Time-delay neural network for continuous emotional dimension prediction from facial expression sequences

"(c) 2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works."Automatic continuous affective state prediction from naturalistic facial expression is a very challenging research topic but very important in human-computer interaction. One of the main challenges is modeling the dynamics that characterize naturalistic expressions. In this paper, a novel two-stage automatic system is proposed to continuously predict affective dimension values from facial expression videos. In the first stage, traditional regression methods are used to classify each individual video frame, while in the second stage, a Time-Delay Neural Network (TDNN) is proposed to model the temporal relationships between consecutive predictions. The two-stage approach separates the emotional state dynamics modeling from an individual emotional state prediction step based on input features. In doing so, the temporal information used by the TDNN is not biased by the high variability between features of consecutive frames and allows the network to more easily exploit the slow changing dynamics between emotional states. The system was fully tested and evaluated on three different facial expression video datasets. Our experimental results demonstrate that the use of a two-stage approach combined with the TDNN to take into account previously classified frames significantly improves the overall performance of continuous emotional state estimation in naturalistic facial expressions. The proposed approach has won the affect recognition sub-challenge of the third international Audio/Visual Emotion Recognition Challenge (AVEC2013)1

An inventory of invasive alien species in China

Invasive alien species (IAS) are a major global challenge requiring urgent action, and the Strategic Plan for Biodiversity (2011–2020) of the Convention on Biological Diversity (CBD) includes a target on the issue. Meeting the target requires an understanding of invasion patterns. However, national or regional analyses of invasions are limited to developed countries. We identified 488 IAS in China’s terrestrial habitats, inland waters and marine ecosystems based on available literature and field work, including 171 animals, 265 plants, 26 fungi, 3 protists, 11 procaryots, and 12 viruses. Terrestrial plants account for 51.6% of the total number of IAS, and terrestrial invertebrates (104 species) for 21.3%. Of the total numbers, 67.9% of plant IAS and 34.8% of animal IAS were introduced intentionally. All other taxa were introduced unintentionally despite very few animal and plant species that invaded naturally. In terms of habitats, 64.3% of IAS occur on farmlands, 13.9% in forests, 8.4% in marine ecosystems, 7.3% in inland waters, and 6.1% in residential areas. Half of all IAS (51.1%) originate from North and South America, 18.3% from Europe, 17.3% from Asia not including China, 7.2% from Africa, 1.8% from Oceania, and the origin of the remaining 4.3% IAS is unknown. The distribution of IAS can be divided into three zones. Most IAS are distributed in coastal provinces and the Yunnan province; provinces in Middle China have fewer IAS, and most provinces in West China have the least number of IAS. Sites where IAS were first detected are mainly distributed in the coastal region, the Yunnan Province and the Xinjiang Uyghur Autonomous Region. The number of newly emerged IAS has been increasing since 1850. The cumulative number of firstly detected IAS grew exponentially

Improving the Efficacy of Conventional Therapy by Adding Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease: A Randomized Controlled Trial

Background. Herb-derived compound andrographolide sulfonate (called Xiyanping injection) recommended control measure for severe hand, foot, and mouth disease (HFMD) by the Ministry of Health (China) during the 2010 epidemic. However, there is a lack of good quality evidence directly comparing the efficacy of Andrographolide Sulfonate combination therapy with conventional therapy. Methods. 230 patients were randomly assigned to 7–10 days of Andrographolide Sulfonate 5–10 mg/Kg/day and conventional therapy, or conventional therapy alone. Results. The major complications occurred less often after Andrographolide Sulfonate (2.6% versus 12.1%; risk difference [RD], 0.94; 95% CI, 0.28–1.61; P=0.006). Median fever clearance times were 96 hours (CI, 80 to 126) for conventional therapy recipients and 48 hours (CI, 36 to 54) for Andrographolide Sulfonate combination-treated patients (χ2=16.57, P<0.001). The two groups did not differ in terms of HFMD-cause mortality (P=1.00) and duration of hospitalization (P=0.70). There was one death in conventional therapy group. No important adverse event was found in Andrographolide Sulfonate combination therapy group. Conclusions. The addition of Andrographolide Sulfonate to conventional therapy reduced the occurrence of major complications, fever clearance time, and the healing time of typical skin or oral mucosa lesions in children with severe HFMD

FINITE ELEMENT ANALYSIS OF THE SEISMIC BEHAVIOR OF THE ASSEMBLED LIGHT STEEL FRAME- LIGHT WALL STRUCTURES

In order to meet the needs of the development of low-rise assembly structure in rural areas, a fabricated light-weight steel frame-composite light wall structure is proposed in this paper. The light-weight steel frames are used to bear the vertical loads. The single-row-reinforced recycled concrete wall-boards are used as lateral members to resist most of the horizontal earthquake loads. The wall-board, EPS (Expanded Polystyrene) insulation modules, and fly ash blocks form the thermally insulated wall. Four fabricated lightweight steel frame-composite light wall structures and one light-weight steel frame (FRA) structure were tested under the low cyclic loads. The influence of wall reinforcement spacing and structural form (be it fly ash block or not) on the seismic performance of this new structure was analysed and the damage process of the specimen was simulated using the ABAQUS® software. The results show that the light steel frames and the single-row-reinforced recycled concrete wall-board can work well together. Furthermore, the structure has two clear seismic lines. Due to the use of EPS insulation modules and fly ash blocks, the structure has good anti-seismic and thermal insulation abilities. Reducing the spacing of bars or compositing fly ash blocks can significantly improve the seismic performance of the structure. The finite element method (FEM) calculations agreed well with the experimental results, which validates the proposed model

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results.</p

BEL1-like Homeodomain Protein BLH6a Is a Negative Regulator of CAl5H2 in Sinapyl Alcohol Monolignol Biosynthesis in Poplar

Lignin is one of the major components of xylem cell walls in tree stems. The lignin in the wood of most flowering plants (dicotyledonous angiosperms) is typically polymerized from three monolignol precursors, coniferyl alcohol, sinapyl alcohol, and p-coumaroyl alcohol, resulting in guaiacyl (G), syringyl (S), and hydroxyphenyl (H) subunits, respectively. In this study, we focus on the transcriptional regulation of a coniferaldehyde 5-hydroxylase (CAld5H2) gene, which encodes a key enzyme for sinapyl alcohol biosynthesis. We carried out a yeast one-hybrid (Y1H) screen to identify candidate upstream transcription factors (TFs) regulating CAld5H2. We obtained 12 upstream TFs as potential regulators of CAld5H2. One of these TF genes, BLH6a, encodes a BEL1-like homeodomain (BLH) protein and negatively regulated the CAld5H2 promoter activity. The direct regulation of CAld5H2 promoter by BLH6a was supported by chromatin immunoprecipitation–quantitative polymerase chain reaction (ChIP–qPCR) and dominant repression of BLH6a in transgenic plants. Luciferase complementation imaging analyses showed extensive protein–protein interactions among these 12 TFs. We propose that BLH6a is a negative regulator of CAld5H2, which acts through combinatorial regulation of multiple TFs for sinapyl alcohol (S monolignol) biosynthesis in poplar

Bile Acids Gate Dopamine Transporter Mediated Currents

Bile acids (BAs) are molecules derived from cholesterol that are involved in dietary fat absorption. New evidence supports an additional role for BAs as regulators of brain function. Sterols such as cholesterol interact with monoamine transporters, including the dopamine (DA) transporter (DAT) which plays a key role in DA neurotransmission and reward. This study explores the interactions of the BA, obeticholic acid (OCA), with DAT and characterizes the regulation of DAT activity via both electrophysiology and molecular modeling. We expressed murine DAT (mDAT) in Xenopus laevis oocytes and confirmed its functionality. Next, we showed that OCA promotes a DAT-mediated inward current that is Na+-dependent and not regulated by intracellular calcium. The current induced by OCA was transient in nature, returning to baseline in the continued presence of the BA. OCA also transiently blocked the DAT-mediated Li+-leak current, a feature that parallels DA action and indicates direct binding to the transporter in the absence of Na+. Interestingly, OCA did not alter DA affinity nor the ability of DA to promote a DAT-mediated inward current, suggesting that the interaction of OCA with the transporter is non-competitive, regarding DA. Docking simulations performed for investigating the molecular mechanism of OCA action on DAT activity revealed two potential binding sites. First, in the absence of DA, OCA binds DAT through interactions with D421, a residue normally involved in coordinating the binding of the Na+ ion to the Na2 binding site (Borre et al., J. Biol. Chem., 2014, 289, 25764\u201325773; Cheng and Bahar, Structure, 2015, 23, 2171\u20132181). Furthermore, we uncover a separate binding site for OCA on DAT, of equal potential functional impact, that is coordinated by the DAT residues R445 and D436. Binding to that site may stabilize the inward-facing (IF) open state by preventing the re-formation of the IF-gating salt bridges, R60-D436 and R445-E428, that are required for DA transport. This study suggests that BAs may represent novel pharmacological tools to regulate DAT function, and possibly, associated behaviors

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al

Applications of high-throughput single B-cell sequencing to accelerate rational vaccine design

Understanding the antibody repertoire response to vaccination is critical for the rational design and evaluation of experimental vaccines. Immune receptors comprise two chains encoded by separate mRNA strands and thus conventional NextGen sequencing fails to identify the native pairings encoded by individual lymphocytes. To overcome this limitation, we are applying recent technical advances in high-throughput sequencing of complete antibodies (i.e., paired heavy and light chain sequencing) to generate a quantitative understanding of experimental vaccine performance and to accelerate vaccine design. We apply repertoire-based metrics of vaccine-elicited antibodies to evaluate and select promising candidate immunogens for inducing HIV-1 Envelope-specific VRC01-class antibodies. The VRC01 class of broadly neutralizing antibodies have been observed in multiple individuals and targets the HIV CD4 binding site via a common recognition motif that requires specific features in both heavy and light chains (e.g., VH1-2 heavy chain V-gene and a short, £5 amino acid light chain CDR3). We are using paired heavy and light chain sequencing to quantify the performance of various candidate HIV immunogens for inducing VRC01-class broadly neutralizing HIV antibodies in transgenic mouse models. We are also elucidating the ontogeny of antibodies in vaccinated and naturally infected human subjects and animal models via interrogation of paired heavy and light chain antibody sequences and antibody synthesis/testing of promising clones, including experimental influenza vaccine trials and a Phase I Ebola vaccine trial. These next-generation immunoanalytic approaches are providing detailed molecular feedback regarding experimental vaccine performance to accelerate vaccine design efforts against pathogens of major public health importance