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1.
J Hazard Mater ; : 124475, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33187801

RESUMO

Both dust/air explosion and flammable gas/dust/air explosion are common forms of energy release. Experiments and simulation models with a multi-step chemical reaction mechanism were used to study the intensity parameters and mechanism of the CH4/air explosion, cornstarch/air explosion and CH4/cornstarch/air explosion in a closed container. Results showed that the peak overpressure, maximum flame temperature, and average flame propagation speed of the stoichiometric CH4/air explosion reach 0.84 MPa, 2614 K and 3.5 m/s, respectively. The optimal concentration of cornstarch explosion is 750 g/m3, and its peak overpressure, maximum flame temperature and average flame propagation speed are 0.76 MPa, 2098 K and 1.77 m/s, respectively. For a three-components system, adding methane can significantly increase the explosive intensity and combustion performance of cornstarch. The explosive intensity parameters (peak overpressure, maximum flame temperature, average flame propagation speed) of a certain concentration of cornstarch first increase and then decrease with the increase of methane concentration. The maximum explosion intensity parameters of a three-components system with a certain concentration of lean-methane/air are higher than that of single-phase, but always lower than that of the stoichiometric methane/air. Moreover, the mutual coordination of dust and combustible gas in energy release and the mutual competition mechanism in oxygen consumption are described.

2.
Plant J ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160290

RESUMO

Plants have evolved numerous receptor-like kinases (RLKs) that modulate environmental stress responses. However, little is known regarding soybean RLKs. We have previously identified that Glycine soja Ca2+ /CAM-binding RLK (GsCBRLK) is involved in salt tolerance. Hence, we report that soluble NSF attachment protein receptor proteins BET1s mediate subcellular localization of calmodulin-binding receptor-like cytoplasmic kinases CRCK1s to modulate salt stress responses. Direct interaction between GsCBRLK and GsBET11a was initially identified via yeast two hybrid and bimolecular fluorescence complementation assays. Further analysis demonstrated conserved interaction between BET1s and CRCK1s. GsCBRLK interacted with all BET1 proteins in wild soybean and Arabidopsis, and GsBET11a strongly associated with GsCRCK1a-1d, but slightly with AtCRCK1. In addition, GsBET11a interacted with GsCBRLK via its C-terminal transmembrane domain (TMD), where the entire TMD, not the sequence, was critical for the interaction. Moreover, the N-terminal variable domain (VD) of GsCBRLK was responsible for interacting with GsBET11a, and the intensity of interaction between GsCBRLK/AtCRCK1 and GsBET11a was dependent on VD. Furthermore, GsBET11a was able to mediate the GsCBRLK subcellular localization via direct interaction with VD. Additionally, knockout of AtBET11 or AtBET12 individually did not alter GsCBRLK localization, while GsBET11a expression caused partial internalization of GsCBRLK from the plasmam membrane (PM). We further suggest the necessity of GsCBRLK VD for its PM localization via N-terminal truncation assays. Finally, GsBET11a was shown to confer enhanced salt stress tolerance when overexpressed in Arabidopsis and soybean. These results revealed the conserved and direct interaction between BET1s and CRCK1s, and suggested their involvement in salt stress responses.

3.
4.
Mil Med Res ; 7(1): 53, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33148321

RESUMO

BACKGROUND: Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS. METHODS: A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6-8 h after the ascent. RESULTS: Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P < 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR) =6.32, P < 0.001), SpO2 change upon exercise at low altitude (OR = 0.63, P = 0.002) and systolic BP change after the ascent (OR = 0.96, P = 0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P = 0.001) and AMS score (P < 0.001) in men but not in women. CONCLUSIONS: Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR1900025728 . Registered 6 September 2019.

5.
J Cell Mol Med ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33210454

RESUMO

Dysregulation of circRNAs is reported to exert crucial roles in cancers, including hepatocellular carcinoma (HCC). So far, the function of circRNAs in HCC development remains poorly known. Currently, our data showed that circ_0008305 was highly elevated in HCC cell lines and 30 paired tissue samples of HCC. As evidenced, suppression of circ_0008305 repressed HCC cell growth significantly. Meanwhile, up-regulation of circ_0008305 significantly reduced HCC cell growth. Mechanistically, we displayed that circ_0008305 could bind with miR-186 by using bioinformatics analysis. miR-186 has been reported to be a crucial tumour oncogene in many cancers. In addition, we proved miR-186 was greatly decreased in HCC. The direct correlation between miR-186 and circ_0008305 was confirmed in our work. In addition, up-regulation of miR-186 obviously restrained HCC progression. Increased expression of transmembrane p24 trafficking protein 2 (TMED2) is significantly related to the unfavourable outcomes in cancer patients. At our present work, we proved that TMED2 could act as a direct target of miR-186. Mechanistically, we demonstrated that circ_0008305 up-regulated TMED2 expression by sponging miR-186, which resulted in significantly induced HCC progression in vitro and in vivo. These revealed the significant role of circ_0008305 in HCC progression, which might indicate a new perspective on circRNAs in HCC development.

6.
Neurology ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046607

RESUMO

OBJECTIVE: To determine whether probiotics are effective for constipation, a common and often difficult-to-treat problem, in Parkinson's disease (PD). METHODS: In this double-blind, randomized placebo-controlled single-centre trial, 280 PD patients were screened and 72 eligible patients were block-randomized (1:1) to receive either multi-strain probiotics capsules (n=34), or identical-appearing placebo (n=38), for four weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last two weeks of intervention, compared with the two-week pre-intervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome. RESULTS: SBM increased by 1.0±1.2/week after treatment with probiotics, and decreased by 0.3±1.0/week in the placebo group (mean difference 1.3, 95%CI: 0.8-1.8, P<0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency (P=0.009) and quality of life related to constipation (P=0.001). In the treatment group, 65.6% reported satisfaction with the intervention, vs. only 21.6% in the placebo group (P<0.001). One patient (2.9%) in the treatment group withdrew due to a non-serious adverse event. Fecal calprotectin did not change significantly during the study. CONCLUSIONS: Multi-strain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for people with PD, multi-strain probiotics significantly increased the average number of spontaneous bowel movements per week. CLINICALTRIALSGOV IDENTIFIER: NCT03377322.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33006442

RESUMO

Hypertension is proved to be associated with severity and mortality in coronavirus disease 2019 (COVID-19). However, little is known about the effects of pre-admission and/or in-hospital antihypertension treatments on clinical outcomes. Thus, this study aimed to investigate the association between in-hospital blood pressure (BP) control and COVID-19-related outcomes and to compare the effects of different antihypertension treatments. This study included 2864 COVID-19 patients and 1628 were hypertensive. Patients were grouped according to their BP during hospitalization and records of medication application. Patients with higher BP showed worse cardiac and renal functions and clinical outcomes. After adjustment, subjects with pre-admission usage of renin-angiotensin-aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14-0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission. Particularly, hypertension patients receiving RAAS inhibitor treatment either before (HR = 0.35, 95%CI 0.13-0.97, P = .043) or after (HR = 0.18, 95%CI 0.04-0.86, P = .031) admission showed a significantly lower risk of adverse clinical outcomes than those receiving application of other antihypertensive medicines. Furthermore, consecutive application of RAAS inhibitors in COVID-19 patients with hypertension showed better clinical outcomes (HR = 0.10, 95%CI 0.01-0.83, P = .033) than non-RAAS inhibitors users. We revealed that COVID-19 patients with poor BP control during hospitalization had worse clinical outcomes. Compared with other antihypertension medicines, RAAS inhibitors were beneficial for improving clinical outcomes in COVID-19 patients with hypertension. Our findings provide direct evidence to support the administration of RAAS inhibitors to COVID-19 patients with hypertension before and after admission.

9.
Medicine (Baltimore) ; 99(40): e22502, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019448

RESUMO

BACKGROUND: Insomnia is a common disease characterized by difficulty falling and/or staying asleep, and accompanied by irritability or fatigue during wakefulness. It is widely reported that insomnia is one of the most extensive mental disorders which the incidence rate is estimated to be about 10%. Insomnia can have serious influences on patients health and quality of life. Electro acupuncture (EA) is reported to be efficacious and widely used for the treatment of insomnia in China. This overview aims to summarize the available evidence from current systematic reviews for the efficacy of electroacupuncture therapy for insomnia. METHODS: We will make a comprehensive retrieval in 7 databases as following:The time is limited from the construction of the library to August 2020. We will use the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool to evaluate methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) will be used in the report checklist to assess the quality of reports in the study. The Grading of the Classification of Recommendations, Evaluation, Development and Evaluation (GRADE) will be used to evaluate the included SRs and meta-analysis. Our reviewers will conduct systematic reviews, qualification evaluation, data extraction, methodological quality and evidence quality screening in pairs. The outcomes of interest include: The Pittsburgh Sleep Quality Index (PSQI), The Insomnia Severity Index (ISI), Athens Insomnia Scale, Sleep parameters measured by either subjective or objective approaches, such as actigraphy, polysomnogram, and electroencephalogram. Or any other scale used to assess the level of illness. The evidence will be synthesized where appropriate based on patient subgroups and outcomes. RESULTS: The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: INPLASY202080087. CONCLUSION: This overview will provide comprehensive evidence of EA for patients with insomnia.


Assuntos
Eletroacupuntura/métodos , Distúrbios do Início e da Manutenção do Sono/terapia , Eletroacupuntura/efeitos adversos , Humanos , Metanálise como Assunto , Qualidade de Vida , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
10.
Artigo em Inglês | MEDLINE | ID: mdl-33073436

RESUMO

OBJECTIVE: To improve the accuracy of clinical diagnosis by analyzing different contrast-enhanced ultrasound (CEUS) imagines of specific subtypes of uterine leiomyomas. METHODS: A total of 147 female patients received preoperative CEUS examination. The scanning plane of the biggest tumors for CEUS was found by common B-mode ultrasonographic scanning on pelvic cavity, then 1.5 mL SonoVue were injected into the median cubital vein. According to the CEUS images, the lesion enhanced time, enhanced level and enhanced morphology were recorded. The time-intensity curve was acquired and analyzed, meanwhile, the relevant parameters were calculated, including rise time (RT), peak intensity (PI), time to peak (TTP) and mean transit time (MTT). RESULTS: In cellular uterine leiomyoma group, the percentage of high enhancement, early enhancement was higher, equal enhancement and synchronic enhancement were lower than those in the common uterine leiomyomas group. In hysteromyoma with hyaline degeneration group, the percentage of high enhancement, early enhancement was lower, while low enhancement and delayed enhancement were higher than those in the common uterine leiomyomas group. The ratio of PI in cellular uterine leiomyoma group was the highest, but the ratios of RT, TTP and MTT were the lowest of the three benign groups. The ratio of PI in hysteromyoma with hyaline degeneration group was the lowest, while the ratios of RT and TTP was the highest among the three benign groups. CONCLUSION: Different pathological types of uterine leiomyomas have their own signal performance on CEUS. CEUS can be used to infer their pathological types and help differential diagnosis.

11.
Chemistry ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073875

RESUMO

Four silver thiolate clusters, [H3O]·[(Ag3S3)(BF4)@Ag27( t BuS)18(hfac)6H2O]·H2O (1; hfac = hexafluoroacetylacetone), [(Ag3S3)(CF3CO2)@Ag30( t BuS)16(CF3CO2)9(CH3CN)4]·CF3CO2·4CH3CN (2), [(Ag3S3)(MoO4)@Ag30( t BuS)16(CF3CO2)9(CH3CN)4]·2CH3CN (3), and [(Ag3S3)(CrO4)@Ag30( t BuS)16(CF3CO2)9(CH3CN)4]·4CH3CN (4), were isolated, which have the similar nest-like structure assembled by a [Ag3S3]3- template together with one of BF4-, CF3CO2-, MoO42- and CrO42- anions. Interestingly, the solid-state emissions of 2-4 are dependent on the templating anions and are tunable from green to orange and then to red by changing templates from CF3CO2- to MoO42- and to CrO42-, which maybe correlate to the charge transfer between these templates to metal atoms. This work helps to understand the templating role of hetero anions and the relationship between structure and properties.

12.
Acta Ophthalmol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33084228

RESUMO

PURPOSE: To evaluate the visual quality of myopic patients after non-toric versus toric implantable collamer lens (ICL and TICL, respectively) V4c, and to investigate the potential risk factors of postoperative night vision disturbances. METHODS: This prospective cohort study included 42 eyes of 21 patients treated with ICL and 46 eyes of 23 patients treated with TICL. Refractive parameters and ocular aberrations were examined before and 6 months after surgery. Subjective quality of vision was scored by a validated questionnaire. RESULTS: The efficacy index at 6 months was 1.14 ± 0.20 for ICL and 1.17 ± 0.16 for TICL; the safety index was 1.20 ± 0.17 for ICL and 1.20 ± 0.19 for TICL. The root mean square of total higher-order aberrations (HOAs) and trefoil was significantly increased, and no statistical differences between groups were detected in HOA changes. Many patients reported haloes (85.7% for ICL and 100% for TICL) and glare (76.2% for ICL and 65.2% for TICL), but most (94.4% for ICL and 95.5% for TICL) were satisfied or very satisfied with visual outcomes. Implantable collamer lens (ICL) toricity was the risk factor for frequency (OR = 2.81, p = 0.01), severity (OR = 3.85, p = 0.003) and bothering effect (OR = 2.89, p = 0.01) of haloes. CONCLUSIONS: Implantable collamer lens and TICL provided comparable efficacy, safety and predictability, induced acceptable level of HOAs and achieved high satisfaction in correcting myopia and myopic astigmatism. Although not severe, haloes and glare have a non-negligible prevalence and ICL toricity is a potential risk factor of haloes.

13.
Arch Biochem Biophys ; 695: 108642, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33098868

RESUMO

BACKGROUND: Micro-ribonucleic acids (miRNAs) have been implicated in the regulation of non-alcoholic fatty liver disease (NAFLD), a leading cause of chronic liver disease worldwide. The mechanisms by which miR-34a influences NAFLD through the Sirtuin 1 (SIRT1)-related pathway were investigated herein. METHODS: Male C57BL/6 mice were injected with a miR-34a lentivirus vector inhibitor or control. HepG2 cells were transfected with a miR-34a mimic, inhibitor, SIRT1 small interfering RNA (siRNA), SIRT1 plasmid, and a negative oligonucleotide control to evaluate their role in oleic acid (OA) and excess iron-induced NAFLD. The accumulation of lipids in the mice liver and HepG2 cells was analyzed by triglyceride (TG) detection and hematoxylin and eosin (HE) staining. Additionally, the indexes of oxidative stress related to lipid metabolism were evaluated by western blotting and real-time PCR (qRT-PCR). The levels of intracellular reactive oxygen species (ROS) and mitochondrial membrane potentials were measured by flow cytometry and laser confocal microscopy, respectively. Finally, the dual luciferase reporter assay was conducted to further confirm whether SIRT1 was a direct target of miR-34a. RESULTS: Overexpression of miR-34a resulted in increased triglyceride accumulation as well as in decreased mitochondrial membrane potential and SIRT1 levels. Silencing of miR-34a increased SIRT1 expression and alleviated triglyceride accumulation in the presence of OA and iron. Additionally, miR-34a directly inhibited SIRT1 by binding to the 3'-untranslated region, as determined via the luciferase reporter assay. CONCLUSIONS: Our results support the existence of a link between the liver cell mitochondria and miR-34a/SIRT1 signaling. Potential endogenous modulators of NAFLD pathogenesis may ultimately provide new tools for therapeutic intervention.

14.
Nat Biotechnol ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106685

RESUMO

Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. PORE-cupine also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants. We show that shared sequences in different transcript isoforms of the same gene can fold into different structures, highlighting the importance of long-read sequencing for obtaining phase information. We also demonstrate that structural differences between transcript isoforms of the same gene lead to differences in translation efficiency. By revealing isoform-specific RNA structure, PORE-cupine will deepen understanding of the role of structures in controlling gene regulation.

16.
Med Sci Monit ; 26: e925051, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32908118

RESUMO

BACKGROUND This study aimed to investigate the value of CA125 dynamic change in PFS prediction for patients with epithelial ovarian carcinoma (EOC). MATERIAL AND METHODS Data analysis was performed using SPSS 24.0 statistical software with progression-free survival (PFS) as an outcome measure. Kaplan-Meier method was used to analyze the relationship between PFS and preoperative and postoperative NLR, PLR and CA125 levels, CA125 half-life, CA125-negative time, age, FIGO stage, histopathology, differentiation, vessel carcinoma embolus, and ascites. The survival curves were compared by the log-rank test. Based on the results of single-factor analysis, the Cox model was used for multifactor analysis to analyze independent risk factors affecting the PFS of epithelial ovarian carcinoma. RESULTS A total of 117 patients with EOC were selected from January 2012 to January 2019 to carry out a retrospective study. Univariate analyses showed that PFS of the patients with EOC was associated with differentiation, vessel carcinoma embolus, FIGO stage, CA125 half-life, CA12- negative time, and preoperative NLR (P<0.05). Multivariate analysis by the Cox model showed that vessel carcinoma embolus, CA125 half-life, differentiation, and preoperative NLR are the independent risk factors for PFS in patients with EOC. CONCLUSIONS The serum CA125 dynamic as reflected by CA125 half-life is the most important independent prognostic factor in patients with EOC. The simplicity of CA125 monitoring and its correlation with EOC patient survival can identify patients with poor prognosis through monitoring CA125 half-life, which can provide a reference value for use in clinical practice.

17.
Opt Express ; 28(19): 28563-28572, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32988123

RESUMO

Photonic microwave generation of high-power pulsed signals in the X-, Ku- and K-band using charge-compensated MUTC photodiodes is demonstrated. The impulse photoresponse without modulation showed a maximum peak voltage of 38.3 V and full-width at half-maximum of 30 ps. High power pulsed microwave signals at 10, 17 and 22 GHz with peak power up to 44.2 dBm (26.3 W), 41.6 dBm (14.5 W) and 40.6 dBm (11.5 W) were achieved, respectively.

18.
Nanoscale ; 12(37): 19375-19382, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32945308

RESUMO

Dual-/multi-heteroatom-doped carbon nanomaterials have been demonstrated to be effective bi-/multi-functional catalysts for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), the critical reactions in fuel cells and metal-air batteries, respectively. However, trial-and-error routes are usually used to search for better catalysts from multi-doped complex material systems, and establishing design principles or intrinsic descriptors would accelerate the discovery of new efficient catalysts. Here, a descriptor based on pz-orbitals of active sites is proposed to describe the catalytic performance of dual-/tri-element-doped graphene catalysts for the ORR and the OER. In addition to multiple doping, the established descriptor is universal in nature and can also predict the contributions of defects and edges or their combinations. The prediction capacity of the descriptor is further enhanced by introducing a correction factor based on crystal orbital Hamilton population (COHP) analysis, which reveals the differences between the adsorption mechanism of edged C and graphitic C on graphene. The predictions are consistent with DFT calculations and experimental results. This work provides a powerful tool for rapidly screening multi-doped complex material systems for the desired ORR and OER bifunctional catalysts.

19.
J Chem Inf Model ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32945673

RESUMO

Although massive data is quickly accumulating on protein sequence and structure, there is a small and limited number of protein architectural types (or structural folds). This study is addressing the following question: how well could one reveal underlying sequence-structure relationships and design protein sequences for an arbitrary, potentially novel, structural fold? In response to the question, we have developed novel deep generative models, namely, semisupervised gcWGAN (guided, conditional, Wasserstein Generative Adversarial Networks). To overcome training difficulties and improve design qualities, we build our models on conditional Wasserstein GAN (WGAN) that uses Wasserstein distance in the loss function. Our major contributions include (1) constructing a low-dimensional and generalizable representation of the fold space for the conditional input, (2) developing an ultrafast sequence-to-fold predictor (or oracle) and incorporating its feedback into WGAN as a loss to guide model training, and (3) exploiting sequence data with and without paired structures to enable a semisupervised training strategy. Assessed by the oracle over 100 novel folds not in the training set, gcWGAN generates more successful designs and covers 3.5 times more target folds compared to a competing data-driven method (cVAE). Assessed by sequence- and structure-based predictors, gcWGAN designs are physically and biologically sound. Assessed by a structure predictor over representative novel folds, including one not even part of basis folds, gcWGAN designs have comparable or better fold accuracy yet much more sequence diversity and novelty than cVAE. The ultrafast data-driven model is further shown to boost the success of a principle-driven de novo method (RosettaDesign), through generating design seeds and tailoring design space. In conclusion, gcWGAN explores uncharted sequence space to design proteins by learning generalizable principles from current sequence-structure data. Data, source codes, and trained models are available at https://github.com/Shen-Lab/gcWGAN.

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