ZetaDesign: an end-to-end deep learning method for protein sequence design and side-chain packing.

Computational protein design has been demonstrated to be the most powerful tool in the last few years among protein designing and repacking tasks. In practice, these two tasks are strongly related but often treated separately. Besides, state-of-the-art deep-learning-based methods cannot provide interpretability from an energy perspective, affecting the accuracy of the design. Here we propose a new systematic approach, including both a posterior probability and a joint probability parts, to solve the two essential questions once for all. This approach takes the physicochemical property of amino acids into consideration and uses the joint probability model to ensure the convergence between structure and amino acid type. Our results demonstrated that this method could generate feasible, high-confidence sequences with low-energy side conformations. The designed sequences can fold into target structures with high confidence and maintain relatively stable biochemical properties. The side chain conformation has a significantly lower energy landscape without delegating to a rotamer library or performing the expensive conformational searches. Overall, we propose an end-to-end method that combines the advantages of both deep learning and energy-based methods. The design results of this model demonstrate high efficiency, and precision, as well as a low energy state and good interpretability.

Inhibition of alternative oxidase disrupts the development and oviposition of Biomphalaria glabrata snails.

BACKGROUND: Biomphalaria glabrata is one of the main intermediate hosts of Schistosoma mansoni, the most widespread species of Schistosoma. Our previous studies proved that alternative oxidase (AOX), the terminal oxidase in the mitochondrial respiratory chain, widely exists in several species of intermediate host snails of Schistosoma. Meanwhile, inhibition of AOX activity in Oncomelania hupensis snails could dramatically enhance the molluscicidal effect of niclosamide. As a hermaphroditic aquatic mollusc, the high fecundity and population density of B. glabrata increase the difficulty of snail control, which is one of the critical strategies for schistosomiasis elimination. The present study aimed to investigate the possible role of AOX in the development and fecundity of B. glabrata snail, which could be manipulated more manageable than other species of intermediate host snails of Schistosoma. METHODS: The dynamic expression of the AOX gene was investigated in different developmental stages and tissues of B. glabrata, with morphological change and oviposition behaviour observed from juvenile to adult snails. Furtherly, dsRNA-mediated knockdown of BgAOX mRNA and the AOX protein activity inhibiting was performed to investigate the effect of AOX on the development and oviposition of snails. RESULTS: The BgAOX gene expression profile is highly related to the development from late juveniles to adults, especially to the reproductive system of snails, with a positive correlation of 0.975 between egg production and BgAOX relative expression in ovotestis of snails. The inhibition of BgAOX at the transcriptional level and AOX activity could efficiently inhibit snail growth. However, the interference at the BgAOX protein activity level led to more severe tissue damage and more significant inhibition of oviposition than at the transcriptional level. This inhibition of growth and oviposition decreased gradually with the increase in the snail size. CONCLUSIONS: The inhibition of AOX could efficiently disrupt the development and oviposition of B. glabrata snails, and the intervention targeting AOX at the juvenile stage is more effective for snails. This investigation explored the role of AOX in the growth and development of snails. It would benefit snail control in the future by providing a potential target while using molluscicides more efficiently.

The identification of alternative oxidase in intermediate host snails of Schistosoma and its potential role in protecting Oncomelania hupensis against niclosamide-induced stress.

BACKGROUND: Snail intermediate hosts are mandatory for the transmission of schistosomiasis, which has to date infected more than 200 million people worldwide. Our previous studies showed that niclosamide treatment caused the inhibition of aerobic respiration and oxidative phosphorylation, and the disruption of energy supply, in one of the intermediate hosts of schistosomiasis, Oncomelania hupensis, which eventually led to the death of the snails. Meanwhile, the terminal oxidase in the mitochondrial respiratory chain, alternative oxidase (AOX), was significantly up-regulated, which was thought to counterbalance the oxidative stress and maintain metabolic homeostasis in the snails. The aims of the present study are to identify the AOXs in several species of snails and investigate the potential activation of O. hupensis AOX (OhAOX) under niclosamide-induced stress, leading to enhanced survival of the snail when exposed to this molluscicide. METHODS: The complete complementary DNA was amplified from the AOXs of O. hupensis and three species of Biomphalaria; the sequence characteristics were analysed and the phylogenetics investigated. The dynamic expression and localisation of the AOX gene and protein in O. hupensis under niclosamide-induced stress were examined. In addition, the expression pattern of genes in the mitochondrial respiratory complex was determined and the production of reactive oxygen species (ROS) calculated. Finally, the molluscicidal effect of niclosamide was compared between snails with and without inhibition of AOX activity. RESULTS: AOXs containing the invertebrate AOX-specific motif NP-[YF]-XPG-[KQE] were identified from four species of snail, which phylogenetically clustered together into Gastropoda AOXs and further into Mollusca AOXs. After niclosamide treatment, the levels of OhAOX messenger RNA (mRNA) and OhAOX protein in the whole snail were 14.8 and 2.6 times those in untreated snails, respectively, but varied widely among tissues. Meanwhile, the level of cytochrome C reductase mRNA showed a significant decrease in the whole snail, and ROS production showed a significant decrease in the liver plus gonad (liver-gonad) of the snails. At 24 h post-treatment, the mortality of snails treated with 0.06-0.1 mg/L niclosamide and AOX inhibitor was 56.31-76.12% higher than that of snails treated with 0.1 mg/L niclosamide alone. CONCLUSIONS: AOX was found in all the snail intermediate hosts of Schistosoma examined here. AOX was significantly activated in O. hupensis under niclosamide-induced stress, which led to a reduction in oxidative stress in the snail. The inhibition of AOX activity in snails can dramatically enhance the molluscicidal effect of niclosamide. A potential target for the development of an environmentally safe snail control method, which acts by inhibiting the activity of AOX, was identified in this study.

Design and Evaluation of Personalized Percutaneous Coronary Intervention Surgery Simulation System.

In recent years, medical simulators have been widely applied to a broad range of surgery training tasks. However, most of the existing surgery simulators can only provide limited immersive environments with a few pre-processed organ models, while ignoring the instant modeling of various personalized clinical cases, which brings substantive differences between training experiences and real surgery situations. To this end, we present a virtual reality (VR) based surgery simulation system for personalized percutaneous coronary intervention (PCI). The simulation system can directly take patient-specific clinical data as input and generate virtual 3D intervention scenarios. Specially, we introduce a fiber-based patient-specific cardiac dynamic model to simulate the nonlinear deformation among the multiple layers of the cardiac structure, which can well respect and correlate the atriums, ventricles and vessels, and thus gives rise to more effective visualization and interaction. Meanwhile, we design a tracking and haptic feedback hardware, which can enable users to manipulate physical intervention instruments and interact with virtual scenarios. We conduct quantitative analysis on deformation precision and modeling efficiency, and evaluate the simulation system based on the user studies from 16 cardiologists and 20 intervention trainees, comparing it to traditional desktop intervention simulators. The results confirm that our simulation system can provide a better user experience, and is a suitable platform for PCI surgery training and rehearsal.

Morphology and activities of cell populations of haemocytes in Oncomelania hupensis following Schistosoma japonicum infection.

Oncomelania hupensis is the only obligatory intermediate host of Schistosoma japonicum, the pathogen of zoonosis schistosomiasis. Haemocytes play a critical role in the cellular immune defence of O. hupensis against S. japonicum challenge. Here, the morphology and classification of haemocytes of O. hupensis were investigated by Giemsa staining and light microscopy, combining with the scanning and transmission electron microscopy and flow cytometry. Granulocytes and hyalinocytes were confirmed as two main types of haemocytes, account for ~ 10% and ~ 90% of all haemocytes, with size varying in 4.3-10.9 µm and 0.4-30.8 µm, respectively. Subpopulations can be identified further by granule feature, shape, size, and surface and inner structure of cells. The heterogeneity in morphology implied varied developmental process and function of haemocyte subpopulations. After the S. japonicum challenge, haemocytes of O. hupensis respond to S. japonicum invasion immediately. The dynamic change of haemocyte subpopulations indicates that the small hyalinocyte could differentiate into a larger one or granulocyte after S. japonicum challenge, and the granulocytes and larger hyalinocytes play leading roles in early defence reaction, but in different ways. Phagocytosis and apoptosis of haemocytes in O. hupensis were proved to be related to immune defence against S. japonicum, with the combined effect of granulocytes and larger hyalinocytes. However, the main pathway of each subpopulation to take effect in different periods need further investigation.

[The Role of Virtual Reality Technology in Medical Education in the Context of Emerging Medical Discipline].

According to Healthy China, a national strategy of the Government of China, new requirements were put forward for high-quality medical education, high-level surgical research, and precise clinical diagnosis and treatment. In the context of Emerging Medical Discipline, a strategic blueprint of medical education in China, this paper reviews the concept and core value of virtual reality (VR) and its significant role in the medical industry. On that basis, we explore the role of VR technology in medical training against the background of Emerging Medicine Discipline. Furthermore, typical cases are presented to help analyze and illustrate in detail the important role of VR technology in the teaching and training of stomatological and clinical procedures, skills assessment, online self-directed training, and clinical thinking skills training. We herein summarize useful information from past experience so as to help build innovative models of medical education in the context of Emerging Medical Discipline.

The genetic variation of different developmental stages of Schistosoma japonicum: do the distribution in snails and pairing preference benefit the transmission?

BACKGROUND: Schistosoma japonicum is a waterborne parasite that causes schistosomiasis in humans and in more than 40 animal species. Schistosoma japonicum shows distinct genetic differentiation among geographical populations and multiple hosts, but the genetic diversity of different developmental stages of S. japonicum from is less studied. Such studies could elucidate ecological mechanisms in disease transmission by analysing feedbacks in individual physiology and population state. METHODS: After infection using cercariae from a pool of snails shedding together (Method I) and infection using mixed equal numbers of cercariae from individually shed snails (Method II), different developmental stages of S. japonicum were genotyped with microsatellite loci, including 346 cercariae, 701 adult worms and 393 miracidia. Genetic diversity and molecular variation were calculated at different population levels. Kinships (I') among cercariae at intra-snail and inter-snail levels were evaluated. Genetic distance (Dsw) was compared between paired and unpaired worms, and partner changing was investigated through paternity identification for miracidia. RESULTS: The cercaria clones in individual snails varied from 1 to 8 and the kinship of cercariae within individual snails was significant higher (P < 0.001) than that among different snails after deleting near-identical multi-locus genotypes (niMLGs). The allelic diversity of worms in Method I was lower (P < 0.001) than that in Method II, and allele frequency among mice in Method I was also less consistent. The parents of some miracidia were worms that were not paired when collected. The Dsw between each female of paired and unpaired males was much larger (P < 0.001) than that between the female and male in each pair. CONCLUSIONS: Most of the infected snails contained multiple miracidia clones. The aggregation of genetically similar S. japonicum miracidia in individual snails and the unbalanced distribution of miracidia among snails suggests a non-uniform genetic distribution of cercariae among snails in the field. This further influenced the genetic structure of adult worms from infections with different cercariae sampling methods. Schistosoma japonicum in mice can change paired partner, preferring to mate with genetically similar worms. These characteristics provide implications for understanding the balance in genetic diversity of S. japonicum related to the transmission of schistosomiasis.

Convolutional demosaicing network for joint chromatic and polarimetric imagery.

Due to the latest progress in image sensor manufacturing technology, the emergence of a sensor equipped with an RGGB Bayer filter and a directional polarizing filter has brought significant advantages to computer vision tasks where RGB and polarization information is required. In this regard, joint chromatic and polarimetric image demosaicing is indispensable. However, as a new type of array pattern, there is no dedicated method for this challenging task. In this Letter, we collect, to the best of our knowledge, the first chromatic-polarization dataset and propose a chromatic-polarization demosaicing network (CPDNet) to address this joint chromatic and polarimetric image demosaicing issue. The proposed CPDNet is composed of the residual block and the multi-task structure with the costumed loss function. The experimental results show that our proposed methods are capable of faithfully recovering full 12-channel chromatic and polarimetric information for each pixel from a single mosaic image in terms of quantitative measures and visual quality.

Context-Interactive CNN for Person Re-Identification.

Despite growing progresses in recent years, cross-scenario person re-identification remains challenging, mainly due to the pedestrians commonly surrounded by highly-complex environment contexts. In reality, the human perception mechanism could adaptively find proper contextualized spatial-temporal clues towards pedestrian recognition. However, conventional methods fall short in adaptively leveraging the long-term spatial-temporal information due to ever-increasing computational cost. Moreover, CNN-based deep learning methods are hard to conduct optimization due to the non-differentiable property of the built-in context search operation. To ameliorate, this paper proposes a novel Context-Interactive CNN (CI-CNN) to dynamically find both spatial and temporal contexts by embedding multi-task Reinforcement Learning (MTRL). The CI-CNN streamlines the multi-task reinforcement learning by using an actor-critic agent to capture the temporal-spatial context simultaneously, which comprises a context-policy network and a context-critic network. The former network learns policies to determine the optimal spatial context region and temporal sequence range. Based on the inferred temporal-spatial cues, the latter one focuses on the identification task and provides feedback for the policy network. Thus, CI-CNN can simultaneously zoom in/out the perception field in spatial and temporal domain for the context interaction with the environment. By fostering the collaborative interaction between the person and context, our method could achieve outstanding performance on various public benchmarks, which confirms the rationality of our hypothesis, and verifies the effectiveness of our CI-CNN framework.

ARL3 subcellular localization and its suspected role in autophagy.

ADP-ribosylation factor-like3 (ARL3) is a member of the ADP-ribosylation factor family of GTP-binding proteins that plays important role in regulating Ciliary trafficking. It ubiquitously expressed in normal tissues and tumor cell lines. However, the location and function of ARL3 in organelles are rarely known. In this study, we explored ARL3 subcellular localization in an all-round way in HEK293T, Neuro-2A and U251 cells by density gradient centrifugation and immunofluorescence. The results showed that ARL3 is expressed in most of organelles, and an iodixonal step gradient was further confirmed that ARL3 is mainly localized to the mitochondria, endosomes, lysosomes, and proteasome. By molecular functional analysis, we observed that ARL3 promotes the aggregation of GFP-LC3, up-regulation of LC3-II/LC3-I and down-regulation of SQSMT1/BECN1, and knocking down of ARL3 inbibits autophagy, which suggested that ARL3 is necessary for autophagy. this study presents a comprehensive evaluation of the subcellular localization for ARL3 and provides important on understanding the functions of ARL3.

Immunization with recombinant schistosome adenylate kinase 1 partially protects mice against Schistosoma japonicum infection.

Highly effective and safe prophylactic vaccines are urgently needed to sustainably control schistosomiasis, one of the most serious endemic zoonoses in China. In this study, we characterized adenylate kinase 1 from Schistosoma japonicum (SjAK1), a phosphotransferase that regulates cellular energy and metabolism, and evaluated its potential as a recombinant vaccine. Based on real-time quantitative PCR, western blot, and immunolocalization, SjAK1 is active throughout the life of the worm, although its expression is higher in 21-day-old schistosomula, adult worms, and eggs deposited in the host liver. Further, the enzyme accumulates in the eggshell, intestinal epithelium, integument of adult worms and in the vitellaria tissue in female worms. A 594-bp full-length complementary DNA (cDNA) encoding SjAK1 was synthesized from total RNA of 3-day-old schistosomes, and immunization with recombinant SjAK1 reduced worm burden by 50%, decreased the density of eggs deposited in the host liver by 40%, and reduced the area of granulomas in the host liver by 56%. ELISA results showed that recombinant SjAK1 also stimulated Th1 cytokines such as IL-2 and IFN-γ, but not IL-5 and IL-4. Collectively, a recombinant form of the enzyme SjAK1 elicits partial protective immunity against Schistosoma japonicum infection and the induction of Th1 cytokines. Thus, the enzyme has potential as a component of a multivalent vaccine against schistosomiasis.

A Layered Approach for Robust Spatial Virtual Human Pose Reconstruction Using a Still Image.

Pedestrian detection and human pose estimation are instructive for reconstructing a three-dimensional scenario and for robot navigation, particularly when large amounts of vision data are captured using various data-recording techniques. Using an unrestricted capture scheme, which produces occlusions or breezing, the information describing each part of a human body and the relationship between each part or even different pedestrians must be present in a still image. Using this framework, a multi-layered, spatial, virtual, human pose reconstruction framework is presented in this study to recover any deficient information in planar images. In this framework, a hierarchical parts-based deep model is used to detect body parts by using the available restricted information in a still image and is then combined with spatial Markov random fields to re-estimate the accurate joint positions in the deep network. Then, the planar estimation results are mapped onto a virtual three-dimensional space using multiple constraints to recover any deficient spatial information. The proposed approach can be viewed as a general pre-processing method to guide the generation of continuous, three-dimensional motion data. The experiment results of this study are used to describe the effectiveness and usability of the proposed approach.

Learning templates for artistic portrait lighting analysis.

Lighting is a key factor in creating impressive artistic portraits. In this paper, we propose to analyze portrait lighting by learning templates of lighting styles. Inspired by the experience of artists, we first define several novel features that describe the local contrasts in various face regions. The most informative features are then selected with a stepwise feature pursuit algorithm to derive the templates of various lighting styles. After that, the matching scores that measure the similarity between a testing portrait and those templates are calculated for lighting style classification. Furthermore, we train a regression model by the subjective scores and the feature responses of a template to predict the score of a portrait lighting quality. Based on the templates, a novel face illumination descriptor is defined to measure the difference between two portrait lightings. Experimental results show that the learned templates can well describe the lighting styles, whereas the proposed approach can assess the lighting quality of artistic portraits as human being does.

[Progress of pattern recognition receptors of molluscs].

Molluscs have established complete innate immunity to defense against pathogens. The pattern recognition receptors (PRRs) are the sensory receptors of molluscs to resist outside invaders, as the first reactor to initiate the innate immune response. Some PRRs have been identified in several molluscs, including Toll-like receptors (TLRs) , C-type lectins, galectins, lipopolysaccharide-ß-1,3-glucan binding protein (LGBP), Clq domain-containing protein (ClqDC), and peptidoglycan recognition protein (PGRP). PRRs have various biological activities and play important roles in the defense system of molluscs. This paper reviews the research progress of PRRs in molluscs.

Geodesic propagation for semantic labeling.

This paper presents a semantic labeling framework with geodesic propagation (GP). Under the same framework, three algorithms are proposed, including GP, supervised GP (SGP) for image, and hybrid GP (HGP) for video. In these algorithms, we resort to the recognition proposal map and select confident pixels with maximum probability as the initial propagation seeds. From these seeds, the GP algorithm iteratively updates the weights of geodesic distances until the semantic labels are propagated to all pixels. On the contrary, the SGP algorithm further exploits the contextual information to guide the direction of propagation, leading to better performance but higher computational complexity than the GP. For video labeling, we further propose the HGP algorithm, in which the geodesic metric is used in both spatial and temporal spaces. Experiments on four public data sets show that our algorithms outperform several state-of-the-art methods. With the GP framework, convincing results for both image and video semantic labeling can be obtained.

GPU-based skin texture synthesis for digital human model.

Skin synthesis is important for the actual appearance of digital human models. However, it is difficult to design a general algorithm to efficiently produce high quality results. This paper proposes a parallel texture synthesis method for large scale skin of digital human models. Two major procedures are included in this method, a parallel matching procedure and a multi-pass optimizing procedure. Compared with other methods, this algorithm is easy to use, requires only a small size of skin image as input, and generates an arbitrary size of skin texture with high quality. As demonstrated by experiments, the effectiveness of this skin texture synthesis method is confirmed.

Multimodal medical image fusion using improved multi-channel PCNN.

Multimodal medical image fusion is a method of integrating information from multiple image formats. Its aim is to provide useful and accurate information for doctors. Multi-channel pulse coupled neural network (m-PCNN) is a recently proposed fusion model. Compared with previous methods, this network can effectively manage various types of medical images. However, it has two drawbacks: lack of control to feed function and low-level automation. The improved multi-channel PCNN proposed in this paper can adjust the impact of feed function by linking strength and adaptively compute the weighting coefficients for each pixel. Experimental results demonstrated the effectiveness of the improved m-PCNN fusion model.

Cloning and characterization of a bone morphogenetic protein homologue of Schistosoma japonicum.

Bone morphogenetic proteins (BMPs) are known to play an important role in the regulation of cell proliferation, survival, differentiation and apoptosis in many vertebrates and invertebrates through the TGF-ß signaling pathway. Although the TGF-ß signaling pathway exists in schistosomes, BMP homologue, a ligand of TGF-ß in Schistosoma japonicum, has not yet been identified. In this study, a BMP homologue of S. japonicum was cloned and characterized. The full length SjBMP cDNA is 3,020 bp and encodes 928 amino acids, which include a TGF-ß superfamily conserved domain at the C-terminus. BLAST analysis showed that, SjBMP has 68%, 51% and 43% homology with BMP from Schistosoma mansoni, Schmidtea mediterranea and Dugesia japonica at the amino acid level, respectively. According to data from real-time PCR, SjBMP was expressed in lung-stage schistosomula, 21-day liver-stage schistosomula, 50-day adult worms (the male and female), and eggs. The PCR data also indicated that, there was a ≈ 27- and ≈ 37-fold increase of SjBMP transcripts in the lung-stage schistosomula and eggs, respectively, and that there was relatively more SjBMP transcript in the adult male worm than in the adult female, in which the hepatic schistosomula was set as the calibrator for calculation. In situ hybridization based on FITC-labeled specific antisense oligonucleotide probes showed that SjBMP mRNA localized to the ovary of female worms and the integument and epithelium of female and male worms. After treatment with double-stranded RNA (dsRNA) at a concentration of 8 × 10(-2) µg/ml, which was added to the culture medium every other day for a week, the level of SjBMP mRNA in the cultured adult mixed-sex S. japonicum decreased at a range of ≈ 25-98% within 7 days compared with the level of SjBMP mRNA in the blank control group. On the 2nd day, the number of eggs produced per pair of worms decreased 28.7%, and the percent of normal eggs also decreased (12.7% vs. 4.3%) in the SjBMP dsRNA-treated group when compared with the eggs laid by the blank control group. No difference was detected between the two groups on the 7th day of treatment, because the eggs of the untreated worms were also mostly abnormal, similar to the eggs laid by the treated group. In addition, no significant difference in the morphological structure of the adult worms was observed. Thus, the preliminary in vitro experiment indicated that SjBMP may be involved in the oviposition behavior of S. japonicum, and further studies based on the recombinant virus vector-induced steady knockdown of SjBMP or in vivo experiments are required for more in-depth investigation.

Face illumination manipulation using a single reference image by adaptive layer decomposition.

This paper proposes a novel image-based framework to manipulate the illumination of human face through adaptive layer decomposition. According to our framework, only a single reference image, without any knowledge of the 3D geometry or material information of the input face, is needed. To transfer the illumination effects of a reference face image to a normal lighting face, we first decompose the lightness layers of the reference and the input images into large-scale and detail layers through weighted least squares (WLS) filter with adaptive smoothing parameters according to the gradient values of the face images. The large-scale layer of the reference image is filtered with the guidance of the input image by guided filter with adaptive smoothing parameters according to the face structures. The relit result is obtained by replacing the largescale layer of the input image with that of the reference image. To normalize the illumination effects of a non-normal lighting face (i.e., face delighting), we introduce similar reflectance prior to the layer decomposition stage by WLS filter, which make the normalized result less affected by the high contrast light and shadow effects of the input face. Through these two procedures, we can change the illumination effects of a non-normal lighting face by first normalizing the illumination and then transferring the illumination of another reference face to it. We acquire convincing relit results of both face relighting and delighting on numerous input and reference face images with various illumination effects and genders. Comparisons with previous papers show that our framework is less affected by geometry differences and can preserve better the identification structure and skin color of the input face.

Dynamic postural stability for double-leg drop landing.

Dynamic postural stability has been widely studied for single-leg landing, but seldom considered for double-leg landing. This study aimed to evaluate the dynamic postural stability and the influence mechanism of muscle activities during double-leg drop landing. Eight recreationally active males and eight recreationally active females participated in this study and dropped individually from three heights (0.32 m, 0.52 m, and 0.72 m). Ground reaction force was recorded to calculate the time to stabilisation. Electromyographic activities were recorded for selected lower-extremity muscles. A multivariate analysis of variance was carried out and no significant influence was found in time to stabilisation between genders or limb laterals (P > 0.05). With increasing drop height, time to stabilisation decreased significantly in two horizontal directions and the lower-extremity muscle activities were enhanced. Vertical time to stabilisation was not significantly influenced by drop height. Dynamic postural stability improved by neuromuscular change more than that required due to the increase of drop height. Double-leg landing on level ground is a stable movement, and the body would often be injured before dynamic postural stability is impaired. It is understandable to protect tissues from mechanical injuries by the sacrifice of certain dynamic postural stability in the design of protective devices or athlete training.