The research of touch screen usability in civil aircraft cockpit.

With the advancement of touch screen technology, the application of touch screens in civil aircraft cockpits has become increasingly popular. However, further analysis and research are required to fully promote its applications. The paper researched the usability of touch screens in aircraft cockpit considering the operation performance and subjective NASA-TLX workload evaluation, conducted experimental research on three touch gestures: click, drag, and zoom. Additionally, a comparative analysis was conducted on the touch performance under different layouts, positions, touch sizes, dragging direction angles, and zoom multiples. The touch performance indicators include operation time, error rate, operation speed, and workload. The experimental results show that the 21 mm size has the minimum operation time and workload, and 18 mm size has the lowest error rate in the clicking tasks. Additionally, the performance and workload of the captain's layout are better than those of the co-pilot's layout, and the performance of the center console position is best. The operation speed of the dragging tasks is faster when performed at position R3 compared to other positions. The dragging moving angles with better operation speed are 80°-190° and 250°-290°. The operation performance and workload of the zooming tasks vary depending on the zoom multiples. As the multiple increases, the operation time and workload also increase. There is no difference in operation performance or workload between zooming in and zooming out. The paper provides experimental support and suggestions based on human operation and subjective NASA-TLX workload evaluation for the application of touch screens in civil aircraft cockpits.

Development of a bispecific antibody targeting PD-L1 and TIGIT with optimal cytotoxicity.

Programmed death-ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are two potential targets for cancer immunotherapy, early clinical studies showed the combination therapy of anti-PD-L1 and anti-TIGIT had synergistic efficacy both in the terms of overall response rate (ORR) and overall survival (OS). It is rational to construct bispecific antibodies targeting PD-L1 and TIGIT, besides retaining the efficacy of the combination therapy, bispecific antibodies (BsAbs) can provide a new mechanism of action, such as bridging between tumor cells and T/NK cells. Here, we developed an IgG1-type bispecific antibody with optimal cytotoxicity. In this study, we thoroughly investigated 16 IgG-VHH formats with variable orientations and linker lengths, the results demonstrated that (G4S)2 linker not only properly separated two binding domains but also had the highest protein yield. Moreover, VHH-HC orientation perfectly maintained the binding and cytotoxicity activity of the variable domain of the heavy chain of heavy-chain-only antibody (VHH) and immunoglobulin G (IgG). Following treatment with BiPT-23, tumor growth was significantly suppressed in vivo, with more cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells infiltration, and selective depletion of Regulatory T cells (Tregs). BiPT-23 represents novel immunotherapy engineered to prevent hyperprogression of cancer with PD-1 blockade, and preferentially killed PD-L1+ tumor cells, and TIGIT+ Tregs but maintained CD11b+F4/80+ immune cells within the tumor microenvironment (TME).

Positive charge in the complementarity-determining regions of synthetic nanobody prevents aggregation.

In the past, specificity and affinity were the priority for synthetic antibody library. However, therapeutic antibodies need good stability for medical use. Through carefully adjust the chemical diversity in CDRs, one hopes to design a synthetic antibody library with good developability. Here we thoroughly analyzed 296 nanobody sequences and structures, constructed a fully-functional synthetic nanobody library, evaluated the relationship between aggregation and isoelectric point, and found that high-pI nanobodies were more resistant to aggregation than low-pIs. As we used the same framework for constructing the library, CDRs charge played a crucial role in mediating nanobody aggregation. We also analyzed the theoretical pI of 296 nanobodies from PDB, about 75% had basic pI, only 25% were acidic. Those results provided useful guidelines for designing next-generation synthetic nanobody libraries and for identifying potent and safe nanobody therapeutics.

Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.

Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly selective, tight-binding antibody from a 1011-member antibody library using combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass spectrometry analyses demonstrate antibody interaction with an N-terminal region of CXCR2 that is part of the IL-8 epitope. The antibody strongly inhibits IL-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and alleviates hCXCR2-dependent experimental autoimmune encephalomyelitis symptoms in mice. As inappropriate neutrophil migration accompanies many diseases including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic obstructive pulmonary disease, and cancer, this antibody has potential for development as a therapeutic agent, akin to anti-TNF antibodies. However, an important difference here is that the antibody targets the chemokine receptor and competes with natural ligand, rather than targeting the ligand itself.

Predictive factors of contralateral occult carcinoma in patients with papillary thyroid carcinoma: a retrospective study.

BACKGROUND: The surgical approach toward unilateral papillary thyroid carcinoma (PTC) has been in controversy. One of the concerns is the existence of contralateral occult carcinoma, which could cause relapse and even lead to re-operation if not dealt with. This study aims to find out risk factors related to contralateral occult PTC, in order to facilitate in surgical approach decision for PTC. METHODS: A total of 921 PTC patients who underwent total/near-total thyroidectomy and central lymph node dissection (CND) with/without lateral lymph node dissection (LND) from January 2014 to Sept 2017 in Guangdong General Hospital were assessed retrospectively. The relations between contralateral occult PTC and clinicopathologic characteristics of PTC were analyzed by univariate and multivariate logistic regression. RESULTS: The incidence of contralateral occult carcinoma in patients with PTC was 16.7% (154 of 921 cases). Univariate analysis showed that multifocality of the primary carcinoma (P=0.000), lymph node metastasis (P=0.001), pathologic tumor size (P=0.014) and contralateral benign nodule (P=0.000) were significantly associated with the increased incidence of contralateral occult PTC. No significant correlations were found between contralateral carcinoma and other variables such as gender (P=0.338), age (P=0.283), BRAF mutation (P=0.187) or extrathyroidal extension (P=0.423). Multivariate logistic regression analysis revealed that contralateral benign nodule (P=0.000), multifocality (P=0.000) and lymph node metastasis (P=0.009) were independent predictors of bilateral PTC of patients whose pre-operation ultrasound (US) show a unilateral carcinoma. CONCLUSIONS: Lymph node metastasis, contralateral benign nodule and multifocality are independent predictors of contralateral occult PTC. For unilateral PTC patients with one or more of these factors, total/near-total thyroidectomy should be considered when making surgical approach decisions.

The Clinicopathological Features of Papillary Thyroid Carcinoma Patients with Positive Hepatitis B Surface Antigen.

BACKGROUND: Hepatitis B virus infection has been reported to be associated with some kinds of cancer. The aim of this study was to investigate clinicopathological features of papillary thyroid carcinoma (PTC) patients with positive hepatitis B surface antigen (HBsAg). MATERIALS AND METHODS: A total of 569 PTC patients were analyzed retrospectively in this study. The relationships of HBsAg with clinicopathologic features of PTC were analyzed by univariate analysis. The relationships of central lymph node metastasis (CLNM) with clinicopathological features of PTC were analyzed by univariate and multivariate logistic regression analysis. RESULTS: The incidence of CLNM in PTC with positive HBsAg was higher than that in PTC with negative HBsAg (71.4 vs. 60.0%, p = 0.047). Univariate analysis showed that positive HBsAg was significantly associated with bilateral tumors (p = 0.043) and lymph node metastasis (LNM) (p = 0.047) in PTC patients. In addition, the incidence of CLNM in patients with PTC was 61.7% (351 of 569 cases). Univariate analysis showed that CLNM of patients with PTC was significantly associated with positive HBsAg (p = 0.047). Multivariate logistic regression analysis revealed that positive HBsAg (p = 0.038) was an independent predictor of CLNM in patients with PTC. CONCLUSIONS: The incidence of CLNM in PTC patients with positive HBsAg was significantly higher than that of patients with negative HBsAg. Positive HBsAg was correlated with LNM and bilateral tumors. In addition to gender, age <45 years, tumor size >2 cm, and lateral LNM, positive HBsAg was also an independent predictor of CLNM in PTC patients.

Resveratrol improves endothelial dysfunction and attenuates atherogenesis in apolipoprotein E-deficient mice.

Endothelial dysfunction is an early and central feature of atherosclerosis. Dietary resveratrol (RSV), a class of flavonoid compounds, have been demonstrated to exert several beneficial effects on human body. In this study, we investigated the protective effects of RSV on high fat diet-induced endothelial dysfunction. Human aortic endothelial cells (HAECs) were treated with RSV to evaluate the gene expression of the endothelial nitric oxide synthase (eNOS). Apolipoprotein E (apoE-/-) mice were fed a high-fat, high-cholesterol diet (HCD) or HCD supplemented with RSV for 8 weeks. Treatment of cultured HAECs with RSV dose-dependently upregulated the eNOS expression as assessed by quantitative RT-PCR and Western blot, respectively. In addition, RSV increased the promoter activity of the human eNOS gene, as determined by luciferase assays of the eNOS promoter gene. The cAMP-response element binding protein (CREB) was identified as the target transcription factor involved in the RSV mediated upregulation of eNOS expression. RSV increased phosphorylation of CREB through protein kinase A (PKA) activation, which induced a CREB-mediated upregulation of eNOS transcription. Consequently, RSV treatment significantly reversed the deleterious effects of oxidized LDL (oxLDL)-induced oxidative stress in HAECs. In vivo, treatment with RSV improves endothelial dysfunction and attenuates atherosclerotic plaque formation in apoE-/- mice through PKA-CREB-dependent pathway. Our findings demonstrate that RSV has an effect of activating eNOS expression, contributing to the prevention of dyslipidemia-induced endothelial dysfunction and atherosclerosis.

Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity.

Demand for monoclonal antibodies (mAbs) in basic research and medicine is increasing yearly. Hybridoma technology has been the dominant method for mAb development since its first report in 1975. As an alternative technology, phage display methods for mAb development are increasingly attractive since Humira, the first phage-derived antibody and one of the best-selling mAbs, was approved for clinical treatment of rheumatoid arthritis in 2002. As a non-animal based mAb development technology, phage display bypasses antigen immunogenicity, humanization, and animal maintenance that are required from traditional hybridoma technology based antibody development. In this protocol, we describe a method for construction of synthetic phage-displayed Fab libraries with diversities of 109-1010 obtainable with a single electroporation. This protocol consists of: 1) high-efficiency electro-competent cell preparation; 2) extraction of uracil-containing single-stranded DNA (dU-ssDNA); 3) Kunkel's method based oligonucleotide-directed mutagenesis; 4) electroporation and calculation of library size; 5) protein A/L-based enzyme-linked immunosorbent assay (ELISA) for folding and functional diversity evaluation; and 6) DNA sequence analysis of diversity.

Predictors of lymph nodes posterior to the right recurrent laryngeal nerve metastasis in patients with papillary thyroid carcinoma: A retrospective study.

The aim of this study was to identify the risk factors associated with lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in patients with papillary thyroid carcinoma (PTC).A total of 81 PTC patients who underwent total/near-total thyroidectomy with LN-prRLN dissection in the Department of General Surgery at Guangdong General Hospital between June 2015 and August 2016 were assessed retrospectively. The relations of LN-prRLN metastasis with clinicopathologic characteristics of PTC were analyzed by univariate and multivariate logistic regression.The incidence of LN-prRLN metastasis in patients with PTC was 51.9% (42 of 81 cases). Univariate analysis showed that lateral LN metastasis (P = .005), VIa central LN metastasis (P = .000), pathologic tumor size (P = .000), capsular invasion (P = .002), and extrathyroidal invasion (P = .018) (P < .05) were significantly associated with the increased incidence of LN-prRLN metastasis in PTC. No significant correlations were found between LN-prRLN metastasis and other variables such as gender (P = .056), age (P = .448), clinical N stage (cN) (P = .063), tumor location (P = .336), tumor site (P = .909), right tumor existence (P = .793), and multifocality (P = .381). Multivariate logistic regression analysis revealed that VIa central LN metastasis (OR: 4.490, P = .027) was independent risk factors of LN-prRLN metastasis in patients with PTC.LN-prRLN metastasis is often indentified in patients with PTC. VIa central LN metastasis is an independent predictors of LN-prRLN metastasis, which allow for selective LN-prRLN dissection in patients with PTC.