Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Actin, Myosin IB and Dynamin A in the Phagocytic Pathway of Dictyostelium discoideum

Dictyostelium discoideum is an amoeba that lives in the soil and feeds on bacteria. This model organism can be used as a surrogate macrophage to study highly conserved processes such as cell motility, phagocytosis, membrane traffic and host-pathogen interactions. This thesis addresses the role of the class I myosin MyoB, Dynamin A and actin dynamics in membrane traffic during phagosome maturation in Dictyostelium.
Genetic dissection of self-renewal pathways during hematopoietic differentiation

Recent studies have begun to elucidate the mechanisms controlling hematopoietic stem cell (HSC) self-renewal. Self-renewal requires the integration of survival signals and proliferation controls with the maintenance of an undifferentiated state. This demands a complex crosstalk between extrinsic signals from the microenvironment with the cell intrinsic regulators of self-renewal. The Polycomb protein, Bmi1, is absolutely required for the maintenance of both adult HSCs and neural stem cells. Evidence from studies in murine and human embryonic stem (ES) cells, point to the dynamic role of polycomb group proteins, in concert with master transcriptional regulators, in actively maintaining an undifferentiated state; similar mechanisms may apply to multiple types of stem cells. Recently, new regulators of HSC maintenance have been identified such as MCL-1, Tel/Etv6, Gfi-1, PTEN, and STAT5. In order to better understand HSC selfrenewal, we need to comprehend how these pathways are coordinated.
The role of the proline rich homeodomain in the regulation of proliferation, survival and migration of breast cells

This thesis demonstrates that the Proline Rich Homeodomain transcription factor (PRH/HHEX) plays an important role in regulating the proliferation and migratory behaviour of breast cells. In tumourigenic MCF-7 breast cells, shRNA knockdown of PRH results in a pro-invasive and pro-proliferative phenotype. Key genes regulated by PRH in MCF-7 cells include TP53, endoglin (ENG) and e-cadherin (CDH1), which regulate migration/invasion in breast cells. Significantly, exogenous PRH functions as an inhibitor of cell proliferation/survival and migration/invasion in all breast cell types examined. Furthermore, the effects of exogenous PRH on cell proliferation/survival are dependent on the DNA binding activity of PRH. This work provides an explanation for the finding that PRH expression is associated with increased overall survival in breast cancer patients. In contrast with this work, MCF-7 xenograft experiments reveal that expression of exogenous PRH in MCF-7 cells is oncogenic. Furthermore, shRNA knockdown experiments in MDA-MB-231 cells show that endogenous PRH increases proliferation of these cells. This thesis therefore demonstrates that the role of PRH can differ dramatically between breast cell types and between ex vivo and in vivo conditions.
Functional analysis of human enhancers using the zebrafish embryo

In the post-genomic era the availability of genome-wide datasets has revealed an unexpected complexity of transcriptional regulation. In this context, where most enhancer predictions are based on computational analyses, functional validations are lacking. This thesis investigated the utility of the transgenic zebrafish embryo as an in vivo vertebrate model to study the function of candidate human enhancers, and detect subtle changes in enhancer function caused by disease-associated variants. Our functional validations indicated that despite the evolutionary distance between human and fish, 60% of the conserved enhancers predicted by a combination of chromatin signatures, TF binding events and bidirectional transcription, lead to reporter expression that recapitulates the patterns of either zebrafish or human genes. To improve the reliability of zebrafish transgenesis, a targeted integration system mediated by PhiC31 integrase was validated for enhancer testing. I demonstrated that this method overcomes position effect variation commonly found in transposon-based assays. However, enhancer-driven expression could not be detected when I attempted to quantitate TCF7L2-associated enhancer variants, indicating the need for further studies to understand the limitations of the zebrafish model. Taken together, my results provide strong support for zebrafish as a valuable in vivo model to study the function of mammalian transcriptional regulatory elements.
Predictors of Flu Vaccination for Persons Living With HIV in Central Texas.

Each year, seasonal influenza (the flu) affects 9.2 to 35.6 million people in the United States and, since 2010, has been responsible for approximately 56,000 deaths each year (Centers for Disease Control and Prevention [CDC], 2016a). Most cases are mild with symptoms of fever, malaise, fatigue, and upper respiratory symptoms (CDC,2017a). However, theflu can lead to severe complications that include pneumonia, myocarditis, encephalitis, and exacerbation of other common comorbidities such as asthma or chronic obstructive pulmonary disease (COPD) (Van Kerkhove et al., 2011). Flu-related illness resulted in the hospitalization of approximately 310,000 people during the 2015–2016 flu season (CDC, 2016a). Children, adults older than 65 years, and people who are immune compromised are populations particularly susceptible to flurelated complications (CDC, 2016a). Persons living with HIV (PLWH) are especially vulnerable to theflu (Sheth,Patel,&Peters, 2011). As a result of both HIV-related antibody and T-cell dysfunction, PLWHwho acquire the flu have prolonged flu symptoms and are at a higher risk of flu-related complications that affect the heart (e.g., congestive heart failure) and lungs (e.g., secondary bacterial pneumonia), causing hospitalizations or death (CDC, 2016b). Flu vaccines are important for PLWHbecause, despite immune cell dysfunction, which causes PLWH to produce a weaker immune response to vaccines (Crum-Cianflone et al., 2011), PLWH who are vaccinated for the flu develop fewer and less severe cases of the flu (Anema, Mills, Montaner, Brownstein, & Cooper, 2008; Kunisaki & Janoff, 2009). Therefore, regardless of the person’s immune function (as measured by CD41 T-cell counts), it is essential that PLWH receive inactivated flu vaccination annually (U.S. Department of Health andHuman Services, 2017a). The purpose of our study was to investigate flu vaccination rates and clinical behaviors associated with receiving the flu vaccination at a regional federally qualified health center (FQHC) for underand non-insured people.
Milk fat in human nutrition

Milk fat contains a number of components of nutritional significance. The first section of the review outlines the composition, structure and certain biochemical and physiological characteristics of these components. In recent times the nutritional image of milk fat has suffered adversely because of the association of saturated fat and cholesterol with coronary heart disease. The various elements that are used to justify this 'lipid-heart disease' hypothesis are discussed and the strength of the evidence is assessed. Contrary evidence, which is mostly overlooked in authoritative reviews, is presented. Trans fatty acid consumption is associated with an increased risk of coronary heart disease; however, the associations generally do not apply to trans acids of animal origin. These acids are mainly vaccenic and rumenic, acids that may possess anti-atherogenic properties. Other health related benefits for rumenic acid, particularly its role in the prevention of mammary tumorigenesis are outlined. Milk fat contains other potential anticancer agents such as sphingomyelin and other sphingolipids, butyric acid, 13-methyltetradecanoic acid, ether lipids and vitamin A. Pasture-derived compounds like β-carotene, β-ionone, gossypol and phytol may also help prevent cancer. Finally, the review discusses the antimicrobial action of milk fat and its role in long-chain polyunsaturated fatty acid metabolism, bone growth, ulcerogenesis, and energy metabolism.
Targeted deletion of Ptp4a3 inhibits colon carcinogenesis and angiogenesis

Protein tyrosine phosphatase 4a3 (Ptp4a3) is an enigmatic member of the Ptp4a family of prenylated protein tyrosine phosphatases, which are highly expressed in many human cancers. Despite strong correlations with tumor metastasis and poor patient prognosis, there is very limited understanding of this gene family’s role in malignancy. A gene targeted mouse knockout model for Ptp4a3, the most widely studied Ptp4a family member, was created. Mice deficient for PTP4A3 were grossly normal. However, fewer homozygous-null males were observed at weaning and they maintained a decreased body mass into adulthood. Although PTP4A3 is normally associated with late-stage cancer and metastasis, increased Ptp4a3 mRNA was observed in the colon of C57BL/6J mice immediately following treatment with the carcinogen azoxymethane. A well characterized murine colitis-associated colon cancer model was used to investigate the role of PTP4A3 in malignancy. Wildtype mice treated with azoxymethane and dextran sodium sulfate (AOM/DSS) developed approximately 7-10 tumors per mouse in the distal colon. The resulting tumor tissue had 4-fold more Ptp4a3 mRNA relative to normal colon epithelium and increased PTP4A3 protein. Ptp4a3-null mice developed 50% fewer colon tumors than wildtype mice after exposure to AOM/DSS. Tumors from the Ptp4a3-null mice had elevated levels of both IGF1Rβ and c-MYC compared to tumors replete with PTP4A3, suggesting an enhanced cell signaling pathway engagement in the absence of the phosphatase. Furthermore, c-MYC activity was able to increase Ptp4a3 gene expression in a fibroblast cell culture model. These results provide the first definitive evidence implicating PTP4A3 in colon carcinogenesis and highlight the potential value of the phosphatase as a therapeutic target for early stage malignant disease. Interestingly, PTP4A3 is also expressed in the tumor vasculature and has been proposed to be a direct target of vascular endothelial growth factor (VEGF) signaling in endothelial cells. Compared to wildtype controls, colon tumor tissue isolated from Ptp4a3-null mice revealed reduced microvessel density demonstrated by CD31 staining. Vascular cells derived from Ptp4a3-null tissue explants exhibited decreased invasiveness ex vivo compared to wildtype tissues. When primary endothelial cells were isolated and cultured in vitro, Ptp4a3-null cells displayed less migration compared to wildtype cells and loss of VEGF-induced phosphorylation of SRC protein. Reduced migration and SRC activation were also observed when human endothelial cells were treated with a small molecule inhibitor of PTP4A3. These findings strongly support a role for PTP4A3 as an important contributor to cancer progression as well as endothelial cell function in vivo.
Adjustment of random regression models on genetic evaluations of Tropicarne cattle

The growth curve of cattle has a sigmoid shape that can be adjusted with random regression models. The objective of this study was to adjust a random regression model based on Legendre polynomials and to estimate components of variance and genetic parameters for data on growth of Tropicarne cattle. Information from 12 890 monthly weighings of 1787 calves, from birth to 24 months old, was analyzed. The pedigree included 2504 animals. Twentyseven linear, quadratic and cubic models were compared for adjustment of the genetic (EGA) and animal permanent environmental (APA) effects, with three structures in residuals variances (homogeneous and heterogeneous of six and twelve classes). Once the model was selected with the animal effects, another nine models were analyzed to determine the possible addition of maternal genetic (EGM) and permanent environmental (APM) effects. The analyses were performed with the DFREML software. Models were compared based on the likelihood ratio test, Akaike’s information criterion, and the Bayesian information criterion. The model with the best fit included the quadratic order EGA and the effects of APA, EGM and APM of cubic order, with heterogeneous residual variance in twelve classes. The phenotypic variances, EGA and EGM, showed a positive trend on age; however, the residual variance showed quadratic behavior in the first eight months of growth after which it remained constant. Average direct heritability was 0.079 with values of 0.006 to 0.06 up to seven months of age; as of eight months it was constant, around 0.11. Average maternal heritability was 0.084, with values of 0.02 to 0.06 up to seven months and 0.07 to 0.16 as of eight months of age. The random regression model was well fitted as of nine months of age, but it underestimated the genetic parameters for younger ages.
Anterior Urethral Valve and Anterior Urethral Diverticulum with an Intradiverticular Stone: A Case Report and a Literature Review

Cite this article as: Çetin S, Koparal MY, Bulut EC, Gürocak S, Tan Ö. Anterior Urethral Valve and Anterior Urethral Diverticulum with an Intradiverticular Stone: A Case Report and a Literature Review. J Urol Surg 2018;5(2):109-111. ©Copyright 2018 by the Association of Urological Surgery / Journal of Urological Surgery published by Galenos Publishing House. Anterior urethral valve (AUV) is a rare but well-defined congenital anomaly. AUV can be isolated or occur in association with anterior urethral diverticulum (AUD). Here, we present the first pediatric case report of AUV and AUD which is complicated with an intradiverticular stone. We also review the literature involving AUV with AUD cases.
Role of the Notch1 TAD in embryonic development and hematopoiesis

The Notch signaling pathway is a highly conserved mode of intercellular communication used extensively in metazoan development to direct cell fate decisions. Originally identified in Drosophila, which contains a single receptor, mammals contain four Notch receptors (Notch1-4). Of these, Notch1 shares the greatest homology with Drosophila Notch. Notch1 is essential for embryonic development and formation of the vascular and hematopoietic systems. Critical Notch1 functions in the hematopoietic system include generating the first hematopoietic stem cells (HSC) and instructing multipotent hematopoietic progenitors to become T cells. Activating Notch1 mutations occur in multiple human cancers, including acute T cell lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). While Notch1 is required to generate the earliest embryonic HSCs, additional physiologic functions for Notch in embryonic HSC biology have not been described as constitutive pan-Notch deletion in early embryogenesis leads to lethality by E10.5. Ex vivo approaches suggest that Notch signaling can expand HSCs raising the question of whether this is a physiologic Notch function. To address this question, we generated mice that express a hypomorphic Notch1 allele. Unlike Notch1-deficient mice, mice lacking the conserved Notch1 transcriptional activation domain (TAD) show attenuated Notch1 function in vivo and survive until late gestation, succumbing to multiple cardiac abnormalities. Notch1 TAD-deficient HSCs emerge from aorta-gonad-mesonephros region and are capable of migrating to the fetal liver, but are present at a decreased frequency and impaired in their ability to provide hematopoietic reconstitution to transplant recipients. This finding was confirmed using an independent system where Notch signaling was conditionally ablated in fetal hematopoietic cells. In vitro analysis of Notch1 TAD-deficient cells shows that the Notch1 TAD is important for the proper assembly of the Notch transcriptional activation complex. Consistent with this, the TAD is also required to promote optimal transcription of known Notch target genes in vitro. Together, these studies reveal an essential role for the Notch1 TAD in fetal development and fetal HSC homeostasis, and identify a novel requirement for Notch1 signaling in HSC function. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Immunology First Advisor Warren S. Pear
Production of high viscosity glucans from hydrolyzed cellulosics

Several organisms tested, including Sclerotium glucanicum NRRL 3006 and Helotium sp. NRRL 3129, were able to make high viscosity glucan polymers from the hydrolysis products of naturally occurring lignocellulosic materials. Hydrolysis of the tested materials was accomplished by swelling in mild alkali for a 24-h period followed by hydrolysis in mild acid for a 30-min period at 121 C. The medium used for polymer production consisted of hydrolyzed lignocellulosic materials, salts, and a trace of yeast extract. Starch also was used as a fermentation feedstock, but was not hydrolyzed. The fermentations were performed over 4- or 5-day periods.
Use of Polyethylene Glycol (PEG) 8000 for Rapid Screening of Potato (Solanum tuberosum L) Genotypes for Water Stress Tolerance

Attempts to develop drought-tolerant potato (Solanum luberosum L.) cultivars have, shown slow progress, partly because conventional breeding programs are painstaking and time consuming. It is of importance to develop rapid screening techniques to shorten the time spent in breeding. The overall goal of this study was to evaluate whether growth reduction of potato genotypes, expressed in root length density reduction (RLDR), root dry weight reduction (RDWR), shoot dry weight reduction (SDWR), leaf area reduction (LAR), and root-to-shoot ratio reduction (RSR) could be used to select potato genotypes for drought tolerance. Twelve potato genotypes grown either in vitro or in the greenhouse were exposed to 0% and 8% PEG8000, their growth reductions at 8% PEG8000 were calculated, and then were ranked from the least and the most reduced in growth. The results showed that Kennebec, known to be drought tolerant in previous studies, showed the least growth reduction in the in vitro study as seen in the RLDR (12.4% and 20.9%), RDWR (20.4% and 38.1%), SDWR (1 I .7% and 47.8%, and RSR (120.1% and -1 8.2%). Furthermore, the linear correlations of RLDR (r2 = 0.89*) and RDWR (2 = 0.78*) results over runs of the experiment were significant, suggesting that the results were consistent. RLDR and RDWR show promise for selecting potato genotypes grown in vitro for drought tolerance. The linear relationship between RLDR and RDWR was also significant (? = 0.86*), suggesting that either one was good for
Regulation of BACH1/FANCJ Function in DNA Damage Repair: A Dissertation

The DNA damage response (DDR) pathway is a complicated network of interacting proteins that function to sense and remove DNA damage. Upon exposure to DNA damage, a signaling cascade is generated. The damage is either removed, restoring the original genetic sequence, or apoptosis is activated. In the absence of DDR, cells are unable to effectively process DNA damage. Unprocessed DNA damage can lead to chromosomal changes, gene mutations, and malignant transformation. Thus, the proteins involved in DDR are critical for maintaining genomic stability. One essential DDR protein is the BRCA1 Associated C-terminal Helicase, BACH1. BACH1 was initially identified through its direct association with the BRCT domain of the Breast Cancer Associated Gene, BRCA1. Similar to BRCA1, germline mutations in BACH1were identified in patients with early onset breast cancer. Interestingly, the disease-associated mutations in BACH1 were shown to have altered helicase activity in vitro, providing a direct link between BACH1 helicase activity and disease development. The correlation between BACH1 and cancer predisposition was further confirmed by the identification of BACH1 as the cancer syndrome Fanconi anemia (FA) gene product, FANCJ. Similar to other FA proteins, suppression of FANCJ leads to decreased
Occupational performance problems identified by 507 patients: An insight that can guide occupation-based hand therapy

Introduction Several barriers challenge the use of occupation-based interventions in hand therapy. An outpatient clinical setting can be prepared in such a way as to address the most common occupational performance problems which might promote an occupation-based intervention. To this end, more knowledge is needed about which problems patients with hand-related disorders consider most important. Methods Interviews using the Canadian Occupational Performance Measure (COPM)were conducted with 507 patients. Data were entered into Microsoft Excel in the COPM categories: Self-care, productivity and leisure and analysed using descriptive statistics. Data concerning main problem areas were categorized according to the Taxonomic Code of Occupational Performance (TCOP). The analysis included the number of prioritized occupational performance problems (NPOPP) in each COPM category/subcategory; the NPOPP in each category is relative to gender and age and the most frequent problems. Results The total NPOPP was 2384. Problems within productivity and self-care constituted the largest proportion, respectively, 46% and 40%. Gender or age affected the NPOPP in each category to a limited extend. Problems were expressed at all levels in the TCOP, except the lowest level. The most frequently expressed problem was use of utensils when eating. Conclusion The problems mostly concern productivity and self-care, regardless of gender or age. Patients consider problems at the levels of occupation, activities, tasks and actions to be important and meaningful to address in their intervention. This study provides useful knowledge that can be applied when preparing a setting to address the most common problems, which could lead to the promotion of occupation-based interventions.
Glucagon-Like Peptide-1 Depots for the Treatment of Type-2 Diabetes

Glucagon-Like Peptide-1 Depots for the Treatment of Type-2 Diabetes by Miriam Amiram Department of Biomedical Engineering Duke University Date:_______________________ Approved: ___________________________ Ashutosh Chilkoti, Supervisor ___________________________ Christopher B. Newgard ___________________________ Kam W. Leong ___________________________ George A. Truskey ___________________________ Charles A. Gersbach ___________________________ Mark N. Feinglos An abstract of a Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biomedical Engineering in the Graduate School of Duke University 2012 Copyright by Miriam Amiram 2012
Polyunsaturated fatty acid production with Mortierella alpina by solid substrate fermentation

Polyunsaturated fatty acids (PUFA) were produced with Mortierella alpina by solid substrate fermentation. Rice bran was the most effective substrate for PUFA production, followed by peanut meal residue, wheat bran, and sweet potato residue. The optimal conditions for PUFA production were rice bran supplemented with 2.3 to 5% nitrogen at an initial moisture content of 65 to 68% and a pH range of 6 to 7. Each gram of substrate carbon yielded 122.2 mg of total PUFA, including 12.8 mg of eicosapentaenoic acid (EPA), 47.8 mg of linoleic acid (LA), 7.1 mg of a-linolenic acid (ALA), and 54.5 mg of arachidonic acid (ARA) for 8 to 12 days incubation. C/N ratios between 14.5 and 18.5 favored EPA and LA production, while C/N ratios between 19.8 and 21 enhanced ARA and total PUFA production. Total PUFA, EPA and ARA production increased 12, 84.4 and 46.1%, respectively, when the culture temperature was shifted from 20℃ to 12℃ on the fifth day. Supplement of soybean and linseed oils increased LA by 84.9 and 36%, ARA by 71 and 42.1%, and EPA by 130.6 and 92.1%, respectively.