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1.
Rev Sci Instrum ; 90(8): 083108, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472666

RESUMO

The simple working principles and versatility of the hydrothermal diamond-anvil cell (HDAC) make it highly useful for synchrotron x-ray studies of aqueous and fluid samples at high pressure-temperature (P-T) conditions. However, safety concerns need to be overcome in order to use the HDAC for synchrotron studies of aqueous radioactive samples at high temperatures and pressures. For accomplishment of such hydrothermal experiments of radioactive materials at synchrotron beamlines, the samples are required to be enclosed in a containment system employing three independent layers of airtight sealing at some synchrotron facilities while enabling access to the sample using several experimental probes, including incoming and outgoing x-rays. In this article, we report the design and implementation of a complete radiological safety enclosure system for an HDAC specialized for high P-T x-ray absorption spectroscopy (XAS) measurements of aqueous solutions containing the actinides at synchrotron beamlines. The enclosure system was successfully tested for XAS experiments using the HDAC with aqueous samples containing depleted uranium at temperatures ranging from 25 to 500 °C and pressures ranging from vapor pressure to 350 MPa.

2.
Med Sci Monit ; 25: 6615-6623, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479436

RESUMO

Primary hepatocellular carcinoma (HCC) is the fifth most frequently reported malignancy, and it is also the second most common cause of cancer-related deaths worldwide. Although most HCC cases have been reported to develop from cirrhosis, accumulating data suggest that HCC is also closely related to non-cirrhotic chronic liver disease. Traditionally, HCC was thought to develop mostly from cirrhosis; however, an increasing number of reports have found that HCC can develop directly from inflammation without cirrhosis. The incidence of HCC in non-cirrhotic liver (HCC-NCL) is high, especially in developed countries. Studies have found that the most common cause of HCC-NCL is neglected fatty liver disease. This type of HCC has unique clinical characteristics and is closely related to metabolic disorders. Unfortunately, the prevention of HCC-NCL has not received enough attention worldwide, and there is also a lack of specific screening methods and clinical guidelines. This article mainly reviews the etiology, incidence, clinical characteristics, and screening markers of HCC-NCL to improve the understanding and prevention of this disease.

3.
Eur Respir J ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515405

RESUMO

Most published studies addressing the role of HIFs in hypoxia-induced PH development employ models that may not recapitulate the clinical setting, including the use of animals having pre-existing lung/vascular defects secondary to embryonic HIF ablation or activation. Further, critical questions including how and when HIF-signalling contributes to hypoxia-induced PH remains unanswered.Normal adult rodents in which global HIF1 or 2 was inhibited by inducible gene deletion or pharmacological inhibition (antisense oligonucleotides-ASO and small molecule inhibitors) were exposed to short-term (4 days) or chronic (4-5 weeks) hypoxia. Hemodynamic studies were performed, the animals euthanized and lungs and heart obtained for pathologic and transcriptomic analysis. Cell-type specific HIF signals for PH initiation were determined in normal pulmonary vascular cells in vitro and in mice (using cell-type specific HIF deletion).Global HIF1α deletion in mice did not prevent hypoxia-induced PH at 5 weeks. Mice with global HIF2α deletion did not survive long-term hypoxia. Partial HIF2α gene deletion, or HIF2-ASO (but not HIF1-ASO) reduced vessel muscularization, rises in pulmonary artery pressures and right ventricular hypertrophy in mice exposed to 4-5 week hypoxia. A small molecule HIF2 inhibitor (PT2567) significantly attenuated early events (monocyte recruitment and vascular cell proliferation) in rats exposed to 4-day hypoxia as well as vessel musculization, tenascin C accumulation and PH development in rats exposed to 5 week hypoxia. In vitro, HIF2 induced a distinct set of genes in normal pulmonary vascular EC, mediating inflammation and proliferation of EC and SMC. EC HIF2α knockout prevented hypoxia-induced PH in mice.Inhibition of HIF2, not HIF1 can provide a therapeutic approach to prevent the development of hypoxia-induced PH. Future studies are needed to investigate the role of HIFs in PH progression and reversal.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31513325

RESUMO

It is vital to understand the oxygen reduction reaction (ORR) mechanism at the molecular level for the rational design and synthesis of high activity fuel cell catalysts. Surface enhanced Raman spectroscopy (SERS) is a powerful technique capable of detecting the bond vibrations of surface species in the low wavenumber range, however using it to probe practical nanocatalysts remains extremely challenging. Herein, shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) was used to investigate ORR processes on the surface of novel bimetallic Pt3Co nanocatlyst satellite structures. Direct spectroscopic evidence of *OOH suggests that ORR undergoes an associative mechanism on Pt3Co in both acidic and basic environments. Density functional theory (DFT) calculations show that the weak *O adsorption arises from electronic effect on the Pt3Co surface and accounts for enhanced ORR activity. This work shows SHINERS is a promising technique for the real-time observation of catalytic processes.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 904-909, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506151

RESUMO

OBJECTIVE: To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin. METHODS: A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome. RESULTS: The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P<0.05). Compared with the normal renal function group, the ARC group had a significantly lower initial trough concentration of vancomycin and a significantly lower proportion of children who achieved the effective trough concentration of vancomycin (10-20 mg/L) (P<0.05). There were no significant differences in bacteriological outcome and clinical outcome between the two groups (P>0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05). CONCLUSIONS: ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.

6.
Medicine (Baltimore) ; 98(33): e16778, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415381

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , China , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
7.
J Photochem Photobiol B ; 198: 111557, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382091

RESUMO

Cistus incanus leaf extract was used to biologically synthesize Copper oxide nanoparticles (CuO NPs). The characteristic UV-vis spectral band of CuO NPs found at 290 nm revealed the successful formation of CuO NPs. By the analysis of TEM and SEM, it is confirmed that the obtained CuO NPs were in spherical structure. By the analysis of Fourier transform infrared (FTIR) spectroscopy, it is evident that the absorption peak was situated at a position of about 480 cm-1 of wavenumber, which is typically considered as an extremely pure CuO NPs. The images of Transmission Electron Microscopy exhibited that the formed CuO NPs were in the size of about 15-25 nm and were relatively uniform in distribution. When related with the treatment of nanomaterials only, the synergistic interaction among CuO NPs and oxidative stress conditions considerably decreased the cardiac-related function catalogs, which includes pathological progressions of myocardium along with an obvious rise in the levels of creatine kinase-MB and cardiac troponin I. When compared to the void reaction of micro-CuO and cardiac operations in alloxan-injected rats, aggravation in the conditions of oxidative stress could be playing a significant part in the heart injury after dual exposing CuO NPs and alloxan. By these results, it is confirmed that the conditions of oxidative stress improved the contrary effects of CuO NPs to the heart, signifying that the utilization of nanomaterials in conditions of stress such as, in the delivery of drug, required to be cautiously monitored.

8.
J Clin Pharm Ther ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31381817

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Regorafenib is a novel multi-targeted tyrosine kinase inhibitor approved for use in refractory metastatic colorectal cancer, advanced gastrointestinal stromal tumours and hepatocellular carcinoma. We report a case of bilateral sensorineural hearing loss caused by regorafenib. CASE SUMMARY: A 48-year-old woman was diagnosed with colon cancer that had metastasized to the liver, ureter and left ovary. She was initially treated with oral regorafenib at the lowest recommended dosage of 80 mg/d for 2 weeks, at which point the dose was increased to 120 mg/d. On the second day after the regorafenib dosage increase (ie, 15 days after starting regorafenib), she suddenly developed a bilateral hearing loss. Regorafenib was discontinued immediately, and the patient was treated with a course of intravenous steroids. Five weeks later, her bilateral hearing had subjective partial improvement. WHAT IS NEW AND CONCLUSION: This is the first report of bilateral sensorineural hearing loss induced by regorafenib.

9.
Thyroid ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31364476

RESUMO

Background: Inherited medullary thyroid carcinoma (MTC) is primarily caused by RET mutations that are commonly localized in exons 5, 8, 10, 11, and 13-16. In this study, we report pedigrees for individuals with MTC that harbor a germline S409Y variant within exon 6 of the RET proto-oncogene. Methods: Targeted sequencing was used to diagnose four apparently sporadic MTC index cases carrying the germline RET S409Y (c.1226 C>A) variant. Subsequently, 27 relatives of these individuals underwent clinical and genetic assessments and/or thyroid surgery. Furthermore, in silico analyses and in vitro assays were performed to predict or verify the potential oncogenic activity of the S409Y variant. Results: Overall, 15 of 31 participants were found to carry the RET S409Y variant. Of these, 6 presented with isolated MTC (mean age 50.2 years; range 41-75 years), of which 3 presented with neck lymph node metastases and 2 presented with distant liver or lung metastases. Among the remaining 9 carriers, 3 (mean age 56 years; range 41-76 years) had elevated serum calcium-stimulated calcitonin (sCtn) or concurrent marginally elevated serum calcitonin (Ctn) levels, whereas the other 6 (mean age 37.5 years; range 14-52 years) exhibited typical Ctn/sCtn levels (p < 0.05). None of the 15 carriers in these 4 families presented clinical evidence of pheochromocytoma, hyperparathyroidism, or Hirschsprung's disease. In silico analyses revealed that S409Y was a "possibly damaging" mutation that could affect the RET protein inter-domain interface. An in vitro assay revealed that the phosphorylation level of RET tyrosine 905 was relatively higher in the RET S409Y mutant than in wild-type (WT) RET. Moreover, transfection of HEK 293 cells with S409Y enhanced the phosphorylation activity of AKT, ERK pathways, and it increased cell proliferation compared with WT RET, but to a lesser degree than that for the RET C618Y and C634Y mutations. Conclusions: This study demonstrates that the novel germline RET S409Y variant is likely pathogenic and is associated with lower penetrance of MTC than that for the C618Y and C634Y mutations. Individuals with S409Y should be managed using a personalized approach, and additionally, "at-risk" family members should be evaluated. Additional studies are needed to elucidate the correlation between the S409Y mutation and multiple endocrine neoplasia type 2-specific tumors.

10.
Bioresour Technol ; 292: 121979, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31445241

RESUMO

In order to evaluate light penetration and its influence on microalgae growth in a raceway pond with alternatively permutated conic baffles (RWP-APCB), 3D numerical simulation of light penetration was performed using computational fluid dynamics in an optimized flow field composed of microalgae cells, CO2 bubbles and culture medium. Results showed that light intensity in the culture medium attenuated faster in accordance with solution depth, with increased microalgae cell concentration, increased bubble volume fraction and decreased CO2 bubble diameter. Light zone fraction (i.e. ratio of light zone length to solution depth) increased with promoted incident irradiation. It was found that around 75% of microalgae cells were distributed in light zone and non-photochemical quenching coefficient of microalgae decreased by 32% in RWP-APCB. This resulted in a 16% increase of the Chlorella pyrenoidosa biomass growth rate, to 0.36 g/L/d.

11.
Food Chem ; 301: 125240, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31387040

RESUMO

Cold plasma is an emerging technology increasingly applied in the agri-food industry. For fruit and vegetables, enzymatic browning is a common phenomenon, causing quality deterioration. The objective of this study was to illustrate the effect of microscale atmospheric-pressure plasma jet (µAPPJ) plasma on the horseradish peroxidase (HRP). Results showed that after plasma treatment for 10 min, the residual activity of HRP was decreased to around 17%, and modification of secondary and tertiary structures were confirmed. The atomic force microscope (AFM) analysis revealed that the aggregation of enzyme protein was enhanced with prolonging treatment time. It was concluded that the activity of HRP could be reduced with destruction of structures and deformation of microstructure induced by µAPPJ plasma. The current study attempted to provide new idea for inhibiting browning enzymes of fruit and vegetables with plasma technology through deeper understanding of the interaction mechanism of plasma active species with enzymes.

12.
Int J Infect Dis ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31374346

RESUMO

BACKGROUND: Tuberculosis (TB) is a critical global public threat, and limited epidemiology studies have been performed to explore the efficacy of active TB screening. METHODS: Three sites located in eastern China were chosen in 2013, and three rounds of systematic screenings were performed in permanent residents aged older than 15 years. RESULTS: The TB incidence showed a downtrend after several rounds of active screening at the three sites, and a significant change was observed at site A in the overall population. In the target population at sites A and B, both the elderly and people with a history of TB had a remarkable decline through the first or second round of screening. The implementation of active case-finding identified more potential cases were 2.36 [1.47,3.81] (2013 vs. 2012) and 1.49 [1.1,2.03] (2013-2015 vs. 2010-2012), than the passive case-finding by the surveillance system at site A. CONCLUSIONS: Active case-finding of tuberculosis might be effective in high prevalence areas with a low economic level, particularly among the elderly and people with a history of TB. Additionally, new rapid diagnosis technology should be considered to decrease the prevalence among people with a history of TB. Ultimately, active screening identified more active TB cases than passive case-finding, particularly in high prevalence areas with underdeveloped economics.

13.
Fish Shellfish Immunol ; 93: 781-788, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31326588

RESUMO

Nile tilapia (Oreochromis niloticus) is a pivotal economic fish that has been plagued by Streptococcus infections. Tumor necrosis factor receptor-associated factor 5 (TRAF5) is a crucial adaptor molecule, which can trigger downstream signaling cascades involved in immune pathway. In this study, Nile tilapia TRAF5 coding sequence (named OnTRAF5) was obtained, which contained typical functional domains, such as RING, zinc finger, coiled-coil and MATH domain. Different from other TRAF molecules, OnTRAF5 had shown relatively low identify with its homolog, and it was clustered into other teleost TRAF5 proteins. qRT-PCR was used to analysis the expression level of OnTRAF5 in gill, skin, muscle, head kidney, heart, intestine, thymus, liver, spleen and brain, In healthy Nile tilapia, the expression level of OnTRAF5 in intestine, gill and spleen were significantly higher than other tissues. While under Streptococcus agalactiae infection, the expression level of OnTRAF5 was improved significantly in all detected organs. Additionally, over-expression WT OnTRAF5 activated NF-κB, deletion of RING or zinc finger caused the activity impaired. In conclusion, OnTRAF5 participate in anti-bacteria immune response and is crucial for the signaling transduction.

14.
Bioresour Technol ; 291: 121850, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31358426

RESUMO

Biological CO2 capture using microalgae is a promising new method for reducing CO2 emission of coal-fired flue gas. The strain of microalgae used in this process plays a vital role in determining the rate of CO2 fixation and characteristics of biomass production. High requirements are put forward for algae strains due to high CO2 concentration and diverse pollutants in flue gas. CO2 can directly diffuse into the cytoplasm of cells by extra- and intracellular CO2 osmotic pressure under high CO2 concentrations. The flue gas pollutants, such as SOx, NOx and fly ashes, have negative effects on the growth of microalgae. This work reviewed the state-of-the-art advances on microalgae strains used for CO2 fixation, focusing on the modification and improvement of strains that are used for coal-fired flue gas. Methods such as genetic engineering, random mutagenesis, and adaptive evolution have the potential to facilitate photosynthesis, improve growth rate and reduce CO2 emission.


Assuntos
Carvão Mineral , Microalgas/metabolismo , Biomassa , Dióxido de Carbono/metabolismo , Cinza de Carvão/química , Centrais Elétricas
15.
Cancer Sci ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31335996

RESUMO

Currently, using biopsy specimens for the early diagnosis of colorectal cancer (CRC) is not entirely reliable due to insufficient sampling amount and inaccurate sampling location. Thus, it is necessary to develop a signature that can accurately identify patients with CRC under these clinical scenarios. Based on the relative expression orderings of genes within individual samples, we developed a qualitative transcriptional signature to discriminate CRC tissues, including CRC adjacent normal tissues from non-CRC individuals. The signature was validated using multiple microarray and RNA sequencing data from different sources. In the training data, a signature consisting of 7 gene pairs was identified. It was well validated in both biopsy and surgical resection specimens from multiple datasets measured by different platforms. For biopsy specimens, 97.6% of 42 CRC tissues and 94.5% of 163 non-CRC (normal or inflammatory bowel disease) tissues were correctly classified. For surgically resected specimens, 99.5% of 854 CRC tissues and 96.3% of 81 CRC adjacent normal tissues were correctly identified as CRC. Notably, we additionally measured 33 CRC biopsy specimens by the Affymetrix platform and 13 CRC surgical resection specimens, with different proportions of tumor epithelial cells, ranging from 40% to 100%, by the RNA sequencing platform, and all these samples were correctly identified as CRC. The signature can be used for the early diagnosis of CRC, which is also suitable for minimum biopsy specimens and inaccurately sampled specimens, and thus has potential value for clinical application.

16.
Food Chem ; 300: 125143, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31326674

RESUMO

Tropomyosin (TM), a myofibrillar protein, is a major allergen in most crustaceans including king pawn (Litopenaeus vannamei). In this study, the structural modifications and allergenic response of TM in fresh king prawn as induced by cold argon plasma jet (CAPJ) were examined. The result showed that the level of α-helix structures declined as treatment time progressed, while the level of ß-sheets and random coils increased. The free sulfhydryl groups decreased as CAPJ treatment progressed due to the formation of disulphide bonds while surface hydrophobicity increased until equilibrium values. In addition, after 15 min of plasma exposure, the maximum reduction recorded for IgE and IgG binding capacities were 17.6% and 26.87% respectively as revealed by ELISA test. These findings correlated with the occurrence of protein unfolding and denaturation, evident by complementary structural analyses conducted. The study indicates that non-thermal plasma maybe a promising tool for developing hypoallergenic food products.

17.
J Am Chem Soc ; 141(31): 12192-12196, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31328527

RESUMO

Investigating the chemical nature of the adsorbed intermediate species on well-defined Cu single crystal substrates is crucial in understanding many electrocatalytic reactions. Herein, we systematically study the early stages of electrochemical oxidation of Cu(111) and polycrystalline Cu surfaces in different pH electrolytes using in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). On Cu(111), for the first time, we identified surface OH species which convert to chemisorbed "O" before forming Cu2O in alkaline (0.01 M KOH) and neutral (0.1 M Na2SO4) electrolytes; while at the Cu(poly) surface, we only detected the presence of surface hydroxide. Whereas, in a strongly acidic solution (0.1 M H2SO4), sulfate replaces the hydroxyl/oxy species. This results improves the understanding of the reaction mechanisms of various electrocatalytic reactions.

18.
Mol Cell Proteomics ; 18(8 suppl 1): S37-S51, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31285282

RESUMO

Tumors are heterogeneous tissues with different types of cells such as cancer cells, fibroblasts, and lymphocytes. Although the morphological features of tumors are critical for cancer diagnosis and prognosis, the underlying molecular events and genes for tumor morphology are far from being clear. With the advancement in computational pathology and accumulation of large amount of cancer samples with matched molecular and histopathology data, researchers can carry out integrative analysis to investigate this issue. In this study, we systematically examine the relationships between morphological features and various molecular data in breast cancers. Specifically, we identified 73 breast cancer patients from the TCGA and CPTAC projects matched whole slide images, RNA-seq, and proteomic data. By calculating 100 different morphological features and correlating them with the transcriptomic and proteomic data, we inferred four major biological processes associated with various interpretable morphological features. These processes include metabolism, cell cycle, immune response, and extracellular matrix development, which are all hallmarks of cancers and the associated morphological features are related to area, density, and shapes of epithelial cells, fibroblasts, and lymphocytes. In addition, protein specific biological processes were inferred solely from proteomic data, suggesting the importance of proteomic data in obtaining a holistic understanding of the molecular basis for tumor tissue morphology. Furthermore, survival analysis yielded specific morphological features related to patient prognosis, which have a strong association with important molecular events based on our analysis. Overall, our study demonstrated the power for integrating multiple types of biological data for cancer samples in generating new hypothesis as well as identifying potential biomarkers predicting patient outcome. Future work includes causal analysis to identify key regulators for cancer tissue development and validating the findings using more independent data sets.

19.
Hum Mutat ; 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31301154

RESUMO

Precision medicine and sequence-based clinical diagnostics seek to predict disease risk or to identify causative variants from sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. In the past, few CAGI challenges have addressed the impact of sequence variants on splicing. In CAGI5, two challenges (Vex-seq and MaPSY) involved prediction of the effect of variants, primarily single-nucleotide changes, on splicing. Although there are significant differences between these two challenges, both involved prediction of results from high-throughput exon inclusion assays. Here, we discuss the methods used to predict the impact of these variants on splicing, their performance, strengths, and weaknesses, and prospects for predicting the impact of sequence variation on splicing and disease phenotypes.

20.
ACS Appl Mater Interfaces ; 11(31): 27717-27726, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31298025

RESUMO

The development of cost-effective catalysts with both high activity and selectivity for carbon-oxygen bond activation is a major challenge and has important ramifications for making value-added chemicals from carbon dioxide (CO2). Herein, we present a one-step pyrolysis of metal organic frameworks that yields highly dispersed cobalt nanoparticles embedded in a carbon matrix which shows exceptional catalytic activity in the reverse water gas shift reaction. Incorporation of nitrogen into the carbon-based supports resulted in increased reaction activity and selectivity toward carbon monoxide (CO), likely because of the formation of a Mott-Schottky interface. At 300 °C and a high space velocity of 300 000 mL g-1 h-1, the catalyst exhibited a CO2 conversion rate of 122 µmolCO2 g-1 s-1, eight times higher than that of a reference Cu/ZnO/Al2O3 catalyst. Our experimental and computational results suggest that nitrogen-doping lowers the energy barrier for the formation of formate intermediates (CO2* + H* → COOH* + *), in addition to the redox mechanism (CO2* + * → CO* + O*). This enhancement is attributed to the efficient electron transfer at the cobalt-support interface, leading to higher hydrogenation activity and opening new avenues for the development of CO2 conversion technology.

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