Emission Patterns and Light Curves of Gamma-Rays in the Pulsar Magnetosphere with a Current-Induced Magnetic Field

We study the emission patterns and light curves of gamma-rays in the pulsar magnetosphere with a current-induced magnetic field perturbation. Based on the solution of a static dipole with the magnetic field induced by some currents (perturbation field), we derive the solutions of a static as well as a retarded dipole with the perturbation field in the Cartesian coordinates. The static (retarded) magnetic field can be expressed as the sum of pure static (retarded) dipolar magnetic field and the static (retarded) perturbation field. We use the solution of the retarded magnetic field to investigate the influence of the perturbation field on the emission patterns and light curves, and we apply the perturbed solutions to calculate the gamma-ray light curves for the case of the Vela pulsar. We find out that the perturbation field induced by the currents will change the emission patterns and then light curves of gamma-rays, especially for a larger perturbation field. Our results indicate that the perturbation field created by the outward-flowing (inward-flowing) electrons (positrons) can decrease the rotation effect on the magnetosphere and makes emission pattern appear to be more smooth relative to that of the pure retarded dipole, but the perturbation field created by the outward-flowing (inward-flowing) positrons (electrons) can make the emission pattern less smooth.Comment: 27 pages, 8 figures, accepted for publication in Ap

Modelling of capillary pore structure evolution in Portland cement pastes based on irregular-shaped cement particles

The pore structure plays a crucial role in durability performance of cement-based materials. However, the pore structure in cement pastes is highly dependent on the initial packing of cement particles and cement hydration process, which seems to be related to the shapes of cement particles. This paper proposed a numerical method to investigate the effect of cement particle shapes on capillary pore structures in cement pastes. In this study, irregular-shaped cement particles with various shapes are generated using a novel central growth model, and then incorporated into CEMHYD3D model to simulate Portland cement hydration. Some home-made programs of determining pore structure parameters including porosity, pore size distribution, connectivity and tortuosity are subsequently performed on the extracted three-dimensional network of capillary pore structure in cement pastes. The modelling results indicate that shape-induced large surface area in more non-equiaxed irregular-shaped cement particles can improve pore structure parameters in hardened cement pastes, but this effect will be slight in the later curing period and at a low water-tocement ratio. In addition, the less considered geometric difference plays a role in pore structure evolution especially for extremely non-equiaxed cement particle. However, the geometric attribute has a weak effect on pore structure parameters overall. The modelling results can provide a new insight into durability design in cement-based materials by means of manipulating cement particle shape in the future

Modelling of Capillary Pore Structure Evolution in Portland Cement Pastes Based on Irregular-Shaped Cement Particles

The pore structure plays a crucial role in durability performance of cement-based materials. However, the pore structure in cement pastes is highly dependent on the initial packing of cement particles and cement hydration process, which seems to be related to the shapes of cement particles. This paper proposed a numerical method to investigate the effect of cement particle shapes on capillary pore structures in cement pastes. In this study, irregular-shaped cement particles with various shapes are generated using a novel central growth model, and then incorporated into CEMHYD3D model to simulate Portland cement hydration. Some home-made programs of determining pore structure parameters including porosity, pore size distribution, connectivity and tortuosity are subsequently performed on the extracted three-dimensional network of capillary pore structure in cement pastes. The modelling results indicate that shape-induced large surface area in more non-equiaxed irregular-shaped cement particles can improve pore structure parameters in hardened cement pastes, but this effect will be slight in the later curing period and at a low water-tocement ratio. In addition, the less considered geometric difference plays a role in pore structure evolution especially for extremely non-equiaxed cement particle. However, the geometric attribute has a weak effect on pore structure parameters overall. The modelling results can provide a new insight into durability design in cement-based materials by means of manipulating cement particle shape in the future

Accurate Characterization of Binding Kinetics and Allosteric Mechanisms for the HSP90 Chaperone Inhibitors Using AI-Augmented Integrative Biophysical Studies

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate constant (koff), enabling a direct assessment of the drug–target residence time. These models demonstrated good predictive performance, where hydrophobic and hydrogen bond interactions significantly influence the koff prediction. In subsequent applications, our models were used to assist in the discovery of new inhibitors for the N-terminal domain of HSP90α (N-HSP90α), demonstrating predictive capabilities on an experimental validation set with a new scaffold. In X-ray crystallography experiments, the loop-middle conformation of apo N-HSP90α was observed for the first time (previously, the loop-middle conformation had only been observed in holo-N-HSP90α structures). Interestingly, we observed different conformations of apo N-HSP90α simultaneously in an asymmetric unit, which was also observed in a holo-N-HSP90α structure, suggesting an equilibrium of conformations between different states in solution, which could be one of the determinants affecting the binding kinetics of the ligand. Different ligands can undergo conformational selection or alter the equilibrium of conformations, inducing conformational rearrangements and resulting in different effects on binding kinetics. We then used molecular dynamics simulations to describe conformational changes of apo N-HSP90α in different conformational states. In summary, the study of the binding kinetics and molecular mechanisms of N-HSP90α provides valuable information for the development of more targeted therapeutic approaches

One-stitch anastomosis through the skin with bicanalicular intubation:a modified approach for repair of bicanalicular laceration

<b>AIM:</b> To evaluate the efficacy and safety of one-stitch anastomosis through the skin with bicanalicular silicone tube intubation in repairing of bicanalicular laceration.<b>METHODS:</b>The clinical data of 15 consecutive patients with both superior and inferior canalicular laceration in one eye who underwent surgical repair using one-stitch anastomosis through the skin and bicanalicular stent were retrospective studied. All the operations were performed under surgical microscope, 5-0 silk sutures were used and were with bicanalicular silicone tube (diameter was 8mm) intubation, for one lacerated canaliculi one-stitch anastomosis through the skin. The stents were left in place for 3 months postoperatively and then removed. The follow-up period was 3 - 36 months (average 14 months).<b>RESULTS:</b>In 15 patients, 13 patients were cured entirely, 1 patient was meliorated, 1 patient with no effects. All patients had got good recovery of eyelid laceration with no traumatic deformity in eyelid and canthus. Complication was seen in one case, for not followed the doctor’s guidance to come back to hospital to had the suture removed on the 7^th day after operation, when he came at the 15^th day, the inferior canalicular wall and eyelid skin were corroded by the suture caused 2mm wound, and the inside silicone tube was exposed, a promptly repair with 10-0 nylon suture was done, the wound healed in a week. There were no early tube protrusions and punctal slits in the patients.<b>CONCLUSION:</b>One-stitch anastomosis through the skin with bicanalicular silicone tube intubation is a good method in repair of bicanalicular laceration in one eye, the cut ends can be anastomosed directly, and with excellent cosmetic results, it is acceptable for the patients. For there is no suture remained in the wound permanently, so there is no suture-related granuloma which may cause obstruction or stenosis of canaliculi. It is simple, economical, effective and safe

Bioactive conformational generation of small molecules: A comparative analysis between force-field and multiple empirical criteria based methods

<p>Abstract</p> <p>Background</p> <p>Conformational sampling for small molecules plays an essential role in drug discovery research pipeline. Based on multi-objective evolution algorithm (MOEA), we have developed a conformational generation method called Cyndi in the previous study. In this work, in addition to Tripos force field in the previous version, Cyndi was updated by incorporation of MMFF94 force field to assess the conformational energy more rationally. With two force fields against a larger dataset of 742 bioactive conformations of small ligands extracted from PDB, a comparative analysis was performed between pure force field based method (FFBM) and multiple empirical criteria based method (MECBM) hybrided with different force fields.</p> <p>Results</p> <p>Our analysis reveals that incorporating multiple empirical rules can significantly improve the accuracy of conformational generation. MECBM, which takes both empirical and force field criteria as the objective functions, can reproduce about 54% (within 1Å RMSD) of the bioactive conformations in the 742-molecule testset, much higher than that of pure force field method (FFBM, about 37%). On the other hand, MECBM achieved a more complete and efficient sampling of the conformational space because the average size of unique conformations ensemble per molecule is about 6 times larger than that of FFBM, while the time scale for conformational generation is nearly the same as FFBM. Furthermore, as a complementary comparison study between the methods with and without empirical biases, we also tested the performance of the three conformational generation methods in MacroModel in combination with different force fields. Compared with the methods in MacroModel, MECBM is more competitive in retrieving the bioactive conformations in light of accuracy but has much lower computational cost.</p> <p>Conclusions</p> <p>By incorporating different energy terms with several empirical criteria, the MECBM method can produce more reasonable conformational ensemble with high accuracy but approximately the same computational cost in comparison with FFBM method. Our analysis also reveals that the performance of conformational generation is irrelevant to the types of force field adopted in characterization of conformational accessibility. Moreover, post energy minimization is not necessary and may even undermine the diversity of conformational ensemble. All the results guide us to explore more empirical criteria like geometric restraints during the conformational process, which may improve the performance of conformational generation in combination with energetic accessibility, regardless of force field types adopted.</p

Clinical study on the optic nerve protection of calcium dobesilate in treating glaucoma

AIM:To observe the protective effect of calcium dobesilate on optic nerve of glaucoma patients whose intraocular pressure has been under control through operation.<p>METHODS: A total of 78 inpatients(89 eyes)with glaucoma in this hospital from January, 2011 to February, 2012 were enrolled. All patients were randomly divided into treatment group and control group with 6 months in a course. The visual acuity, visual field(mean sensibility, MS), and intraocular pressure were measured at the experiment onset and 6 months later to evaluate the clinical effect.<p>RESULTS: There were no statistically significant differences in the visual acuity, intraocular pressure between the two groups neither at the experiment onset nor after 6 months(<i>P</i>>0.05). The mean sensibility(MS)of the treatment group was obviously improved(14.56±5.03 <i>vs </i>18.9±5.77, <i>P</i><0.05)with statistically significant differences before and after the treatment, while the MS remained unchanged in the control group(14.75±5.17 <i>vs </i>13.48±4.69). There are statistically significant difference between the treatment group and the control group. Compared to the ratio of improvement, stability, and deterioration in the control group(10.3%, 48.7%, 41.0%), the indexes were changed obviously in the treatment group(64.1%, 28.2%, 7.7%,<i>P</i><0.05)with statistically significant difference between the two groups.<p>CONCLUSION:Calcium dobesilate can improve mean retinal sensitivity and protect the optic nerve in glaucoma patients whose intraocular pressure has been controlled