Fusion with extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 leads to enhancement of immunogenicity of Hantaan virus DNA vaccines in C57BL/6 mice

<p>Abstract</p> <p>Background</p> <p>Hantaan virus (HTNV) is the causative agent of the most severe form of a rodent-borne disease known as hemorrhagic fever with renal syndrome (HFRS). A safe and effective HTNV vaccine is needed. Vaccination with DNA constructs expressing fused antigen with bioactive factors, has shown promising improvement of immunogenicity for viral agents in animal models, but the effect of fusion strategy on HTNV DNA vaccine has not been investigated.</p> <p>Results</p> <p>DNA plasmids encoding the HTNV nucleocapsid protein (N) and glycoprotein (Gn and Gc) in fusion to the extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 (eCTLA-4) targeting to antigen presenting cells (APCs) were constructed. Intramuscular immunization of mice with plasmids expressing eCTLA-4-HTNV-N/GP fusion proteins leads to a significant enhancement of the specific antibody response as well as cytotoxic T-lymphocyte (CTL) response in C57BL/6 mice. Moreover, this effect could be further augmented when co-administered with CpG motifs.</p> <p>Conclusions</p> <p>Modification of viral antigen in fusion to bioactive factor will be promising to confer efficient antigen presentation and improve the potency of DNA vaccine in mice.</p

Variable-Length Bit Mapping and Error-Correcting Codes for Higher-Order Alphabet PUFs

Device-specific physical characteristics provide the foundation for PUFs, a hardware primitive for secure storage of cryptographic keys. So far, they have been implemented by either directly evaluating a binary output or by mapping outputs from a higher-order alphabet to a fixed-length bit sequence. However, the latter causes a significant bias in the derived key when combined with an equidistant quantization. To overcome this limitation, we propose a variable-length bit mapping that reflects the properties of a Gray code in a different metric, namely the Levenshtein metric instead of the classical Hamming metric. Subsequent error-correction is therefore based on a custom insertion/deletion correcting code. This new approach effectively counteracts the bias in the derived key already at the input side. We present the concept for our scheme and demonstrate its feasibility based on an empirical PUF distribution. As a result, we increase the effective output bit length of the secret by over 40% compared to state-of-the-art approaches while at the same time obtaining additional advantages, e.g., an improved tamper-sensitivity. This opens up a new direction of Error-Correcting Codes (ECCs) for PUFs that output responses with symbols of higher-order output alphabets

Generation, Characterization and Epitope Mapping of Two Neutralizing and Protective Human Recombinant Antibodies against Influenza A H5N1 Viruses

The development of new therapeutic targets and strategies to control highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is urgently needed. Broadly cross-neutralizing recombinant human antibodies obtained from the survivors of H5N1 avian influenza provide an important role in immunotherapy for human H5N1 virus infection and definition of the critical epitopes for vaccine development.We have characterized two recombinant baculovirus-expressed human antibodies (rhAbs), AVFluIgG01 and AVFluIgG03, generated by screening a Fab antibody phage library derived from a patient recovered from infection with a highly pathogenic avian influenza A H5N1 clade 2.3 virus. AVFluIgG01 cross-neutralized the most of clade 0, clade 1, and clade 2 viruses tested, in contrast, AVFluIgG03 only neutralized clade 2 viruses. Passive immunization of mice with either AVFluIgG01 or AVFluIgG03 antibody resulted in protection from a lethal H5N1 clade 2.3 virus infection. Furthermore, through epitope mapping, we identify two distinct epitopes on H5 HA molecule recognized by these rhAbs and demonstrate their potential to protect against a lethal H5N1 virus infection in a mouse model.Importantly, localization of the epitopes recognized by these two neutralizing and protective antibodies has provided, for the first time, insight into the human antibody responses to H5N1 viruses which contribute to the H5 immunity in the recovered patient. These results highlight the potential of a rhAbs treatment strategy for human H5N1 virus infection and provide new insight for the development of effective H5N1 pandemic vaccines

Study on Overburden Movement and Fissure Evolution Law of Protective Layer Mining in Shallow Coal Seam

This study aims to effectively solve the problem of the destruction of the coal roof and floor overlying rock after mining the protective layer, and determines whether the gas in the protected layer can be effectively released. We do this based on the engineering background of the Weng&rsquo;an Coal Mine; research and analysis of the movement of the roof and floor overlying rocks; the evolution of cracks and the pressure relief characteristics of the protected layer after mining the protective layer; and through theoretical analysis and similar simulation experiments. Through numerical simulation, it was found that the protected layer was depressurized due to the mining of the protective layer, and the decompression rate of the protected layer was 0.2&ndash;0.8. In addition, the overall expansion rate of the protected layer was greater than the requirements of the &ldquo;Detailed Rules for Prevention and Control of Coal and Gas Outbursts&rdquo; for coal mines, and the investigation of the residual gas pressure and content of the protected layer revealed that the protected coal seam had been mined in the upper protective layer coal face. The gas pressure dropped to 50.7% of the original coal seam gas pressure, the rate of decrease was 49.3%, the residual gas content dropped by 68.67%, and the gas concentration in the return airway was 0.31% on average, meeting the national regulations that require its value to be less than or equal to 1%. The study comprehensively demonstrates that mining of the protective layer is beneficial to the release of gas from the protected layer, and provides a practical reference for coal and gas outbursts in mines

Study on Overburden Movement and Fissure Evolution Law of Protective Layer Mining in Shallow Coal Seam

This study aims to effectively solve the problem of the destruction of the coal roof and floor overlying rock after mining the protective layer, and determines whether the gas in the protected layer can be effectively released. We do this based on the engineering background of the Weng’an Coal Mine; research and analysis of the movement of the roof and floor overlying rocks; the evolution of cracks and the pressure relief characteristics of the protected layer after mining the protective layer; and through theoretical analysis and similar simulation experiments. Through numerical simulation, it was found that the protected layer was depressurized due to the mining of the protective layer, and the decompression rate of the protected layer was 0.2–0.8. In addition, the overall expansion rate of the protected layer was greater than the requirements of the “Detailed Rules for Prevention and Control of Coal and Gas Outbursts” for coal mines, and the investigation of the residual gas pressure and content of the protected layer revealed that the protected coal seam had been mined in the upper protective layer coal face. The gas pressure dropped to 50.7% of the original coal seam gas pressure, the rate of decrease was 49.3%, the residual gas content dropped by 68.67%, and the gas concentration in the return airway was 0.31% on average, meeting the national regulations that require its value to be less than or equal to 1%. The study comprehensively demonstrates that mining of the protective layer is beneficial to the release of gas from the protected layer, and provides a practical reference for coal and gas outbursts in mines

Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice

Nootkatone (NKT), a major ingredient of Alpinia oxyphylla, exhibited potential nephroprotective effects; however, the precise molecular mechanisms remain poorly understood. This study aimed to study the nephroprotective effects of NKT and the underlying mechanisms in a mouse model. Our results showed that NKT pretreatment at the doses of 5, 10, and 20 mg/kg per day for 7 days significantly attenuates carbon tetrachloride (CCl4)-induced increases of serum BUN and CRE and kidney pathology injury. NKT pretreatment also markedly inhibited oxidative stress, inflammatory response, and the activation of caspases-9 and -3 in kidneys of mice exposed to CCl4. Meanwhile, NKT pretreatment downregulated the expression of NOX4, IL-1β, IL-6, and TNF-α proteins and NO levels in the kidney tissues. Moreover, NKT pretreatment upregulated the expression of Nrf2 and HO-1 mRNAs, and downregulated the expression of NF-κB, IL-1β, IL-6, TNF-α, and iNOS mRNAs in the kidneys of mice, compared to those in the CCl4 alone treatment group. In conclusion, our results reveal that NKT supplementation could protect against CCl4 exposure-induced oxidative stress and inflammatory response in the kidneys by inhibiting NOX4 and NF-κB pathways and activating the Nrf2/HO-1 pathway. Our current study highlights the therapeutic application of NKT for kidney diseases

Comprehensive Identification of Surface Subsidence Evaluation Grades of Mines in Southwest China

Due to their complex geological structure, it is difficult to systematically analyze the surface subsidence of coal mines in southwest China, and the factors that cause surface subsidence are also different from other coal mines. Focusing on the problem of surface subsidence caused by mining in southwest China’s mines, a grade evaluation system for surface subsidence of southwest mines is constructed based on the analytic hierarchy process, and ten evaluation indicators are established from the perspectives of mining disturbance and geological structure. A matter–element model of surface subsidence based on matter–element extension theory and a cloud model of surface subsidence based on cloud theory are then constructed. A coal mine in Anshun, Guizhou, is taken as an example to calculate the evaluation level of surface subsidence and thus verify the scientificity of extension theory and cloud theory. The results show that the main factors that affect the surface subsidence of southwest mines are the number of coal seam layers, mining height and comprehensive Platt hardness of rock, similar to that of northern plain coal mines. Surface slope and subsidence area are also very important. The comprehensive correlation degree of each grade of the coal mine is −0.29836, 0.192232, −0.1093 and −0.46531, and the coal mine is concluded to be in grade 2. The calculated similarity of the overall index evaluation cloud map of the coal mine and each grade is 0, 0.3453, 0.7872 and 0, respectively. The coal mine is in grade 2, which is a relatively safe state. Consistent with the calculation results of the extension model and in line with the field situation, the extension matter–element model and cloud model built in this paper can verify each other and have a certain scientificity

Health Risk Assessment for Inhalation Exposure to Methyl Tertiary Butyl Ether at Petrol Stations in Southern China

Methyl tertiary butyl ether (MTBE), a well known gasoline additive, is used in China nationwide to enhance the octane number of gasoline and reduce harmful exhaust emissions, yet  little is known regarding the potential health risk associated with occupational exposure to MTBE in petrol stations. In this study, 97 petrol station attendants (PSAs) in southern China were recruited for an assessment of the health risk associated with inhalation exposure to MTBE. The personal exposure levels of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS, and the demographic characteristics of the PSAs were investigated. Cancer and non-cancer risks were calculated with the methods recommended by the United States Environmental Protection Agency. The results showed that the exposure levels of MTBE in operating workers were much higher than among support staff (p &lt; 0.01) and both were lower than 50 ppm (an occupational threshold limit value). The calculated cancer risks (CRs) at the investigated petrol stations was 0.170 to 0.240 per 106 for operating workers, and 0.026 to 0.049 per 106 for support staff, which are below the typical target range for risk management of 1 × 10−6 to 1 × 10−4; The hazard quotients (HQs) for all subjects were &lt;1. In conclusion, our study indicates that the MTBE exposure of PSAs in southern China is in a low range which does not seem to be a significant health risk