分类: 生物学 >> 生物医药 分类: 计算机科学 >> 计算机应用技术 提交时间: 2022-05-26
摘要: 直至现在,图像质量评价都没有涉及色彩问题。图像质量评价的文献多是评价图像质量(在压缩、传输等图像处理过程中)的变差(降质)程度。平面图像是一种二维的亮度分布。亮度是图像视觉质量的核心参量,没有亮度就没有图像,也就没有论及图像质量的可能。本文提出了三个层次的图像视觉感知质量评价(VPQA)指标:单幅单参数图像质量评价(SS_IQA),单幅五参数精细图像质量评价(SF_IQA),考虑彩色保真性的增强图像质量评价(CF_IQA)。横向论,可分为单幅的图像质量评价(SIQA),多幅图像质量比较,图像增强中的质量评价等三个方面。图像视觉质量评价是智能最佳化图像增强的不可或缺的工具。
分类: 生物学 >> 生物医药 提交时间: 2017-08-08
摘要: 由于生物医药产业具有巨大的经济效益、社会效益,生物医药产业已经成为许多国家的朝阳产业。对于佛山市的产业发展来说,因为生物医药有着广阔的发展前景,将是佛山市今后的大力发展方向。本论文通过对佛山市的生物医药相关技术领域内的专利进行检索分析,从专利文献研究的角度分析技术领域内研究现状,梳理技术布局,了解相关技术研发的主要应用方向以及优劣势,对比佛山市自身的技术特点,制定专利布局实施方案建议。包括提高专利保护、管理、运用意识;优化产业结构及布局,把握各产业不同发展方式;提升现有技术竞争能力;建立风险预警机制,推送专利信息服务;优化发展环境等方面的具体建议。
分类: 生物学 >> 生物医药 分类: 生物学 >> 病毒学 提交时间: 2017-07-11
摘要: Objective: Viral clearance of human HBV infection largely depends on the age of exposure, so a mouse model with age-dependent immune response and immune-tolerance for HBV infection is essential. Methods: HBVRag1 mice were generated by crossing Rag1-/- mice with HBV-Tg mice. The differences between adult and young HBVRag1 mice were detected after adoptive transfer of splenocytes. Immune tolerance was evaluated by quantitative hepatitis B core antibody (qAnti-HBc) assay, adoptive transfer, and modulation of gut microbiota with antibiotic. Results: After HBVRag1 mouse reconstitution, adult mice showed obvious HBV-dependent inflammation and hepatocytes damage, cleared HBsAg and generated HBsAb and HBcAb, but young mice never developed ALT elevation, and only generated HBcAb with persistence of HBsAg. In addition, for adult mice, more hepatic CD8+T and B cells promoted clearance of HBsAg 30 days after lymphocytes transfer, and for young mice, higher levels of cytokines link to the persistence of viral antigens during initiation of immune response towards HBV. The level of qAnti-HBc increased significantly with the time of adoptive transfer in young mice, but decreased significantly in adult within our model. This mimics kinetic changes of human HBV infection regarding qAnti-HBc level. Also, the age-related tolerance in this model was different from which was in HBV-Tg mice, and can be regulated through modulation of gut microbiota. Meanwhile, GS-9620 can achieve inhibition of HBsAg, but HBV vaccine just clears limited HBsAg within the model. Conclusions: Here, we described a mouse model with age-dependent immune response and immune tolerance of HBV infection which could mimic chronic HBV infection in human. It will open a door for evaluating new therapeutic approaches before clinical trials.
分类: 生物学 >> 生物医药 提交时间: 2017-07-03
摘要: 由于生物医药产业具有相当可观的经济和社会效益,其已经成为许多国家重点发展的朝阳产业。为推动生物医药相关产业的发展,诸如美国、日本、印度等国家把生物技术产业作为了提高本国竞争力的手段,并制定了相应的法律法规规范生物医药产业的发展和保障生物医药的知识产权。本论文首先从宏观层面进行各角度数据分析,包括全球、我国的生物医药产业知识产权发展态势分析,然后以广东省生物医药产业为例,对其知识产权密集型情况指标的数据进行分析,并与其他省份的产业经济和专利情况等指标数据进行对比,最后提出有效提高广东省生物医药产业发展和运用知识产权,增强产业竞争力的对策和建议。
分类: 生物学 >> 生物医药 提交时间: 2017-05-23
摘要: 摘要:知识产权密集型产业具备较为明显的专利优势,依赖技术创新与知识产权参与市场摘要:知识产权密集型产业具备较为明显的专利优势,依赖技术创新与知识产权参与市场竞争。生物医药产业具有巨大的经济效益和社会效益,是广东大力扶持的新兴产业。本文选取广东高技术产业、先进制造业及传统产业下的若干产业与生物医药产业进行知识产权密集型情况对比,并通过发展现状、经济贡献及研发创新三个维度进行了对比,最后利用SPSS工具对广东省生物医药专利发展进行预测,为增强广东生物医药知识产权密集型产业竞争力提供建议。
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: A PCR-based subtractive hybridization technique was used to identify genes up-regulated in the hibernating bat brain to explore the molecular mechanism of hibernation. Three genes, Liprin-a2, PTP4A2 and CAMKKb were differentially expressed in hibernating bat brain tissue compared to active bat brain tissue. One of them, Liprin-a2, which has recently been shown to have the key function in the organization of presynaptic and postsynaptic multiprotein complexes was studied in detail. We demonstrated that the expression level of Liprin-a2 was up-regulated almost 4-fold in hibernating bat brains by RT-PCR compared to levels in active bats. The differential expression pattern of Liprin-a2 was also detected in muscle, fat, brain and heart tissue of hibernating bats by real-time quantitative PCR. The result indicated that Liprin-a2 was over-expressed in brain and heart tissue and down-regulated in muscle and fat. In brain tissue of hibernating bats, Liprin-a2 expression was statistically significantly higher than in brain tissue of active controls (P = 0.029). The precise control of transcriptional level and the distinctively differential expression pattern of Liprin-a2 in different organs during circannual hibernation may have important physiological significance, not only in maintaining normal function of many key organs but also in effectively conserving limited energy resources without physiological damage.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: Simple, accurate, and stable diagnostic tests are essential to control viral infectious diseases such as avian influenza virus. The current technologies are often inaccessible to people who need them, mainly because of the specialized equipment and the need for highly trained technologists. Here, we describe a rapid isothermal nucleic acid detection assay (RIDA) that can be used to detect both DNA and RNA targets. Using chemically modified probes, we designed a lateral-flow (LF) immunoassay that can be used in combination with RIDA for equipment-free nucleic acid target detection. RIDA is a “probe amplification” assay that uses the single-strand nicking activity of restriction nicking endonucleases to repeatedly cleave synthetic probes hybridizing to the same target sequences. In the RIDA-LF combined assay, chemically labeled probes are covalently conjugated to magnetic microbeads, which is propitious to separate cleaved probes from the reaction solution. The cleaved probes in the solution are then detected with an LF immunoassay. The real-time assay shows that RIDA is able to specifically detect target sequences in 5 to 15 min. The RIDA-LF combined assay can specifically detect nucleic acid targets without sophisticated equipment. In this report, our data suggest that RIDA is a flexible simple assay that could be applied for point-of-care detection. The modified-RIDA described in this report further extends the application of this technology. © 2008 Elsevier Inc. All rights reserved.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: Nanog was identified by its ability to sustain the LIF-independent self-renewal of mouse embryonic stem (ES) cells and has recently been shown to play a role in reprogramming adult fibroblasts into pluripotent stem cells. However, little is known about the structural basis of these remarkable activities of Nanog. We have previously identified an unusually strong transactivator named CD2 at its C terminus. Here we demonstrate that CD2 is required for Nanog to mediate ES cell self-renewal. Furthermore, deletion and point mutation analysis revealed that CD2 relies on at least seven aromatic amino acid residues to generate its potent transactivating activity. A mutant Nanog bearing alanine substitutions for these seven residues fails to confer LIF-independent self-renewal in mouse ES cells. Substitution of CD2 by the viral transactivator VP16 gave rise to Nanog-VP16, which is 10 times more active than wild-type Nanog in ES cells. Surprisingly, the expression of Nanog-VP16 in mouse ES cells induces differentiation and is thus unable to sustain LIF-independent self-renewal for mouse ES cells. Taken together, our results demonstrate that the CD2 domain of Nanog is a unique transactivator that utilizes aromatic residues to confer specific activity absolutely required for ES self-renewal.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor #1; (RAR#1;) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G1/G0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RAR#1; degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: This study was to investigate the effect of donor liver adenoviral cardiotrophin-1 (CT-1) gene transfer on early graft survival and function in rat small-for-size liver transplantation. We constructed a recombinant murine CT-1 adenoviral vector. Donor rats were transduced in vivo with adenoviruses expressing CT-1 (AdCT-1) or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40% of weight, and transplanted. A syngeneic rat orthotopic liver transplantation model was performed using 40% small-for-size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cell survival signaling pathways were assessed. AdCT-1 pretreatment markedly improved liver function and the survival of small-for-size grafts. In the CT-1 treatment group, hepatic architecture was well protected, apoptotic and necrotic cells were reduced; anti-apoptotic protein bcl-2 was up-regulated and proapoptotic cleaved caspase-3 was down-regulated, cell survival signaling pathways were activated by phosphorylation of protein kinase B (Akt), extracellular-regulated kinase (ERK) and Signal transducer and activator of transcription-3 (Stat- 3) after transplantation. In conclusion, donor liver adenoviral CT-1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosis in small-for-size liver transplantation, mediated in part by activation of the Akt, ERK, and Stat-3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small-for-size liver grafts.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: An efficient method for the synthesis of disubstituted thioureas via the reaction of N,N0-di-Boc-substituted thiourea 5 with alkyl and aryl amines under mild conditions has been developed. In the presence of NaH as a base, trifluoroacetic anhydride (TFAA) reacted with 5 providing intermediate 6, which then reacted with amines giving thioureas 7 in excellent yields. This reaction conditions tolerated other functional groups such as amide, ester, enol ether and hydroxyl groups.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: MicroRNAs (miRNAs) are one class of short, endogenous RNAs which can regulate gene expression at the post-transcriptional level. Previous analysis revealed that mammalian miRNAs tend to cluster on chromosomes. However, the functional consequences of this clustering and conservation property are largely unknown. In this study we present a method to identify signaling pathways targeted by clustered miRNAs. We performed a computational screen for mouse signaling pathways targeted by miRNA clusters. Here, we report that the target genes of 3 miRNA clusters are overrepresented in 15 signaling pathways. We provided experimental evidence that one miRNA cluster, mmu-mir-183–96–182 targets Irs1, Rasa1, and Grb2, all of which are located in the insulin signaling pathway. Theses results suggest that by targeting components with different roles along a signaling pathway, different members of one miRNA cluster can act as a whole to coordinately control the signal transduction process.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The synergy of the activities between chloroquine and various human immunodeficiency virus protease inhibitors was investigated in chloroquine-resistant and -sensitive malaria parasites. In both in vitro and in vivo assay systems, ritonavir was found to be the most potent in potentiating the antimalarial action of chloroquine.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The role of AMP-activated protein kinase (AMPK) in adipocyte differentiation is not completely understood. Here we reported that an AMPK inhibitor, compound C, significantly inhibited adipogenic differentiation of 3T3-L1 cells in a dose dependent manner, and this inhibitory effect was primarily effective in the initial stage of differentiation. Compound C prevented the mitotic clonal expansion (NICE) of preadipocytes, probably by hibiting expression of CCAAT/enhancer-binding protein (C/EBP)beta and delta, and subsequently blocked the expression of C/EBP alpha and peroxisome proliferator-activated receptor (PPAR)gamma and transcriptional activation of genes that produce the adipocyte phenotype. AMPK activity was also suppressed by compound C treatment during the early phase of adipogenic differentiation, which indicated that suppressed activation of AMPK by compound C may inhibit the MCE process of preadipocytes. Our results suggest that compound C might serve as a useful molecule in both basic and clinical research on adipogenesis and as a potential lead compound for the treatment of, obesity.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The von Hippel-Lindau (VHL) tumor suppressor gene regulates extracellular matrix deposition. InVHLnegative renal cancer cells, VHL(-), the lack of fibronectin matrix assembly is thought to promote and maintain tumor angiogenesis allowing vessels to infiltrate tumors. Therefore, and considering the importance of this process in tumor growth, we aimed to study why VHL(-) renal cancer cells fail to form a proper extracellular matrix. Our results showed that VHL(-) cells were not defective in fibronectin production and that the fibronectin produced by these cells was equally functional in promoting cell adhesion and matrix assembly as that produced by VHL(-) cells. We have previously reported that VHL(-) cells fail to form beta 1 integrin fibrillar adhesions and have a diminished organization of actin stress fibers; therefore, we aimed to study if the small GTPase family is involved in this process. We found that activation of the RhoA GTPase was defective in VHL(-) cells, and this was possibly mediated by an increased activation of its inhibitor, p190RhoGAP. Additionally, the expression of constitutively active RhoA in VHL(-) cells resulted in formation of a fibronectin matrix. These results strongly suggest an important role for RhoA in some of the defects observed in renal cancer cells.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: Signal transducer and activator of transcription (STAT) proteins play an important role in cytokine signaling pathways and regulation of immune responses. The balance of the phosphorylated (activated) STAT1 (pSTAT1) and STAT3 (pSTAT3) has been documented in cancer immunology. In this study, we investigated the dynamic balance of pSTAT1 and pSTAT3 in C57BL/6 mice infected with either a nonlethal (Py17XNL) or lethal (Py17XL) strain of Plasmodium yoelii. Both Py17XNL and Py17XL infections induced a maximum activation of STAT1 and STAT3 on the first day after parasite inoculation. Additionally, the Py17XNL infection induced a pSTAT1-dominant response in mice during the early stage of infection, with the resolution of parasitemia. In contrast, Py17XL infection induced a pSTAT3-dominant response during the early phase of infection, with the death of the animals. Our results indicated that maximum activation of STAT1 and STAT3 occurred much earlier than the peak levels of cytokines induced by Plasmodium yoelii infection based on previous reports and that infection with Py17XNL and Py17XL induced different dynamic patterns of pSTAT1 and pSTAT3 balance. Cellular & Molecular Immunology
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: Chronic myeloid leukemia (CML) represents the first human malignancy successfully treated with a tyrosine kinase inhibitor (TKI; imatinib). However, early relapses and the emergence of imatinib-resistant disease are problematic. Evidence suggests that imatinib and other inhibitors may not effectively eradicate leukemic stem/progenitor cells, and that combination therapy directed to complimentary targets may improve treatment. Abelson helper integration site 1 (Ahi-1)/AHI-1 is a novel oncogene that is highly de-regulated in CML stem/progenitor cells where levels of BCR-ABL transcripts are also elevated. Here, we demonstrate that overexpression of Ahi-1/AHI-1 in murine and human hematopoietic cells confer growth advantages in vitro and induce leukemia in vivo, enhancing effects of BCR-ABL. Conversely, RNAi-mediated suppression of AHI-1 in BCR-ABL-transduced lin(-)CD34(+) human cord blood cells and primary CML stem/progenitor cells reduces their growth autonomy in vitro. Interestingly, coexpression of Ahi-1 in BCR-ABL-inducible cells reverses growth deficiencies exhibited by BCR-ABL down-regulation and is associated with sustained phosphorylation of BCR-ABL and enhanced activation of JAK2-STAT5. Moreover, we identified an AHI-1-BCR-ABL-JAK2 interaction complex and found that modulation of AHI-1 expression regulates phosphorylation of BCR-ABL and JAK2-STAT5 in CML cells. Importantly, this complex mediates TKI response/resistance of CML stem/progenitor cells. These studies implicate AHI-1 as a potential therapeutic target downstream of BCR-ABL in CML.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: We recently described the discovery, genome, clinical features, genotypes and evolution of a novel and global human respiratory virus named human coronavirus HKU1 (HCoV-HKU1) which is not yet culturable. We expressed a C-terminal FLAG-tagged CoV-HKU1 spike (S) protein by the Semliki Forest Virus (SFV) system and investigated its maturation profile. Pulse chase labeling revealed that S-FLAG was expressed as high-mannose N-glycans of monomers and trimers. It was predominantly cleaved into subdomains S1 and S2 during maturation. S1 was secreted into the medium. Immunofluorescence analysis visualized S along the secretory pathway from endoplasmic reticulum to plasma membrane. Cleavage of S and release of HCoV-HKU1 S pseudotyped virus were inhibited by furin or furin-like enzyme inhibitors. The cell-based expressed full-length S-FLAG could be recognized by the convalescent serum obtained from a patient with HCoV-HKU1 pneumonia. The data suggest that the native form of HCoV-HKU1 spike expressed in our system can be used in developing serological diagnostic assay and in understanding the role of S in the viral life cycle. Exp Biol Med 233:1527-1536, 2008
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The genetic program of embryonic stem (ES) cells is orchestrated by a core of transcription factors that has OCT4, SOX2, and NANOG as master regulators. Protein levels of these core factors are tightly controlled by autoregulatory and feed-forward transcriptional mechanisms in order to prevent early differentiation. Recent studies have shown that knockdown of Esrrb (estrogen-related-receptor beta), a member of the nuclear orphan receptor family, induces differentiation of mouse ES cells cultured in the presence of leukemia inhibitory factor. It was however not known how knocking down Esrrb exerts this effect. Herein we have identified two ESRRB binding sites in the proximal 5'-untranslated region of the mouse Oct4 gene, one of which is in close proximity to a NANOG binding site. Both ESRRB and NANOG are necessary for maintaining the activity of this promoter in ES cell lines. We have also demonstrated that the two transcription factors interact through their DNA binding domains. This interaction reciprocally modulates their transcriptional activities and may be important to fine-tune ES cell pluripotency. Supporting all of these data, stable transfection of Esrrb in ES cell lines proved sufficient to sustain their characteristics in the absence of leukemia-inhibitory factor. In summary, our experiments help to understand how Esrrb coordinates with Nanog and Oct4 to activate the internal machinery of ES cells.
分类: 生物学 >> 生物医药 提交时间: 2017-03-30
摘要: Efficient and selective palladium porphyrins-catalyzed olimerization of tert-butyl acetylene to form (3Z,5Z)-2,2,7,7-tetramethyl-3,6-dihalo-3,5-octadiene has been developed in environmentfriendly ionic liquids. The reaction proceeded readily with effective recycling of the ionic liquids and easy isolation of the products.