| 721. |
- Meng, Wen-Jian, et al.
(författare)
-
MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer
- 2015
-
Ingår i: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 94:32
-
Tidskriftsartikel (refereegranskat)abstract
- The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.
|
|
| 722. |
- Mueller, Stefanie H., et al.
(författare)
-
Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
-
Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
|
|
| 723. |
- Ng, Chun Chet, et al.
(författare)
-
When IC meets text: Towards a rich annotated integrated circuit text dataset
- 2024
-
Ingår i: Pattern Recognition. - 0031-3203. ; 147
-
Tidskriftsartikel (refereegranskat)abstract
- Automated Optical Inspection (AOI) is a process that uses cameras to autonomously scan printed circuit boards for quality control. Text is often printed on chip components, and it is crucial that this text is correctly recognized during AOI, as it contains valuable information. In this paper, we introduce \textit{ICText}, the largest dataset for text detection and recognition on integrated circuits. Uniquely, it includes labels for character quality attributes such as low contrast, blurry, and broken. While loss-reweighting and Curriculum Learning (CL) have been proposed to improve object detector performance by balancing positive and negative samples and gradually training the model from easy to hard samples, these methods have had limited success with one-stage object detectors commonly used in industry. To address this, we propose Attribute-Guided Curriculum Learning (AGCL), which leverages the labeled character quality attributes in \textit{ICText}. Our extensive experiments demonstrate that AGCL can be applied to different detectors in a plug-and-play fashion to achieve higher Average Precision (AP), significantly outperforming existing methods on \textit{ICText} without any additional computational overhead during inference. Furthermore, we show that AGCL is also effective on the generic object detection dataset Pascal VOC. Our code and dataset will be publicly available at \href{https://github.com/chunchet-ng/ICText-AGCL}{https://github.com/chunchet-ng/ICText-AGCL}.
|
|
| 724. |
- Nie, Huizhen, et al.
(författare)
-
The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
- 2021
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
-
Tidskriftsartikel (refereegranskat)abstract
- Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
|
|
| 725. |
- Pallon, J., et al.
(författare)
-
Ion beam evaluation of silicon carbide membrane structures intended for particle detectors
- 2016
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 371, s. 132-136
-
Tidskriftsartikel (refereegranskat)abstract
- Thin ion transmission detectors can be used as a part of a telescope detector for mass and energy identification but also as a pre-cell detector in a microbeam system for studies of biological effects from single ion hits on individual living cells. We investigated a structure of graphene on silicon carbide (SiC) with the purpose to explore a thin transmission detector with a very low noise level and having mechanical strength to act as a vacuum window. In order to reach very deep cavities in the SiC wafers for the preparation of the membrane in the detector, we have studied the Inductive Coupled Plasma technique to etch deep circular cavities in 325 μm prototype samples. By a special high temperature process the outermost layers of the etched SiC wafers were converted into a highly conductive graphitic layer. The produced cavities were characterized by electron microscopy, optical microscopy and proton energy loss measurements. The average membrane thickness was found to be less than 40 μm, however, with a slightly curved profile. Small spots representing much thinner membrane were also observed and might have an origin in crystal defects or impurities. Proton energy loss measurement (also called Scanning Transmission Ion Microscopy, STIM) is a well suited technique for this thickness range. This work presents the first steps of fabricating a membrane structure of SiC and graphene which may be an attractive approach as a detector due to the combined properties of SiC and graphene in a monolithic materials structure.
|
|
| 726. |
- Pan, Lang, et al.
(författare)
-
8-Oxoguanine targeted by 8-oxoguanine DNA glycosylase 1 (OGG1) is central to fibrogenic gene activation upon lung injury
- 2023
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 51:3, s. 1087-1102
-
Tidskriftsartikel (refereegranskat)abstract
- Reactive oxygen species (ROS) are implicated in epithelial cell-state transition and deposition of extracellular matrix upon airway injury. Of the many cellular targets of ROS, oxidative DNA modification is a major driving signal. However, the role of oxidative DNA damage in modulation profibrotic processes has not been fully delineated. Herein, we report that oxidative DNA base lesions, 8-oxoG, complexed with 8-oxoguanine DNA glycosylase 1 (OGG1) functions as a pioneer factor, contributing to transcriptional reprogramming within airway epithelial cells. We show that TGFβ1-induced ROS increased 8-oxoG levels in open chromatin, dynamically reconfigure the chromatin state. OGG1 complexed with 8-oxoG recruits transcription factors, including phosphorylated SMAD3, to pro-fibrotic gene promoters thereby facilitating gene activation. Moreover, 8-oxoG levels are elevated in lungs of mice subjected to TGFβ1-induced injury. Pharmacologic targeting of OGG1 with the selective small molecule inhibitor of 8-oxoG binding, TH5487, abrogates fibrotic gene expression and remodeling in this model. Collectively, our study implicates that 8-oxoG substrate-specific binding by OGG1 is a central modulator of transcriptional regulation in response to tissue repair.
|
|
| 727. |
- Parbey, Joseph, et al.
(författare)
-
High-performance solid oxide fuel cells with fiber-based cathodes for low-temperature operation
- 2020
-
Ingår i: International Journal of Hydrogen Energy. - : Elsevier BV. - 0360-3199. ; 45:11, s. 6949-6957
-
Tidskriftsartikel (refereegranskat)abstract
- Low-temperature operation of solid oxide fuel cells (SOFCs) results in deterioration in electrochemical performance due to sluggish oxygen reduction reaction (ORR) at the cathode. To enhance the reaction pathway for ORR, La0.8Sr0.2MnO3 (LSM) nanofibers were fabricated by electrospinning and used for low-temperature solid oxide fuel cells operated at 600–700 °C. The morphological and structural characteristics show that the electrospun LSM nanofiber has a highly crystallized perovskite structure with a uniform elemental distribution. The average diameter of the LSM nanofiber after sintering is 380 nm. A symmetric cell of nanofiber-based LSM cathode on scandia-stabilized zirconia (SSZ) electrolyte pellet exhibits much lower area specific resistances compared to commercial LSM powder-based cathode. A single cell based on the nanofiber LSM cathode on yttrium-doped barium cerate-zirconia (BCZY) electrolyte exhibits a power density of 0.35 Wcm−2 at 600 °C, which increases to 0.85 Wcm−2 at 700 °C. The cell has an area specific resistance (ASR) of 0.46 Ωcm2 at 600 °C, which decreases to 0.07 Ωcm2 at 700 °C. The results indicate that the LSM electrode fabricated by the electrospinning process produces a nanostructured porous electrode which optimizes the microstructure and significantly enhances the ORR at the cathode of SOFCs.
|
|
| 728. |
- Parbey, Joseph, et al.
(författare)
-
Progress in the use of electrospun nanofiber electrodes for solid oxide fuel cells : A review
- 2019
-
Ingår i: Reviews in Chemical Engineering. - : Walter de Gruyter GmbH. - 2191-0235 .- 0167-8299. ; 36:8, s. 879-931
-
Tidskriftsartikel (refereegranskat)abstract
- The application of one-dimensional nanofibers in the fabrication of an electrode greatly improves the performance of solid oxide fuel cells (SOFCs) due to its advantages on electron transfer and mass transport. Various mixed ionic-electronic conducting materials with perovskites and Ruddlesden-Popper-type metal oxide structures are successfully electrospun into nanofibers in recent years mostly in solvent solution and some in melt forms, which are used as anode and cathode electrodes for SOFCs. This paper presents a comprehensive review of the structure, electrochemical performance, and development of anode and cathode nanofiber electrodes including processing, structure, and property characterization. The focuses are first on the precursor, applied voltage, and polymer in the material electrospinning process, the performance of the fiber, potential limitation and drawbacks, and factors affecting fiber morphology, and sintering temperature for impurity-free fibers. Information on relevant methodologies for cell fabrication and stability issues, polarization resistances, area specific resistance, conductivity, and power densities are summarized in the paper, and technology limitations, research challenges, and future trends are also discussed. The concluded information benefits improvement of the material properties and optimization of microstructure of the electrodes for SOFCs.
|
|
| 729. |
- Peng, Qin, et al.
(författare)
-
Assessment of bioavailability of selenium in different plant-soil systems by diffusive gradients in thin-films (DGT)
- 2017
-
Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 225, s. 637-643
-
Tidskriftsartikel (refereegranskat)abstract
- Uptake of selenium (Se) by plants largely depend on the availability of Se in soil. Soils and plants were sampled four times within 8 weeks of plant growth in pot experiments using four plant species. Sequential extraction and diffusive gradients in thin-films (DGT) method were employed to measure Se concentrations in potted soils in selenite- or selenate-amended soils. Results showed that DGT-measured Se concentrations (C-DGT-Se) were generally several folds higher for selenate than selenite amended soils, which were obviously affected by the plant species and the duration of their growth. For example, the folds in soil planted with mustard were 1.49-3.47 and those in soils planted with purple cabbage and broccoli, which grew for 3 and 4 weeks after sowing, were 1.06-2.14 and only 0.15-0.62 after 6 weeks of growth. The selenate-amended soil planted with wheat showed an extremely high C-DGT-Se compared with selenite-amended soil, except the last harvest. Furthermore, minimal changes in C-DGT-Se and soluble Se(IV) were found in selenite-amended soils during plant growth, whereas significant changes were observed in selenate-amended soils (p < 0.05). Additionally, Se distribution in various fractions of soil remarkably changed; the soils planted with purple cabbage and broccoli showed the most obvious change followed by wheat and mustard. Soluble Se(VI) and exchangeable Se(VI) were likely the major sources of C-DGT-Se in selenate-amended soils, and soluble Se(IV) was the possible source of C-DCT-Se in selenite-amended soils. In selenate-amended soils, soluble Se(VI) and exchangeable Se(VI) were significantly correlated with Se concentrations in purple cabbage, broccoli, and mustard; in wheat, Se concentration was significantly correlated only with soluble Se(VI) but not with exchangeable Se. C-DGT-Se eventually became positively correlated with Se concentrations accumulated by different plants, indicating that DGT is a feasible method in predicting plant uptake of selenate but not of selenite.
|
|
| 730. |
- Pettersson, Håkan, et al.
(författare)
-
Quantum Dots-in-a-Well Infrared Photodetectors-Electronic Structure and Optical Properties
- 2010
-
Ingår i: Bulletin of American Physical Society. - : American Physical Society.
-
Konferensbidrag (refereegranskat)abstract
- Quantum dots-in-a-well (DWELL) infrared photodetectors is a new class of nanophotonic devices with the potential of significantly increasing the performance and reducing the cost of infrared detectors. Here we present a comprehensive study of DWELL photodetector structures using a variety of optical techniques (PL, PLE, and PC). Complementary tunnel capacitance measurements support the electronic structure obtained from the optical measurements. A detailed energy level scheme based on the experimental findings is presented and compared to theoretical modeling. The presented work show the importance of combining different electrical and optical techniques to obtain a consistent model of complicated quantum structures which is crucial for the development of future nanophotonic devices.
|
|
