This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a norm...This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a normal group and a SIRT1 gene knock-out group(6 mice in each group). In these groups, one side of the knee anterior cruciate ligament was traversed, and the ipsilateral medial meniscus was cut to establish an osteoarthritis model of knee joint. The countralateral synovial bursa was cut out, serving as controls. The knee joint specimens were then divided into four groups: SIRT1^(+/+) control group(group A, n=6); SIRT1^(+/+) osteoarthritis group(group B, n=6); SIRT1^(–/–) control group(group C, n=6); SIRT1^(–/–) osteoarthritis group(group D, n=6). HE staining, Masson staining, Safranin O-Fast Green staining and Van Gieson staining were used to observe the morphological changes in the articular cartilage of the knee. Immunohistochemical staining was employed to detect the expression of SIRT1, SREBP2, VEGF, AKT, HMGCR and type Ⅱ collagen proteins. SA-β-gal staining was utilized to evaluate chondrocyte aging. The results showed clear knee joint cartilage destruction and degeneration in the SIRT1^(–/–) osteoarthritis group. The tidal line was twisted and displaced anteriorly. Type Ⅱ collagen was destroyed and distributed unevenly. Compared with the SIRT1^(+/+) osteoarthritis group and SIRT1^(–/–) control group, SIRT1 protein expression was not obviously changed in the SIRT1^(–/–) osteoarthritis group(P〉0.05), while the expression levels of the SREBP2, VEGF and HMGCR proteins were significantly increased(P〈0.05) and the levels of AKT and type Ⅱ collagen proteins were significantly decreased(P〈0.05). SIRT1 gene knock-out may aggravate cartilage degeneration in osteoarthritis by activating the SREBP2 protein-mediated PI3K/AKT signalling pathway, suggesting that SIRT1 gene may play a protective role against osteoarthritis.展开更多
Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and ad...Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three- dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.展开更多
Based on the loading conditions of engine, applying difference method to solve the hydrodynamic lubrication equation of piston skirt movement, the force acting on piston skirt and the moment on wrist pin were obtained...Based on the loading conditions of engine, applying difference method to solve the hydrodynamic lubrication equation of piston skirt movement, the force acting on piston skirt and the moment on wrist pin were obtained. A computer program for simulating the piston second order motion was conducted to calculate the lateral motion of the upper part and the bottom part of piston skirts of the engine of automotive model CA1091. From the simulated result, the maximal impacting phase and the maximal impacting region of the piston were obtained. The result can be used for designing engine, diagnosing the noise of piston knocking cylinder wall and explaining many practical fault phenomena in theory.展开更多
This study aimed to compare the efficiencies of clustered regulatory interspaced short palindromic repeat(CRISPR)/Cas9-mediated gene knock-ins with zinc finger nucleases(ZFNs) and transcription activator-like effe...This study aimed to compare the efficiencies of clustered regulatory interspaced short palindromic repeat(CRISPR)/Cas9-mediated gene knock-ins with zinc finger nucleases(ZFNs) and transcription activator-like effector nucleases(TALENs) in bovine and dairy goat fetal fibroblasts. To test the knock-in efficiency, a set of ZFNs and CRISPR/Cas9 plasmids were designed to edit the bovine myostatin(MSTN) gene at exon 2, while a set of TALENs and CRISPR/Cas9 plasmids were designed for editing the dairy goat β-casein gene at exon 2. Donor plasmids utilizing the ZFNs, TALENs, and CRISPR/Cas9 cutting sites were constructed in theGFP-PGK-Neo R plasmid background, including a 5′ and 3′ homologous arm flanking the genes humanized Fat-1(h Fat-1) or enhanced green fluorescent protein(eGFP). Subsequently, the ZFNs, TALENs, or CRISPR/Cas9 and thehFat-1 or eGFP plasmids were co-transfected by electroporation into bovine and dairy goat fetal fibroblasts. After G418(Geneticin) selection, single cells were obtained by mouth pipetting, flow cytometry or a cell shove. The gene knock-in events were screened by PCR across the homologous arms. The results showed that in bovine fetal fibrobalsts, the efficiencies of ZFNs-mediated eGFP andhFat-1 gene knock-ins were 13.68 and 0%, respectively. The efficiencies of CRISPR/Cas9-mediated eGFP andhFat-1 gene knock-ins were 77.02 and 79.01%, respectively. The eGFP gene knock-in efficiency using CRISPR/Cas9 was about 5.6 times higher than when using the ZFNs gene editing system. Additionally, thehFat-1 gene knock-in was only obtained when using the CRISPR/Cas9 system. The difference of knockin efficiencies between the ZFNs and CRISPR/Cas9 systems were extremely significant(P〈0.01). In the dairy goat fetal fibroblasts, the efficiencies of TALENs-mediated eGFP andhFat-1 gene knock-ins were 32.35 and 26.47%, respectively. Theefficiencies of eGFP and hFat-1 gene knock-ins using CRISPR/Cas9 were 70.37 and 74.29%, respectively. The knock-in efficiencies difference between the TALENs and CRISPR/Cas9 systems were extremely significant(P〈0.01). This study demonstrated that CRISPR/Cas9 was more efficient at gene knock-ins in domesticated animal cells than ZFNs and TALENs. The CRISPR/Cas9 technology offers a new era of precise gene editing in domesticated animal cell lines.展开更多
The present work used a methane-air mixture chemical kinetics scheme consisting of 119 elementary reaction steps and 41 chemical species to develop a simplified combustion model for prediction of the knock in dual fue...The present work used a methane-air mixture chemical kinetics scheme consisting of 119 elementary reaction steps and 41 chemical species to develop a simplified combustion model for prediction of the knock in dual fuel engines. Calculated values by the model for natural gas operation showed good agreement with corresponding experimental values over a broad range of operating conditions.展开更多
Experiments were conducted on a diesel-methanol dual-fuel(DMDF)engine modified by a six-cylinder,turbocharged,inter-cooled diesel engine.According to the number of diesel injection,the experiments are divided to two p...Experiments were conducted on a diesel-methanol dual-fuel(DMDF)engine modified by a six-cylinder,turbocharged,inter-cooled diesel engine.According to the number of diesel injection,the experiments are divided to two parts:the single injectionmode and double injectionmode.The results show that,at the double injectionmode,themaximumof pressure rise rate is small and the engine runs smoothly,however,knock still occurswhen the cocombustion ratio(CCR)is big enough.Under knock status,the power density of the block vibration concentrating at some special frequencies rises dramatically,and the special frequency of single injection mode(about 4.1 kHz)is lower than that of double injection mode(7–9 kHz).The cylinder pressure oscillations of knock status are very different fromthe non-knock status.Under knock status,cylinder pressure oscillations become more concentrated and fiercer at some special frequencies,and the same as the block vibration.The special frequency of single injection mode(3–6 kHz)is lower than that of double injection mode(above 9 kHz).展开更多
The application of railway wheel noise compensation method is considered. The effect can be obtained by shift a pair of usual parallel rail joints on a pair of offset rail joints, for example, the right rail joint is ...The application of railway wheel noise compensation method is considered. The effect can be obtained by shift a pair of usual parallel rail joints on a pair of offset rail joints, for example, the right rail joint is shifted concerning the left rail joint on the certain distance. The distance is depend on the speed of train and promotes the correlation interconnection between excited acoustical pulses. The intensity wheel knock spectrograms corresponding of different distance between rail joints registered by the microphone are estimated. The spectrograms considerably differed from each other in low frequency band are analyzed. The result of practical using the acoustic noise compensation method is proved.展开更多
海上拖航合同中的Knock For Knock条款的效力在实践中一直存在争议。本文通过分析《海商法》第162条,结合Knock For Knock条款的性质进行讨论,得出结论《海商法》第162条可以作为订立Knock For Knock条款的依据,但是不能作为该条款在任...海上拖航合同中的Knock For Knock条款的效力在实践中一直存在争议。本文通过分析《海商法》第162条,结合Knock For Knock条款的性质进行讨论,得出结论《海商法》第162条可以作为订立Knock For Knock条款的依据,但是不能作为该条款在任何情形下均有效的依据。并且通过对Knock For Knock条款效力的进一步探讨,可知海上拖航中的承拖方不得以该条款对抗被拖方提出的由于承拖方的故意或重大过失行为造成其损失的赔偿请求。除此之外,本文将借鉴国外判例,结合我国国情,提出减少Knock For Knock条款实践纠纷的建议。展开更多
Dear Editor,The emergence of CRISPR/Cas9-based genome editing technology has energized many applied biotechnology fields,including livestock breeding(Zhao et al.,2019).Given that the most naturally occurring beneficia...Dear Editor,The emergence of CRISPR/Cas9-based genome editing technology has energized many applied biotechnology fields,including livestock breeding(Zhao et al.,2019).Given that the most naturally occurring beneficial variants in farm animals are regulatory alleles(Georges et al.,2019),practical livestock editing should mostly involve knocking-in of the natural variants,or of designed elements to regulate key genes.展开更多
Otoancorin(OTOA)is a glycosylphosphatidylinositol(GPI)-anchored protein mediating the attachment of the tectorial membrane(TM)to the spiral limbus(SL)in the inner ear.Homozygous or compound heterozygous mutations in O...Otoancorin(OTOA)is a glycosylphosphatidylinositol(GPI)-anchored protein mediating the attachment of the tectorial membrane(TM)to the spiral limbus(SL)in the inner ear.Homozygous or compound heterozygous mutations in OTOA cause autosomal recessive deafness(DFNB22).We performed short-read exome sequencing(SRS)in a 10-monthold boy with sensorineural hearing loss,identifying a potential p.Glu787*variant in OTOA.Interestingly,this variant is common among normal-hearing individuals,leading us to question its pathogenic potential.展开更多
In this extensive investigation,the impact of borax decahydrate as a fuel additive in a diesel single-cylinder engine was rigorously examined.Borax decahydrate was introduced at concentrations of 5,15,25 and 35 g in 5...In this extensive investigation,the impact of borax decahydrate as a fuel additive in a diesel single-cylinder engine was rigorously examined.Borax decahydrate was introduced at concentrations of 5,15,25 and 35 g in 500 ml of biodiesel,forming five unique fuel mixtures with conventional diesel:90%diesel+10%spirulina biodiesel(SB10),SB10+1 g borax decahydrate(SB10B1),SB10+3 g borax decahydrate(SB10B3),SB10+5 g borax decahydrate(SB10B5)and SB10+7 g borax decahydrate(SB10B7).The investigation encompassed four diverse loading conditions and yielded insightful findings.Notably,at full load,SB10B3 exhibited a higher cylinder peak pressure than diesel,reaching 69.25 bar.Heat release rate profiles demonstrated superior efficiency for SB10 at 50%load,with a cumulative heat release rate of 950 J/°CA,which is lower than the 1050 J/°CA of diesel.Knock intensity(KI)evaluations revealed that,although SB10 and SB10B1 exhibited higher KI than diesel at full load due to elevated peak pressure,SB10B7 showed no knocking across all loads,indicative of reduced in-cylinder combustion.This meticulous numerical analysis emphasizes the potential of borax decahydrate as a catalyst and enhancer,providing valuable insights into the combustion dynamics of these alternative fuel blends and their viability for sustainable and efficient engine performance.In summary,out of all the blends,SB10B3 could be a potential diesel fuel replacement fuel for compression-ignition engines.展开更多
Words are like magic.They can lift you up,or they can knock you down.They are the most powerful tool we have.When I was in Grade 7,I performed badly in a math test.
Pre-Authentication and Post-Connection(PAPC)plays a crucial role in realizing the Zero Trust security model by ensuring that access to network resources is granted only after successful authentication.While earlier ap...Pre-Authentication and Post-Connection(PAPC)plays a crucial role in realizing the Zero Trust security model by ensuring that access to network resources is granted only after successful authentication.While earlier approaches such as Port Knocking(PK)and Single Packet Authorization(SPA)introduced pre-authentication concepts,they suffer from limitations including plaintext communication,protocol dependency,reliance on dedicated clients,and inefficiency under modern network conditions.These constraints hinder their applicability in emerging distributed and resource-constrained environments such as AIoT and browser-based systems.To address these challenges,this study proposes a novel port-sequence-based PAPC scheme structured as a modular model comprising a client,server,and ephemeral Key Management System(KMS).The system employs the Advanced Encryption Standard(AES-128)to protect message confidentiality and uses a Hash-Based Message Authentication Code(HMAC-SHA256)to ensure integrity.Authentication messages are securely fragmented and mapped to destination port numbers using a signature-based avoidance algorithm,which prevents collisions with unsafe or reserved port ranges.The server observes incoming port sequences,retrieves the necessary keys from the KMS,reconstructs and verifies the encrypted data,and conditionally updates firewall policies.Unlike SPA,which requires decrypting all incoming payloads and imposes server-side overhead,the proposed system verifies only port-derived fragments,significantly reducing computational burden.Furthermore,it eliminates the need for raw socket access or custom clients,supporting browser-based operation and enabling protocol-independent deployment.Through a functional web-based prototype and emulated testing,the system achieved an F1-score exceeding 95%in detecting unauthorized access while maintaining low resource overhead.Although port sequence generation introduces some client-side cost,it remains lightweight and scalable.By tightly integrating lightweight cryptographic algorithms with a transport-layer communication model,this work presents a conceptually validated architecture that contributes a novel direction for interoperable and scalable Zero Trust enforcement in future network ecosystems.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81272032)the Research and Development Projects of Shenzhen of China(Nos.JCYJ20150403091443275)
文摘This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a normal group and a SIRT1 gene knock-out group(6 mice in each group). In these groups, one side of the knee anterior cruciate ligament was traversed, and the ipsilateral medial meniscus was cut to establish an osteoarthritis model of knee joint. The countralateral synovial bursa was cut out, serving as controls. The knee joint specimens were then divided into four groups: SIRT1^(+/+) control group(group A, n=6); SIRT1^(+/+) osteoarthritis group(group B, n=6); SIRT1^(–/–) control group(group C, n=6); SIRT1^(–/–) osteoarthritis group(group D, n=6). HE staining, Masson staining, Safranin O-Fast Green staining and Van Gieson staining were used to observe the morphological changes in the articular cartilage of the knee. Immunohistochemical staining was employed to detect the expression of SIRT1, SREBP2, VEGF, AKT, HMGCR and type Ⅱ collagen proteins. SA-β-gal staining was utilized to evaluate chondrocyte aging. The results showed clear knee joint cartilage destruction and degeneration in the SIRT1^(–/–) osteoarthritis group. The tidal line was twisted and displaced anteriorly. Type Ⅱ collagen was destroyed and distributed unevenly. Compared with the SIRT1^(+/+) osteoarthritis group and SIRT1^(–/–) control group, SIRT1 protein expression was not obviously changed in the SIRT1^(–/–) osteoarthritis group(P〉0.05), while the expression levels of the SREBP2, VEGF and HMGCR proteins were significantly increased(P〈0.05) and the levels of AKT and type Ⅱ collagen proteins were significantly decreased(P〈0.05). SIRT1 gene knock-out may aggravate cartilage degeneration in osteoarthritis by activating the SREBP2 protein-mediated PI3K/AKT signalling pathway, suggesting that SIRT1 gene may play a protective role against osteoarthritis.
基金supported by National Natural Science Foundation of China(Grant No. 51176138)Tianjin Municipal Natural Science Foundation of China(Grant No. 12TJZDTJ28800)
文摘Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three- dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.
文摘Based on the loading conditions of engine, applying difference method to solve the hydrodynamic lubrication equation of piston skirt movement, the force acting on piston skirt and the moment on wrist pin were obtained. A computer program for simulating the piston second order motion was conducted to calculate the lateral motion of the upper part and the bottom part of piston skirts of the engine of automotive model CA1091. From the simulated result, the maximal impacting phase and the maximal impacting region of the piston were obtained. The result can be used for designing engine, diagnosing the noise of piston knocking cylinder wall and explaining many practical fault phenomena in theory.
基金supported by the National Transgenic Project of China (2016ZX08010001-002)the National Natural Science Foundation of China (81471001)+1 种基金the Inner Mongolia Science and Technology Program, China (201502073)the National 863 Prgram of China (2009AA10Z111)
文摘This study aimed to compare the efficiencies of clustered regulatory interspaced short palindromic repeat(CRISPR)/Cas9-mediated gene knock-ins with zinc finger nucleases(ZFNs) and transcription activator-like effector nucleases(TALENs) in bovine and dairy goat fetal fibroblasts. To test the knock-in efficiency, a set of ZFNs and CRISPR/Cas9 plasmids were designed to edit the bovine myostatin(MSTN) gene at exon 2, while a set of TALENs and CRISPR/Cas9 plasmids were designed for editing the dairy goat β-casein gene at exon 2. Donor plasmids utilizing the ZFNs, TALENs, and CRISPR/Cas9 cutting sites were constructed in theGFP-PGK-Neo R plasmid background, including a 5′ and 3′ homologous arm flanking the genes humanized Fat-1(h Fat-1) or enhanced green fluorescent protein(eGFP). Subsequently, the ZFNs, TALENs, or CRISPR/Cas9 and thehFat-1 or eGFP plasmids were co-transfected by electroporation into bovine and dairy goat fetal fibroblasts. After G418(Geneticin) selection, single cells were obtained by mouth pipetting, flow cytometry or a cell shove. The gene knock-in events were screened by PCR across the homologous arms. The results showed that in bovine fetal fibrobalsts, the efficiencies of ZFNs-mediated eGFP andhFat-1 gene knock-ins were 13.68 and 0%, respectively. The efficiencies of CRISPR/Cas9-mediated eGFP andhFat-1 gene knock-ins were 77.02 and 79.01%, respectively. The eGFP gene knock-in efficiency using CRISPR/Cas9 was about 5.6 times higher than when using the ZFNs gene editing system. Additionally, thehFat-1 gene knock-in was only obtained when using the CRISPR/Cas9 system. The difference of knockin efficiencies between the ZFNs and CRISPR/Cas9 systems were extremely significant(P〈0.01). In the dairy goat fetal fibroblasts, the efficiencies of TALENs-mediated eGFP andhFat-1 gene knock-ins were 32.35 and 26.47%, respectively. Theefficiencies of eGFP and hFat-1 gene knock-ins using CRISPR/Cas9 were 70.37 and 74.29%, respectively. The knock-in efficiencies difference between the TALENs and CRISPR/Cas9 systems were extremely significant(P〈0.01). This study demonstrated that CRISPR/Cas9 was more efficient at gene knock-ins in domesticated animal cells than ZFNs and TALENs. The CRISPR/Cas9 technology offers a new era of precise gene editing in domesticated animal cell lines.
文摘The present work used a methane-air mixture chemical kinetics scheme consisting of 119 elementary reaction steps and 41 chemical species to develop a simplified combustion model for prediction of the knock in dual fuel engines. Calculated values by the model for natural gas operation showed good agreement with corresponding experimental values over a broad range of operating conditions.
基金funded by the Science Research Project of State Grid Shaanxi Electric Power Company(5226 KY22001J)Yulin Science and Technology Planning Project(CXY-2020-024)+1 种基金Natural Science Basic Research Plan of Shaanxi(2018JQ5115,2020JM-243)the Special Fund for Basic Scientific Research of Central Colleges,Chang’an University(2018JQ5115).
文摘Experiments were conducted on a diesel-methanol dual-fuel(DMDF)engine modified by a six-cylinder,turbocharged,inter-cooled diesel engine.According to the number of diesel injection,the experiments are divided to two parts:the single injectionmode and double injectionmode.The results show that,at the double injectionmode,themaximumof pressure rise rate is small and the engine runs smoothly,however,knock still occurswhen the cocombustion ratio(CCR)is big enough.Under knock status,the power density of the block vibration concentrating at some special frequencies rises dramatically,and the special frequency of single injection mode(about 4.1 kHz)is lower than that of double injection mode(7–9 kHz).The cylinder pressure oscillations of knock status are very different fromthe non-knock status.Under knock status,cylinder pressure oscillations become more concentrated and fiercer at some special frequencies,and the same as the block vibration.The special frequency of single injection mode(3–6 kHz)is lower than that of double injection mode(above 9 kHz).
文摘The application of railway wheel noise compensation method is considered. The effect can be obtained by shift a pair of usual parallel rail joints on a pair of offset rail joints, for example, the right rail joint is shifted concerning the left rail joint on the certain distance. The distance is depend on the speed of train and promotes the correlation interconnection between excited acoustical pulses. The intensity wheel knock spectrograms corresponding of different distance between rail joints registered by the microphone are estimated. The spectrograms considerably differed from each other in low frequency band are analyzed. The result of practical using the acoustic noise compensation method is proved.
文摘海上拖航合同中的Knock For Knock条款的效力在实践中一直存在争议。本文通过分析《海商法》第162条,结合Knock For Knock条款的性质进行讨论,得出结论《海商法》第162条可以作为订立Knock For Knock条款的依据,但是不能作为该条款在任何情形下均有效的依据。并且通过对Knock For Knock条款效力的进一步探讨,可知海上拖航中的承拖方不得以该条款对抗被拖方提出的由于承拖方的故意或重大过失行为造成其损失的赔偿请求。除此之外,本文将借鉴国外判例,结合我国国情,提出减少Knock For Knock条款实践纠纷的建议。
基金supported by the National Key Research and Development Program of China(NKPs)(2021YFF1000700 and 2019YFA0802802)by the National Natural Science Foundation of China(32172735).
文摘Dear Editor,The emergence of CRISPR/Cas9-based genome editing technology has energized many applied biotechnology fields,including livestock breeding(Zhao et al.,2019).Given that the most naturally occurring beneficial variants in farm animals are regulatory alleles(Georges et al.,2019),practical livestock editing should mostly involve knocking-in of the natural variants,or of designed elements to regulate key genes.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2021R1C1C1007980 to B.J.K.)Chungnam National University Sejong Hospital Research Fund,2022,and Chungnam National University(to B.J.K.)+6 种基金supported by the Basic Science Research Program through the NRF,funded by the Ministry of Education(No.2021R1A2C2092038 to B.Y.C.)Bio Core Facility Center program(No.NRF-2022M3A9G1014007 to B.Y.C.)the Basic Research Laboratory program through the NRF,funded by the Ministry of Education(No.RS-2023-0021971031482092640001 to B.Y.C.)the Technology Innovation Program(No.K_G012002572001 to B.Y.C.)funded By the Ministry of Trade,Industry&Energy(MOTIE,Korea)funded by SNUBH(Seoul National University Bundang Hospital)intramural research fund(No.13-2022-0010,02-2017-0060,16-2023-0002,13-2023-0002,16-2022-0005,13-2024-0004,and 13-2017-0013 to B.Y.C.)supported by the National Institute on Deafness and Other Communication Disorders(NIDCD)part of the US National Institutes of Health(No.R01DC018814 to S.P.).
文摘Otoancorin(OTOA)is a glycosylphosphatidylinositol(GPI)-anchored protein mediating the attachment of the tectorial membrane(TM)to the spiral limbus(SL)in the inner ear.Homozygous or compound heterozygous mutations in OTOA cause autosomal recessive deafness(DFNB22).We performed short-read exome sequencing(SRS)in a 10-monthold boy with sensorineural hearing loss,identifying a potential p.Glu787*variant in OTOA.Interestingly,this variant is common among normal-hearing individuals,leading us to question its pathogenic potential.
文摘In this extensive investigation,the impact of borax decahydrate as a fuel additive in a diesel single-cylinder engine was rigorously examined.Borax decahydrate was introduced at concentrations of 5,15,25 and 35 g in 500 ml of biodiesel,forming five unique fuel mixtures with conventional diesel:90%diesel+10%spirulina biodiesel(SB10),SB10+1 g borax decahydrate(SB10B1),SB10+3 g borax decahydrate(SB10B3),SB10+5 g borax decahydrate(SB10B5)and SB10+7 g borax decahydrate(SB10B7).The investigation encompassed four diverse loading conditions and yielded insightful findings.Notably,at full load,SB10B3 exhibited a higher cylinder peak pressure than diesel,reaching 69.25 bar.Heat release rate profiles demonstrated superior efficiency for SB10 at 50%load,with a cumulative heat release rate of 950 J/°CA,which is lower than the 1050 J/°CA of diesel.Knock intensity(KI)evaluations revealed that,although SB10 and SB10B1 exhibited higher KI than diesel at full load due to elevated peak pressure,SB10B7 showed no knocking across all loads,indicative of reduced in-cylinder combustion.This meticulous numerical analysis emphasizes the potential of borax decahydrate as a catalyst and enhancer,providing valuable insights into the combustion dynamics of these alternative fuel blends and their viability for sustainable and efficient engine performance.In summary,out of all the blends,SB10B3 could be a potential diesel fuel replacement fuel for compression-ignition engines.
文摘Words are like magic.They can lift you up,or they can knock you down.They are the most powerful tool we have.When I was in Grade 7,I performed badly in a math test.
基金supported by Institute for Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(No.RS-2022-II221200)Convergence Security Core Talent Training Business(Chungnam National University).
文摘Pre-Authentication and Post-Connection(PAPC)plays a crucial role in realizing the Zero Trust security model by ensuring that access to network resources is granted only after successful authentication.While earlier approaches such as Port Knocking(PK)and Single Packet Authorization(SPA)introduced pre-authentication concepts,they suffer from limitations including plaintext communication,protocol dependency,reliance on dedicated clients,and inefficiency under modern network conditions.These constraints hinder their applicability in emerging distributed and resource-constrained environments such as AIoT and browser-based systems.To address these challenges,this study proposes a novel port-sequence-based PAPC scheme structured as a modular model comprising a client,server,and ephemeral Key Management System(KMS).The system employs the Advanced Encryption Standard(AES-128)to protect message confidentiality and uses a Hash-Based Message Authentication Code(HMAC-SHA256)to ensure integrity.Authentication messages are securely fragmented and mapped to destination port numbers using a signature-based avoidance algorithm,which prevents collisions with unsafe or reserved port ranges.The server observes incoming port sequences,retrieves the necessary keys from the KMS,reconstructs and verifies the encrypted data,and conditionally updates firewall policies.Unlike SPA,which requires decrypting all incoming payloads and imposes server-side overhead,the proposed system verifies only port-derived fragments,significantly reducing computational burden.Furthermore,it eliminates the need for raw socket access or custom clients,supporting browser-based operation and enabling protocol-independent deployment.Through a functional web-based prototype and emulated testing,the system achieved an F1-score exceeding 95%in detecting unauthorized access while maintaining low resource overhead.Although port sequence generation introduces some client-side cost,it remains lightweight and scalable.By tightly integrating lightweight cryptographic algorithms with a transport-layer communication model,this work presents a conceptually validated architecture that contributes a novel direction for interoperable and scalable Zero Trust enforcement in future network ecosystems.