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We describe a genome-wide screening strategy to identify target genes whose modulation increases the capacity of a cell to produce recombinant adeno-associated viral (AAV) vector. Specifically, a single-guide RNA (sgRNA) library for a CRISPR-based genome-wide transcriptional activation screen was inserted into an AAV vector, and iterative rounds of viral infection and rescue in HEK293 producer cells enabled the enrichment of sgRNAs targeting genes whose upregulation increased AAV production. Numerous gain-of-function targets were identified, including spindle and kinetochore associated complex subunit 2 (SKA2) and inositol 1, 4, 5-trisphosphate receptor interacting protein (ITPRIP). Furthermore, individual or combinatorial modulation of these targets in stable producer cell lines increased vector genomic replication and loading into AAV virions, resulting in up to a 3.8-fold increase in AAV manufacturing capacity. Our study offers an efficient approach to engineer viral vector producer cell lines and enhances our understanding of the roles of SKA2 and ITPRIP in AAV packaging., Graphical abstract, Schaffer and colleagues implemented a genome-wide activation screen to identify host cell target genes that promote AAV production. In particular, SKA2 and ITPRIP upregulation significantly increased AAV production, due to their roles in promoting vector genome replication and the AAV full/empty capsid ratio.

The aim of this study was to optimize the target, moderator, and collimator (TMC) in a neutron beam generator for the accelerator-based BNCT (A-BNCT) system. The optimization employed the Monte Carlo Neutron and Photon (MCNP) simulation. The optimal geometry for the target was decided as the one with the highest neutron flux among nominates, which were called as angled, rib, and tube in this study. The moderator was optimized in terms of consisting material to produce appropriate neutron energy distribution for the treatment. The optimization of the collimator, which wrapped around the target, was carried out by deciding the material to effectively prevent the leakage radiations. As results, characteristic of the neutron beam from the optimized TMC was compared to the recommendation by the International Atomic Energy Agent (IAEA). The tube type target showed the highest neutron flux among nominates. The optimal material for the moderator and collimator were combination of Fluental (Al203+AlF3) with 60Ni filter and lead, respectively. The optimized TMC satisfied the IAEA recommendations such as the minimum production rate of epithermal neutrons from thermal neutrons: that was 2.5 times higher. The results can be used as source terms for shielding designs of treatment rooms.

Efforts to identify mutations that underlie inherited genetic diseases combined with strides in the development of gene therapy vectors over the last three decades have culminated in the approval of several adeno-associated virus (AAV)-based gene therapies. Genetic diseases that manifest in the lung such as cystic fibrosis (CF) and surfactant deficiencies, however, have so far proven to be elusive targets. Early clinical trials in CF using AAV serotype 2 (AAV2) achieved safety, but not efficacy endpoints; however, importantly, these studies provided critical information on barriers that need to be surmounted to translate AAV lung gene therapy toward clinical success. Bolstered with an improved understanding of AAV biology and more clinically relevant lung models, next-generation molecular biology and bioinformatics approaches have given rise to novel AAV capsid variants that offer improvements in transduction efficiency, immunological profile, and the ability to circumvent physical barriers in the lung such as mucus. This review discusses the principal limiting barriers to clinical success in lung gene therapy and focuses on novel engineered AAV capsid variants that have been developed to overcome those challenges.

3C protease (3Cpro), a chymotrypsin-like cysteine protease encoded by the foot-and-mouth disease virus (FMDV), plays an essential role in processing the FMDV P1 polyprotein into individual viral capsid proteins in FMDV replication. Previously, it has been shown that 3Cpro is involved in the blockage of the host type-I interferon (IFN) responses by FMDV. However, the underlying mechanisms are poorly understood. Here, we demonstrated that the protease activity of 3Cpro contributed to the degradation of RIG-I and MDA5, key cytosolic sensors of the type-I IFN signaling cascade in proteasome, lysosome and caspase-independent manner. And also, we examined the degradation ability on RIG-I and MDA5 of wild-type FMDV 3Cpro and FMDV 3Cpro C142T mutant which is known to significantly alter the enzymatic activity of 3Cpro. The results showed that the FMDV 3Cpro C142T mutant dramatically reduce the degradation of RIG-I and MDA5 due to weakened protease activity. Thus, the protease activity of FMDV 3Cpro governs its RIG-I and MDA5 degradation ability and subsequent negative regulation of the type-I IFN signaling. Importantly, FMD viruses harboring 3Cpro C142T mutant showed the moderate attenuation of FMDV in a pig model. In conclusion, our results indicate that a novel mechanism evolved by FMDV 3Cpro to counteract host type-I IFN responses and a rational approach to virus attenuation that could be utilized for future vaccine development.

During viral infection, virus-derived cytosolic nucleic acids are recognized by host intracellular specific sensors. The efficacy of this recognition system is crucial for triggering innate host defenses, which then stimulate more specific adaptive immune responses against the virus. Recent studies show that signal transduction pathways activated by sensing proteins are positively or negatively regulated by many modulators to maintain host immune homeostasis. However, viruses have evolved several strategies to counteract/evade host immune reactions. These systems involve viral proteins that interact with host sensor proteins and prevent them from detecting the viral genome or from initiating immune signaling. In this review, we discuss key regulators of cytosolic sensor proteins and viral proteins based on experimental evidence., Viral infection: Evasion strategies subvert antiviral defenses Viruses escape the body’s immune surveillance mechanisms by manipulating and subverting key intracellular sensors of viral RNA or DNA. In a review article, Jong-Soo Lee and colleagues from Chungnam National University in Daejeon, South Korea, discuss the strategies used by viral pathogens to avoid detection by immune receptors or to block activation of these receptors and the associated signaling molecules, thus preventing expression of antiviral genes. These strategies include modifying viral nucleic acids or making them inaccessible, and interference with sensor proteins, either though degradation, altered processing or relocalization within the cell. The authors summarize rapid advances in scientists’ understanding of sensor-mediated antiviral responses at the molecular level, and highlight how that knowledge could help guide the development of novel vaccines and antiviral agents.

본 연구는 고객 관점에서 항공 서비스를 정확하게 평가할 수 있는 텍스트 애널리틱스 기반의 새로운 순위결정 체계를 제안한다. 새로운 랭킹 체계를 통해 개선하고자하는 문제점은 크게 두 가지로 (1)가장 보편적으로 활용되는 설문조사의 샘플링이 갖는 한계와, (2) 현재 제공되는 항공서비스 랭킹 체계가 비즈니스 모델 차이를 세부적으로 반영하지 못하는 문제이다. 일반적인 설문조사에 의한 데이터 수집은 실시간 데이터 축적의 어려움, 수집 비용 및 시간의 문제, 데이터셋 크기의 문제, 무응답과 부정확한 응답 또는 샘플의 불완전한 대표성에 따른 통계적 오류 등의 문제가 존재한다. 반면에 온라인리뷰는 실시간으로 끊임없이 축적되므로 대용량의 데이터셋 확보가 가능하고, 고객의 자발적인 피드백이라는 점에서 무응답과 부정확한 응답에 해당하지 않고 직접적이고 솔직한 고객의 인식을 담고 있으며, 수집 비용이나 시간의 문제가 없다. 또한 정해진 데이터 추출 기준에 의해 전체 데이터셋을 수집하기 때문에 샘플링에서 일반적으로 발생하는 선택 편의에 의한 통계적 오류가 발생할 가능성을 최소화할 수 있다. 이러한 장점을 갖는 온라인 리뷰를 텍스트 애널리틱스에 적용하여, 도출된 고객의 인식을 포함한 모델링 결과들(토픽, 토픽 중요도, 단어 빈도)을 랭킹 방법에서 각각 평가 항목, 가중치와 평가 점수로 활용하기 때문에 온전히 고객 관점의 평가가 가능하게 된다. 특히 온라인 리뷰에서 도출된 대형 항공사와 저비용 항공사간의 토픽(평가 항목)이 상당한 차이를 보이기 때문에, 즉 두 비즈니스모델간 고객 인식이 상당한 차이를 보이기 때문에, 이를 반영한 랭킹 결과는 그렇지 않은 기존 방식보다 우월한 성능을 보인다. 제안된 랭킹의 성능 파악을 위해 Skytrax의 랭킹을 비교 대상으로 삼아 기업성과와의 상관관계 분석을 통해 제안한 방법의 효과를 검증한다. 분석 결과 제안된 랭킹이 Skytrax의 랭킹 보다 기업의 성과와 높은 상관관계를 보였고, 이는 고객 인식을 반영한 텍스트 애널리틱스 기반의 랭킹이 고객의 서비스 품질에 대한 평가를 더 잘 반영한 결과라고 할 수 있다.

항공 운송 산업에서 공항의 중요성은 지속적으로 증가하고 있고 공항 간 경쟁은 더욱 심화되고 있다. 고품질의 공항 서비스가 공항의 생존을 위해 어느 때보다 중요해 지고 있다. 공항 서비스의 무형적 요소와 관련된 연구들은 다방면으로 진행되고 있지만, 유형적 요소인 서비스스케이프에 대한 연구는 충분하지 않은 상황이다. 본 연구는 고객에게 긍정적인 경험을 제공할 수 있는 고객 지향적 서비스스케이프 구성을 위하여 공항 이용객들의 공항 서비스스케이프에 대한 인식을 분석하고자 한다. 최근 주목받고 있는 고객의 즉각적이고 생동적인 피드백인 온라인 리뷰를 텍스트 분석을 이용하여 분석하고, 고객이 중요하게 인식하는 서비스스케이프 구성요소와 속성이 무엇인지 도출한다. 인천국제공항을 포함한 7개 주요 경쟁 공항 이용객들이 직접 작성한 약 8,600개의 온라인 리뷰를 대표적 텍스트 분석 기법인 토픽 모델링을 이용하여 시사점을 도출하였다. 그 결과 지역 공항과 비교되는 환승 공항만의 특성을 확인할 수 있었고, 서비스스케이프에 대한 인식의 특성을 기준으로 인천국제공항과 비교대상인 공항들을 세 권역(일본, 동남아시아, 중동아시아)으로 구분할 수 있었다. 지역 공항과 비교시 인천국제공항은 대표적인 아시아의 환승 공항으로서 서비스스케이프의 기능성이 가장 부각되어 인식되었다. 주요 경쟁 환승 공항과의 비교에서 서비스스케이프의 구성요소에 대한 인식은 일본과 가장 이질적이었고, 중동아시아와 가장 유사한 경향을 나타냈다. 이러한 비교·분석을 통해 이용객이 인식하는 공항의 서비스스케이프 현황에 대한 통찰이 가능하고, 이를 기반으로 이용객의 특성을 고려한 고객 관점의 서비스스케이프를 구성하는데 실질적인 시사점을 제공한다.

This letter proposes a real-options pricing model and determinants influencing retail rents from real-estate finance in an attempt to shed light on pricing airport duty-free leasing. A real-options...

The present study attempted to improve film cooling effectiveness by installing a Coanda effect-inducing protrusion, called a Coanda bump, at the exit of the 45-degree inclined slot. The inclined slot used in this study was rectangular in shape with dimensions of 4 mm by 50 mm. For optimization, three geometric Coanda bump parameters – the width, height, and streamwise position of the peak point – were selected. The Box-Behnken design (BBD) method was employed to calculate the cases, and the response surface method (RSM) was applied to optimize the Coanda bump. The objective function (i.e., the area averaged film cooling effectiveness) was numerically investigated via a Reynolds-averaged Navier-Stokes (RANS) analysis. The results showed that when the optimized Coanda bump was applied to the slot exit, secondary flows such as the kidney vortex decreased and the coolant lift-off diminished compared to the reference design point without the Coanda bump. The area averaged film cooling effectiveness of the optimized design points improved by about 1.3, 2.4, and 7.6% at blowing ratios of 1.0, 1.5, and 2.0, respectively, compared to that of the reference design point.

Film cooling techniques have been widely applied to gas turbine engines to protect the components from hot combustion gas. In this study, the shape of the laidback fan-shaped hole with a lateral expansion angle of 10 degrees was optimized through the Reynolds Averaged Navier-Stokes (RANS) analysis. Results by numerical analysis were validated with the corresponding experimental results obtained by the pressure sensitive paint technique (PSP). For optimal hole shape derivation, the design points were selected through the Latin Hypercube Sampling (LHS) method for three design variables: injection angle, metering length, and forward expansion angle. The overall averaged effectiveness was used as the objective function. Results showed that the overall film cooling effectiveness of the optimal holes derived by the response surface method and the Kriging method were higher than that of the reference hole by 4.5% and 7.5%, respectively. Generally, holes with a higher area ratio (AR) showed higher overall film cooling effectiveness. However, the interaction between each shape parameter should be considered to derive the optimal hole shape.

We apply latent Dirichlet allocation topic modeling to a vast number of passenger-authored online reviews for airline services to compare service quality between full service carriers (FSCs) and lo...

NF‐κB essential modulator (NEMO) is a key regulatory protein that functions during NF‐κB‐ and interferon‐mediated signaling in response to extracellular stimuli and pathogen infections. Tight regulation of NEMO is essential for host innate immune responses and for maintenance of homeostasis. Here, we report that the E3 ligase MARCH2 is a novel negative regulator of NEMO‐mediated signaling upon bacterial or viral infection. MARCH2 interacted directly with NEMO during the late phase of infection and catalyzed K‐48‐linked ubiquitination of Lys326 on NEMO, which resulted in its degradation. Deletion of MARCH2 resulted in marked resistance to bacterial/viral infection, along with increased innate immune responses both in vitro and in vivo. In addition, MARCH2−/− mice were more susceptible to LPS challenge due to massive production of cytokines. Taken together, these findings provide new insight into the molecular regulation of NEMO and suggest an important role for MARCH2 in homeostatic control of innate immune responses., MARCH2 interacts with the NF‐κB modulator NEMO and initiates its ubiquitin‐dependent degradation for homeostatic control of innate immune responses to viral and bacterial infection.

Purpose Lower urinary tract symptoms (LUTS) can be distressing and socially isolating, and the economic impact can be substantial. Further data to characterize the epidemiology and effects of LUTS in South Korea would be beneficial. Materials and methods In an international, internet-based survey, the prevalence and impact of LUTS was evaluated in adults aged ≥40 years. Questions related to International Continence Society (ICS) symptom definitions and the bother associated with each symptom. The international prostate symptom score (IPSS) and the overactive bladder symptom score (OABSS) were assessed. Results Of the 2,080 participants from South Korea, 1,090 (52.4%) were women and 740 (35.6%) were aged ≥60 years. The prevalence of LUTS according to ICS criteria was 68.2% (men, 70.6%; women, 66.0%). LUTS prevalence increased significantly with age (p=0.01 in men and women). Storage symptoms only were reported in 16.2% of men and 30.5% of women, making this the most common ICS symptom group overall. Individual symptoms with the highest prevalence in the overall population were nocturia, frequency, and weak stream (36%, 30%, and 29%, respectively). IPSS results showed that 40.1% of participants had at least moderate symptoms. The prevalence of OABSS-defined overactive bladder was 19.7% (men, 19.5%; women, 19.9%). Fourteen percent of individuals with any LUTS visited healthcare professionals regarding urinary symptoms. Conclusions LUTS affect the majority of adults aged ≥40 years in South Korea. The low percentage of individuals with LUTS consulting healthcare professionals regarding urinary symptoms indicates a need to improve rates of diagnosis and treatment.

Facile fabrication of polyacrylic acid-polyvinyl chloride (PAA-PVC) composite adsorbents and their evaluation for Cd(II) adsorption is reported in this study. The sorbents were prepared via a simple phase inversion process by spinning PAA-PVC polymer blends into mixed solution of water and methanol. The prepared fibers were characterized by scanning electron microscopy, energy disperse X-ray microscopy and Fourier transform infra-red microscopy, and their sorption performances were evaluated by batch sorption experiments. Through sorption isotherm, the maximum sorption capacity was estimated as 331.59 mg/g using the Langmuir isotherm model. Intra-particle diffusion played a major role in reaching the adsorption equilibrium. Ion-exchange between the charged carboxyl groups of PAA and the Cd(II) solution was observed to be the main mechanism of Cd(II) sorption. This study is believed to pave way for preparing cost-effective polymeric composite sorbents for the removal of heavy metals from polluted waters.

BACKGROUND This multicenter study was performed to develop a prognosis-prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non-small cell lung cancer (NSCLC) patients. METHODS A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression. RESULTS Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis-prediction model, we categorized patients into low, intermediate, and high-risk groups, which had greater accuracy in predictive ability (log-rank statistics = 54.66) than the conventional tumor node metastasis staging (log-rank statistics = 39.56). Next, we generated a prognosis-prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high-risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy. CONCLUSIONS This prognosis-prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.

We introduce a new importance-performance analysis (IPA) methodology while making use of direct service experience perceptions represented by online reviews with numerical ratings. The proposed IPA, which we call the text analytics-based IPA (TAIPA), allows the real-time calculation of importance using the probability distribution of word frequency via the latent Dirichlet allocation (LDA) application to online reviews, and of performance using numerical rating values. The importance is also adjusted with the help of a sentiment analysis of online reviews to provide more precise measurements for service experience perceptions. To ensure an evaluation of the entire service process, we employ service encounters, in which service experiences occur and thus most customer perceptions are created, as a set of attributes composed of LDA topics that contain direct perceptions of service experiences. We investigate statistical correlations between TAIPA calculations and typical benchmarks of firm performance in the air-transport industry to verify how effective the proposed TAIPA is with respect to the degree that customer satisfaction is represented. As a primary result, TAIPA is more effective than comparison targets in that it shows stronger correlations with firm performance. TAIPA is specialized in determining which service step (i.e., a one-to-one relationship with a service encounter) needs to be improved. Moreover, TAIPA is flexible in considering multiple competitors.

The herbs Plantago asiatica and Clerodendrum trichotomum have been commonly used for centuries in indigenous and folk medicine in tropical and subtropical regions of the world. In this study, we show that extracts from these herbs have antiviral effects against the respiratory syncytial virus (RSV) in vitro cell cultures and an in vivo mouse model. Treatment of HEp2 cells and A549 cells with a non-cytotoxic concentration of Plantago asiatica or Clerodendrum trichotomum extract significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and also blocked syncytia formation. Interestingly, oral inoculation with each herb extract significantly improved viral clearance in the lungs of BALB/c mice. Based on reported information and a high-performance liquid chromatography (HPLC) analysis, the phenolic glycoside acteoside was identified as an active chemical component of both herb extracts. An effective dose of acteoside exhibited similar antiviral effects as each herb extract against RSV in vitro and in vivo. Collectively, these results suggest that extracts of Plantago asiatica and Clerodendrum trichotomum could provide a potent natural source of an antiviral drug candidate against RSV infection.

This study investigates the repurchase intention of passengers who have experienced premium economy class. To achieve the research purpose, we examine the relationship among psychological factors, perceived price, perceived service quality, perceived value and repurchase intention using a research model extended from the theory of planned behavior (TPB). The survey data were collected both airside and landside at two major Korean international airports from 382 passengers who used premium economy class. The results show that the repurchase intention of passengers is influenced by the attitude, perceived behavioral control, and perceived value derived from price and service quality, repurchase intention is not influenced by the subjective norm. These findings will enable air carriers to better understand the intention of premium economy passengers with respect to psychological and service value perspectives. They can also be used to improve marketing capabilities and the sustainable profitability of premium economy service.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5–7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio 3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3–8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

At border crossings around the world, plastic scintillator-based radiation portal monitors (RPMs) are employed to detect the presence of illicit radioactive materials in large trailer trucks. However, the RPM system shows a low energy resolution owing to the large size and physical characteristics of plastic scintillators; and thus, the identification of illicit artificial isotopes from naturally occurring radioactive material is difficult. This study aims to develop an advanced algorithm for radionuclide identification with commercial RPMs based on commercial plastic scintillators to reduce the occurrence of frequent nuisance alarms. Subsequently, machine learning models, namely, a convolutional neural network (CNN) was applied. The spectral distributions of energy weighted spectra were used as features of the CNN model. The energy spectra of 137Cs, 60Co, 226Ra, and 40K measured under static and moving conditions were used to implement the identification model. To evaluate the performance of the implemented model, the F-score was used. The trained CNN model correctly identified most of the radionuclides. That is, despite the theoretical Compton edge energies of 60Co and 40K being similar, the spectral distributions of 40K are distinctively different from those of 60Co. The result demonstrates that the CNN model-based identification algorithm performs robust radionuclide identification, thereby reducing the frequency of nuisance alarms at border crossings. Furthermore, considering that the actual cases of cargo passing by the RPMs are becoming more complicated, the algorithm would need to be continuously improved and trained with more complex scenarios in the future.

Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A2 (PLA2), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.

The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs+/−) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.

Among various technologies for capturing and storing CO2, mineral carbonation technology stores CO2 by reacting natural minerals and industrial by-products containing a lot of Ca or Mg with CO2, and resultantly forming carbonate minerals. Mineral carbonation is one of the safest methods for the sequestration of CO2 as thermodynamically stable carbonate minerals. As a method for CO2 sequestration, this study utilized the neutralization process of mine drainage using hydrated lime. This method captures CO2 through CO2 injection into the neutralization process, resultantly forming calcium carbonate. The carbonation treatment was conducted using mine drainage collected from abandoned coal mines. The carbonation treatment of the neutralized mine drainage samples from three mine areas resulted in forming calcite precipitates of different amounts, and no additional environmental problems occurred through CO2 injection into the mine drainage. The estimated capacity of CO2 sequestration through the carbona...

VP1, a pivotal capsid protein encoded by the foot-and-mouth disease virus (FMDV), plays an important role in receptor-mediated attachment and humoral immune responses. Previous studies show that amino acid changes in the VP1 protein of cell culture-adapted strains of FMDV alter the properties of the virus. In addition, FMDV VP1 modulates host IFN signal transduction. Here, we examined the ability of cell culture-adapted FMDV VP1(83K) and wild-type FMDV VP1(83E) to evade host immunity by blocking mitochondrial antiviral signaling protein (MAVS)/TNF Receptor Associated Factor 3 (TRAF3) mediated cellular innate responses. Wild-type FMDV VP1(83E) interacted specifically with C-terminal TRAF3-binding site within MAVS and this interaction inhibited binding of TRAF3 to MAVS, thereby suppressing interferon-mediated responses. This was not observed for cell culture-adapted FMDV VP1(83K). Finally, chimeric FMDV harboring VP1(83K) showed very low pathogenicity in pigs. Collectively, these data highlight a critical role of VP1 with respect to suppression of type-I IFN pathway and attenuation of FMDV by the E83K mutation in VP1., Author summary Foot-and-Mouth disease (FMD), a highly contagious viral disease of cloven-hoofed animals, causes huge economic losses. To generate a FMD vaccine, cell culture-adapted strains of FMDV that show improved growth properties and allow repeated passage are needed. Generally, adaptation of field-isolated FMDV is accompanied by changes in viral properties, including amino acid mutations. A VP1 E83K mutation in cell culture-adapted FMDV was identified previously; here, we examined the impact of VP1 E83K on virus pathogenicity and type-I IFN pathway. Cell culture-adapted FMDV O1 Manisa, and highly virulent strain of O/Andong/SKR/2010, acquired the E83K mutation in the VP1 protein, which attenuated the virus via disposing VP1 mediate negative regulation ability of host cellular IFN responses. The data suggest a rational approach to viral propagation in cell culture and virus attenuation, which could be utilized for future development of FMDV vaccines.

A radiation portal monitoring (RPM) system, which detects illegal radioactive materials at ports or airports, mainly consists of plastic scintillators made of polyvinyl toluene with poor energy resolution. Therefore, it is difficult to expect accurate nuclide analysis. Hence, in this study, we validated an energy weighted algorithm proposed in a previous study by identifying the energy weighted spectra of dynamic 137Cs, 60Co, 226Ra, and 238U using a commercialized RPM. The spectrum data in the static and dynamic conditions of all the sources were measured using a sedan vehicle. The peak detection of 137Cs and 60Co according to the measurement distance and source speed was evaluated and compared with that identified using a NaI(Tl)-based RPM. Even at the source speeds of 5 and 10 km/h, the peak of the energy weighted spectrum was successfully detected. In particular, when 137Cs and 60Co over 70 μCi were moved at 30 km/h, all the peaks were detected within the designated peak detection range. The experiment presented in this study is a methodological analysis, however, the energy weighted algorithm can be applied in primary RPM inspection.

Tryptophanyl-tRNA synthetase (WRS) is one of the aminoacyl-tRNA synthetases (ARSs) that possesses noncanonical functions. Full-length WRS is released during bacterial infection and primes the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to elicit innate immune responses. However, the role of WRS in viral infection remains unknown. Here, we show that full-length WRS is secreted by immune cells in the early phase of viral infection and functions as an antiviral cytokine. Treatment of cells with recombinant WRS protein promotes the production of inflammatory cytokines and type I interferons (IFNs) and curtails virus replication in THP-1 and Raw264.7 cells but not in TLR4(−/−) or MD2(−/−) bone marrow-derived macrophages (BMDMs). Intravenous and intranasal administration of recombinant WRS protein induces an innate immune response and blocks viral replication in vivo. These findings suggest that secreted full-length WRS has a noncanonical role in inducing innate immune responses to viral infection as well as to bacterial infection. IMPORTANCE ARSs are essential enzymes in translation that link specific amino acids to their cognate tRNAs. In higher eukaryotes, some ARSs possess additional, noncanonical functions in the regulation of cell metabolism. Here, we report a novel noncanonical function of WRS in antiviral defense. WRS is rapidly secreted in response to viral infection and primes the innate immune response by inducing the secretion of proinflammatory cytokines and type I IFNs, resulting in the inhibition of virus replication both in vitro and in vivo. Thus, we consider WRS to be a member of the antiviral innate immune response. The results of this study enhance our understanding of host defense systems and provide additional information on the noncanonical functions of ARSs.

This paper proposes a genetic algorithm (GA) to find the pseudo-optimum of integrated process planning and scheduling (IPPS) problems. IPPS is a combinatorial optimization problem of the NP-complete class that aims to solve both process planning and scheduling simultaneously. The complexity of IPPS is very high because it reflects various flexibilities and constraints under flexible manufacturing environments. To cope with it, existing metaheuristics for IPPS have excluded some flexibilities and constraints from consideration or have built a complex structured algorithm. Particularly, GAs have been forced to construct multiple chromosomes to account for various flexibilities, which complicates algorithm procedures and degrades performance. The proposed new integrated chromosome representation makes it possible to incorporate various flexibilities into a single string. This enables the adaptation of a simple and typical GA procedure and previously developed genetic operators. Experiments on a set of benchmark problems showed that the proposed GA improved makespan by an average of 17% against the recently developed metaheuristics for IPPS in much shorter computation times.