Modelling Rod-like Flexible Biological Tissues for Medical Training

This paper outlines a framework for the modelling of slender rod-like biological tissue structures in both global and local scales. Volumetric discretization of a rod-like structure is expensive in computation and therefore is not ideal for applications where real-time performance is essential. In our approach, the Cosserat rod model is introduced to capture the global shape changes, which models the structure as a one-dimensional entity, while the local deformation is handled separately. In this way a good balance in accuracy and efficiency is achieved. These advantages make our method appropriate for the modelling of soft tissues for medical training applications

Beads-on-String Model for Virtual Rectum Surgery Simulation

A beads-on-string model is proposed to handle the deformation and collision of the rectum in virtual surgery simulation. The idea is firstly inspired by the observation of the similarity in shape shared by a rectum with regular bulges and a string of beads. It is beneficial to introduce an additional layer of beads, which provides an interface to map the deformation of centreline to the associated mesh in an elegant manner and a bounding volume approximation in collision handling. Our approach is carefully crafted to achieve high computational efficiency and retain its physical basis. It can be implemented for real time surgery simulation application

Superhydrophobic Waveguide: Liquid-core air-cladding waveguide platform for optofluidics

In this paper, we present an optofluidic waveguide platform consisting of liquid as a core material and air as cladding, enabled by using a superhydrophobic channel featured with hydrophobized high-aspect-ratio sharp-tip nanostructures. The contact of the liquid core with the superhydrophobic channel wall is minimized with an air layer retained between them so that the effective refractive index of the cladding layer is close to that of air. Thus, when light is introduced through the core liquid having a higher refractive index than that of the cladding air at the incident angle parallel to the channel direction less than a critical angle, it is reflected at the liquid-gas interface by the total internal reflection. When the cladding layer is filled with water (i.e., Wenzel state), the waveguide losses for the incident angles of 0 and 10° were ∼3.9 and ∼6.8 dB/cm, respectively. In contrast, when the cladding layer is retained with air (i.e., Cassie-Baxter state), the waveguide losses for the same incident angles were as low as ∼0.1 and ∼1.8 dB/cm, respectively. The significantly lowered waveguide losses at the Cassie-Baxter state indicate that superhydrophobic channels can provide the effective waveguide platform for optofluidics, exploiting the air layer as the cladding material

Augmented reality-based visual-haptic modeling for thoracoscopic surgery training systems

Background: Compared with traditional thoracotomy, video-assisted thoracoscopic surgery (VATS) has less minor trauma, faster recovery, higher patient compliance, but higher requirements for surgeons. Virtual surgery training simulation systems are important and have been widely used in Europe and America. Augmented reality (AR) in surgical training simulation systems significantly improve the training effect of virtual surgical training, although AR technology is still in its initial stage. Mixed reality has gained increased attention in technology-driven modern medicine but has yet to be used in everyday practice. Methods: This study proposed an immersive AR lobectomy within a thoracoscope surgery training system, using visual and haptic modeling to study the potential benefits of this critical technology. The content included immersive AR visual rendering, based on the cluster-based extended position-based dynamics algorithm of soft tissue physical modeling. Furthermore, we designed an AR haptic rendering systems, whose model architecture consisted of multi-touch interaction points, including kinesthetic and pressure-sensitive points. Finally, based on the above theoretical research, we developed an AR interactive VATS surgical training platform. Results: Twenty-four volunteers were recruited from the First People's Hospital of Yunnan Province to evaluate the VATS training system. Face, content, and construct validation methods were used to assess the tactile sense, visual sense, scene authenticity, and simulator performance. Conclusions: The results of our construction validation demonstrate that the simulator is useful in improving novice and surgical skills that can be retained after a certain period of time. The video-assisted thoracoscopic system based on AR developed in this study is effective and can be used as a training device to assist in the development of thoracoscopic skills for novices

Effective inhibition of foot-and-mouth disease virus (FMDV) replication in vitro by vector-delivered microRNAs targeting the 3D gene

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals. RNAi triggered by small RNA molecules, including siRNAs and miRNAs, offers a new approach for controlling viral infections. There is no report available for FMDV inhibition by vector-delivered miRNA, although miRNA is believed to have more potential than siRNA. In this study, the inhibitory effects of vector-delivered miRNAs targeting the 3D gene on FMDV replication were examined.</p> <p>Results</p> <p>Four pairs of oligonucleotides encoding 3D-specific miRNA of FMDV were designed and selected for construction of miRNA expression plasmids. In the reporter assays, two of four miRNA expression plasmids were able to significantly silence the expression of 3D-GFP fusion proteins from the reporter plasmid, p3D-GFP, which was cotransfected with each miRNA expression plasmid. After detecting the silencing effects of the reporter genes, the inhibitory effects of FMDV replication were determined in the miRNA expression plasmid-transfected and FMDV-infected cells. Virus titration and real-time RT-PCR assays showed that the p3D715-miR and p3D983-miR plasmids were able to potently inhibit the replication of FMDV when BHK-21 cells were infected with FMDV.</p> <p>Conclusion</p> <p>Our results indicated that vector-delivered miRNAs targeting the 3D gene efficiently inhibits FMDV replication <it>in vitro</it>. This finding provides evidence that miRNAs could be used as a potential tool against FMDV infection.</p

Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells

<p>Abstract</p> <p>Background</p> <p>shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV) receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF) and cell enzyme linked immunosorbent assays (cell ELISA), and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells.</p> <p>Results</p> <p>Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 10⁶TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 10²TCID₅₀of FMDV.</p> <p>Conclusions</p> <p>Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.</p

Identifying the proton loading site cluster in the ba₃ cytochrome c oxidase that loads and traps protons

Cytochrome c Oxidase (CcO) is the terminal electron acceptor in aerobic respiratory chain, reducing O₂ to water. The released free energy is stored by pumping protons through the protein, maintaining the transmembrane electrochemical gradient. Protons are held transiently in a proton loading site (PLS) that binds and releases protons driven by the electron transfer reaction cycle. Multi-Conformation Continuum Electrostatics (MCCE) was applied to crystal structures and Molecular Dynamics snapshots of the B-type Thermus thermophilus CcO. Six residues are identified as the PLS, binding and releasing protons as the charges on heme b and the binuclear center are changed: the heme a₃ propionic acids, Asp287, Asp372, His376 and Glu126B. The unloaded state has one proton and the loaded state two protons on these six residues. Different input structures, modifying the PLS conformation, show different proton distributions and result in different proton pumping behaviors. One loaded and one unloaded protonation states have the loaded/unloaded states close in energy so the PLS binds and releases a proton through the reaction cycle. The alternative proton distributions have state energies too far apart to be shifted by the electron transfers so are locked in loaded or unloaded states. Here the protein can use active states to load and unload protons, but has nearby trapped states, which stabilize PLS protonation state, providing new ideas about the CcO proton pumping mechanism. The distance between the PLS residues Asp287 and His376 correlates with the energy difference between loaded and unloaded states

Linking Incomplete Reprogramming to the Improved Pluripotency of Murine Embryonal Carcinoma Cell-Derived Pluripotent Stem Cells

Somatic cell nuclear transfer (SCNT) has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS) have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC) cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19) were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells) were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR). The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the transition between tumorigenesis and pluripotency

Star formation triggered by non-head-on cloud-cloud collisions, and clouds with pre-collision sub-structure

In an earlier paper, we used smoothed particle hydrodynamics (SPH) simulations to explore star formation triggered by head-on collisions between uniform-density 500 M clouds, and showed that there is a critical collision velocity, vCRIT. At collision velocities below vCRIT, a hub-and-spoke mode operates and delivers a monolithic cluster with a broad mass function, including massive stars (M 10 M) formed by competitive accretion. At collision velocities above vCRIT, a spider’s-web mode operates and delivers a loose distribution of small sub-clusters with a relatively narrow mass function and no massive stars. Here we show that,if the head-on assumption is relaxed, vCRIT is reduced. However, if the uniform-density assumption is also relaxed, the collision velocity becomes somewhat less critical: a low collision velocity is still needed to produce a global hub-and-spoke system and a monolithic cluster, but, even at high velocities, large cores – capable of supporting competitive accretion and thereby producing massive stars – can be produced. We conclude that cloud–cloud collisions may be a viable mechanism for forming massive stars – and we show that this might even be the major channel for forming massive stars in the Galaxy

Evolutionary Analysis of Structural Protein Gene VP1 of Foot-and-Mouth Disease Virus Serotype Asia 1

Foot-and-mouth disease virus (FMDV) serotype Asia 1 was mostly endemic in Asia and then was responsible for economically important viral disease of cloven-hoofed animals, but the study on its selection and evolutionary process is comparatively rare. In this study, we characterized 377 isolates from Asia collected up until 2012, including four vaccine strains. Maximum likelihood analysis suggested that the strains circulating in Asia were classified into 8 different groups (groups I–VIII) or were unclassified (viruses collected before 2000). On the basis of divergence time analyses, we infer that the TMRCA of Asia 1 virus existed approximately 86.29 years ago. The result suggested that the virus had a high mutation rate (5.745 × 10−3 substitutions/site/year) in comparison to the other serotypes of FMDV VP1 gene. Furthermore, the structural protein VP1 was under lower selection pressure and the positive selection occurred at many sites, and four codons (positions 141, 146, 151, and 169) were located in known critical antigenic residues. The remaining sites were not located in known functional regions and were moderately conserved, and the reason for supporting all sites under positive selection remains to be elucidated because the power of these analyses was largely unknown