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1.
Gene ; 725: 144143, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31629816

RESUMO

Atherosclerosis is a common cardiovascular disorder and is characterized by damage of endothelial cells, cell inflammation, hyper-proliferation of vascular smooth muscle cells and the accumulation of extracellular lipids and fibrous tissues. In this study, we firstly examined the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in homocysteine (Hcy)-stimulated human aortic smooth muscle cells (HASMCs), and then looked into the potential molecular signaling axis of linc-ROR in regulating the proliferation and migration of HASMCs. Hcy promoted HASMC proliferation and up-regulated linc-ROR expression. Functional studies showed that linc-ROR exerted enhanced actions on the proliferation and migration of HASMCs. In addition, linc-ROR acted as a competing endogenous RNA for miR-195-5p and repressed the miR-195-5p expression in HASMCs. Linc-ROR was up-regulated the miR-195-3p was down-regulated in the plasma from CAD patients when compared to normal controls. Furthermore, fibroblast growth factor 2 (FGF2) was identified as a target of miR-195-5p and was negatively regulated by miR-195-5p in HASMCs. The rescue experiments revealed that linc-ROR-mediated HASMC proliferation and migration may be via regulating miR-195-5p/FGF2 axis. Linc-ROR inhibition blocked the miR-195-5p/FGF2 signaling in Hcy-treated HASMCs, and this effect may also involve in the miR-195-5p/FGF2 axis. To summarize, the data of the present study identified the up-regulation of linc-ROR in Hcy-stimulated HASMCs, and further mechanistic functional studies revealed that linc-ROR promoted HASMC proliferation and migration via regulating miR-195-5p/FGF2 axis. The present study provided the novel actions of linc-ROR in regulating HASMC proliferation and migration, which may be related to the pathophysiology of atherosclerosis.

2.
J Med Virol ; 92(1): 124-127, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31469172

RESUMO

We examined the seroprevalence change of anti-hepatitis D virus (HDV) antibodies in Taiwan from 2006 to 2019. A total of 1147 patients who had chronic hepatitis B virus (HBV) infection were assessed. Of them, 51 (4.4%) were positive for anti-HDV antibodies. Comparison between anti-HDV-positive and negative groups was performed to examine clinical and virological factors related to anti-HDV positivity. It was found that the median HBV-DNA concentration was 1.6 × 105 IU/mL (range, <20-4.5 × 1010 IU/mL) and <20 IU/mL (range, <20-2.0 × 109 IU/mL) for patients with negative and positive anti-HDV antibodies, respectively (P < .001). In addition, a progressive year-to-year decrease of anti-HDV seroprevalence was unveiled. For patients who had HBV-DNA >15 000 IU/mL, the year-to-year (calculated every 2 years) seropositive rates of anti-HDV were 10.0%, 7.9%, 0.7%, 0.3%, 0%, 0%, and 0% (P < .001). For patients who had HBV-DNA <15 000 IU/mL, the year-to-year seropositive rates were 18.6%, 12.8%, 7.8%, 5.0%, 7.3%, 8.0%, and 3.7% (P < .001). In conclusion, seropositive of anti-HDV was inversely associated with HBV-DNA levels. A progressive decrease of anti-HDV seroprevalence was found with no anti-HDV-positive cases detected in high HBV-DNA patient group after 2014.

4.
J Nanosci Nanotechnol ; 20(5): 2705-2712, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635605

RESUMO

A novel sensing material of cobalt oxide-bismuth phosphate (Co3O4-BiPO4) was prepared by the hydrothermal method. Thus prepared sensing material was characterized by X-ray diffraction analysis (XRD) and transmission electron microscopy (TEM). The sensor was used for the determination of epinephrine by using modified Co3O4-BiPO4 on glassy carbon electrode (GCE). The cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods showed a wide linear response to a concentration range, from 1.71 to 55.00 µM, and the epinephrine detection limit for this sensing system was found to be 1.334 µM. The Co3O4-BiPO4 electrode has very high selectivity towards the detection of epinephrine supported by an interference test. The epinephrine sensor seems very advantageous for future clinical health and medical sectors.

5.
IEEE Trans Vis Comput Graph ; 26(1): 590-600, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31443001

RESUMO

Traditional radio monitoring and management largely depend on radio spectrum data analysis, which requires considerable domain experience and heavy cognition effort and frequently results in incorrect signal judgment and incomprehensive situation awareness. Faced with increasingly complicated electromagnetic environments, radio supervisors urgently need additional data sources and advanced analytical technologies to enhance their situation awareness ability. This paper introduces a visual analytics approach for electromagnetic situation awareness. Guided by a detailed scenario and requirement analysis, we first propose a signal clustering method to process radio signal data and a situation assessment model to obtain qualitative and quantitative descriptions of the electromagnetic situations. We then design a two-module interface with a set of visualization views and interactions to help radio supervisors perceive and understand the electromagnetic situations by a joint analysis of radio signal data and radio spectrum data. Evaluations on real-world data sets and an interview with actual users demonstrate the effectiveness of our prototype system. Finally, we discuss the limitations of the proposed approach and provide future work directions.

6.
Anal Chim Acta ; 1094: 70-79, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761049

RESUMO

To explore how hypochlorous acid (HClO) affects human health, a highly sensitive, selective, and trace detection method for hypochlorite (ClO-) is crucial for determining its non-negligible function in both environment and living systems. Herein, a dicyanoisophorone-phenylboronic acid-based novel ratiometric near-infrared fluorescent probe (Probe 1) was designed for the rapid and specific detection of ClO- based on the intramolecular charge transfer (ICT) mechanism. Excess addition of HClO to the Probe 1 solution, 186-times ratio (I652/I582) augment were gained. And this probe provided a colorimetric and ratiometric fluorescence response to ClO- with a high selectivity, a rapid response (within 30 s), and had an extremely low detection limit (15.7 nM). In addition, owing to the good sensing properties and low cytotoxicity of Probe 1, it can be used to expediently visualize exogenous ClO- in HepG2 cells and endogenous ClO- in RAW264.7 macrophage cells. Furthermore, the probe was successfully used for the bioimaging of zebrafish with an acute inflammation. Thus, Probe 1 is a promising vehicle to identify the level of HClO in animals with associated diseases.

7.
Enzyme Microb Technol ; 132: 109413, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731953

RESUMO

t-Butyl 6-cyano-(3R,5R)-dihydroxyhexanoate ((3R,5R)-2) is an important building-block of atorvastatin. In our previous work, a variant KlAKR-Y295W-W296 L (designated as M1) of Kluyveromyces lactis aldo-keto reductase (wild type (WT) KlAKR, M0) was developed, which possessed strict diastereoselectivity but moderate activity towards t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate ((5R)-1). To further improve its catalytic performance, semi-rational engineering of M1 was performed in present work, and the "best" varaint KlAKR-Y295W-W296L-I125V-S30P-Q212R-I63W (M8) was developed. M8's KmB towards (5R)-1 was 2.02 mM, and the catalytic efficiency (kcat/KmB) value was 36.31 s-1 mM-1, which was 1.9-fold higher than that of the parent M1. Compared with M1, the half-life t1/2, TS5050 and TP5050 of M8 were improved. Under the optimized conditions, (5R)-1 at load of up to 80 g L-1 was completely reduced in 1.5 h by M8 along with Exiguobacterium sibiricum glucose dehydrogenase (EsGDH) for cofactor regeneration, producing (3R,5R)-2 in dep > 99.5% and space-time yields (STY) of 660.0 g L-1d-1.

8.
Chemosphere ; 238: 124600, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31446277

RESUMO

A high-gravity rotating packed bed (HiGee RPB) is very efficient at removing pollution because it exerts a strong high centrifugal and allows tiny droplets to form, which allows the control of gaseous and particulate air pollution. In this study, fine particles that are removed from integrated circuit (IC) chip carbonization process using a RPB are evaluated under different high gravity factors and liquid-to-gas ratios. The greatest number of particles captured per energy consumption is 17.77 mg kWh-1 in a RPB. This allow greater energy efficiency for the HiGee technology prevents an air-energy nexus. The maximum available particle removal efficiency for a RPB is determined using a response surface model (RSM). 99.5% of particles are removed at a high gravity factor of 262 and a liquid-to-gas ratio of 0.24. A semi-theoretical model is developed to determine the particle removal efficiency individually in packing and cavity zones of the RPB. More particles are removed in a cavity zone than in the packing zone as the high gravity factor increases. An empirical model shows that the particle removal efficiency depends on the operating factors. Finally, a comparison analysis of particulate matter treatment in various types of RPB is used to validate the performance in terms of particle removal using high-gravity technology for different industries.

9.
J Mol Cell Cardiol ; 137: 119-131, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31669609

RESUMO

Coronary microvessel endothelial dysfunction and nitric oxide (NO) depletion contribute to elevated passive tension of cardiomyocytes, diastolic dysfunction and predispose the heart to heart failure with preserved ejection fraction. We examined if diastolic dysfunction at the level of the cardiomyocytes precedes coronary endothelial dysfunction in prediabetes. Further, we determined if myofilaments other than titin contribute to impairment. Utilizing synchrotron microangiography we found young prediabetic male rats showed preserved dilator responses to acetylcholine in microvessels. Utilizing synchrotron X-ray diffraction we show that cardiac relaxation and cross-bridge dynamics are impaired by myosin head displacement from actin filaments particularly in the inner myocardium. We reveal that increased PKC activity and mitochondrial oxidative stress in cardiomyocytes contributes to rho-kinase mediated impairment of myosin head extension to actin filaments, depression of soluble guanylyl cyclase/PKG activity and consequently stiffening of titin in prediabetes ahead of coronary endothelial dysfunction.

10.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1130-1131: 121788, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670109

RESUMO

Multilayer print designs are commonly used in commercial food packaging to attract consumers. UV-curable ink is generally used in this type of printing due to its ease of application, space saving, and rapid drying; however, there have been a number of health alerts related to the contamination of food by photoinitiators in UV-curable ink. In this study, we established a multi-analyte method by which to detect 30 photoinitiators simultaneously. We then applied this method to the analysis of five breakfast cereals and ten types of packaged juice to detect the presence of photoinitiator contamination. Sample treatment was performed using the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for the extraction of photoinitiators. Chromatographic separation of two isomers, methylbenzophenone (MBP) and isopropylthioxanthone (ITX), was achieved using a pentafluorophenyl propyl (PFP) column (1.7 µm, 100 × 2.1 mm i.d.) and MeOH: 5 mM formic acid-ammonium formate (pH 4.0) in gradient elution. The average recovery of photoinitiators from cereal was between 62.0 and 120.3%, with a coefficient of variation between 0.4 and 14.4%. The average recovery of photoinitiators from packaged juices was between 84.4 and 122.9% with a coefficient of variation between 0.5 and 9.5%. The contamination results were as follows: 13.1 ng/g triphenyl phosphate (TPP) was detected in one breakfast cereal, and 2-hydroxy-4-methoxy benzophenone (BP-3), 1-hydroxycyclohexyl phenyl-ketone (Irgacure 184), methyl-2-benzoylbenzoate (MOBB), and 2,4-diethyl-9H-thioxanthen-9-one (DETX) were detected in one of the packaged juices at levels ranging from 2.2 to 152.9 ng/g.

11.
Biomolecules ; 9(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683805

RESUMO

De novo protein synthesis by the ribosome and its multitude of co-factors must occur in a tightly regulated manner to ensure that the correct proteins are produced accurately at the right time and, in some cases, also in the proper location. With novel techniques such as ribosome profiling and cryogenic electron microscopy, our understanding of this basic biological process is better than ever and continues to grow. Concurrently, increasing attention is focused on how translational regulation in the brain may be disrupted during the progression of various neurological disorders. In fact, translational dysregulation is now recognized as the de facto pathogenic cause for some disorders. Novel mechanisms including ribosome stalling, ribosome-associated quality control, and liquid-liquid phase separation are closely linked to translational regulation, and may thus be involved in the pathogenic process. The relationships between translational dysregulation and neurological disorders, as well as the ways through which we may be able to reverse those detrimental effects, will be examined in this review.

12.
Opt Express ; 27(21): 29924-29929, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684247

RESUMO

We propose and experimentally demonstrated a light-panel and image sensor based visible light communication (VLC) system using machine learning (ML) algorithm. The ML algorithm is compared with the traditional demodulation scheme and the experimental results show that even at very high noise-ratio (NR) light-panel display content, the proposed ML algorithm shows significant bit error rate (BER) improvement.

13.
Int J Mol Sci ; 20(22)2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718025

RESUMO

Lagerstroemia indica is an important ornamental tree worldwide. The development of cultivars with colorful leaves and increased ornamental value represents one of the current main research topics. We investigated the anthocyanin profiles in two contrasting cultivars for leaf color phenotypes and explored the underlying molecular basis. Both cultivars display purple-red young leaves (Stage 1), and when the leaves mature (Stage 2), they turn green in HD (Lagerstroemia Dynamite) but remain unchanged in ZD (Lagerstroemia Ebony Embers). Seven different anthocyanins were detected, and globally, the leaves of ZD contained higher levels of anthocyanins than those of HD at the two stages with the most pronounced difference observed at Stage 2. Transcriptome sequencing revealed that in contrast to HD, ZD tends to keep a higher activity level of key genes involved in the flavonoid-anthocyanin biosynthesis pathways throughout the leaf developmental stages in order to maintain the synthesis, accumulation, and modification of anthocyanins. By applying gene co-expression analysis, we detected 19 key MYB regulators were co-expressed with the flavonoid-anthocyanin biosynthetic genes and were found strongly down-regulated in HD. This study lays the foundation for the artificial manipulation of the anthocyanin biosynthesis in order to create new L. indica cultivars with colorful leaves and increased ornamental value.

14.
Sci Rep ; 9(1): 16032, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690742

RESUMO

Pain is a major primary health care problem. Emerging studies show that inhibition of spinal microglial activation reduces pain. However, the precise mechanisms by which microglial activation contributes to nociceptive synaptic transmission remain unclear. In this study, we measured spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in rat spinal cord superficial dorsal horn (SDH, laminae I and II) neurons. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) increased the frequency, but not amplitude, of mEPSCs in SDH neurons. Microglial inhibitors minocycline and paeonol, as well as an astrocyte inhibitor, a P2Y1 receptor (P2Y1R) antagonist, and a metabotropic glutamate receptor 5 (mGluR5) antagonist, all prevented LPS-induced enhancement of mEPSC frequency. In mouse behavioral testing, minocycline and paeonol effectively reduced acetic acid-induced writhing and LPS-induced hyperalgesia. These results indicate that LPS-activated microglia release ATP, which stimulates astrocyte P2Y1Rs to release glutamate, triggering presynaptic mGluR5 receptors and increasing presynaptic glutamate release, leading to an increase in mEPSC frequency and enhancement of nociceptive transmission in SDH neurons. We propose that these effects can serve as a new electrophysiological model for evaluating pain. Moreover, we predict that pharmacologic agents capable of inhibiting the LPS-induced enhancement of mEPSC frequency in SDH neurons will have analgesic effects.

15.
BMC Infect Dis ; 19(1): 937, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694555

RESUMO

BACKGROUND: Infective endocarditis (IE) especially in the elderly is a serious disease, with a worse prognosis. METHODS: A retrospective cohort study was conducted. A total of 405 patients with definite IE were divided into three groups: 205 patients under 50 years old, 141 patients between 50 and 64 years old and 59 patients over 65 years old. RESULTS: For older patients, clinical symptoms such as fever, anemia, and heart murmur were as common as the younger patients. IE in old patients had more frequent nosocomial origin (P = 0.007) and tended to be more frequent with bad oral hygiene (p = 0.008). The most frequent isolated pathogens in the old groups was streptococci and coagulase-negative staphylococci. The old patients had a lower operation rate (40.7% vs 58.9% vs 62.4%, P = 0.012) and higher in-hospital mortality (20.3% vs 10.6% vs 8.8%, P = 0.044) compared with the younger patients. Surgical treatment was a significant predictor of one-year mortality even after adjusting for the confounders (HR = 2.45, 95% CI 1.027-10.598, P = 0.009). The one-year survival rate was higher for older patients with surgical intervention than those without (95.8% vs 68.6%, P = 0.007). CONCLUSIONS: Older patients with IE presented with more comorbidities, bad oral hygiene, more nosocomial origin and a more severe prognosis than younger patients. Streptococci was the most frequent micro-organisms in this group. Surgery were underused in old patients and those with surgical treatment had better prognosis.

16.
J Virol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723026

RESUMO

Kaposi's sarcoma associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), an acquired immunodeficiency syndrome (AIDS)-defining cancer with abnormal angiogenesis. The high incidence of KS in human immunodeficiency viruses (HIV)-infected AIDS patients has been ascribed to HIV-1 and KSHV interaction, focusing on secretory proteins. HIV-1 secreted protein HIV-Tat has been found to synergize with KSHV lytic proteins to induce angiogenesis. However, the impact and underlying mechanisms of HIV-Tat in KSHV-infected endothelial cells undergoing viral lytic reactivation remain unclear. Here, we identified LINC00313 as a novel KSHV reactivation-activated long non-coding RNA (lncRNA) that interacts with HIV-Tat. We found that LINC00313 overexpression inhibits cell migration, invasion and tube formation, and this suppressive effect was relieve by HIV-Tat. In addition, LINC00313 bound to polycomb repressive complex 2 (PRC2) complex components and this interaction was disrupted by HIV-Tat suggesting that LINC00313 may mediate transcription repression through recruitment of PRC2 and HIV-Tat alleviates repression through disruption of this association. This notion was further supported by bioinformatics analysis of transcriptome profiles in LINC00313 overexpression combined with HIV-Tat treatment. Ingenuity Pathway Analysis (IPA) showed that LINC00313 overexpression negatively regulates cell movement and migration pathways, and enrichment of these pathways was absent in the presence of HIV-Tat. Collectively, our results illustrate that an angiogenic repressive lncRNA, LINC00313 that is up-regulated during KSHV reactivation interacts with HIV-Tat to promote endothelial cell motility. These results demonstrate that a lncRNA serves as a novel connector in HIV-KSHV interactions.IMPORTANCE KS is a prevalent tumor associated with two distinct viral infections, KSHV and HIV. Since KSHV and HIV infect distinct cell types, the viral-viral interaction associated with KS formation has focused on secretory factors. HIV-Tat is a well-known RNA binding protein secreted by HIV. Here, we revealed LINC00313, an lncRNA up-regulated during KSHV lytic reactivation, as a novel HIV-Tat interacting lncRNA that potentially mediates HIV-KSHV interactions. We found that LINC00313 can repress endothelial cell angiogenesis-related properties potentially through interacting with chromatin remodeling complex PRC2 and down-regulation of cell migration regulating genes. Interaction between HIV-Tat and LINC00313 contributed to dissociation of PRC2 from LINC00313 and disinhibition of LINC00313-induced repression of cell motility. Given that lncRNAs are emerging as key players in tissue physiology and disease progression, including cancer, the mechanism identified in this study may help decipher the mechanisms underlying KS pathogenesis induced by HIV and KSHV co-infection.

17.
J Clin Pathol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690565

RESUMO

AIMS: To describe the clinical utility of lymph node retrieval and prognostic value of tattooing in rectal cancer (RC) patients undergoing neoadjuvant concurrent chemoradiotherapy (CCRT). METHODS: A total 97 RC patients underwent preoperative CCRT, and 38 patients had preoperative endoscopic tattooing. Surgical intervention was performed after CCRT and the specimens were sampled as standard protocol in all patients. Other clinicopathological parameters correlated with lymph node retrieval status were also analysed. RESULTS: Fifteen patients (39.5%) of 38 RC patients in the tattooing group (TG) had adequate lymph node retrieval (>12) compared with 12 (20.3%) of 59 in the non-tattooing group. Higher lymph node retrieval rate was noted in the TG (p=0.04). In multivariable analysis, it showed tattooing was an independent predictive factor for higher lymph node retrieval in RC patients after CCRT (p=0.024) by logistic regression modelling. Besides histological grade, positive lymphovascular invasion, presence of lymph node metastasis, poor CCRT response and advanced pathological stage, inadequate lymph node retrieval was significantly associated with poor survival (all p<0.05) by Kaplan-Meier analysis. In multivariable analyses, the results revealed that lymph node retrieval (p=0.005), pathological stage (p=0.001) and tumour progression grade (p=0.02) were independent prognostic markers in RC patients receiving CCRT. CONCLUSION: Preoperative endoscopic tattooing is a useful technique for RC patient receiving neoadjuvant CCRT. It can improve lymph node retrieval and provide an adequate diagnosis for proper treatment and prognosis.

18.
Oxid Med Cell Longev ; 2019: 8130481, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687087

RESUMO

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the ATXN3/MJD1 gene. The expanded CAG repeats encode a polyglutamine (polyQ) tract at the C-terminus of the ATXN3 protein. ATXN3 containing expanded polyQ forms aggregates, leading to subsequent cellular dysfunctions including an impaired ubiquitin-proteasome system (UPS). To investigate the pathogenesis of SCA3 and develop potential therapeutic strategies, we established induced pluripotent stem cell (iPSC) lines from SCA3 patients (SCA3-iPSC). Neurons derived from SCA3-iPSCs formed aggregates that are positive to the polyQ marker 1C2. Treatment with the proteasome inhibitor, MG132, on SCA3-iPSC-derived neurons downregulated proteasome activity, increased production of radical oxygen species (ROS), and upregulated the cleaved caspase 3 level and caspase 3 activity. This increased susceptibility to the proteasome inhibitor can be rescued by a Chinese herbal medicine (CHM) extract NH037 (from Pueraria lobata) and its constituent daidzein via upregulating proteasome activity and reducing protein ubiquitination, oxidative stress, cleaved caspase 3 level, and caspase 3 activity. Our results successfully recapitulate the key phenotypes of the neurons derived from SCA3 patients, as well as indicate the potential of NH037 and daidzein in the treatment for SCA3 patients.

19.
Math Biosci Eng ; 16(6): 7526-7545, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31698627

RESUMO

Technology has reshaped the workplace and the rapid improvements have transformed how we work nowadays. In the pursuit of industry 4.0, we build smart machines and robots to replace manual labor. While the manual labor is replaced by machines, in many cases, humans are trans-formed into desktop software users. Jobs such as testing, quality inspection, data monitoring, data entry, and routine editing remain to be done by humans in front of desktop computers. The operations to software applications in principle can be reduced to screen output understanding and mouse and keyboard operations. When the characteristics of these jobs are repetitive, tedious, and monotonous, they can be replaced by GUI automation techniques. GUI automation can be achieved by different un-derlying technologies, each has its pros and cons. In this paper, we describe a tool-Korat, which uses computer-vision to achieve maximum cross-platform capability for industrial applications, including test automation and robotic process automation. Although Korat has been successfully adopted by several industrial customers, difficult problems remain to be addressed. The problems and difficulties in applying computer vision for GUI automation are discussed and studied in this paper, particularly the experiences of applying open source OCR to GUI automation over color screenshots. By intro-ducing critical pre-processing stages and algorithms, the recognition rate is significantly increased and becomes feasible for practical usage.

20.
Drug Metab Dispos ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699807

RESUMO

Generating accurate in vitro data is crucial for in vitro to in vivo extrapolation and pharmacokinetic predictions. The use of HEK293 cells overexpressing OATP1B1 and OATP1B3 in protein-free buffer and 100% human plasma incubations was explored for the uptake of four OATP substrates, pravastatin, rosuvastatin, repaglinide and pitavastatin. Differences were observed for each parameter (Km,u, Vmax, CLint, and Pdif,u) obtained from the buffer and human plasma incubations in both cells, and in general, the fold differences increased as plasma protein binding increased. The fold change in Km,u values ranged from 2.03-1020, and the fold change in Vmax values ranged from 1.22-97.4. As a result, the CLint values generated in the plasma incubations were 1.66-51.9 fold higher than the values generated in protein-free buffer in both cells. The unbound passive diffusion was also consistently higher in the human plasma incubations for all four compounds, with a fold difference range of 2.06-38.4. These shifts in the presence and absence of human plasma suggest that plasma proteins may play a role in both the active uptake and passive diffusion processes. The results also support the idea of a transporter-induced protein-binding shift, where high protein binding may not limit the uptake of compounds that have high affinity for transporters. The addition of plasma to incubations leading to higher CLint values for transporter substrates helps mitigate the underprediction commonly noted with in vitro to in vivo extrapolation. SIGNIFICANCE STATEMENT: The current investigation brought new perspective on how to mitigate the underprediction commonly noted with in vitro to in vivo extrapolation for OATP substrates. It also supports the idea of a transporter-induced protein-binding shift, where high protein binding may not limit the uptake of compounds that have high affinity for transporters.

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