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1.
Neurosci Lett ; : 134752, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31927056

RESUMO

Event-related potential (ERP)-based brain-computer interface (BCI) has been widely used in robot control. Increasing the amplitude of the ERPs is key for improving the performance of ERP-based BCI. However, using images of robot motion as visual stimuli has not been studied widely. The aim of this study is to explore the concreteness of robot motion images on ERPs. Fifteen subjects used five kinds of visual spellers employing different images as visual stimuli: squares, arrows, a single kind of robot motion, multiple kinds of robot motions, and multiple kinds of robot motions with arrows. The three robot motion stimuli induced larger N200 and P300 potentials than non-robot motion stimuli. The topography shows that robot motion stimuli also evoke stronger negativities in the anterior and occipital areas. Concrete images provide more information to the subject about the robot motion, which might help the brain extract the meaning of the image more automatically. We use a support vector machine to detect the subject's intentions. There is substantial improvement in the classification performance when using robot motion images as visual stimuli, which implies that concrete visual stimuli improve the performance of the ERP-based BCI.

2.
Environ Res ; 182: 109119, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31927246

RESUMO

Aquaculture wetlands, particularly those located within urban areas, are fragile ecosystems which are generally heavily impacted by urban and aquaculture activities. However, there are, to date, no reports on adverse effects related to polycyclic aromatic hydrocarbons (PAHs) in sediments from aquaculture wetlands in metropolitan areas. The characterization, sources, and incidence of adverse effects on aquatic biota of PAHs were studied in the riverine and estuarine sediments of the Rongjiang River in an aquaculture wetland in Chaoshan metropolis. The total PAH concentrations varied from 46.0 to 1665.2 ng/g (dry weight), with a mean of 246.4 ng/g, indicating lower concentrations than those of other comparable rivers and estuaries worldwide. High-molecular-weight PAHs were the major PAH species, with fluorene, benzo(b)fluoranthene, and benzo(a)pyrene as the dominant components. These PAHs are likely to be mainly derived from oil and coal/biomass combustion. Probability risk assessment indicated a moderate PAH ecological risk in the Rongjiang River and its estuary (RJE). Accordingly, a comprehensive management plan should be established to ensure sustainable aquaculture wetlands.

3.
Dalton Trans ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894791

RESUMO

Dissolution-recrystallization structural transformation (DRST) is a powerful tool to unravel unequivocally the mechanism of dynamic conversion processes, based on the structures of the initial reactants, final products and sometimes intermediates isolated from the reaction mixture. Herein, we illustrate the details of the conversion processes of (CuIpz)3 into [CuII(OH)pz]6 (pzH = 4-chloro-3,5-diphenylpyrazole) through DRSTs. Based on crystal structure determination and spectroscopic methods, the most encountered species, (CuIpz)3, is in equilibrium with (CuIpz)4 in solution with the tetramer becoming dominant at low temperature, indicating an entropy-controlled conversion between these two structural isomers. The CuI trimer/tetramer in solution further experiences an oxidation if exposed to the open air, resulting in the formation of a pentanuclear mixed-valence intermediate CuI3CuII2(OMe)2pz5 which can be isolated as single crystals at -20 °C and has been structurally characterized for the first time. The final product isolated from the solution is the fully oxidized hexanuclear [CuII(OMe)pz]6, which is easily transformed into [CuII(OH)pz]6 in the presence of humidity.

4.
Blood Adv ; 4(1): 141-153, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935288

RESUMO

Hematopoietic cell kinase (HCK) is an SRC family member that is aberrantly upregulated in B-cell neoplasms dependent on MYD88-activating mutations and supports their growth and survival. We showed herein that activation of Toll-like receptor (TLR) signaling in MYD88 wild-type B cells also triggered HCK expression, denoting on path regulatory function for HCK by MYD88. To clarify the signaling cascades responsible for aberrant HCK expression in MYD88-mutated B-cell lymphomas, we performed promoter-binding transcription factor (TF) profiling, PROMO weighted TF consensus binding motif analysis, and chromatin immunoprecipitation studies. We identified PAX5, and the mutated MYD88 downstream signaling mediators STAT3, NF-κB, and AP-1, as important drivers of HCK transcription. Knockdown of PAX5, a crucial regulatory factor required for B-cell commitment and identity, abrogated HCK transcription in MYD88-mutated lymphoma cells. Among AP-1 complex components, JunB showed greatest relevance to TLR/MYD88 signaling and HCK transcription regulation. In MYD88-mutated Waldenström macroglobulinemia and activated B-cell-diffuse large B-cell lymphoma cells, knockdown of MYD88 reduced phosphorylation of JunB but not c-Jun, and knockdown of JunB reduced HCK protein levels. Deletion of STAT3, NF-κB, and AP-1 binding sites reduced corresponding TFs binding and HCK promoter activity. Moreover, inhibitors to STAT3, NF-κB, and AP-1 reduced HCK promoter activity and messenger RNA levels, particularly in combination, in MYD88-mutated lymphoma cells. The findings provide new insights into the transcriptional regulation of HCK prosurvival signaling by mutated MYD88, and the importance of JunB as a downstream mediator of the MYD88-directed signaling apparatus.

5.
J Clin Pharm Ther ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954070

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Corticosteroids are recommended by almost all international guidelines for the management of exacerbations of chronic obstructive pulmonary disease (COPD). Nevertheless, due to their side effects, there are still concerns regarding the use of systemic corticosteroids (SCs). The Global Initiative for Chronic Obstructive Lung Disease guideline states nebulized budesonide (NB) may be a suitable alternative to SCs for treating COPD exacerbations. We conducted this study to systematically compare the efficacies of NB and SCs by using a meta-analysis. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from database inception to 10 October 2019. Our main end points were change in pulmonary function and blood gas analysis. Secondary end points were numbers of exacerbations and hyperglycaemia. RESULTS AND DISCUSSION: Of 645 identified studies, 6 were eligible and were included in our analysis (N = 867 participants). Compared with SCs, NB was non-inferior on the change in FEV1 %predicted at 24 hours, 48-72 hours and 5-7 days; FEV1 at 5-7 days; FEV1 /FVC at 7 days. For blood gas analysis, our meta-analysis indicated that PaO2 , PaCO2 at 24 hours, 48-72 hours and 7-10 days and SaO2 at 24 hours and 7-10 days showed a non-significant difference in both groups, whereas the SaO2 was significant higher in NB group at 48-72 hours after treatment. Hyperglycaemia was less frequent with NB (odds ratio, 0.1; 95% CI, 0.01-0.85; P = .04). WHAT IS NEW AND CONCLUSION: Based on our meta-analysis, NB was not inferior to SCs when used in the treatment of COPD exacerbations. However, additional well-designed prospective studies are needed to identify the optimal dose of nebulized budesonide and the effects of nebulized budesonide in outpatients, or patients in ICU settings.

6.
IEEE Trans Haptics ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31940555

RESUMO

This paper presents a novel approach to haptic teleoperation. Specifically, we use control barrier functions (CBFs) to generate force feedback to help human operators safely fly quadrotor UAVs. CBFs take a control signal as input and output a control signal that is as close as possible to the initial control signal, while also meeting specified safety constraints. In the proposed method, we generate haptic force feedback based on the difference between a command issued by the human operator and the safe command returned by a CBF. In this way, if the user issues an unsafe control command, the haptic feedback will help guide the user towards the safe input command that is closest to their current command. We conducted a within-subject user study, in which 12 participants flew a simulated UAV in a virtual hallway environment. Participants completed the task with our proposed CBF-based haptic feedback, no haptic feedback, and haptic feedback generated via parametric risk fields, which is a state-of-the-art method described in the literature. The results of this study show that CBF-based haptic feedback can improve a human operator's ability to safely fly a UAV and reduce the operator's perceived workload, without sacrificing task efficiency.

8.
Pest Manag Sci ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943722

RESUMO

BACKGROUND: The intensifying weed resistance has challenged the use of existing acetohydroxyacid synthase (AHAS)-inhibiting herbicides. Hence, there is currently an urgent requirement for the discovery of new AHAS inhibitor to effectively control AHAS herbicide-resistant weed species caused by target mutation. RESULTS: To combat weed resistance caused by AHAS with P197L mutation, we built a structure library consisting of pyrimidinyl-salicylic acid derivatives in this work. Using pharmacophore-linked fragment virtual screening (PFVS) approach, hit compound 8 bearing 6-phenoxymethyl substituent was identified as a potential AHAS inhibitor with antiresistance effect. Subsequently, derivatives of compound 8 were synthesized and evaluated for their inhibitory activities. The study of the enzyme-based structure-activity relationship and structure-resistance relationship studies led to the discovery of a qualified candidate 28. This compound not only significantly inhibited the activity of wild-type Arabidopsis thaliana (At) AHAS and P197L mutant, but also exhibited good antiresistance property (RF= 0.79). Notably, compared with bispyribac at 37.5-150 grams of active ingredient per hectare (g ai/ha), compound 27 exhibited higher growth inhibition against both sensitive and resistant Descurainia sophia, CONCLUSION: The title compounds have great potential to be developed as new leads to effectively control herbicide-resistant weeds comprising AHAS with P197L mutation. Also, our study provided a positive case of discovery of novel, potent and antiresistance inhibitors using fragment-based drug design approach. This article is protected by copyright. All rights reserved.

9.
Environ Int ; 136: 105445, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31918332

RESUMO

BACKGROUND: There has been increasing interest in the concept that exposure to environmental chemicals may be contributing factors to epidemics of diabetes mellitus (DM). Triclocarban and triclosan (TCs) are synthetic antibacterial chemicals that are widely used in personal care products. Studies have shown that TCs are endocrine disruptors that alter metabolic conditions. However, it remains unclear whether exposure to TCs is a risk factor for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). OBJECTIVE: We explored the hypothesis that TCs exposure is associated with an increased risk of IGT and T2DM. METHOD: To test our hypothesis, we analyzed the U.S. National Health and Nutrition Examination Survey (NHANES) cross-sectional data from 2013 to 2014. IGT and T2DM were diagnosed based on an oral glucose tolerance test (OGTT) and the WHO standards. The levels of urinary TCs were measured using an HPLC-MS/MS method that NHANES investigators developed. The association between urinary TCs status and IGT and T2DM was examined separately in men and women using multivariable logistic regression models adjusted for age, race, BMI, education, ratio of family income to poverty, smoking, exercise and hypertension. RESULTS: Nine hundred US participants (429 men and 471 women) were included in the analysis, of whom 242 (26.89%) were diagnosed with T2DM and 117 (13.00%) had IGT. Among women, there was a significant positive association between triclocarban, but not triclosan exposure and T2DM (OR: 1.79, 95% CI: 1.05, 2.05) after adjusting for potential confounding factors. Among men, no significant association between TCs exposure and IGT or T2DM was observed. CONCLUSIONS: Triclocarban exposure may increase the risk of T2DM in the women, although additional studies are needed to confirm the results of this study and to investigate the underlying mechanisms.

10.
Int J Biol Macromol ; 147: 10-17, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923483

RESUMO

Although pullulan has many uses in industry, the detailed mechanisms of its biosynthesis still require clarification. In this study, it was found that a short α-1,4-glucosyl chain (pullulan primer) synthesized by the glycogenins Glg1 and Glg2 for initiation of glycogen biosynthesis was also needed for pullulan synthesis. The primers were also synthesized on sterol glycosides and glucosylceramides by catalysis of sterol glucosyltransferase (Sgt1) and ceramide ß-glucosyltransferase (Gcs1). All the primers might be elongated to be long α-1,4-glucosyl chain (pullulan precursor) by catalysis of the glycogen synthetase domain of the AmAgs2 as previously reported. Then, the amylase domain of the same AmAgs2 was responsible for pullulan biosynthesis. Removal of all the genes encoding Glg1, Glg2, Gcs1 and Sgt1 made all the mutants produce much less pullulan than the strain P16. However, pullulan synthesis could not be stopped totally in these mutants, suggesting that any other unknown alternative pullulan primers may exist in the yeast cells. Complementation of all the genes in the mutants restored pullulan biosynthesis. This is the first time to report that like starch and glycogen biosynthesis, alternative primers are also required for pullulan biosynthesis in Aureobasidium melanogenum P16.

11.
Eur J Radiol ; 124: 108822, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31951895

RESUMO

PURPOSE: To propose an automatic approach based on a convolutional neural network (CNN) to evaluate the quality of T2-weighted liver magnetic resonance (MR) images as nondiagnostic (ND) or diagnostic (D). MATERIALS AND METHODS: We included 150 T2-weighted liver MR imaging examinations in this retrospective study. Each slice of liver image was annotated with a label D or ND by two radiologists with seven and six years of experience, respectively. Additionally, the radiologists segmented the liver region manually as the ground truth for liver segmentation. A CNN was trained to segment the liver region and another CNN was used to classify the qualities of patches extracted from the liver region. The quality of an image was obtained from the percentage of nondiagnostic patches in all liver patches in the image. Treating nondiagnostic as positive, the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic curve (AUC), and confusion matrix were used to evaluate our model. A Mann-Whitney U test was performed with the statistical significance set at 0.05. RESULTS: Our model achieved good performance with an accuracy of 88.3 %, sensitivity of 86.0 %, specificity of 89.4 %, PPV of 78.6 %, NPV of 93.4 %, and AUC of 0.911 (95 % confidence interval: 0.882-0.939, p < 0.05). The confusion matrix of our model indicated good concordance with that of the radiologists. CONCLUSIONS: The proposed two-step patch-based model achieved excellent performance when assessing the quality of liver MR images.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31956954

RESUMO

PURPOSE: Compact master manipulators have inherent advantages, since they can have practical deployment within the general surgical environments easily and bring benefits to surgical training. To assess the advantages of compact master manipulators for surgical skills training and the performance of general robot-assisted surgical tasks, Hamlyn Compact Robotic Master (Hamlyn CRM) is built up and evaluated in this paper. METHODS: A compact structure for the master manipulator is proposed. A novel sensing system is designed while stable real-time motion tracking can be realized by fusing the information from multiple sensors. User studies were conducted based on a ring transfer task and a needle passing task to explore a suitable mapping strategy for the compact master manipulator to control a surgical robot remotely. The overall usability of the Hamlyn CRM is verified based on the da Vinci Research Kit (dVRK). The master manipulators of the dVRK control console are used as the reference RESULTS: Motion tracking experiments verified that the proposed system can track the operators' hand motion precisely. As for the master-slave mapping strategy, user studies proved that the combination of the position relative mapping mode and the orientation absolute mapping mode is suitable for Robot-Assisted Minimally Invasive Surgery (RAMIS), while key parameters for mapping are selected. CONCLUSION: Results indicated that the Hamlyn CRM can serve as a compact master manipulator for surgical training and has potential applications for RAMIS.

13.
J Magn Reson Imaging ; 51(1): 273-285, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31271488

RESUMO

BACKGROUND: The histopathological basis of monoexponential diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) in the characterization of sinonasal malignant tumors is still unclear. PURPOSE: To explore the correlations of histogram metrics from monoexponential DWI, IVIM, and DKI with histopathologic features in sinonasal malignant tumors. STUDY TYPE: Retrospective. SUBJECTS: In all, 76 patients with sinonasal malignant tumors. FIELD STRENGTH/SEQUENCE: Fourteen different b values (b = 0, 50, 100, 150, 200, 250, 300, 350, 400, 800, 1000, 1500, 2000, and 2500 sec/mm2 ) were used to perform different DWI models at 3.0T. ASSESSMENT: The whole-tumor histogram metrics were calculated on the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), diffusion kurtosis (K), and diffusion coefficient (Dk) maps. Histopathologic features, including nuclear, cytoplasmic, cellular, stromal fractions, and the nuclear-to-cytoplasmic (N/C) ratio, were measured. STATISTICAL TESTS: Spearman correlations and stepwise multiple linear regression analyses were performed to determine the correlations between histogram metrics and histopathologic features. RESULTS: ADC, Dk, and f histogram metrics showed significant correlations with investigated histopathologic features; D and K histogram metrics were significantly correlated with cellular, stromal, and nuclear fractions (all P < 0.05). Significant correlations between the 75th percentile of D and cytoplasmic fraction and between the kurtosis of K and the N/C ratio were observed (P < 0.05). The skewness of Dk, K, and the 75th percentile of D were independently associated with cellular and nuclear fractions; the skewness of Dk and K were independently associated with stromal fraction (P < 0.05). DATA CONCLUSION: Monoexponential and advanced DWI histogram parameters were significantly correlated with histopathologic features in sinonasal malignancies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:273-285.

14.
Proc Natl Acad Sci U S A ; 117(1): 448-453, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871187

RESUMO

Voltage-gated calcium 3.1 (CaV3.1) channels are absent in healthy mouse ß cells and mediate minor T-type Ca2+ currents in healthy rat and human ß cells but become evident under diabetic conditions. Whether more active CaV3.1 channels affect insulin secretion and glucose homeostasis remains enigmatic. We addressed this question by enhancing de novo expression of ß cell CaV3.1 channels and exploring the consequent impacts on dynamic insulin secretion and glucose homeostasis as well as underlying molecular mechanisms with a series of in vitro and in vivo approaches. We now demonstrate that a recombinant adenovirus encoding enhanced green fluorescent protein-CaV3.1 subunit (Ad-EGFP-CaV3.1) efficiently transduced rat and human islets as well as dispersed islet cells. The resulting CaV3.1 channels conducted typical T-type Ca2+ currents, leading to an enhanced basal cytosolic-free Ca2+ concentration ([Ca2+]i). Ad-EGFP-CaV3.1-transduced islets released significantly less insulin under both the basal and first phases following glucose stimulation and could no longer normalize hyperglycemia in recipient rats rendered diabetic by streptozotocin treatment. Furthermore, Ad-EGFP-CaV3.1 transduction reduced phosphorylated FoxO1 in the cytoplasm of INS-1E cells, elevated FoxO1 nuclear retention, and decreased syntaxin 1A, SNAP-25, and synaptotagmin III. These effects were prevented by inhibiting CaV3.1 channels or the Ca2+-dependent phosphatase calcineurin. Enhanced expression of ß cell CaV3.1 channels therefore impairs insulin release and glucose homeostasis by means of initial excessive Ca2+ influx, subsequent activation of calcineurin, consequent dephosphorylation and nuclear retention of FoxO1, and eventual FoxO1-mediated down-regulation of ß cell exocytotic proteins. The present work thus suggests an elevated expression of CaV3.1 channels plays a significant role in diabetes pathogenesis.

15.
Per Med ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797717

RESUMO

Aim: This study investigated the association between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4. Materials & methods: Thirty-eight adult patients who received voriconazole therapy were included in the study. Genotype of CYP2C19 was detected using gene chip hybrid analysis. The UGT1A4 142T>G was genotyped using PCR-RFLP analysis. Results: Ten patients (26.3%) had voriconazole-induced liver injury and were considered as the case group There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19 *2 and UGT1A4 142T>G (p > 0.05), however, the GA frequency of CYP2C19 *3 in the drug-induced liver injury case group was higher than that in the control group (p < 0.05). Compared with patients carrying *1/*1 or *1/*2, there was no significant difference in voriconazole trough concentration of the patients with *1/*3 (p > 0.05). Conclusion: There was no significant correlation between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4.

16.
Sci Total Environ ; : 135141, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31822401

RESUMO

Water supply safety of riverbank filtration wells (RBFWs) have attracted a great deal of attention in recent years as their role in water supply is increasingly valued. In this study, this issue was revealed from the perspective of water level, quality and supply capacity of RBFWs based on an interference-pumping test with three pumping wells near the Songhua River in Northeast China followed by a recovery test. The results showed that a stable cone of depression of groundwater level in the riverbank filtration (RBF) formed after pumping for about five days with the maximum drawdown of the groundwater level of 10.42 m. The corresponding water capacity of the well group maintained 2.78 × 104 m3/d from then until the end of the test, 60% of which were captured directly from the river. The groundwater level could return to the level before the pumping test after the pumping test stopped for one day. The RBF could provide turbidity, trace organic substances and major cations and anions (except for Ca2+ and Mg2+) pre-treatment of the river water with the removal rates of 29%-95% for some water quality indicators. However, limited improvement of water quality was observed with respect to some inorganic contaminants (Fe, Mn and NH4+-N) because the background concentrations of them in the groundwater were higher than in the river water. When compared with the impact on water level and supply capacity, the impact of the surface water-groundwater interaction on the mechanisms of water quality evolution was more complicated. Taken together, the results of this study indicate that RBFWs can ensure a sustainable water supply of stable quality, which can also simplify the post-treatment processes of waterworks and reduce costs.

17.
Pest Manag Sci ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785188

RESUMO

BACKGROUND: Plutella xylostella is a devastating agricultural insect pest of cruciferous plants including crops. Plant-mediated RNAi is currently being developed for plant protection. In this study, we investigated the response of P. xylostella exposed to transgenic Arabidopsis thaliana plants that expressed dsRNA targeting P. xylostella genes of arginine kinase (PxAK) and integrin ß1 subunit (Pxß). RESULTS: Transgenic plants producing dsRNAs of 384-bp fragment of PxAK (dsAK plants), 497-bp fragment of Pxß (dsß plants), and 881 bp of the combination of both genes (dsAK-ß plants) were generated and verified. Insect bioassay with these transgenic plants showed that the development of P. xylostella was affected causing longer developmental time, and lower pupal weight and pupation rate. P. xylostella mortality rates were 25.0% when exposed to dsAK plants, 22.5% with dsß plants, and 30.0% with dsAK-ß plants, which were all higher than 7.5% for wild-type plant. PxAK and Pxß in P. xylostella were suppressed by 26.6% - 79.7% at the transcription level by the transgenic plants. CONCLUSION: These results suggest that plant-mediated RNAi targeting single gene or both of PxAK and Pxß may have the potential to control P. xylostella. This article is protected by copyright. All rights reserved.

18.
Eur J Cell Biol ; : 151057, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31810635

RESUMO

Succinate dehydrogenase (SDH), also named as complex II or succinate:quinone oxidoreductases (SQR) is a critical enzyme in bioenergetics and metabolism. This is because the enzyme is located at the intersection of oxidative phosphorylation and tricarboxylic acid cycle (TCA); the two major pathways involved in generating energy within cells. SDH is composed of 4 subunits and is assembled through a multi-step process with the aid of assembly factors. Not surprisingly malfunction of this enzyme has marked repercussions in metabolism leading to devastating tumors such as paraganglioma and pheochromocytoma. It is already known that mutations in the genes encoding subunits lead to tumorigenesis, but recent discoveries have indicated that mutations in the genes encoding the assembly factors also contribute to tumorigenesis. The mechanisms of pathogenesis of tumorigenesis have not been fully understood. However, a multitude of signaling pathways including succinate signaling was determined. We, here discuss how defective SDH may lead to tumor development at the molecular level and describe how yeast, as a model system, has contributed to understanding the molecular pathogenesis of tumorigenesis resulting from defective SDH.

19.
Med Image Anal ; 60: 101595, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31811981

RESUMO

Late gadolinium enhancement magnetic resonance imaging (LGE MRI) appears to be a promising alternative for scar assessment in patients with atrial fibrillation (AF). Automating the quantification and analysis of atrial scars can be challenging due to the low image quality. In this work, we propose a fully automated method based on the graph-cuts framework, where the potentials of the graph are learned on a surface mesh of the left atrium (LA) using a multi-scale convolutional neural network (MS-CNN). For validation, we have included fifty-eight images with manual delineations. MS-CNN, which can efficiently incorporate both the local and global texture information of the images, has been shown to evidently improve the segmentation accuracy of the proposed graph-cuts based method. The segmentation could be further improved when the contribution between the t-link and n-link weights of the graph is balanced. The proposed method achieves a mean accuracy of 0.856 ± 0.033 and mean Dice score of 0.702 ± 0.071 for LA scar quantification. Compared to the conventional methods, which are based on the manual delineation of LA for initialization, our method is fully automatic and has demonstrated significantly better Dice score and accuracy (p < 0.01). The method is promising and can be potentially useful in diagnosis and prognosis of AF.

20.
Int J Pediatr Otorhinolaryngol ; 130: 109806, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31812001

RESUMO

OBJECTIVE: Waardenburg Syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance and highly genetic heterogeneity. To date, mutations of PAX3, SOX10, MITF, EDNRB, EDN3 and SNAI2 have been implicated in the pathogenesis of WS. In this study, we aimed to identify pathogenic genes among WS families and to analyze the pathogenic relationship between genotypes and phenotypes. METHODS: In this study, all six families studied were from Hubei province, China.WS patients underwent screening for all deafness genes including PAX3, SOX10, MITF, EDNRB, EDN3 and SNAI2 using Massively Parallel Sequencing (MPS) and validation of mutations using Sanger sequencing. RESULTS: Clinical evaluation revealed prominent phenotypic variability in Hubei WS patients. Two WS1 families and four WS2 families were diagnosed in six families. Sensorineural hearing loss was the most common, followed by iris pigmentary abnormality. Molecular genetic analysis of the WS genes for six families revealed five novel heterozygous mutations. Two mutations occurred in the PAX3 gene: one nonsense mutation c.667C > T(p.Arg223Ter) and one missense mutation c.220C > T(p.Arg74Cys).One missense mutation c.331T > C (p.Phe111Leu) and one nonsense mutation c.346C > T(p.Gln116Ter) were detected in the SOX10 gene. Two mutations were detected in the MITF gene: one splice site mutation c.859-1G > A and one nonsense mutation c.859G > T(p.Glu287Ter). Among them, the mutations (SOX10 c.331T > C and MITF c.859G > T) were de novo mutations. CONCLUSION: In this study, six mutations were found to be associated with the phenotype of patients. Our data helped illuminate the phenotypic and genotypic spectrum of WS in Hubei province and could have implications for the genetic counseling of WS in Hubei province.

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