Estimating the instantaneous reproduction number (Rt) by using particle filter.

Background: Monitoring the transmission of coronavirus disease 2019 (COVID-19) requires accurate estimation of the effective reproduction number (Rt). However, existing methods for calculating Rt may yield biased estimates if important real-world factors, such as delays in confirmation, pre-symptomatic transmissions, or imperfect data observation, are not considered. Method: To include real-world factors, we expanded the susceptible-exposed-infectious-recovered (SEIR) model by incorporating pre-symptomatic (P) and asymptomatic (A) states, creating the SEPIAR model. By utilizing both stochastic and deterministic versions of the model, and incorporating predetermined time series of Rt, we generated simulated datasets that simulate real-world challenges in estimating Rt. We then compared the performance of our proposed particle filtering method for estimating Rt with the existing EpiEstim approach based on renewal equations. Results: The particle filtering method accurately estimated Rt even in the presence of data with delays, pre-symptomatic transmission, and imperfect observation. When evaluating via the root mean square error (RMSE) metric, the performance of the particle filtering method was better in general and was comparable to the EpiEstim approach if perfectly deconvolved infection time series were provided, and substantially better when Rt exhibited short-term fluctuations and the data was right truncated. Conclusions: The SEPIAR model, in conjunction with the particle filtering method, offers a reliable tool for predicting the transmission trend of COVID-19 and assessing the impact of intervention strategies. This approach enables enhanced monitoring of COVID-19 transmission and can inform public health policies aimed at controlling the spread of the disease.

Modeling Incorporating the Severity-Reducing Long-term Immunity: Higher Viral Transmission Paradoxically Reduces Severe COVID-19 During Endemic Transition.

Natural infection with severe acute respiratory syndrome-coronavirus-2 or vaccination induces virus-specific immunity protecting hosts from infection and severe disease. While the infection-preventing immunity gradually declines, the severity-reducing immunity is relatively well preserved. Here, based on the different longevity of these distinct immunities, we develop a mathematical model to estimate courses of endemic transition of coronavirus disease 2019 (COVID-19). Our analysis demonstrates that high viral transmission unexpectedly reduces the rates of progression to severe COVID-19 during the course of endemic transition despite increased numbers of infection cases. Our study also shows that high viral transmission amongst populations with high vaccination coverages paradoxically accelerates the endemic transition of COVID-19 with reduced numbers of severe cases. These results provide critical insights for driving public health policies in the era of 'living with COVID-19.'

Analyzing the effects of social distancing on the COVID-19 pandemic in Korea using mathematical modeling.

OBJECTIVES: During the 6 months since the first coronavirus disease 2019 (COVID-19) patient was diagnosed in Korea on January 20, 2020, various prevention and control measures have been implemented according to the COVID-19 epidemic pattern. Therefore, this study aimed to estimate the reproductive numbers (R) for each epidemic stage to analyze the effects of the preventive measures and to predict the COVID-19 transmission trends. METHODS: We estimated the transmission rates for each epidemic stage by fitting a COVID-19 transmission model, based on a deterministic mathematical model, to the data on confirmed cases. The effects of preventive measures such as social distancing by time period were analyzed, and the size and trends of future COVID-19 outbreaks were estimated. RESULTS: The value of R was 3.53 from February18, 2020 to February 28, 2020, and the mean R reduced to 0.45 from March 14, 2020 to April 29, 2020, but it significantly increased to 2.69 from April 30, 2020 to May13, 2020 and it was maintained at 1.03 from May 14, 2020 to July 23, 2020. CONCLUSIONS: According to the estimated R, it had fallen to below 1 and was maintained at that level owing to the isolation of infected persons by the public health authorities and social distancing measures followed by the general public. Then, the estimated R increased rapidly as the contact among individuals increased during the long holiday period from April 30, 2020 to May 5, 2020. Thereafter, the value of R dropped, with the continued use of preventive measures but remained higher than 1.00, indicating that the COVID-19 outbreak can be prolonged and develop into a severe outbreak at any time.

Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China.

BACKGROUND: On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations. RESULTS: We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095-0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473-4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China. CONCLUSION: The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.

Estimating the reproductive number and the outbreak size of COVID-19 in Korea.

OBJECTIVES: Since the first novel coronavirus disease 2019 (COVID-19) patient in Korea was diagnosed on January 20, 2020, 30 patients were diagnosed until February 17, 2020. However, 5,298 additional patients were confirmed until March 4, 2020. Therefore, our objective was to estimate the reproduction number (R) and evaluate the effectiveness of preventive measures. METHODS: A COVID-19 transmission model (SEIHR) was established to suit the Korean outbreak. The number of daily confirmed cases in Daegu and North Gyeongsang Province (NGP), the main area of outbreak, was used. The first patient' symptom onset date in the Daegu/NGP outbreak was assumed as January 22, 2020. The R according to the start date of the effect of preventive measures was estimated. RESULTS: The estimated R in Hubei Province, China, was 4.0281, whereas the estimated initial R in Korea was 0.555, but later in Daegu/NGP, the value was between 3.472 and 3.543. When the transmission period decreases from 4-day to 2-day, the outbreak ends early, but the peak of the epidemic increases, and the total number of patients does not change greatly. It was found that, if transmission rate decreases, the outbreak ends early, and the size of the peak and the total number of patients also decreases. CONCLUSIONS: To end the COVID-19 epidemic, efforts to reduce the spread of the virus, such as social distancing and wearing masks, are absolutely crucial with the participation of the public, along with the policy of reducing the transmission period by finding and isolating patients as quickly as possible through the efforts of the quarantine authorities.

LiI-Doped Sulfide Solid Electrolyte: Enabling a High-Capacity Slurry-Cast Electrode by Low-Temperature Post-Sintering for Practical All-Solid-State Lithium Batteries.

All-solid-state lithium batteries (ASSLBs) based on sulfide solid electrolytes (SEs) have received great attention because of the high ionic conductivity of the SEs, intrinsic thermal safety, and higher energy density achievable with a Li metal anode. However, studies on practical slurry-cast composite electrodes show an extremely limited battery performance than the binder-free pelletized electrodes because of the poor interfacial robustness between the active materials and SEs by the presence of a polymeric binder. Here, we employ a low-temperature post-sintering process for the slurry-cast composite electrodes in order to overcome the binder-induced detrimental effects on the electrochemical performance. The LiI-doped Li3PS4 SEs are chosen because the addition of iodine not only improves the Li-ion conductivity and Li metal compatibility but also lowers the glass-transition and crystallization temperatures. Low-temperature post-sintering of composite cathodes consisting of a LiNi0.6Co0.2Mn0.2O2-active material, LiI-doped Li3PS4 SE, polymeric binder, and conducting agent shows a significantly improved electrochemical performance as compared to a conventional slurry-cast electrode containing pre-annealed SEs. Detailed analyses by electrochemical impedance spectroscopy and galvanostatic intermittent titration technique confirm that post-sintering effectively reduces the interfacial resistance and enhances the chemomechanical robustness at solid-solid interfaces, which enables the development of practical slurry-cast ASSLBs with sulfide SEs.

Anti-inflammatory effect of a selective 11ß-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts inactive cortisone to the active cortisol. 11ß-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a selective 11ß-HSD1 inhibitor, in lipopolysaccharide (LPS)-activated C57BL/6J mice and macrophages. LPS increased 11ß-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11ß-HSD1 activity. Thus, we concluded that the selective 11ß-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.

Optimal intervention strategy for prevention tuberculosis using a smoking-tuberculosis model.

In this paper, we developed a dynamic model of smoking-tuberculosis (TB) transmission in South Korea, and investigated the effects of control strategies on the number of incidence of TB using optimal control theory. Model parameters regarding TB and smoking are estimated through least-squares fitting to real data. We considered three TB controls (distancing, case-finding, and case-holding) and two smoking controls (distancing and quitting), in order to minimize the number of exposed and infectious individuals and the cost of control. Numerical simulations for the various control strategies highlight that implementing the smoking controls, not with TB controls, can effectively reduce the incidence of TB transmission.

A new simple method for point contact Andreev reflection (PCAR) using a self-aligned atomic filament in transition-metal oxides.

Point contact Andreev reflection (PCAR) has become a standard method for measuring the spin polarization (P) of spintronic materials due to its unique simplicity and the firm physical ground, but it is still challenging to achieve a clean point contact between a superconductor (SC) and a metal (N) for implementing PCAR. In this work, we suggest a much simpler method for PCAR measurement, where a point contact between SC and N is provided by a metallic filament in a transition-metal oxide generated by electrical bias. This method has been successfully demonstrated using a structure composed of Nb/NiO/Pt, where P of the Ni filament was estimated to be about 40%, consistent with the known value of the bulk Ni. In addition, we investigated the dependence of the conductance spectrum on the measurement temperature and the magnetic field. We found that the superconductivity is not fully suppressed until 9 T far above the critical field of Nb, which is associated with the nm-sized constriction of our SC/N junction, much smaller than the coherence length of the SC.

Optimal tuberculosis prevention and control strategy from a mathematical model based on real data.

A mathematical control model for the transmission dynamics of tuberculosis (TB) in South Korea is developed on the basis of the reported active-TB and relapse-TB incidence data. In this work, optimal control theory is used to propose optimal TB prevention and control strategy and rearrange the government TB budget for the best TB elimination plan. The impact of distancing, case finding, and/or case holding controls are investigated when the number of infected and infectious individuals are minimized, while the intervention costs are kept low. The implementation of optimal control measures shows that the distancing control, such as isolation of infectious people, early TB patient detection, and educational program/campaign for healthy control, is the most effective control factor for the prevention of TB transmission in South Korea.

BAT1, a putative acyltransferase, modulates brassinosteroid levels in Arabidopsis.

Brassinosteroids (BRs) are essential for various aspects of plant development. Cellular BR homeostasis is critical for proper growth and development of plants; however, its regulatory mechanism remains largely unknown. BAT1 (BR-related acyltransferase 1), a gene encoding a putative acyltransferase, was found to be involved in vascular bundle development in a full-length cDNA over-expressor (FOX) screen. Over-expression of BAT1 resulted in typical BR-deficient phenotypes, which were rescued by exogenously applied castasterone and brassinolide. Analyses of BR profiles demonstrated that BAT1 alters levels of several brassinolide biosynthetic intermediates, including 6-deoxotyphasterol, typhasterol and 6-deoxocastasterone. BAT1 is mainly localized in the endoplasmic reticulum. BAT1 is highly expressed in young tissues and vascular bundles, and its expression is induced by auxin. These data suggest that BAT1 is involved in BR homeostasis, probably by conversion of brassinolide intermediates into acylated BR conjugates.

A dynamic model for tuberculosis transmission and optimal treatment strategies in South Korea.

We have developed a dynamic model for tuberculosis (TB) transmission in South Korea using a SEIR model with the time-dependent parameters. South Korea ranked the highest TB incidence among members of the Organization for Economic Cooperation and Development (OECD) in 2005 yr. The observed data from the Korea Center for Disease Control and Prevention (KCDC) shows a certain rise of active-TB incidence individuals after 2001 yr. Because of this sudden jump, we have considered two different periods for best fitting the model: prior to 2001 yr and posterior to 2001 yr. The least-squares fitting has been used for estimating model parameters to the observed data of active-TB incidence. Our model agrees well with the observed data. In this work, we also propose optimal treatment strategies of TB model in South Korea for the future. We have considered three control mechanisms representing distancing, case finding and case holding efforts. Optimal control programs have been proposed in various scenarios, in order to minimize the number of exposed and infectious individuals and the cost of implementing the control treatment.

The histidine kinases CYTOKININ-INDEPENDENT1 and ARABIDOPSIS HISTIDINE KINASE2 and 3 regulate vascular tissue development in Arabidopsis shoots.

The development and activity of the procambium and cambium, which ensure vascular tissue formation, is critical for overall plant architecture and growth. However, little is known about the molecular factors affecting the activity of vascular meristems and vascular tissue formation. Here, we show that the His kinase CYTOKININ-INDEPENDENT1 (CKI1) and the cytokinin receptors ARABIDOPSIS HISTIDINE KINASE2 (AHK2) and AHK3 are important regulators of vascular tissue development in Arabidopsis thaliana shoots. Genetic modifications of CKI1 activity in Arabidopsis cause dysfunction of the two-component signaling pathway and defects in procambial cell maintenance. CKI1 overexpression in protoplasts leads to cytokinin-independent activation of the two-component phosphorelay, and intracellular domains are responsible for the cytokinin-independent activity of CKI1. CKI1 expression is observed in vascular tissues of inflorescence stems, and CKI1 forms homodimers both in vitro and in planta. Loss-of-function ahk2 and ahk3 mutants and plants with reduced levels of endogenous cytokinins show defects in procambium proliferation and an absence of secondary growth. CKI1 overexpression partially rescues ahk2 ahk3 phenotypes in vascular tissue, while the negative mutation CKI1H405Q further accentuates mutant phenotypes. These results indicate that the cytokinin-independent activity of CKI1 and cytokinin-induced AHK2 and AHK3 are important for vascular bundle formation in Arabidopsis.