Predicting protein-ligand binding residues with deep convolutional neural networks.

BACKGROUND: Ligand-binding proteins play key roles in many biological processes. Identification of protein-ligand binding residues is important in understanding the biological functions of proteins. Existing computational methods can be roughly categorized as sequence-based or 3D-structure-based methods. All these methods are based on traditional machine learning. In a series of binding residue prediction tasks, 3D-structure-based methods are widely superior to sequence-based methods. However, due to the great number of proteins with known amino acid sequences, sequence-based methods have considerable room for improvement with the development of deep learning. Therefore, prediction of protein-ligand binding residues with deep learning requires study. RESULTS: In this study, we propose a new sequence-based approach called DeepCSeqSite for ab initio protein-ligand binding residue prediction. DeepCSeqSite includes a standard edition and an enhanced edition. The classifier of DeepCSeqSite is based on a deep convolutional neural network. Several convolutional layers are stacked on top of each other to extract hierarchical features. The size of the effective context scope is expanded as the number of convolutional layers increases. The long-distance dependencies between residues can be captured by the large effective context scope, and stacking several layers enables the maximum length of dependencies to be precisely controlled. The extracted features are ultimately combined through one-by-one convolution kernels and softmax to predict whether the residues are binding residues. The state-of-the-art ligand-binding method COACH and some of its submethods are selected as baselines. The methods are tested on a set of 151 nonredundant proteins and three extended test sets. Experiments show that the improvement of the Matthews correlation coefficient (MCC) is no less than 0.05. In addition, a training data augmentation method that slightly improves the performance is discussed in this study. CONCLUSIONS: Without using any templates that include 3D-structure data, DeepCSeqSite significantlyoutperforms existing sequence-based and 3D-structure-based methods, including COACH. Augmentation of the training sets slightly improves the performance. The model, code and datasets are available at https://github.com/yfCuiFaith/DeepCSeqSite .

Effects of left atrium on intraventricular flow in numerical simulations.

With the aid of cardiac imaging techniques, recent numerical simulations of left ventricular flow can be patient-specific to better mimic physiological conditions. However, studies with a dynamic mitral valve (MV) remain extremely limited. Even so, the left atrium (LA) is usually simplified to be tubular regardless of its complex structure. Studies on the effect of this simplification are limited and observations are controversial. In this study, both tubular and generic atriums were incorporated in patient-specific simulations with and without the MV to qualitatively and quantitatively estimate the effects of the atrial model on downstream ventricular flow. The patient-specific model was generated based on cardiac magnetic resonance (CMR) images of a healthy volunteer, and the dynamic motion of the MV was defined by the contours acquired along long-axis images. Based on the simulations, the influence of the atrial vortices on ventricular flow was significant in the valveless models in terms of flow structure, kinetic energy (KE) and circulation. Although these effects were suppressed in the presence of the MV, the atrial vortices that survived the passage were not trivial, which was evidenced by reduced strength of circulation and undesired flow pattern in the apical region. The flow structure in the generic atrium also dominated the development of ventricular flow in the valveless model. After the MV was incorporated, its effects on the downstream ventricular flow were considerably reduced but not eliminated. Therefore, a proper modelling of atrial flow is necessary, especially for subjects with high ejection fraction (EF).

Numerical simulation of patient-specific left ventricular model with both mitral and aortic valves by FSI approach.

Intraventricular flow is important in understanding left ventricular function; however, relevant numerical simulations are limited, especially when heart valve function is taken into account. In this study, intraventricular flow in a patient-specific left ventricle has been modelled in two-dimension (2D) with both mitral and aortic valves integrated. The arbitrary Lagrangian-Eulerian (ALE) approach was employed to handle the large mesh deformation induced by the beating ventricular wall and moving leaflets. Ventricular wall deformation was predefined based on MRI data, while leaflet dynamics were predicted numerically by fluid-structure interaction (FSI). Comparisons of simulation results with in vitro and in vivo measurements reported in the literature demonstrated that numerical method in combination with MRI was able to predict qualitatively the patient-specific intraventricular flow. To the best of our knowledge, we are the first to simulate patient-specific ventricular flow taking into account both mitral and aortic valves.

[Tadalafil improves total testosterone, IIEF score and SEP in old and middle-aged males with late-onset hypogonadism].

OBJECTIVE: To observe the clinical effect of tadalafil combined with testosterone undecanoate on late-onset hypogonadism (LOH) in old and middle-aged males. METHODS: A total of 125 old and middle-aged (40 to 60 years) males with LOH were randomly assigned to a treatment group (n = 65) and a control group (n = 60) to be treated with tadalafil + testosterone undecanoate and testosterone undecanoate alone, respectively. We compared the levels of total testosterone (T), IIEF scores and the patients' sexual encounter profile (SEP) diaries before and 4 weeks after medication. RESULTS: The T level, IIEF score and SEP score were significantly improved in both groups after medication as compared with the baseline (P < 0.05), and even more so in the treatment than in the control group (P < 0.05). CONCLUSION: Tadalafil combined with testosterone undecanoate, superior to testosterone undecanoate alone, can improve the T level, IIEF score and SEP score in old and middle-aged males with LOH and increase their sexual satisfaction and self-confidence.

Validation of an axial flow blood pump: computational fluid dynamics results using particle image velocimetry.

A magnetically suspended axial flow blood pump is studied experimentally in this article. The pump casing enclosed a three-blade straightener, a two-blade impeller shrouded by a permanent magnet-embedded cylinder, and a three-blade diffuser. The internal flow fields were simulated earlier using computational fluid dynamics (CFD), and the pump characteristic curves were determined. The simulation results showed that the internal flow field was basically streamlined, except the diffuser region. Particle image velocimetry (PIV) measurement of the 1:1 pump model was conducted to validate the CFD result. In order to ensure the optical access, an acrylic prototype was fabricated with the impeller driven by a servomotor instead, as the magnet is opaque. In addition to the transparent model, the blood analog fluid with the refractive index close to that of acrylic was used to avoid refraction. According to the CFD results, the axial flow blood pump could generate adequate pressure head at the rotating speed of 9500rpm and flow rate of 5L/min, and the same flow condition was applied during the PIV measurement. Through the comparisons, it was found that the experimental results were close to those obtained by CFD and had thus validated the CFD model, which could complement the limitation of the measurement in assessing the more detailed flow fields of the axial flow pump.

[Effects of Seroxat on premature ejaculation: a clinical trial].

OBJECTIVES: To evaluate the effects of antidepressant Seroxat on premature ejaculation. METHODS: After having taken Seroxat 20 mg every noon for four weeks, the patients were asked to fill the investigating questionaire about the effects and side effects before and after the treatment. RESULTS: After the treatment, 43 cases in our study had increased their ejaculation latency time, enhanced the quality of their sexy lives and their wives', and had significant difference compared with pre-treatment(P < 0.001). They had good effects on improving premature ejaculation after taking Seroxat (11.26 +/- 5.79) days; and after having stopped taking seroxat for (20.94 +/- 8.04) days, the situation of premature ejaculation in 32 cases were as same as that of before. There were seven cases whose sexuality and oomph increased, and two cases whose sexuality were decreased. A few patients had constipation, dry in mouth, insomnia and itch in skin, after taking the drugs. CONCLUSIONS: Antidepressant Seroxat has rather good effects on premature ejaculation and should be used and studied further.