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Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

Botulinum neurotoxin type A (BoNT/A) is traditional medicine and well known for its therapeutic use as an anesthetic and in cosmetic applications that work through the inhibition of acetylcholine exocytosis in neuronal cells. BoNT/A also has the potential to function as a biological weapon due to its high mortality rate and ease of dispersal. Emerging evidence suggests that BoNT/A exhibits biological effects on nonneuronal cells. In cytology experiments, BoNT/A induces global gene expression alterations. However, pulmonary effects from exposure to aerosolized BoNT/A have not been evaluated. This study investigated the global transcriptional profile of lung tissues after botulism inhalation. A mice model of inhaled botulism was established using intratracheal exposure to aerosolized BoNT/A and described through histological examination and flow cytometry. Transcriptomic analysis revealed that genes related to acute inflammatory responses were upregulated at 12-h postexposure. Increased expression of multiple anti-inflammatory marker genes and decreased expression of pro-inflammatory marker genes were observed at 48- to 72-h postexposure, underscoring a transcriptional shift toward a pro-reparative phenotype. Histological examination and cell proportions analysis mirrored these expression patterns. Accordingly, the orchestration of a quick phenotype transition prompted by BoNT/A may have the potential for promoting the resolution of the inflammatory lung. To our knowledge, this study represents the first research to investigate the pulmonary transcriptional responses of aerosolized BoNT/A exposure; the results may provide new insights in elucidating the molecular mechanism for pulmonary inhaled botulism and highlight the potential therapeutic application of BoNT/A in mitigating inflammatory conditions.

Aimed at fatigue damage in the antenna structure caused by large amplitude vibration with long time fluctuating wind loads, this paper use the harmonic synthesis method to transform power spectrum of Davenport fluctuating wind to fluctuating wind speed time series based on time domain. Then comprehensively considering the surface roughness coefficient, wind pressure coefficient of variation with height, wind vibration coefficient in Beijing area ,it transforms the fluctuating wind speed into the fluctuating wind pressure curve, takes the structural dynamics simulation and is obtained the dynamic response of the antenna structure in turbulent wind Loads; By the method of rain-flow counting , the fatigue life is analyzed with the statistics for the dangerous location of the antenna structure coursed of fatigue stress with time.

There is no explicit definition for critical ice shapes, and it is only mentioned in some ACs. Here, a rational and applicable definition for critical ice shapes is given based on well understanding of present literatures. Then, the available icing certification guidance concerning the various “critical ice shapes” is outlined. Different methods for determination of ice shapes as well as procedures are presented, and their characteristics are compared and analyzed. Based on the Combination Airfoil Assumption first presented by Glahn et al and developed by Farooq Saeed, we suggest a simple and useful method to determine the critical ice shapes on a normal airfoil which can be called combination airfoil comparison method. This method can be used to quickly get a preliminary ice shape for icing certification, but its criticality should be verified by other means of determining critical ice shapes. In order to examine the availability of this method, examples of Airbus aircraft types that have passed icing certification will be given. We hope that our findings and recommendations will be helpful to the applicant and icing certification team during aircraft icing certification.

For advanced airplane, the Safety of Flight tends to be dependent on complex flight control system. The result is a greatly increased emphasis on flight control system failure effects. FAR25 airworthiness standards are based on, and incorporate, the techniques of the fail-safe design concept. Critical FAR25 airworthiness clauses and Special Conditions about flight control system failures are analyzed. Airworthiness requirements and methods of compliance are studied. Key works in flight control system development are summarized. System safety assessments and failure state verification test are conducted for showing the compliance with airworthiness requirements.

In order to meet the airworthiness requirements (FAR33.70) of large commercial aero-engines, a new approach of probabilistic risk assessment linked durability is presented, and aiming at the issue of low-failure probabilities of key aero-engine structures, probabilistic risk assessment based on the Monte Carlo Radius-Outside Sampling (MCROS) in combination with the Kriging is used, then random factors such as the material, loading and environment can be considered in the given method. Example of probabilistic risk assessment based on fatigue for lower pressure compressor disk of aero-engine demonstrates the applicability, versatility and accuracy of the approach.

The development of safety critical systems becomes even harder sine the integrity and complexity of system functions and architecture grows continuously, and this kind of process involves cooperative work between safety and system engineerings during the development of products. The article presents a new approach called automated safety integrity analysis for complex system relying on functional model, and the process of safety integrity is studied by linking functional design phase using SysML(System Model Language) and Altarica Data Flow language based on risk engineering, and the given method can be analyzed automatically and iteratively during the whole life in order to unify the process between the system design and safety assessment.At last, the approach is exemplified by fuel system of aircraft to demonstrate the applicability and versatility, which explores the engineering research for the analysis technology for safety of the complex system.

PROBLEM The association between IL-10 gene promoter polymorphisms and the risk of recurrent miscarriages (RM) remains controversial. The present meta-analysis was performed to derive a precise estimate of the relationship. METHOD OF STUDY We searched the PubMed and EMBASE for studies related to the association between the IL-10 gene polymorphism and the risk of RM. Summary odds ratio (OR) with 95% confidence interval (CI) was estimated to assess the associations. RESULTS Thirteen studies, including 2047 RM cases and 2055 control samples, were identified. The results showed a significant association between rs1800896, rs1800871 and RM risk (for rs1800896: GA+GG vs AA: OR=1.20, 95% CI=1.04-1.39, P=.02; for rs1800871: CT+TT vs CC: OR=1.64, 95% CI=1.13-2.36, P=.009). No evidence of association was noted between rs1800872 haplotype and RM risk. CONCLUSION IL-10 gene promoter polymorphisms, rs1800896 and rs1800871, play a potential role in increasing the risk of RM.

With the increase of military and civil aircraft system complexity, the shortage of traditional safety analysis technology goes distinctly, while the Model-based Safety Analysis technology attaches more and more importance. Therefore, this paper presents the background, basic concept and research and application situation of Model-based Safety Analysis technology, identifies the benefit of it. This paper also presents a framework of taking Model-based Safety Analysis into airplane safety assessment process, and a case study of performing MBSA in powerplant system is given to shown the effect of MBSA. Finally, this paper analyses the shortage and challenge of Model-based Safety Analysis considering its application in aircraft safety assessment process.

As an important part of airborne avionics system, aircraft safety critical software (ASCS) plays an essential role to the safety of the aircraft, and to ensure its quality and reliability is one of the key problems we are facing. Formal methods have become important means for modeling and verifying safety critical software. In this paper, formal method is introduced into the ASCS verification field and the real-time extended finite state machine model (RT-EFSM) is studied, which includes the detailed real-time extension schemes and its validation methods. The verification process of ASCS based on RT-EFSM is also proposed. Furthermore, combined with the verification of an aircraft inertial/satellite navigation systems, a timed unique input/output sequence (t_UIO) is presented and the automatic generation algorithm of sub-transfer sequences based on t_UIO is given. Finally, the test adequacy criteria are discussed and a time condition coverage criterion is proposed. The actual engineering project application shows that the method proposed in this paper is of great value for the ASCS, which can be generally and effectively used in engineering.

The motion of main rotor head of helicopter rotor system is complex. Its reliability influences flying qualities and safety of helicopter directly. But, traditional experiments and deterministic simulation have been difficult to measure movement (flapping, lead-laging and pitching angles) and analyze motion reliability of main rotor head quantitatively. The virtual prototype model was built in the integrating simulation environment, which integrated Catia, MSC. Simdesigner and Adams. On the platform of Adams, we used the deformation of torsional spring to fit the moving angles. The kinematic and dynamic properties were simulated and analyzed deterministically. According to the compared result with the test data, it is shown that the virtual prototype is true and the result is feasible. Finally, we implemented reliability software-ARES which has been developed independently to call Adams and computed the flapping reliability quantitatively. The reliability and the sensitive parameters were obtained. Combined with the results and practical engineering, we presented an effective way to improve the flapping reliability from 0.9904 to 0.9993.

The aircraft power plant becomes even harder since the complexity and integrity of system function, and the traditional system safety analysis, influenced by the personal skills and experience of analysis, may cause error and system failure condition and effects. The paper presents a new approach called Model-based Safety Analysis (MBSA) for complex system, and the process of MBSA is studied by linking function modeling using formal language and fault propagation based on Altarica, and the given method can be introduced to aircraft power plant system in order to unify the process the system development and system safety assessment, and versatility and feasibility of the approach are demonstrated with the case study of aircraft power plant.