drawing of the testing environment. Akin to younger adults, older adults made less errors and biases, and faster responses with valid cues. This suggests that older adults can employ selective attention to improve auditory localization, similar to younger adults.
Non-Invasive Methods of Human Embryo Quality Assessment: Exploring Morphokinetic, Metabolomic and Secretome Parameters That Predict Pregnancy Outcome in IVF
Keywords: Embryo Selection
Extracellular Vesicles
Human
IVF
Metabolomics
Morphokinetics

In-vitro fertilization (IVF) is a commonly used infertility treatment involving fertilization of the oocyte by sperm outside of the body. Morphological assessment is the primary non-invasive criteria used to select embryos for uterine transfer, however, using this method, the current success rate is around 30%. Thus, more non-invasive tools are needed to improve the process of embryo selection. The objective of this thesis is to explore and assess additional non-invasive methods, including morphokinetics, metabolic profiling and extracellular vesicle release, as biomarkers for selecting the embryo with the highest implantation potential. Results show some morphokinetic parameters are correlated with implantation and metabolomic analysis can provide further insight in understanding embryo physiology. Moreover, we show for the first time, the possibility of the release of extracellular vesicles from human pre-implantation embryos. This data provides validation that these techniques have the potential to be brought into routine clinical use for embryo selection.
Improving Network Performance for Applications Running over Wide Area Networks
Keywords: optimization
routing algorithm
wide area network

In recent years, research on wide area networks has gradually spread to more and more applications. However, due to bandwidth limitation of wide area networks, it is necessary to tackle with to provide better services for users, while in traditional applications operating within a single region, the link bandwidth is no concern. In this thesis, we propose and implement different routing algorithms for two types of applications, delay-sensitive applications and streaming analytics applications, respecting their own demands and working conditions. For applications with stringent requirements on latency, we implement our delay-optimized routing mechanisms to minimize packet delay explicitly for applications with high priorities. We then concentrate on streaming analytics application, which is another popular topic recently. On the basis of existing batch-based stream processing system, Spark Streaming, we propose an algorithm jointly considering query routing and batch sizing to exploit detoured high-bandwidth links.
Adjuvants to Mechanical Ventilation for Acute Respiratory Failure
Keywords: Adjuvants
Adoption
Continuous Neuromuscular Blockading Agents
Extracorporeal Membrane Oxygenation
Inhaled Nitric Oxide

OBJECTIVES: To evaluate use of adjuvants to mechanical ventilation for acute respiratory failure (ARF;2008-2013) and the impact of landmark publications on adoption and de-adoption. METHODS: Adult patients with ARF who underwent mechanical ventilation were evaluated using a large US quality improvement database. Adjuvant use was identified using International Classification of Disease, 9th Edition codes and billing data. RESULTS: Among 514,913 ARF patients, 11,567 (2.3%) were treated with adjuvants. There was an increase in recent years of extracorporeal membrane oxygenation and inhaled epoprostenol but no change in inhaled nitric oxide or continuous paralysis over time. Segmented regression analysis used to evaluate whether clinical practice was in accordance with evidence from landmark studies, did not reveal any change in use following publication with the exception of inhaled epoprostenol. CONCLUSIONS: The use of adjuvants is infrequent across our population. Published evidence to support current adoption/de-adoption appear to have had limited effect on practice.
New Sequential Wave Imprinting Machines Visualize Waves in Real-space and Real-time by Augmediating Reality
Keywords: Augmediated Reality
Augmented Reality
Efficiency Measurement
Efficiency Meter

New wearable Sequential Wave Imprinting Machines (SWIMs) based on Steve Mannâ s invention, have been designed, built and used as augmediated reality oscilloscopes, to teach concepts of wavelength measurement in real-time and real-space in an immersive and convincing way, by means of phenomenological augmented reality. Several new SWIM devices are reported on, which are made to meet objectives of wearability, high luminosity and high resolution. Presented are a wrist-worn SWIM device, as well as a ring-worn SWIM device. A new modular wearable lock-in-amplifier is presented, which completes a wearable SWIM system allowing for visualization of soundwaves in nearly any setting desired. A systems level analogy is realized between the concepts of the lock-in-amplifier, and of power measurement. The idea of an electrical efficiency meter is explored and a combination efficiency meter/lock-in-amplifier has been designed and built which has several advantages over existing power analyzers which are reported on.
Broadband Mid-infrared Light Source for Near-field Microscopy Using Ultrashort Near-infrared Laser Pulses
Keywords: broadband near-field imaging
femtosecond near-field infrared spectroscopy
infrared nano-spectroscopy
near-field microscopy
s-SNOM

Scattering-type scanning near-field optical microscopy (s-SNOM) is a hybrid scanning probe/spectroscopic technique that can achieve a spatial resolution of tens of nanometers in the mid-infrared region. The scanning probe tip strongly localizes and enhances the spectroscopic capabilities, while recording sample topology. Although traditionally a monochromatic technique, making s-SNOM broadband is desirable; data acquisition becomes less time-consuming and there are fewer irreproducibilities. The most promising solution uses difference-frequency generation (DFG) to produce the broadband mid-IR light. Here I attempt to replicate an ultrashort DFG setup that has been shown to provide adequate illumination for and data from broadband s-SNOM experiments. To this effect I use two near-IR lasers â one essentially monochromatic, the other a supercontinuum â with ~80 fs pulse durations. At the time of writing, the broad mid-IR frequencies have not been observed, although temporal overlap of the pulses in the nonlinear medium, GaSe, has been confirmed through sum frequency generation.
The Role of Stressors and Oxytocin upon Vocalizations and Social Behaviour in Octodon degus
Keywords: Degu
Oxytocin
Reunion
Social Behaviour
Social Isolation
Vocalizations

Stressors such as social deprivation and painful stimuli are salient motivating factors for social interaction. It remains unknown, however, whether social behaviours elicited by different stressors such as social separation and aversive events can be dissociated at the behavioural and vocalization level in rodents. To address this, I used the rodent Octodon degus, which demonstrate a complex repertoire of vocalizations and social behaviour. I examined vocalization and grooming behaviour of pairs of adult female cage-mates when re-united after two different types of stressful events. I also investigated the effect of blockade of central oxytocin receptors on the vocalization and behaviour of degus after social separation. Degus increased the frequency of vocalizations and all social grooming behaviours after social separation while they only increased certain types of social grooming behaviour after footshock compared to controls. Furthermore, blockade of oxytocin receptors attenuated vocalizations, but not grooming, during reunion after social isolation.
Mechanical Properties of Nanocrystalline Nominally Multilayered Hexagonal Cobalt Electrodeposits
Keywords: cobalt
hexagonal
multilayer
nanocrystalline

The microstructure and mechanical properties of electrodeposited nanocrystalline cobalt were investigated and compared to cobalt electrodeposits produced under waveforms that would result in a nominal multilayered material by alternating electrodeposition conditions in the same electrolytic solution. All sample types were of the hexagonal crystal structure and a preferred orientation was prominent with the introduction of nominal multilayers, in which the basal plane preferentially was oriented parallel to the surface of the deposit. Transmission electron microscopy was used to compare the starting microstructure and post-failure microstructure of cobalt electrodeposits. Tensile tests were performed at a strain rate of 5 x 10-4 s-1 and microhardness tests were performed under a 100g load. The average hardness, yield, ultimate tensile and fracture strengths increased when the electrodeposited cobalt followed a nominal multilayered pulse train. Tensile elongation for cobalt electrodeposits with 100 nm nominal layer thicknesses are more than twice that observed for monolithic cobalt.
Effect of Cytochrome P450 2C19 Genotyping and Therapeutic Drug Monitoring on Efficacy and Toxicity of Voriconazole Therapy
Keywords: CYP2C19
pharmacogenetics
TDM
voriconazole

Invasive fungal infections are a significant cause of morbidity and mortality in immunocompromised patients and voriconazole is often prescribed because of its potent activity. Treatment success of voriconazole therapy is highly dependent on maintaining therapeutic concentrations which is challenging due to the high inter- and intra-patient variability in drug exposure. The complex kinetics of voriconazole renders current manufacturersâ dosing guidelines ineffective. The variability in drug exposure observed in clinical settings has been linked to genetic polymorphisms in the cytochrome P450 2C19 gene, which encodes for the enzyme primarily responsible for voriconazole metabolism. Therapeutic drug monitoring has been found to increase efficacy of voriconazole treatment. However, there is still inconsistency and delay in getting patients to reach target voriconazole concentrations. The aim of this thesis is to examine if implementation of cytochrome P450 2C19 real-time genotyping as part of voriconazoleâ s existing dosing algorithm can improve clinical outcomes.
Automated Cell Tracking Identifies Mechanically-Oriented Cell Divisions During Drosophila Axis Elongation
Keywords: cell divisions
image analysis
laser ablation
machine learning
morphogenesis
time-lapse microscopy

Axis elongation is a conserved process in which embryos establish their anterior-posterior (AP) axis. Drosophila axis elongation occurs in an epithelial monolayer, the germband, and is driven by cell intercalation, cell shape changes and oriented cell divisions at the posterior end of the tissue. We found that anterior germband cells divided during axis elongation. We developed automated image analysis and machine learning algorithms to investigate anterior divisions. In the anterior germband, mesectoderm cells, which form the ventral midline, divided parallel to the AP axis, while lateral cells displayed a uniform distribution of division orientations. Mesectoderm cells did not intercalate and exhibited greater AP strain before division. Using laser ablation, we isolated mesectoderm cells from anterior-posterior or dorsal-ventral forces, and we found that oriented divisions required AP-oriented forces. Our data suggest that AP-oriented forces deform germband cells, and mesectoderm cells alleviate their deformation by dividing along the axis of greater strain.
A Pre-clinical Assessment of Lithium to Enhance Fracture Healing in Healthy and Impaired Bone Rat Model
Keywords: Fracture healing
Lithium
Treatment

Fracture healing is a complex biologic process that fails in 5-10% of cases. There is a critical need for an adjunct treatment that can enhance fracture healing, particularly in osteoporotic bone. Lithium, the standard treatment for bipolar disorder, has been reported to improve fracture healing via the canonical Wnt pathway. Recently, a pre-clinical study in our laboratory utilized a design of experiments approach to optimize the lithium administration parameters, resulting in improved strength (~46%) of healing femurs in otherwise healthy rats. In this thesis, the optimized lithium regimen was verified in healthy rats (~44% improvement). This regimen did not significantly impact healing of simple or comminuted fractures in osteoporotic rats. The lithium onset time may need to be extended to better target and enhance osteogenic activity in fractured osteoporotic bones. This thesis supports clinical evaluation of lithium for healthy long-bone fractures and will guide pre-clinical lithium optimization in impaired bones.
Developing a Novel Task to Investigate the Cognitive and Neural Processes Involved in Switching between Multiple Goals
Keywords: Goal hierarchy
Goals
Goal switching
Neuroscience
Psychology

Coordinating and switching appropriately between multiple goals is an important challenge. What processes are used by the human mind and brain to solve this challenge? A novel task was developed and pilot tested to study these processes as involved in three types of goal-switching: switching between substitutable means to the same ends, prioritizing among multiple necessary means to an end, and switching goals at different levels of goal-hierarchy. Results confirmed that people switched between goals in the task in ways predicted by the current model of multiple goal pursuit. This study will provide the basis for a planned neuroimaging study to investigate the neural correlates of these goal-switching processes.
Inhibition of Holocellulose Active Enzymes due to Steric Hindrances and Non-specific Binding on Lignocellulose Surfaces
Keywords: Lignin surface
non-productive binding
Quartz Crystal Microbalance with Dissipation
xylanase

The adsorption of xylanases from Thermobifida fusca (TfuXyn10B and TfuXyn11A) onto lignin samples derived from kraft and organosolv pulping processes was monitored using a quartz crystal microbalance with dissipation (QCM-D). While TfuXyn11A comprises a C-terminal family 2b carbohydrate-binding module (CBM) and bound to lignin surfaces, TfuXyn10B lacking a CBM did not bind any lignin source. Pretreatment with bovine serum albumin effectively prevented TfuXyn11A adsorption. Enzyme adsorption was limited to a surface interaction and did not lead to swelling of the lignin coating. A novel approach was developed to distinguish between the mass of protein and protein-bound water binding to the lignin surfaces. Kinetic analysis of enzyme association and dissociation revealed that kinetics driving desorption of TfuXyn11A from each lignin source were similar. By contrast, the adsorption kinetics was highest for TfuXyn11A binding to kraft lignin. A lignocellulose composite surface composed of lignin, cellulose and xylan was developed to study impedance of cellulase action
Folate and Folic Acid Supplement Use and Breast Cancer Risk in BRCA1/2 Mutation Carriers
Keywords: BRCA
Folate
Hereditary Breast Cancer
Vitamin B12
Vitamin B6

The relationship between folate (a B vitamin important in DNA synthesis and methylation reactions) and cancer risk among BRCA1/2 mutation carriers with a genetic predisposition for developing breast cancer is unclear. Therefore this study investigated the association between plasma folate and folic acid supplement use, along with other B vitamins, and breast cancer risk in BRCA1/2 mutation carriers. Women with high plasma folate concentrations had significantly increased risks for breast cancer, compared with women with low plasma folate concentrations. However, women who never used folic acid-containing supplements had significantly increased risks for breast cancer. Similarly, never use of vitamin B6- or vitamin B12-containing supplements tended to be associated with increased breast cancer risk. These findings support a â Uâ -shaped association of folate and breast cancer risk and suggests that moderate B vitamin supplement use may be protective for BRCA1/2-associated breast cancer, however BRCA1/2 mutation carriers should be cautious of over-supplementation.
Optimization methods for high dose rate brachytherapy treatment planning
Keywords: Brachytherapy
Inverse planning

Optimization approaches for treatment planning in two novel high-dose-rate (HDR) brachytherapy techniques, direction-modulation brachytherapy (DMBT) and energy-modulated brachytherapy (EMBT), are investigated for cervical cancer and prostate cancer. Brachytherapy is a form of radiation therapy where a radioactive source is placed inside the body to irradiate the tumour internally. Conventionally, only one source is used and it is unshielded, thus providing an isotropic dose distribution. DMBT makes use of a new shielded applicator that is capable of delivering highly directional radiation distributions. In EMBT, three HDR sources, 192Ir, 60Co, and 169Yb, are used in combination to provide variety in dose profiles. To investigate the benefit of these two new techniques over conventional brachytherapy, we use an inverse planning approach to generate the treatment plans. We model the treatment planning problem as a quadratic program and use an interior point constraint generation algorithm to generate the treatment plans.
The Effect of Dairy Products on Satiety, Food Intake and Post-prandial Glycemia in Young and Older Adults
Keywords: Appetite
Dairy
Food Intake
Glycemia
Milk
Satiety

The hypothesis that dairy products consumed with glycemic carbohydrate at a breakfast meal decrease appetite, food intake (FI) and post-prandial glycemia (PPG) compared with non-dairy beverages in healthy young and older adults was explored in two experiments. Experiment 1 compared 250 mL of 1% milk, yogurt beverage, soy beverage, almond beverage and water consumed with cereal by young adults (20-30 years). Appetite was lowest after yogurt beverage and FI at 120 min was lowest after milk. Soy beverage resulted in the lowest post-treatment blood glucose but despite higher carbohydrate content, dairy beverages did not increase blood glucose more than almond beverage and water. Experiment 2 also sought to compare different forms of dairy using 250 mL of 2% milk and soy beverage, 175 g of 2% Greek yogurt and 30 g of Cheddar cheese consumed with bread and jam by older adults (60-70 years). Yogurt and cheese suppressed appetite more than milk and attenuated blood glucose compared to milk and soy beverage but there were no differences in FI. In conclusion, satiety is higher and blood glucose is lower after high glycemic carbohydrates are consumed at breakfast with dairy products as well as non-dairy beverages, but semi-solid or solid forms may be more efficacious than liquid forms.
The Use of Continuous Monitoring of Heart Rate as a Prognosticator of Readmission in Heart Failure Patients
Keywords: Heart Failure Management
Photoplethysmography
Wearables

In this study we validated the accuracy of heart rate measurements of two consumer-grade heart rate and activity tracking wearable devices in 8 healthy participants. In a clinical setting and using the Holter monitor as the reference, participants exercised on a stationary bike for 10 minutes with a 10-watts step protocol. The two devices reported better correlation with the Holter monitor at higher workload levels, hence, at higher heart rates with a 90% confidence interval for overall measurement accuracy. We also examined the feasibility of the two devices in remote monitoring 8 heart failure patients (NYHA II-NYHA III) for two weeks. The two devices reported lower daily physical activity, lower total step count and higher resting heart rate for NYHA III patients when compared to NYHA II patientsâ data. Therefore, with the wearable devices we differentiated different classes of heart failure based on heart rate and physical activity.