Role of the co-transcriptional regulators Yap/Taz in the normal and fibrotic lung epithelia

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that exhibits patterns of usual interstitial pneumonia with honeycombing. IPF is characterized by damaged distal lung epithelium with excessive tissue scarring and extracellular matrix remodeling. The etiology of IPF is unknown and current therapies cannot end or reverse disease progression. Aberrant reactivation of developmental pathways is evident in IPF. Among these developmental actors are the co-transcriptional regulators Yap and Taz (YT). YT modulate processes such as proliferation, differentiation, and organ size and are regulated by the Hippo pathway. YT do not have a DNA binding domain but act through interaction with other transcription factors (TFs). YT play a role in fibrotic fibroblasts, but their role is not yet known in the fibrotic lung epithelium. The aim of this thesis project is to develop the tools needed to explore the role of Hippo-YT in fibrotic lung epithelium and to identify the TFs that YT interact with to exert their various functions.We first developed a method to simultaneously isolate proximal and distal lung progenitor cells from an individual mouse with the aid of a 3D printed surgical guide and found that the precision of dissecting the lung lobes affects the purity of the isolated distal progenitors and how they behave in organoid assays. We further found the Hippo pathway to be dysregulated in the fibrotic lung epithelium which led to increases in nuclear YT as well as known downstream targets. Interestingly, we found epithelial YT signaling to be actively involved in extracellular matrix remodeling in the fibrotic lung epithelium through modulation of lysyl oxidase expression, a collagen crosslinking enzyme. Targeting YT in vivo using an FDA approved drug ameliorated the fibrotic phenotype, indicating that YT targeting may be an option to treat fibrosis. We further used cleavage under target and release using nuclease (CUT&RUN) to identify the exact motif sequences on the genome where complexes containing YT bind in the normal and fibrotic lung epithelial. We further identified putative TFs that are known to bind the motif sequences identified. We found that YT have different interaction partners in the proximal and distal lung epithelium and further identified specific YT interactions in the human fibrotic lung epithelium.This current research project sets the basis for the identification of exact targeting mechanisms for finding therapeutics for IPF. YT are known to be responsible for a wide range of biologic processes and targeting YT’s profibrotic activity and promoting their pro-regenerative activities may result in beneficial effects for IPF patients

Deep Generative Modeling-based Data Augmentation with Demonstration using the BFBT Benchmark Void Fraction Datasets

Deep learning (DL) has achieved remarkable successes in many disciplines such as computer vision and natural language processing due to the availability of ``big data''. However, such success cannot be easily replicated in many nuclear engineering problems because of the limited amount of training data, especially when the data comes from high-cost experiments. To overcome such a data scarcity issue, this paper explores the applications of deep generative models (DGMs) that have been widely used for image data generation to scientific data augmentation. DGMs, such as generative adversarial networks (GANs), normalizing flows (NFs), variational autoencoders (VAEs), and conditional VAEs (CVAEs), can be trained to learn the underlying probabilistic distribution of the training dataset. Once trained, they can be used to generate synthetic data that are similar to the training data and significantly expand the dataset size. By employing DGMs to augment TRACE simulated data of the steady-state void fractions based on the NUPEC Boiling Water Reactor Full-size Fine-mesh Bundle Test (BFBT) benchmark, this study demonstrates that VAEs, CVAEs, and GANs have comparable generative performance with similar errors in the synthetic data, with CVAEs achieving the smallest errors. The findings shows that DGMs have a great potential to augment scientific data in nuclear engineering, which proves effective for expanding the training dataset and enabling other DL models to be trained more accurately.Comment: 27 pages, 6 figure

Interaction between controlled natural lighting and IEQ: integrated double skin facades approach applied on an office building

Double skin facades can be used as a balanced solution to facilitate natural lighting into buildings and control the amount of admitted solar radiation. This study aims to identify an optimal solution for daylight and energy performance within an office building by optimizing the façade's opening size and panel rotation. The goal is to generate a flexible model that contributes to the overall performance and thermal comfort. The paper provides a methodology using parametric tools of Grasshopper via Energy-plus/ladybug to analyze and evaluate the thermal performance of different iterations of a double skin façade. Although various IEQ aspects affect comfort levels, few studies have investigated the interaction between IEQ and thermal performance levels regulated by double-skin façade. The results concluded that the proposed skin facade could reduce 30% of the total radiation of the original office building. While, the rotation of the facade panels proved to be a significant factor as it resulted in the highest reduction in radiation, up to 32%.publishedVersio

Benefit of Digital Transformation for Telecommunication Organaization

This paper intends to outline the benefits that are realized by telecommunications industry when they transform digitally. The paper will also review some of the existing literature about the impacts that has already been realized by various telecommunications companies upon transforming digitally. Recommendations about how telecommunication organizations can better realize the benefits of digital transformation have also been covered. Keywords: digital transformation, telecommunication industry

Small Business Owners’ Perception of Balanced Scorecard for Business Survival and Growth

The United States Small Business Administration (SBA) defines Small Business Enterprises (SMEs) business establishments that are independently owned managed or operated. Small business organization indicates that some of them have found the Balanced Scorecard to be very significant in boosting general performance in two key perspectives: higher complexity and management capability and drives change and enhance rapid growth. However, in the recent past, there has been increased study on the adoption of BSC in small organizations. The objective of this study was to determine the how small business owners in the United States perceive the aspects of balance score card in regard to business survivability, growth and competitiveness. Hypotheses that were to be answered include H1: Small business owners’ perceive learning and growth as the most significant perspective for their business survival, growth, and competitiveness beside the financial perspective. H2: Small business owners’ perceive customers as the most significant perspective for business growth, survival, and competitiveness. H3: Small businesses owners perceive internal business processes as the most significant perspective for their business growth, survival, and competitiveness. The philosophy adopted is positivist with explanatory and descriptive strategies. The approach of the research is quantitative using ANOVA analysis. The 100 sample companies were selected from the Best 100 small business in the SBA website and survey questionnaire sent online to this selected companies. The result of the research indicated that the most significant Balanced Scorecard perspective is the customer. At the end of the research, it was deciphered that all initiatives that the small business listed in SBA undertake when applying the BSC, customer focus is always the guiding force. Therefore, it can be stated overly that there a significant positive perception of the Balanced Scorecard as a tool to enhance growth and survivability among small businesses

A Song for Reconciliation

In lieu of an abstract, below is the essay\u27s first paragraph. Far away from the land noises of the vehicles and factories, there lies my peaceful small Syrian village, surrounded by wide green fields. Among these green fields there is a narrow stream of water, which is the source of life for this corner of the world. As the sun rises in the blue sky, it makes the surface of the water glitter like a shimmering stream of silver

Preparation and characterization of hydroquinone based polyoxalate and its application in the removal of heavy metals from water

Hydroquinone based polyoxalate was synthesized from oxalyl chloride and hydroquinone. The polymer was characterized with FTIR, 1H-NMR, 13C-NMR, PXRD, SEM and thermal analysis. The chelation behaviour of the polymer towards Pb(II), Cd(II), and Hg(II) in aqueous solutions was studied by batch technique as a function of contact time and pH. The polymer showed high metal uptake toward Pb(II) and Cd(II) and moderate metal uptake toward Hg(II). The adsorption capacity was not affected by the pH of solution. The adsorption data were fitted with second order kinetic model and the isotherms models of Langmuir and Freundlich. Thermodynamics measurements showed that sorption process was spontaneous. Furthermore, the chelating polymer was loaded with metal ions using fixed bed column. For regenerating the loaded polymer, different eluting agents include HNO3, H2SO4, and EDTA was investigated. The highest recovery of metal ions was achieved using HNO3, indicating that desorption process was governed by the solubility factor and cation exchange mechanism.Â

Knowledge, Attitudes and Practices of Yemeni Women Attending Primary Healthcare Centers in Sana’a City towards Family Planning

Objective: To investigate the knowledge, attitudes and practices (KAPs) of Yemeni women attending primary healthcare centers (PHCCs) in Sana’a city towards family planning (FP).Methods: A descriptive, cross-sectional study was conducted among women attending three PHCCs in Sana'a city; namely, in Hadah, Al-Soneinah and Madhbah zones, between 21 November and 1 December 2011. The study included a sample of 281 married women, where data about socio-demographic characteristics and the KAPs towards FP were collected by interviewing women using a pre-designed, structured questionnaire and then analyzed using appropriate statistical tests.Results: Of the married women attending the PHCCs in Sana'a, the majority of respondents were from urban areas (96.4%; 271/281), aged between 25–29 years old (23.1% 65/281), employed (75.8%; 213/281) and with primary or secondary levels of education (60.9%; 171/281). In addition, the majority of women had a marriage length of 6–11 years (65.5%; 182/281) and 3–4 children (44.8%; 126/281). The majority of respondents (89.7%) knew about FP, and 60.2% considered it as birth spacing. Moreover, most respondents (87.5%) were aware of at least four methods of FP, and 53.6% heard of modern FP contraceptive methods. Of them, 85.9% and 74.0% heard of contraceptive pills and intrauterine contraceptive devices (ICDU), respectively; however, the least known contraceptive method was the use of male condoms (28.1%). Healthcare providers were the source of information on FP for the majority of respondents (60.5%). The majority of respondents believed that the optimum spacing between births should be two or three years, being 31.7% and 38.8%, respectively. In addition, most respondents (80.8%) believed that both couples must share the decision-making on FP. Socio-cultural beliefs and values were thought to be the most common (57.3%) barriers to the practice of FP.Conclusions: Although the majority of Yemeni women seeking healthcare after marriage have a good level of knowledge of several traditional and modern methods of FP and their preference of long birth spacing, the use of such methods is still limited to contraceptive pills and ICDU. Therefore, attention should be paid to health education of women on the benefits of using other alternative methods of FP for better family lifestyle, health and well-being

Spatial-Temporal Evolution of Drought Characteristics Over Hungary Between 1961 and 2010

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An integration of bioclimatic, soil, and topographic indicators for viticulture suitability using multi-criteria evaluation: a case study in the Western slopes of Jabal Al Arab-Syria

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