FIBROBLAST GROWTH FACTOR SIGNALING REGULATES TUMOR ANGIOGENESIS AND CANCER METABOLISM

Acquisition of ectopic expression of type 1 receptor for the fibroblast growth factor receptor type1 (FGFR1) in prostate cancer (PCa) is well documented. However, while it is known that FGFR confers a growth advantage and promotes cell survival, how this aberrantly expressed transmembrane receptor tyrosine kinase contributes to PCa progression is not fully understood. Therefore, we investigated the roles of FGF signaling in both cancer metabolism and tumor angiogenesis. In first part of our study, we used a TRAMP mouse model with tissue specific deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key adaptor protein of the FGF signaling, in the prostate epithelium to investigate whether epithelial FGF signaling affects blood vessel cell functionality. Results showed that deletion of Frs2α decreased the blood vessels in prostate tumors. Similarly, conditioned medium of Frs2α knockdown prostate cancer cells inhibited the tube formation of human umbilical vein endothelial cells (HUVEC). Frs2α knockdown also decreased the ability of tumor cells to recruit HUVECs. We also discovered that ablation of Frs2α decreased the production of vascular endothelial growth factor A (VEGFA) primarily through preventing the binding of transcription factors HIF1α and c-Jun to its promoter region in prostate cancer cells and in vivo. We also demonstrated that hyperactivity of Frs2α, as well as upregulation of c-Jun and HIF1α, were positively associated with vessel density and progression of human PCa. In the second part of this study, we reported that FGFR1 tyrosine kinase promoted aerobic glycolysis via regulating the expression pattern of lactate dehydrogenase (LDH): it tyrosine phosphorylated type A LDH (LDHA) and enhanced its stability, which favors the conversion of pyruvate to lactate, and therefore, decreases oxidative phosphorylation. Concurrently, FGFR1 downregulated the expression of type B LDH (LDHB) via increasing promoter methylation, which favors the conversion of lactate to pyruvate. Furthermore, consistent with the expression level of ectopic FGFR1, high levels of phosphorylated LDHA accompanied by diminished LDHB were associated with short overall survival and biochemical recurrence free survival time in PCa patients. This suggests that the dysregulated expression of LDH isozymes is of clinical value for PCa prognosis

FIBROBLAST GROWTH FACTOR SIGNALING REGULATES TUMOR ANGIOGENESIS AND CANCER METABOLISM

Acquisition of ectopic expression of type 1 receptor for the fibroblast growth factor receptor type1 (FGFR1) in prostate cancer (PCa) is well documented. However, while it is known that FGFR confers a growth advantage and promotes cell survival, how this aberrantly expressed transmembrane receptor tyrosine kinase contributes to PCa progression is not fully understood. Therefore, we investigated the roles of FGF signaling in both cancer metabolism and tumor angiogenesis. In first part of our study, we used a TRAMP mouse model with tissue specific deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key adaptor protein of the FGF signaling, in the prostate epithelium to investigate whether epithelial FGF signaling affects blood vessel cell functionality. Results showed that deletion of Frs2α decreased the blood vessels in prostate tumors. Similarly, conditioned medium of Frs2α knockdown prostate cancer cells inhibited the tube formation of human umbilical vein endothelial cells (HUVEC). Frs2α knockdown also decreased the ability of tumor cells to recruit HUVECs. We also discovered that ablation of Frs2α decreased the production of vascular endothelial growth factor A (VEGFA) primarily through preventing the binding of transcription factors HIF1α and c-Jun to its promoter region in prostate cancer cells and in vivo. We also demonstrated that hyperactivity of Frs2α, as well as upregulation of c-Jun and HIF1α, were positively associated with vessel density and progression of human PCa. In the second part of this study, we reported that FGFR1 tyrosine kinase promoted aerobic glycolysis via regulating the expression pattern of lactate dehydrogenase (LDH): it tyrosine phosphorylated type A LDH (LDHA) and enhanced its stability, which favors the conversion of pyruvate to lactate, and therefore, decreases oxidative phosphorylation. Concurrently, FGFR1 downregulated the expression of type B LDH (LDHB) via increasing promoter methylation, which favors the conversion of lactate to pyruvate. Furthermore, consistent with the expression level of ectopic FGFR1, high levels of phosphorylated LDHA accompanied by diminished LDHB were associated with short overall survival and biochemical recurrence free survival time in PCa patients. This suggests that the dysregulated expression of LDH isozymes is of clinical value for PCa prognosis

Synthesis of Healable Organic Semiconductor Through Dioxaborolane Bond

The field of organic semiconductors have gained enormous attention the past few decades. Organic materials offer numerous advantages over their inorganic counterparts. Recently a number of works have demonstrated organic semiconductors with healable properties. We aim to investigate the healable ability of an organic semiconductor by mimicking a vitrimer system through the reversible dioxaborolane bond. Vitrimers are polymers with reversible crosslink system. It has been reported that the use of the borane-oxygen bond as the crosslink showed good mechanical performance. The electrical properties will be inspected for the vitrimer-like polymer. In this report we describe a Diketopyrrolopyrrole base polymer incorporating reversible dioxaborolane bonds synthesized through borane esterification. The electrical properties and the healing properties of the polymer will be investigated. Here, we present the progress of synthesizing to the monomer, and we report the trials for the reactions. The predicted result for the overall yield of the monomer is 30-40%

ARST: Auto-Regressive Surgical Transformer for Phase Recognition from Laparoscopic Videos

Phase recognition plays an essential role for surgical workflow analysis in computer assisted intervention. Transformer, originally proposed for sequential data modeling in natural language processing, has been successfully applied to surgical phase recognition. Existing works based on transformer mainly focus on modeling attention dependency, without introducing auto-regression. In this work, an Auto-Regressive Surgical Transformer, referred as ARST, is first proposed for on-line surgical phase recognition from laparoscopic videos, modeling the inter-phase correlation implicitly by conditional probability distribution. To reduce inference bias and to enhance phase consistency, we further develop a consistency constraint inference strategy based on auto-regression. We conduct comprehensive validations on a well-known public dataset Cholec80. Experimental results show that our method outperforms the state-of-the-art methods both quantitatively and qualitatively, and achieves an inference rate of 66 frames per second (fps).Comment: 11 Pages, 3 figure

Fabrications and Applications of Micro/nanofluidics in Oil and Gas Recovery: A Comprehensive Review

Understanding fluid flow characteristics in porous medium, which determines the development of oil and gas oilfields, has been a significant research subject for decades. Although using core samples is still essential, micro/nanofluidics have been attracting increasing attention in oil recovery fields since it offers direct visualization and quantification of fluid flow at the pore level. This work provides the latest techniques and development history of micro/nanofluidics in oil and gas recovery by summarizing and discussing the fabrication methods, materials and corresponding applications. Compared with other reviews of micro/nanofluidics, this comprehensive review is in the perspective of solving specific issues in oil and gas industry, including fluid characterization, multiphase fluid flow, enhanced oil recovery mechanisms, and fluid flow in nano-scale porous media of unconventional reservoirs, by covering most of the representative visible studies using micro/nanomodels. Finally, we present the challenges of applying micro/nanomodels and future research directions based on the work

A Comprehensive Review of Experimental Evaluation Methods and Results of Polymer Micro/nanogels for Enhanced Oil Recovery and Reduced Water Production

In recent years, polymer micro/nanogels which are re-crosslinked polymers with 3D networks, have attracted a lot of interest in Enhanced Oil Recovery (EOR) field. In size of micro/nanometers, these gel particles are designed to be conformance control agents for in-depth fluid diversion, and various experimental research have been undertaken to investigate the possibilities of applying micro/nanogels in oilfield. However, it is still unclear that how to utilize micro/nanogels to their full potential in oilfield because the transport mechanisms and EOR mechanisms of micro/nanogels are not well studied currently. By reviewing experimental evaluations and corresponding results of micro/nanogels, including evaluation of particle physiochemical properties, transport, and potential EOR mechanisms, the review aims to discuss the evaluation of micro/nanogel particles, transport issue in many experimental designs and the debates of EOR mechanisms. Finally, we present the current challenges of micro/nanogels application and recommend the future research directions based on the review

NeRRF: 3D Reconstruction and View Synthesis for Transparent and Specular Objects with Neural Refractive-Reflective Fields

Neural radiance fields (NeRF) have revolutionized the field of image-based view synthesis. However, NeRF uses straight rays and fails to deal with complicated light path changes caused by refraction and reflection. This prevents NeRF from successfully synthesizing transparent or specular objects, which are ubiquitous in real-world robotics and A/VR applications. In this paper, we introduce the refractive-reflective field. Taking the object silhouette as input, we first utilize marching tetrahedra with a progressive encoding to reconstruct the geometry of non-Lambertian objects and then model refraction and reflection effects of the object in a unified framework using Fresnel terms. Meanwhile, to achieve efficient and effective anti-aliasing, we propose a virtual cone supersampling technique. We benchmark our method on different shapes, backgrounds and Fresnel terms on both real-world and synthetic datasets. We also qualitatively and quantitatively benchmark the rendering results of various editing applications, including material editing, object replacement/insertion, and environment illumination estimation. Codes and data are publicly available at https://github.com/dawning77/NeRRF