Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

This is the published version. Copyright 2003 American Society for Microbiology.The cellular immunogenicity of formulated plasmid DNA and replication-defective human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized human immunodeficiency virus type 1 gag gene was examined in baboons. The Ad5 vaccine was capable of inducing consistently strong, long-lived CD8+-biased T-cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune responses were weaker than those elicited by the Ad5 vaccine and highly variable; formulation with chemical adjuvants led to moderate increases in the levels of Gag-specific T cells. Increasing the DNA-primed responses with booster doses of either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in the relative levels of cytotoxic and helper responses. The implications of these results are discussed

Differential Effects of MYH9 and APOL1 Risk Variants on FRMD3 Association with Diabetic ESRD in African Americans

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9—a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E−7 additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E−4). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes

Research on performance measurement and simulation of civil air defense PPP projects using system dynamics

Public Private Partnership (PPP) mode is increasingly applied in civil air defense (CAD) projects to improve project quality and reduce the government’s financial pressure. Because CAD project has different attributes during wartime and peacetime states, it’s necessary to comprehensively consider the project performance under different states to conduct scientific performance measurement. This paper focuses on the process of construction, operation, and handover of CAD PPP project to construct a unified project performance measurement indicator system, then a system dynamics (SD) model is established to carry out dynamic performance measurement and simulation of CAD PPP project under different social states respectively. A case study is conducted to verify the effectiveness of the proposed SD model, model validation, sensitivity analysis and result analysis were included as well. The study result can make the project performance management of CAD PPP more scientific and reasonable, and help decision-makers to formulate effective performance improvement strategies. It’s found out that government plays an important role in CAD PPP projects, when resources are limited, the government should give priority to measures such as reducing tax rates and increasing subsidies to ensure project benefits. The research methods can also provide reference for performance measurement of other PPP projects

Research on Resilience Evaluation and Enhancement of Deep Foundation Pit Construction Safety System

Deep foundation pit (DFP) projects have been a high incidence area of safety accidents because of their own high danger and complexity. Therefore, it is necessary to study the resilience of their construction safety system. This paper systematically identifies the key factors affecting the resilience of deep foundation pit construction based on the analysis of the composition of the deep foundation pit construction safety system (DFPCTSS), the synergistic relationship of its subsystems in the face of the interference and impact of internal and external disaster-causing factors, and the causal mechanism of typical accidents in DFP accidents and the emergent process of system resilience. A resilience evaluation indicator system based on four capacity dimensions of prevention absorption, resistance, recovery, and learning adaptation was constructed by using the fuzzy Delphi method, which is characterized by the resilience emergence process. Then the correlation and weight of evaluation indexes were analyzed based on the DEMATEL–ANP method, the boundary cloud parameters of the resilience evaluation grade were set according to the normal extension cloud model, and the membership degree of the resilience evaluation level was calculated to complete the evaluation of the resilience level. Finally, taking a DFP project of a metro station as an example, the above model was used to evaluate the resilience level of its construction safety system, and suggestions for resilience enhancement were put forward. The results show that the evaluation results are consistent with the actual situation of the project, and the evaluation model is conducive to providing a systematic analysis method and improvement countermeasures for deep foundation pit construction safety management from the perspective of resilience

Research on Resilience Evaluation and Enhancement of Deep Foundation Pit Construction Safety System

Deep foundation pit (DFP) projects have been a high incidence area of safety accidents because of their own high danger and complexity. Therefore, it is necessary to study the resilience of their construction safety system. This paper systematically identifies the key factors affecting the resilience of deep foundation pit construction based on the analysis of the composition of the deep foundation pit construction safety system (DFPCTSS), the synergistic relationship of its subsystems in the face of the interference and impact of internal and external disaster-causing factors, and the causal mechanism of typical accidents in DFP accidents and the emergent process of system resilience. A resilience evaluation indicator system based on four capacity dimensions of prevention absorption, resistance, recovery, and learning adaptation was constructed by using the fuzzy Delphi method, which is characterized by the resilience emergence process. Then the correlation and weight of evaluation indexes were analyzed based on the DEMATEL–ANP method, the boundary cloud parameters of the resilience evaluation grade were set according to the normal extension cloud model, and the membership degree of the resilience evaluation level was calculated to complete the evaluation of the resilience level. Finally, taking a DFP project of a metro station as an example, the above model was used to evaluate the resilience level of its construction safety system, and suggestions for resilience enhancement were put forward. The results show that the evaluation results are consistent with the actual situation of the project, and the evaluation model is conducive to providing a systematic analysis method and improvement countermeasures for deep foundation pit construction safety management from the perspective of resilience

Influencing Factor Identification and Simulation for Urban Metro System Operation Processes—A Resilience Enhancement Perspective

When confronted with rainstorms and flood disturbances, the operational processes of urban metro systems demonstrate vulnerabilities to attacks, inadequate resistance, and sluggish recovery characteristics. The flood resilience of UMS operational processes requires urgent enhancements. This paper aims to enhance the flood resilience of urban metro operation processes by proposing a three-stage PEL resilience enhancement framework: prevention resilience, response resilience, and learning resilience. Additionally, it summarizes the influencing factors on UMS flood resilience from five dimensions: natural-physical-social-management-economic (NPSME). By employing system dynamics as a simulation tool, this study elucidates the logical interconnections among these influential factors. Furthermore, by utilizing economic change conditions as an illustrative example, it effectively simulates the response characteristics of both standardized benchmark scenarios and economic change scenarios. Based on these simulation results, corresponding strategies for flood resilience enhancement are proposed to offer valuable insights for metro operation management. The Nanjing metro system was taken as a case study, where relevant historical data were collected and strategies were simulated for different development scenarios to validate the effectiveness and rationality of the proposed method for enhancing resilience. The simulation results demonstrate that changes in economic conditions and population structure are the primary factors influencing the enhancement of flood resilience in UMS operations

Using a novel approach to characterize the surface reactivities of silica-rich ferrihydrite and biogenic cyanobacteria-ferrihydrite aggregates and the implications for Archean ocean geochemistry

Precambrian banded iron formations (BIF) are iron- and silica-rich chemical sedimentary rocks that are commonly used as paleo-redox proxies for Archean and Paleoproterozoic seawater geochemistry. At the onset of the Great Oxidation Event (herein GOE) around 2.4 Ga, cyanobacteria flourished with increasing nutrient fluxes due to oxidative weathering on land. In turn, this led to increased primary productivity that facilitated the permanent shift from a reducing Earth atmosphere to an oxidizing one. Interestingly, the duration of GOE also overlapped with one of the most prolific periods of BIF deposition.It is widely accepted that cyanobacteria were likely responsible for BIF formation during the GOE. Oxidation of dissolved Fe(II) by oxygen produced from cyanobacteria forms a metastable and amorphous mineral phase ferrihydrite, Fe(OH)3. As an essential component in both ancient BIF deposits and various modern ecosystems, the surface reactivity of ferrihydrite has been extensively studied under different conditions (i.e., pH and ionic strengths). Not only are the highly reactive surfaces of ferrihydrite particles important shuttles for trace element transport from the water column to the sediment pile, but previous studies have also demonstrated that cyanobacterial cells and ferrihydrite tend to aggregate at seawater pH. This means that ferrihydrite was also a vector for the transport of organic carbon to the seafloor. However, a complicating issue is how co-ions affect the surface reactivity of ferrihydrite, specifically dissolved silica which was abundant in ancient seawater. Although previous studies have demonstrated that silica can passivate the surface reactivity of ferrihydrite, what remains unclear is how silica impacts ferrihydrite-biomass aggregation.To fill this knowledge gap, we formed both silica-spiked ferrihydrite and cyanobacteria-ferrihydrite aggregates in situ and subsequently conducted empirical potentiometric acid-base titrations and Cd adsorption experiments on the fresh aggregate samples at three different ionic strengths (0.56 M, 0.1 M and 0.01 M). We minimized sample processing (i.e., drying and powdering) to a simple washing step, in which the aggregate pellets remained hydrated to avoid any mineral transformation thus altering their true surface reactivity in seawater. Experimental results were then fitted with non-electrostatic model to predict both surface charges and metal-adsorption behavior of ferrihydrite aggregates. Different from previous surface-complexation modelling studies, here we used a novel and more powerful modelling program called Phreefit. It utilizes the global optimization algorithms instead of more commonly used Newton-Raphson method in FITEQL program, which is often too limited for precisely modelling complex systems such as the two samples in this study. Furthermore, we also measured the surface charges of both samples over the pH range from 3 to 9 on a Malvern Zetasizer and characterized the surface functional groups through Fourier-Transform Infrared Spectroscopy to help with our interpretation of the experimental data.Preliminary results show that cyanobacteria-ferrihydrite aggregates formed primarily due to ionic bridging. Cyanobacterial cells likely facilitated the precipitation of dissolved silica. Findings from titration and Cd adsorption experiments indicate that the surface reactivity and capacity of both silica-rich ferrihydrite cyanobacteria-ferrihydrite aggregates to adsorb trace elements differ from their individual components, likely due to site blockage. This distinction is particularly prominent when considering the expected Archean seawater pH from 6 to 8. This disparity implies that the biogenic ferrihydrite aggregates do not exhibit an additive surface reactivity, which is in agreement with similar previous studies. Our combined results are crucial to accurately predict the adsorption of trace elements onto the aggregate surface and, ultimately, comprehend the archive of trace elements in sedimentary rocks used to reconstruct Precambrian ocean chemistry

Finite element analysis of the angle range in trans-inferior alveolar nerve implantation at the mandibular second molar

Abstract Background Trans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle. Methods Cone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height < 9 mm in the edentulous area were selected. The distances from the mandibular nerve canal to the buccal cortex, the lingual cortex and the alveolar ridge crest were measured by using a combination of software. The angular ranges of the buccal-lingual inclination of simulated trans-IAN implants were measured and three-dimensional finite element models were constructed in the mandibular second molar area according to the differences of the inclination angles. A vertical load (200N) was then applied to analyze the biomechanical conditions of the implant-bone interface during median occlusion. Results The distance at the second molar from the nerve canal to the buccal cortex, lingual cortex and alveolar crest were 6.861 ± 1.194 mm, 2.843 ± 0.933 mm and 7.944 ± 0.77 mm. Trans-IAN implantation was feasible in 73.33% of patients. The minimum angle and maximum angles of the buccal-lingual inclination of the simulated implant were 19.135 ± 6.721° and 39.282 ± 6.581°. When a vertical static load of 200N was applied, the tensile stress in cortical bone gradually increased with the increase of the implant tilt angle. When the inclination angle reached 30°, the tensile stress (105.9 MPa) exceeded the yield strength (104 MPa) of cortical bone. Compared with the conventional implants, the stress peak value of the vertical ultra-short implant in cortical bone was greater than the stress peak value of the conventional implants at 10°(79.81 MPa) and 20°(82.83 MPa) and was smaller than the stress of the implant at 30°(105.9 MPa) and 40°(107.8 MPa). Therefore, when the bone mass allows, conventional-length implants should be selected whenever possible, and an operative range of the trans-IAN implantation in the mandibular second molar could be retained with an inclination angle of < 30°. Conclusions The mandibular nerve canal at the mandibular second molar was obviously biased to the lingual side, which ensured sufficient bone mass at the buccal side. In most patients with severe mandibular atrophy, it was possible to maintain a safe distance from the nerve canal with conventional-length implants via the trans-IAN implantation technique