Energetics and Kinetics of Dislocation Initiation in the Stressed Volume at Small Scales

Instrumented nanoindentation techniques have been widely used in characterizing mechanical behavior of materials in small length scales. For defect-free single crystals under nanoindentation, the onset of elastic-plastic transition is often shown by a sudden displacement burst in the measured load-displacement curve. It is believed to result from the homogeneous dislocation nucleation because the maximum shear stress at the pop-in load approaches the theoretical strength of the material and because statistical measurements agree with a thermally activated process of homogeneous dislocation nucleation. For single crystals with defects, the pop-in is believed to result from the sudden motion of pre-existing dislocations or heterogeneous dislocation nucleation. If the sample is prestrained before nanoindentation tests, a monotonic decrease of the measured pop-in load with respect to the increase of prestrain on Ni and Mo single crystals is observed. A similar trend is also observed that the pop-in load will gradually decrease if the size of indenter tip radius increases. This dissertation presents a systematic modeling endeavor of energetics and kinetics of defect initiation in the stressed volume at small scales. For homogeneous dislocation nucleation, an indentation Schmid factor is determined as the ratio of maximum resolved shear stress to the maximum contact pressure. The orientation-depended nanoindentation pop-in loads are predicted based on the indentation Schmid factor, theoretical strength of the material, indenter radius, and the effective indentation modulus. A good agreement has been reached when comparing the experimental data of nanoindentation tests on NiAl, Mo, and Ni, with different loading orientations to theoretical predictions. Statistical measurements generally confirm the thermal activation model of homogeneous dislocation nucleation, because the extracted dependence of activation energy on resolved shear stress is almost unique for all the indentation directions. For pop-in due to pre-existing defects, the pop-in load is predicted to be dependent on the defect density and the critical strength for heterogeneous dislocation nucleation. The cumulative probability of pop-in loads contains convoluted information from the homogenous dislocation nucleation, which is sensitive to temperature and loading rate, and heterogeneous dislocation nucleation due to the unstable change of existing defect network, which is sensitive to the initial defect distribution

Deformation and failure analysis of pinch-torsion based thermal runaway risk evaluation method of Li-ion cells

A new pinch-torsion test is developed for safety of Li-ion batteries that shows the stable capability of making small internal short-circuit spots effectively. The further deformation and failure analysis is conducted by finite element analysis and experiments. Two different loading conditions, pure pinch and pinch-torsion, are evaluated and compared which demonstrates that the addition of the torsion component significantly increased the maximum principal strain, and thus the internal short circuit induction. In addition, the vertical load in the pinch-torsion test is significantly less than it in the pinch test to generate the failure inside the battery, thus dramatically improving the applicability of the pinch test. Finally, an analytical stick-slip model rationalizes deformation mechanisms and the conclusion is made that the additional torsion only facilitates the failure of separator at the early stage which is typically a few degrees of rotation. The systematic investigation of the Li-ion cell deformation and failure provides insight for the optimization of the future battery safety experiment design

Vehicle Detection from 3D Lidar Using Fully Convolutional Network

Abstract-Convolutional network techniques have recently achieved great success in vision based detection tasks. This paper introduces the recent development of our research on transplanting the fully convolutional network technique to the detection tasks on 3D range scan data. Specifically, the scenario is set as the vehicle detection task from the range data of Velodyne 64E lidar. We proposes to present the data in a 2D point map and use a single 2D end-to-end fully convolutional network to predict the objectness confidence and the bounding boxes simultaneously. By carefully design the bounding box encoding, it is able to predict full 3D bounding boxes even using a 2D convolutional network. Experiments on the KITTI dataset shows the state-ofthe-art performance of the proposed method

Calculation model of concrete-filled steel tube arch bridges based on the “arch effect”

In view of the limitations of the current code based on the equivalent beam-column method with the “rod mode” instead of the “arch mode” for the calculation of concrete-filled steel tube arch bridges, this paper takes the real bearing mechanism of the arch as the starting point and analyzes the different bearing mechanisms of the arch and eccentric pressurized column. The concrete-filled steel tube arch model test was carried out to analyze the deformation state and damage mode, and the geometric non-linear bending moment of the measured arch was compared with the bending moment value calculated by the eccentricity increase coefficient of the “rod mode.” The results showed that the transfer of internal force is from the axial force to the arch axis, causing the vertical reaction force and horizontal thrust. However, the eccentric compression column only produced the vertical force at the bottom and combines with the lateral deformation indirectly generated by the eccentric distance. In addition, the deformation stage of the arch is basically the same as that of the eccentric compression column. The final failure mode of the arch is 4-hinge damage, and the final failure mode of the eccentric compression column is single-hinge damage. The preliminary geometric non-linear bending moment value obtained by the two modes accords well. Therefore, the main factors for the difference in the bearing mechanism between the two modes are different force structures, force transmission routes, and sources of deformation. Due to the difference in the bearing mechanism, the final failure mode is different, and the deformation ability of the arch is weakened by using the “rod mode” instead of the “arch mode.” The geometric non-linear bending moment of the control section calculated by the eccentricity increase coefficient is conservative, but the influence of the geometric non-linearity of other sections is not considered enough

A Fault Diagnosis Method for Power Transmission Networks Based on Spiking Neural P Systems with Self-Updating Rules considering Biological Apoptosis Mechanism

Power transmission networks play an important role in smart girds. Fast and accurate faulty-equipment identification is critical for fault diagnosis of power systems; however, it is rather difficult due to uncertain and incomplete fault alarm messages in fault events. This paper proposes a new fault diagnosis method of transmission networks in the framework of membrane computing. We first propose a class of spiking neural P systems with self-updating rules (srSNPS) considering biological apoptosis mechanism and its self-updating matrix reasoning algorithm. The srSNPS, for the first time, effectively unitizes the attribute reduction ability of rough sets and the apoptosis mechanism of biological neurons in a P system, where the apoptosis algorithm for condition neurons is devised to delete redundant information in fault messages. This simplifies the complexity of the srSNPS model and allows us to deal with the uncertainty and incompleteness of fault information in an objective way without using historical statistics and expertise. Then, the srSNPS-based fault diagnosis method is proposed. It is composed of the transmission network partition, the SNPS model establishment, the pulse value correction and computing, and the protection device behavior evaluation, where the first two components can be finished before failures to save diagnosis time. Finally, case studies based on the IEEE 14- and IEEE 118-bus systems verify the effectiveness and superiority of the proposed method

Antibody-based cancer immunotherapy by targeting regulatory T cells

Regulatory T cells (Tregs) are among the most abundant suppressive cells, which infiltrate and accumulate in the tumor microenvironment, leading to tumor escape by inducing anergy and immunosuppression. Their presence has been correlated with tumor progression, invasiveness and metastasis. Targeting tumor-associated Tregs is an effective addition to current immunotherapy approaches, but it may also trigger autoimmune diseases. The major limitation of current therapies targeting Tregs in the tumor microenvironment is the lack of selective targets. Tumor-infiltrating Tregs express high levels of cell surface molecules associated with T-cell activation, such as CTLA4, PD-1, LAG3, TIGIT, ICOS, and TNF receptor superfamily members including 4-1BB, OX40, and GITR. Targeting these molecules often attribute to concurrent depletion of antitumor effector T-cell populations. Therefore, novel approaches need to improve the specificity of targeting Tregs in the tumor microenvironment without affecting peripheral Tregs and effector T cells. In this review, we discuss the immunosuppressive mechanisms of tumor-infiltrating Tregs and the status of antibody-based immunotherapies targeting Tregs

The feasibility and safety of sharp recanalization for superior vena cava occlusion in hemodialysis patients: A retrospective cohort study

Introduction: Hemodialysis catheter‐related superior vena cava (SVC) occlusions can cause considerable morbidity for patients and be challenging to treat if refractory to conventional guide wire transversal. This pilot study assessed the feasibility and safety of sharp recanalization of SVC occlusion in hemodialysis patients.Methods: This study retrospectively enrolled hemodialysis patients treated in West China Hospital diagnosed with SVC occlusion who failed traditional guide wire transversal from January 2014 to November 2017. In brief, a guide wire from the femoral approach was advanced to the lower end of the obstructive lesion to act as a target, while the stiff end of hydrophilic wire was advanced though a jugular approach. Under fluoroscopic guidance in biplane imaging, the occlusive SVC lesion was penetrated with the stiff wire that was snared and pulled through. Graded dilation of the SVC and subsequent tunneled‐cuffed catheter implantation were performed. Demographic information and clinical outcomes were recorded and evaluated.Findings: Sixteen patients with a mean age of 62 ± 13 years (13 females and 3 males) who received SVC sharp recanalization were included in this study. The sharp recanalization procedure was successfully performed in 14 patients (87.5%). Two patients were complicated with SVC laceration and hemopericardium but remained asymptomatic and required no surgical repair. One patient suffered ventricular fibrillation during procedure. Despite the return of spontaneous circulation, the patient unfortunately died of gastrointestinal tract bleeding after 3 days in ICU. Follow‐up suggested the 6‐month catheter patency to be 92.85% and 12‐month catheter patency to be 58.33%. No long‐term procedure‐related complications were recorded.Discussion: Sharp recanalization might be a feasible strategy in managing SVC occlusion in hemodialysis patients. The potential life‐threatening complications (cardiac arrhythmia and SVC laceration) necessitate strict eligibility screening, skillful operation, and avoidance of over‐dilation of SVC.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153765/1/hdi12804.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153765/2/hdi12804_am.pd

Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology

Background:  Whether metformin is related to nonalcoholic fatty liver disease (NAFLD) is controversial. Our aim was to investigate the relationship between metformin and NAFLD that may predict the metformin potential of these lesions and new prevention strategies in NAFLD patients. Methods:  The meta-analysis was analyzed by Revman 5.3 softwares systematically searched for works published through July 29, 2022. Network pharmacology research based on databases, Cytoscape 3.7.1 software and R software respectively. Results:  The following variables were associated with metformin in NAFLD patients: decreased of alanine aminotransferase (ALT) level (mean difference [MD] = −10.84, 95% confidence interval [CI] = −21.85 to 0.16, P = .05); decreased of aspartate amino transferase (AST) level (MD = −4.82, 95% CI = −9.33 to −0.30, P = .04); decreased of triglyceride (TG) level (MD = −0.17, 95% CI = −0.26 to −0.08, P = .0002); decreased of total cholesterol (TC) level (MD = −0.29, 95% CI = −0.47 to −0.10, P = .003); decreased of insulin resistance (IR) level (MD = −0.42, 95% CI = −0.82 to −0.02, P = .04). In addition, body mass index (BMI) (MD = −0.65, 95% CI = −1.46 to 0.16, P = .12) had no association with metformin in NAFLD patients. 181 metformin targets and 868 NAFLD disease targets were interaction analyzed, 15 core targets of metformin for the treatment of NAFLD were obtained. The effect of metformin on NAFLD mainly related to cytoplasm and protein binding, NAFLD, hepatitis B, pathway in cancer, toll like receptor signaling pathway and type 2 diabetes mellitus (T2DM). The proteins of hypoxia inducible factor-1 (HIF1A), nuclear factor erythroid 2-related factor (NFE2L2), nitric oxide synthase 3 (NOS3), nuclear receptor subfamily 3 group C member 1 (NR3C1), PI3K catalytic subunit alpha (PIK3CA), and silencing information regulator 2 related enzyme 1 (SIRT1) may the core targets of metformin for the treatment of NAFLD. Conclusion:  Metformin might be a candidate drug for the treatment of NAFLD which exhibits therapeutic effect on NAFLD patients associated with ALT, AST, TG, TC and IR while was not correlated with BMI. HIF1A, NFE2L2, NOS3, NR3C1, PIK3CA, and SIRT1 might be core targets of metformin for the treatment of NAFLD

Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV

In recent years, tremendous efforts have been made in the engineering of bispecific or multi-specific antibody-based therapeutics by combining two or more functional antigen-recognizing elements into a single construct. However, to the best of our knowledge there has been no reported cases of effective antiviral antibody-peptide bispecific fusion proteins. We previously developed potent fully human monoclonal antibodies and inhibitory peptides against Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a novel coronavirus that causes severe acute respiratory illness with high mortality. Here, we describe the generation of antibody-peptide bispecific fusion proteins, each of which contains an anti-MERS-CoV single-chain antibody m336 (or normal human IgG1 CH3 domain as a control) linked with, or without, a MERS-CoV fusion inhibitory peptide HR2P. We found that one of these fusion proteins, designated as m336 diabody-pep, exhibited more potent inhibitory activity than the antibody or the peptide alone against pseudotyped MERS-CoV infection and MERS-CoV S protein-mediated cell-cell fusion, suggesting its potential to be developed as an effective bispecific immunotherapeutic for clinical use