141 research outputs found

    A Feasibility Study of Geometric-Decomposition Coil Compression in MRI Radial Acquisitions

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    Receiver arrays with a large number of coil elements are becoming progressively available because of their increased signal-to-noise ratio (SNR) and enhanced parallel imaging performance. However, longer reconstruction time and intensive computational cost have become significant concerns as the number of channels increases, especially in some iterative reconstructions. Coil compression can effectively solve this problem by linearly combining the raw data from multiple coils into fewer virtual coils. In this work, geometric-decomposition coil compression (GCC) is applied to radial sampling (both linear-angle and golden-angle patterns are discussed) for better compression. GCC, which is different from directly compressing in k-space, is performed separately in each spatial location along the fully sampled directions, then followed by an additional alignment step to guarantee the smoothness of the virtual coil sensitivities. Both numerical simulation data and in vivo data were tested. Experimental results demonstrated that the GCC algorithm can achieve higher SNR and lower normalized root mean squared error values than the conventional principal component analysis approach in radial acquisitions

    The Herb Medicine Formula “Chong Lou Fu Fang” Increases the Cytotoxicity of Chemotherapeutic Agents and Down-Regulates the Expression of Chemotherapeutic Agent Resistance-Related Genes in Human Gastric Cancer Cells In Vitro

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    The herb medicine formula “Chong Lou Fu Fang” (CLFF) has efficacy in inhibiting the proliferation of human gastric cancer in vitro and in vivo. To explore the potentially useful combination of CLFF with chemotherapeutic agents commonly used in gastric cancer therapy, we assess the interaction between CLFF and these chemotherapeutic agents in both SGC-7901 cell lines and BGC-823 cell lines using a median effect analysis and apoptosis analysis, and we also investigate the influence of CLFF on chemotherapeutic agent-associated gene expression. The synergistic analysis indicated that CLFF had a synergistic effect on the cytotoxicity of 5-fluorouracil (5-FU) in a relative broad dose inhibition range (20–95% fraction affected in SGC-7901cell lines and 5–65% fraction affected in BGC-823 cell lines), while the synergistic interaction between CLFF and oxaliplatin or docetaxel only existed in a low dose inhibition range (≤50% fraction affected in both cell lines). Combination of CLFF and chemotherapeutic agents could also induce apoptosis in a synergistic manner. After 24 h, CLFF alone or CLFF combination with chemotherapeutic agents could significantly suppress the levels of expression of chemotherapeutic agent resistance related genes in gastric cancer cells. Our findings indicate that there are useful synergistic interactions between CLFF and chemotherapeutic agents in gastric cancer cells, and the possible mechanisms might be partially due to the down-regulation of chemotherapeutic agent resistance related genes and the synergistic apoptotic effect

    Cloning of a gene encoding glycosyltransferase from Pueraria lobata (Wild.) Ohwi and its expression in Pichia pastoris

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    The key enzyme of puerarin biosynthesis in Pueraria lobata (Willd.) Ohwi was unclear but may involve glycosylation. To investigate the regulation of puerarin biosynthesis, a putative UDP-dependent glycosyltransferase (UGT) gene, PlUGT1 was isolated from P. lobata root, which contained abundant puerarin. PlUGT1 encoded 480 deduced amino acid residues with a conserved UDP-glucose-binding domain, which has 61 to 84% similarity to homologues from other plant species. SDS polyacrylamide gel electrophoresis and western blotting results showed that, fusion protein migrated as a single protein band with a molecular weight of 55 kDa. A yeast expression vector pPICZA-PlUGT1 was constructed and was transformed into Pichia pastoris strain GS115. Several recombinants containing multi-copy expression cassettes were obtained on the zeocin-YPD plate and confirmed by southern dot blotting. The yield of PlUGT1 attained 0.05 g/l when recombinant cells were cultured at pH 5.5, 30°C and induced with 0.5% methanol for 72 h. The expression of PlUGT1 protein correlates positively with the copy numbers of PlUGT1 in transformed yeast cells. These results suggest that, the PlUGT1 protein can be expressed efficiently in the P. pastoris expression system and may supply a new economic and convenient way for the production of PlUGT1 protein.Keywords: Pueraria lobata (Willd.) Ohwi, glycosyltransferase, cloning, expression, Pichia pastori

    HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

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    The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery

    Reticulation is a Risk Factor of Progressive Subpleural non-Fibrotic Interstitial Lung Abnormalities

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    Rationale: Interstitial lung abnormalities (ILAs) are being increasingly identified in clinical practice. In particular for subpleural non-fibrotic ILAs, the risk of progression over time and the risk factors for progressive behavior are still largely unknown. Objectives: To determine the age band prevalence of ILAs and the risk of radiological progression of subpleural non-fibrotic ILAs over time in a large health check-up population, and to identify how reticulation contributes to the risk of radiological progression. Methods: Based on ILAs definition by the Fleischner Society, low-dose chest CT images from community-dwelling population undergone health check-up were evaluated for ILAs. Multivariable logistic regression was used to assess the risk of radiological progression. Measurements and Main Results: Among 155,539 individuals, 3,300 (2.1%) were confirmed to have ILAs: the vast majority (81.7%) were defined as subpleural non-fibrotic ILAs. The prevalence of ILAs increased linearly with age (P for trend<0.0001). Of 454 individuals with subpleural non-fibrotic ILAs, 198 (43.6%) had radiological progression over 4 years. The presence of reticulation on initial imaging was an independent predictor of radiological progression (OR 1.9; 95%CI 1.2-3.0, P=0.0040). No difference in radiological progression was identified between subpleural non-fibrotic ILAs with extensive reticulation and subpleural fibrotic ILAs (73.0% vs. 68.8%, P=0.7626). Conclusions: The prevalence of ILAs increases linearly with age. Nearly half of subpleural non-fibrotic ILAs progress radiologically over 4 years. The presence of reticulation is a risk factor for radiological progression. Subpleural non-fibrotic ILAs with extensive reticulation are likely to be a feature of subpleural fibrotic ILAs

    The influence of methotrexate-related transporter and metabolizing enzyme gene polymorphisms on peri-engraftment syndrome and graft-versus-host disease after haplo-hematopoietic stem cell transplantation in pediatric patients with malignant hematological diseases

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    BackgroundMethotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported.MethodsHere, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center.ResultsWe discovered all gene polymorphisms were in the Hardy–Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II–IV aGvHD (HR = 2.604, p = 0.039).ConclusionIn summary, our findings prove that the host’s genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis

    A pan-cancer proteomic perspective on The Cancer Genome Atlas.

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    Protein levels and function are poorly predicted by genomic and transcriptomic analysis of patient tumours. Therefore, direct study of the functional proteome has the potential to provide a wealth of information that complements and extends genomic, epigenomic and transcriptomic analysis in The Cancer Genome Atlas (TCGA) projects. Here we use reverse-phase protein arrays to analyse 3,467 patient samples from 11 TCGA 'Pan-Cancer' diseases, using 181 high-quality antibodies that target 128 total proteins and 53 post-translationally modified proteins. The resultant proteomic data are integrated with genomic and transcriptomic analyses of the same samples to identify commonalities, differences, emergent pathways and network biology within and across tumour lineages. In addition, tissue-specific signals are reduced computationally to enhance biomarker and target discovery spanning multiple tumour lineages. This integrative analysis, with an emphasis on pathways and potentially actionable proteins, provides a framework for determining the prognostic, predictive and therapeutic relevance of the functional proteome

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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