Development of a three-dimensional in vitro model to study the effect of vitamin D on bone metastatic breast cancer

Breast cancer has a high prevalence among women and most patients suffer from metastasis to bone. The mechanisms involved in breast cancer bone metastasis are poorly understood. Three-dimensional (3D) tissue culture systems are becoming a focus of biomedical engineering. The 3D cultures can mimic the in vivo microenvironment and have much greater biological relevance than the traditional two-dimensional (2D) monolayer cell culture systems. There is a need for developing reliable in vitro models to study the mechanism of bone metastasis in breast cancer. We established a 3-dimensional (3D) collagen matrix tissue culture model to study metastatic breast cancer. Calcitriol or 1, 25 dihydroxyvitamin D3 has anti-tumor effects by inhibiting cancer cell proliferation and inducing differentiation. There are few research studies investigating its role in metastasis. None of the research studies were based on bio-mimetic 3D models. We used this novel 3D tissue culture system to test 1, 25 dihydroxyvitamin D3¡¯s role in breast cancer bone metastasis. Our results demonstrate vitamin D pretreated breast cancer cells had significantly decreased (p ¡Ü 0.0001) migration rate, in association with significantly decreased (p ¡Ü 0.05) cell surface expression of CXCR4. This result proved the hypothesis vitamin D inhibits breast cancer bone metastasis by down regulating CXCR4 expression. Our data showed in the 3D system, breast cancer migration rate increased significantly compared with those in 2D system. In our pilot study, CXC12 expression data suggest that the decrease in migration was not due to the CXCR4-CXCL12 axis because there was no significant difference (p ¡Ý 0.05) of CXCL12 expression between 3D and 2D osteoblast cells. The CXC12 studies needs to be validated with a larger sample size. Alternatively, this observation suggests that there are other signaling pathways which influence the migration of breast cancer cells towards osteoblast cells and bone matrix

Identification of Cell Types in scRNA-seq Data via Enhanced Local Embedding and Clustering

Identifying specific cell types is a significant step for studying diseases and potentially leading to better diagnosis, drug discovery, and prognosis. High-throughput single-cell RNA-Seq (scRNA-seq) technologies have advanced in recent years, enabling researchers to investigate cells individually and understand their biological mechanisms. Computational techniques such as clustering, which are categorized in the form of unsupervised learning methods, are the most suitable approach in scRNA-seq data analysis when the cell types have not been characterized. These techniques can be used to identify a group of genes that belong to a specific cell type based on their similar gene expression patterns. However, due to the sparsity and high-dimensional nature of scRNA-seq data, classical clustering methods are not efficient. Therefore, the use of non-linear dimensionality reduction techniques to improve clustering results is crucial. We introduce a pipeline to identify representative clusters of different cell types by combining non-linear dimensionality reduction techniques such as modified locally linear embedding (MLLE) and clustering algorithms. We assess the impact of different dimensionality reduction techniques combined with the clustering of thirteen publicly available scRNA-seq datasets of different tissues, sizes, and technologies. We evaluate the intra- and inter-cluster performance based on the Silhouette score before performing a biological assessment. We further performed gene enrichment analysis across biological databases to evaluate the proposed method\u27s performance. As such, our results show that MLLE combined with independent component analysis yields overall the best performance relative to the existing unsupervised methods across different experiments

Neither Irish nor English: The Scotish Presence in Ulster

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), 2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentors: Derek Hirst and Christine Johnso

Generative ai and eu copyright law: Exploring Exceptions and the Derivative Works Concept

The text explores the challenges that generative AI poses to EU copyright law, focusing on two main issues: the use of copyrighted materials in developing AI models and the publication of generated digital content. The inquiry assesses the applicability of existing copyright exceptions for tasks like data mining, temporary reproduction, and database rights during the development of AI models. For the publication of generated content, the focus is on determining conditions for legal recognition as a derivative work. The text argues that generative AI falls under the flexible concepts of Arts. 3 and 4 CDSMD, with potential support for AI models generating marketing or entertainment content. However, existing exceptions do not fully support the generative AI development process. Commercial deployment of generated output may not be covered by exceptions, and its classification as a lawful derivative work depends on further clarification from the EU legislator or CJEU. The text suggests that non-authorial output should be allowed as derivative works, considering the low threshold for originality and recognizability criteria. To be lawful, derivative AI works should incorporate original parts that fade into the background, with personal style not protected by copyright but considered in an adapted derivatives test. Fair remuneration is proposed for generative AI services to address economic impacts on creatives

A Sustainability Assessment of The Solarize Philly Program

Solar energy is known as a green and clean source of energy and programs such as the Solarize Philly promote its use so people can enjoy its benefits. However, one cannot overlook the fact that producing electricity via solar panels produces emissions at various stages along the life cycle. In this paper, a sustainability analysis of the Solarize Philly program was carried out with aims to quantify and depict the environmental and monetary costs and benefits of the program as a whole and to its individual customers. The analysis includes a Life Cycle Assessment (LCA) to estimate the environmental impact in terms of Carbon Dioxide equivalent (CO2e) emissions produced per kWh of electricity generated. The analysis is further followed by a Cost Benefit Analysis (CBA) of five households that participated in the program representing a range of installation costs. The LCA showed that the average life cycle emissions of a panel used in the program is 99.8 gCO2e/kWh and can offset up to 395 gCO2e/kWh of emissions coming from conventional grid electricity. The CBA was conducted for five installations with system sizes ranging from 5kW to 8kW and installation prices ranging from $16,000 to$28,000. All these projects were observed to be cost – effective. The average Net Present Value (NPV) for all projects was $11,941and the average Discounted Payback Time (DPT) was 8.26 years which is well within the project duration of 25 years. As of April 2020, Solarize Philly has enabled 654 homeowners in Philadelphia install solar on their rooftops with additional projects in the installation pipeline. This study quantifies the environmental impact that Solarize Philly participants have had over three phases of the program and highlights its benefits

Art gallery Prague

Umělecká galerie Praha Lannova Obsahem této diplomové práce je návrh umělecké galerie v zajímavé, ale nyní zanedbané lokalitě na Praze 1. Důležitý předpoklad pro oživení dané lokality bylo vyřešení nevhodné dopravní situace a napojení území na okolní čtvrti a Náplavku. Můj vedoucí motiv byla "fraktalizace" - rozdrobení prvku do jeho menších částí, při zachování své siluety. Řídí se tím například hmota galerie: tradiční vnitroblok byl rozštěpen do menších částí, vnitroblok byl otevřen veřejnosti a celý komplex tak je perforován pro lepší propojení města s Vltavou. Návrh se snaží dodat centru Prahy nový plášť na jeho severním pobřeží, ale zároveň mu nechce konkurovat, což se odráží ve zvolené hmotě a ve volbě materiálu.Umělecká galerie Praha Lannova Obsahem této diplomové práce je návrh umělecké galerie v zajímavé, ale nyní zanedbané lokalitě na Praze 1. Důležitý předpoklad pro oživení dané lokality bylo vyřešení nevhodné dopravní situace a napojení území na okolní čtvrti a Náplavku. Můj vedoucí motiv byla "fraktalizace" - rozdrobení prvku do jeho menších částí, při zachování své siluety. Řídí se tím například hmota galerie: tradiční vnitroblok byl rozštěpen do menších částí, vnitroblok byl otevřen veřejnosti a celý komplex tak je perforován pro lepší propojení města s Vltavou. Návrh se snaží dodat centru Prahy nový plášť na jeho severním pobřeží, ale zároveň mu nechce konkurovat, což se odráží ve zvolené hmotě a ve volbě materiálu

EVALUASI KELAYAKAN PENDIRIAN PASAR TRADISIONAL DI KENEGERIAN KOPAH KECAMATAN KUANTAN TENGAH KABUPATEN KUANTAN SINGINGI

Pasar merupakan tempat bertemunya antara penjual dan pembeli dimana mereka  terlibat kegiatan jual beli. Saat ini pasar sangat dibutuhkan apalagi dalam sebuah kota. Suatu kota wajib memiliki pasar yang dilengkapi dengan sarana dan prasarana pasar. Meskipun dengan kondisi yang tidak menguntungkan, tetap ditemukan bahwa pasar mampu bertahan karena masyarakat sekitar yang membutuhkan keberadaan pasar tersebut. Walaupun banyak kekurangan, pasar tersebut tetap beraktifitas dan pembeli tetap datang untuk belanja. Kelebihan pasar adalah kekhasannya yang dimiliki seperti jual beli dengan tawar menawar harga dan suasana yang memungkinkan penjual dan pembeli menjalin kedekatan.  Rumusan masalah pada penelitian ini yaitu Bagaimana Kelayakan Pasar Tradisional Kenegerian Kopah. Tujuan Penelitian yang ingin dicapai adalah untuk mengevalusi kelayakan Pasar Tradisional Kenegerian Kopah. Metode analisis yang digunakan adalah metode Deskriptif Kualitatif, yang merupakan metode yang lebih menekankan pada aspek pengukuran secara obyektif terhadap fenomena sosial.  Berdasarkan dari hasil penelitian di Kenegerian Kopah layak dibangun satu pasar, karena Kenegerian Kopah telah memenuhi 4 aspek pendirian suatu pasar yaitu, Tingkat kepadatan penduduk dan pertumbuhan penduduk, Potensi perekonomian, Aksesibilitas wilayah, dan Dukungan keamanan