VictorJuiz/thesis huggingface dataset:
Modulating Autophagy in a Murine Model of Severe Malnutrition Enteropathy
Keywords: Autophagy
Enteropathy
Intestinal Barrier
Malnutrition
Mouse
Tight Junction

Severe acute malnutrition (SAM) remains pervasive in developing countries. It is associated with enteric dysfunction, but its pathophysiology is poorly understood. Evidence suggests that dysregulated autophagy contributes to the intestinal dysfunction in SAM. A novel murine model of SAM was induced in male weanling C57Bl6 mice through a protein deficient diet (1% protein) and compared to mice fed a control diet (18% protein). Malnourished mice showed significant weight loss, a significant decrease in villous height in the small intestine and a significant decrease in crypt depth, and goblet cell density were observed in the colon. Malnourished mice had increased intestinal permeability assessed via FITC-dextran uptake and upregulation of Claudin 2. Induction of autophagy in malnourished mice through intraperitoneal rapamycin injections restored the increase in intestinal permeability and Claudin 2 levels. This study will help characterize intestinal pathology associated with severe acute malnutrition, and potentiallyÂ identify new targets for intervention.
Biocompatibility of Bone Allograft Toughened with a Novel Sterilization Method for Critically-Sized Segmental Defects: An In Vivo Rabbit Study
Keywords: Biocompatibility
Bone allograft
Bony union
New Zealand White rabbit
Ribose
Îł-irradiation

PURPOSE: Bone allografts often undergo γ-irradiation to decrease infection risk. This consequently degrades bone collagen and makes the bone brittle. Our laboratory found pre-treatment with ribose could protect the bone. This thesis aimed to determine if ribose-treated γ-irradiated allografts were biocompatible in vivo. MATERIALS AND METHODS: Using the New Zealand White rabbit (NZWr), we first aimed to establish a proper in vivo model to test the graft using intramedullary wire fixation (Study 1), and then tested the biocompatibility of ribose-treated grafts (compared to untreated and conventionally-irradiated grafts) (Study 2). Healing/union was assessed with radiographs, μCT, histomorphometry, backscatter electron microscopy, and torsion testing. RESULTS: Intramedullary fixation achieved stable reconstructions. All grafts achieved bony union. No differences were found in radiographic and biomechanical parameters tested. However, irradiated grafts had less bone volume (p=0.000) but greater bone forming properties (p
The Alzheimer's Spectrum: Diagnostic Challenges and Nosology in a Clinically Heterogeneous Disease
Keywords: Alzheimer's disease
Brain imaging
Clinical criteria
Diagnosis
Heterogeneity
Phenotype

Hypothesis: Alzheimer's disease (AD) is not a unitary condition but a phenotype spectrum. Rationale: Mounting evidence suggests AD is more complex than previously thought. A new AD conceptualization accounting for this biologic and clinical complexity is needed. Aim: To review existing evidence for, provide a specific example of, and investigate the nosological impact of AD heterogeneity. Methods: Three studies were done using (1) literature review, (2) imaging analysis case series, and (3) systematic chart review. Results: AD is heterogeneous and sub-syndromes exist. Extreme heterogeneity results in syndrome mimicry with blending of imaging markers. Wide variation in diagnostic classification occurs even with standardized application of consensus criteria. Conclusions: AD is not a single disease but a spectrum of sub-syndromes (core phenotype and atypical sub-syndromes). The AD conceptual framework must evolve to acknowledge, define, and anticipate this complexity, harnessing it to improve diagnostic precision and facilitate treatment discovery.
The Contribution of IgG Fc Glycans on Antibody-mediated Immune Suppression (AMIS) to Murine Erythrocytes
Keywords: alloimmunization
AMIS
anti-D
HDFN
red cell antibodies

The ability of anti-D to prevent hemolytic disease of the fetus and newborn (HDFN) is an example of antibody-mediated immune suppression (AMIS). A recombinant monoclonal antibody to replace anti-D is desired, however, none of the developed therapies have been as effective and some antibodies have unexpectedly led to enhanced immune responses. The requirement for IgG glycosylation for AMIS was analyzed for five antibodies reactive with erythrocytes in a murine model. The antibodies recognized the HOD (hen egg lysozyme [HEL] linked to ovalbumin and the human Duffy transmembrane protein) antigen. It was observed that glycosylation in the Fc region of polyclonal AMIS-inducing antibodies was not essential for complete suppression. In contrast, monoclonal AMIS-inducing antibodies were partially sensitive to removal of the glycan structure. These results may help explain the superiority of polyclonal antibodies to monoclonal therapeutics for AMIS induction and could influence the development of effective therapies to replace anti-D.
Life Cycle External Cost Evaluation of Crude Oil Transportation Options
Keywords: Life Cycle Assessment
Life Cycle Costing
Pipeline
Transportation Externalities

Widespread concerns associated with crude oil transportation which could drive decision-making motivate the life cycle evaluation of crude oil transportation options. This thesis integrates life cycle assessment, economic input output life cycle assessment, and life cycle costing to examine the internal and external costs of pipeline, rail, and tanker transportation. The case studies used in this work illustrate the difference in impacts and costs between pipeline and rail transport for similar original-to-destination routes (including tanker, where relevant). Results show that pipeline costs are lower for each of case studies compared to the equivalent rail routes. No changes within the plausible ranges of input values for transport operation, greenhouse gas emissions, health impact, volume transported and discount rate would change the overall outcome from a preference for pipelines to rail (tanker costs included where relevant), however, cross-over between favoring pipeline over rail is possible with varying changes in the capital costs.
A Comparative Study of Quality of Life in Patients with Low-and Intermediate-risk Prostate Cancer Treated at a Single Institution: Stereotactic Radiotherapy vs. High dose-rate Brachytherapy Monotherapy vs. High dose-rate Brachytherapy Boost
Keywords: prostate cancer
Quality of life
radiation therapy

This retrospective cohort analysis aims to compare health-related quality of life (HRQoL) deterioration at 12 months in 648 low-and intermediate-risk prostate cancer (PCa) patients treated with three radiation strategies: stereotactic ablative radiation therapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost. Urinary, bowel and sexual HRQoL were prospectively measured at baseline and 12 months using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline â Ľ 0.5 standard deviation of baseline score. Univariate and multivariable logistic regression analyses using generalized estimating equations were used to compare the proportion of patients having MID between groups. SABR and HDR monotherapy were associated with less deterioration in the urinary (OR:0.543, 95%CI:0.320-0.922, p-value=0.024, OR: 0.468, 95%CI:0.432-0.507, p-value
Ileal Fatty Acid Sensing Mechanisms Regulate Glucose Homeostasis In Vivo
Keywords: Diabetes
glucagon-like peptide-1
glucose production
ileum
intestine
rats

Long-chain-fatty acids (LCFAs) are found in the diet, whereas short-chain fatty acids (SCFAs) are byproducts of fermentation in the distal intestine. It remains to be determined if the ileum regulates glucose production (GP). Since the GLP-1 receptor (GLP-1R) on vagal afferents is near intestinal GLP-1 secretion, receptor activation and vagal firing may mediate the effects of FAs. Intraileal LCFAs oleic acid (OA) and linoleic acid (LA), and SCFA propionate infusions decreased GP during the basal insulin-euglycemic clamp. The GP lowering effect of OA and LA required LCFA-CoA formation where the GP lowering effect of propionate was dependent on ileal GPR43 signaling, demonstrated by inhibitor co-infusion or targeted knockdown approaches, respectively. The effects of FA infusions were diminished with coinfusion of exendin-9, a GLP-1R antagonist, or tetracaine, a local anesthetic. Collectively, LCFAs and SCFA activate an ileal GLP-1R dependent neuronal network to lower GP via LCFA-CoA formation or GPR43 activation, respectively.
Controlled Release as a Strategy to Prevent Solution-mediated Phase Transformation in Amorphous Solid Dispersions: Effect of Dosage Form Design
Keywords: controlled release
dosage form design
poorly soluble drugs
solid dispersion

The purpose of this study was to define the limits of developing a controlled-release amorphous solid dispersion (CRSD) system intended for enhancing the bioavailability of poorly water soluble drugs. Feasibility of multiple solid oral CRSD dosage form designs, such as spray dried powders, coated beads and compressed matrices (dry granulations and tablets) was evaluated. Solid dispersion powders were characterized in terms of ability to establish and maintain amorphicity in the dry form (by DSC and XRD) and ability to circumvent events leading to solution-mediated phase transformation (SMPT), or recrystallization during dissolution. While all dosage forms could successfully be produced with the amorphous dispersion, great differences in dissolution/recrystallization profiles were found, depending on how the controlled release agent was incorporated. These studies reveal that when designing a solid dispersion system, greater benefit can be derived by selecting the appropriate dosage form design, granting the formulator the much sought-after control over the challenge of SMPT.
Defining the Role of Hedgehog-GLI Signaling in the Renal Cortical Stroma
Keywords: Foxd1
hedgehog
kidney development
nephrogenesis
stroma

In the mammalian kidney, Foxd1-positive stroma interacts with nephron progenitors to control nephrogenesis. Here we establish a non-cell autonomous role for stromal-Hedgehog (HH) signaling in controlling nephron progenitor differentiation and self-renewal. Stromal-specific inhibition of Smo, the HH signal transducer, results in an expanded domain of nephron progenitors and an increase in cell proliferation. Smo-deficient kidneys exhibit a specific inhibition in the formation of renal vesicles, a nephron intermediary structure. In parallel, Lim1 expression, a requirement for the progression of nephrogenesis, is decreased. HH signaling mediates its downstream effects by promoting GLI transcriptional activator levels while inhibiting GLI3 processing to a transcriptional repressor (GLI3R). Deletion of Gli3 in Smo-deficient mice normalized kidney volume and nephron number. Stromal-specific expression of Gli3R (obligate and conditional) phenocopies Smo-deficient mice, thus further supporting a deleterious role for GLI3R in the stroma. Together, our results provide novel insight into HH-GLI dependent interactions within the nephrogenic niche.
Processing of Emotions in Speech in Healthy Older and Young Adults
Keywords: Aging
Emotion processing
Lexical content
Prosody
Speech

Emotions in speech are conveyed through the lexical content and prosody. With increasing age, healthy older adults have trouble recognizing affective prosody, however, literature pertaining to the concurrent role of lexical content and prosody in emotion processing is scarce. Therefore, this study examines the role of lexical content and prosody in emotion recognition in healthy older and young adults. Two different versions of a novel tool, the Test for Recognition of Emotions in Speech or T-RES, were used to study emotion processing in spoken language and specifically, to examine how emotion processing is influenced by selective attention and a potential positivity bias in healthy older adults. The results gathered from these tools demonstrate impairment in selective attention, particularly when attending to the prosody and stronger positivity bias in healthy older adults compared to young adults. Moreover, both tools can be used for emotion processing assessments, as they provide similar data.
A MICROARCHITECTURAL ANALYSIS OF MACHINE LEARNING ALGORITHMS ON SPARK
Keywords: Apache Spark
Computer Engineering
Hardware
Machine Learning
Microarchitecture
Software

Analysis of large data sets utilizing Machine Learning Algorithms (MLAs) is an important research and application area. This thesis resents a comprehensive performance analysis of MLAs on the ApacheTM Spark platform, identifying bottlenecks at the microarchitectural level, and associating them to higher-level code constructs. In addition, we propose solutions to address the discovered performance issues. Our results indicate that: 1) The majority of MLAs are backend-bound, in particular memory-bound. 2) The dot product is the main bottleneck in a considerable number of MLAs. 3) Garbage collection and high-level abstractions are a major source of overhead in Spark. 4) Enabling Hyper-Threading is a recommended feature that improves performance up to 52%. 5) The improved data representation of the Dataset API results in performance improvements of up to 64% over the RDD API. 6) Enabling software caching in the right place improves the performance between 6%-23%.
Timing and Location of Brain Areas Involved in Cognitive Theory of Mind in Children with Autism Spectrum Disorder
Keywords: autism
development
MEG
theory of mind

Cognitive theory of mind (ToM), or the ability to recognize the different mental states of others, is a social cognitive skill that is often impaired in children with autism spectrum disorder (ASD). This study enriches our understanding of ToM in ASD by using magnetoencephalography (MEG) to determine the temporal properties of brain regions active during a false belief task, a domain that has not been explored in this field, and yet is a significant component of brain activity. We found that whereas typically-developing children activate familiar ToM regions, such as the precuneus and the left temporoparietal junction, children with ASD appear to rely more on working memory and inhibition regions, such as the right dorsal temporoparietal junction and the right inferior frontal gyrus. This atypical activation suggests that children with ASD make use of alternative strategies to compensate for their deficits in ToM.
Confucian Multiculturalism: A Communitarian Theory of Intercultural Dialogue
Keywords: Communitarianism
Confucianism
Intercultural Dialogue
Liberalism
Multiculturalism

This paper argues that the liberal-communitarian debate in political philosophy is still significant today. While some have argued that communitarian concerns have been absorbed by liberal approaches to the accommodation of moral and cultural diversity, I show that such efforts are not properly sensitive to and respectful of other cultures because they do not acknowledge the particularity of the liberal tradition. To emphasize this, I draw on the intellectual resources of a particular communitarian tradition – Confucianism – to develop a more sensitive and respectful accommodation of cultural diversity called Confucian multiculturalism. I show that Confucian multiculturalism can be realized through an intercultural dialogue that, in the modern context, should take place in universities which can provide the right intercultural education and environment. I conclude that the liberal-communitarian debate, when taken seriously, can be expanded to take the form of an intercultural dialogue that enriches all cultures and probes our common humanity.
Apolipoprotein A-IV: Novel αIIbβ3 Integrin Ligand and Endogenous Thrombotic Inhibitor
Keywords: Apolipoprotein A-IV
Inhibitor
Ligand
Platelet
Thrombosis
αIIbβ3 Integrin

Apolipoprotein A-IV (apoA-IV) is a lipid binding protein that is synthesized in the small intestine during lipid absorption. Although reports suggest that plasma apoA-IV levels are inversely correlated with coronary artery disease (CAD), its role in platelet function and thrombosis, the major cause of CAD, is unknown. Here, I demonstrated that apoA-IV inhibited platelet aggregation and thrombus growth - with enhanced inhibition at higher shear rates - while lacking apoA-IV resulted in accelerated thrombosis. Using intravital microscopy, I found a unique pattern of apoA-IV deposition on thrombi. Through collaboration, we found the direct binding force between apoA-IV and platelet αIIbβ3 integrin. ApoA-IV competitively inhibited pro-thrombotic fibrinogen binding to αIIbβ3. We demonstrated apoA-IV N-terminal aspartic acids (D5 and D13) are required for αIIbβ3 binding and the inhibition of platelet aggregation and thrombosis. Thus, apoA-IV is a novel αIIbβ3 ligand and endogenous thrombotic inhibitor, representing the novel mechanisms of prevention for CAD.
Expression of and Regulation by Nanos in Drosophila Early Embryos
Keywords: Drosophila
embryogenesis
local translational regulation
nanos
post-transcriptional regulation
RNA binding protein

Three categories of cytoplasmic post-transcriptional regulation that modulate mRNA stability, subcellular localization, and translation are coordinated to precisely control when and where a protein is expressed. In Drosophila oocytes and early embryos, subcellular mRNA localization and local translation play fundamental roles in determining the body axes and specifying the germline. Nanos protein is one of the determinants whose subcellular localization is accomplished through local translation of its transcripts in the posterior germ plasm. I quantified Nanos protein in early embryos at closely spaced stages and revealed that nanos mRNA is indeed translated at the posterior pole of embryos. I then tested the role of an RNA-binding protein, Staufen, as a nos translational activator competitive binding with the RNA-binding protein Smaug. I further started to uncover the role of Nanos in target transcript regulation as a co-factor together with the RNA-binding proteins Pumilio and Brain Tumor.
Intestinal microRNA Response to Citrobacter rodentium in the Presence and Absence of Bifidobacterium bifidum MIMBb75
Keywords: enteropathogen
gene expression regulation
intestine
mouse
probiotic

The continuous crosstalk between gut microbiota and the host epithelium is essential for intestinal homeostasis. Presence of harmful or beneficial bacteria can impinge host gene expression and affect homeostasis. Yet, the molecular basis underlying host-bacterial crosstalk is unclear. The objectives of this project were to determine if pathogen infection impacts microRNA-mediated posttranscriptional regulation of gene expression in mouse intestine and if probiotic treatment improves pathogen-induced pathologies and microRNA alterations. It was found that Citrobacter rodentium infection alters murine colonic microRNA signature with implications in modulating host gene expression involved in the apoptosis pathway, contributing to the epithelial hyperplasia in response to Citrobacter rodentium pathogenicity. Probiotic Bifidobacterium bifidum MIMBb75 supplementation did not attenuate intestinal pathology nor normalize microRNA alterations. Overall, these findings indicate that host-bacterial crosstalk is potentially mediated by microRNA modulation, and this particular strain of Bifidobacterium bifidum did not confer apparent benefits in Citrobacter rodentium infection.
The Role of LXR in Glucocorticoid-Induced Osteoporosis and Muscle Wasting
Keywords: Bone
Cushing's syndrome
Glucocorticoids
Liver X Receptor
Muscle
Nuclear Receptor

Synthetic glucocorticoids (GCs) have unparalleled anti-inflammatory and immunosuppressive properties that are crucial for the treatment of many inflammatory diseases. Unfortunately, a remaining limitation for the long-term therapeutic use of GCs is the development of major metabolic side effects, including Cushing’s syndrome, a disease characterized by metabolic dysregulations such as hyperglycemia, muscle wasting and osteoporosis. The glucocorticoid receptor (GR) and liver X receptor (LXR) are members of the nuclear receptor superfamily that regulate distinct but overlapping transcriptional programs. Using a Cushing’s mouse model of GC excess, as well as in vitro cell lines treated with synthetic GCs, we find that LXR antagonism is protective from GC-induced osteoclast activation, but not from the anti-osteoblastogenic or muscle atrophy effect of GCs; suggesting a cell type specific effect. Together, these studies show the selective regulation of LXR antagonism may be useful in preventing GC-induced osteoclast activation.
Antisaccadic Eye Movements as a Correlate for Response Inhibition and White Matter Integrity in Mild Traumatic Brain Injury
Keywords: Antisaccades
Diagnosis
Executive Functioning
Magnetic Resonance Imaging
Mild Traumatic Brain Injury
Symptom Burden

Antisaccades are thought to involve higher level inputs from neural centers involved in rapid eye movement inhibition and control. Previous work has demonstrated that performance on the antisaccade task can help in assessment of injury in acute and/or chronic Mild Traumatic Brain Injury (mTBI). We validated antisaccade performance in mTBI assessment against gold standard assessments of symptom burden, diffusion tensor imaging, and a neuropsychological test of response inhibition. Significant deficits in antisaccade median latency and prosaccade mean duration were found between patient groups and controls, despite overall integrity of the pupillary light reflex; the former was correlated with loss of white matter integrity in the splenium of the corpus callosum in acute mTBI. Furthermore, antisaccade median latency was also associated with poor performance on executive functioning tasks, and greater symptom burden in the acute patients. This research suggests that the antisaccade task is useful as a neurological marker for mTBI.
The Safety of Diclectin® in Breastfeeding
Keywords: adverse drug reaction
breastfeed
breast milk
diclectin
doxylamine
pyridoxine

Background and Rationale: Diclectin® is a delayed-release medication indicated for nausea and vomiting of pregnancy. Some mothers who are concurrently pregnant and breastfeeding also take Diclectin®. Hence, components of Diclectin® in breast milk may cause adverse events in the breastfed infants. This had not been studied before. Objective: To determine the safety and clinical significance of doxylamine exposure through breast milk in infants breastfed by mothers taking Diclectin®. Methods: 41 mothers concurrently taking Diclectin® and breastfeeding completed a telephone questionnaire regarding occurrence of adverse events in themselves and their breastfed infants. Data were analyzed and compared with results from other studies. Results: Maternal adverse events included sedation (29), dizziness (2), weakness (4), constipation (2), reduced lactation (2), abdominal pain (1), and increased appetite (1). Infant adverse events included sedation (5), constipation (1), slept less (1), and loose bowel (1). Conclusion: Mothers taking Diclectin® and their breastfed infants may experience sedation.