The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty ...of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.
In order to design an ocean wave energy generator robot, a novel wave energy converter with parallel mechanism is designed and analyzed. A creative thinking that parallel mechanism can be applied to ...the wave energy converter is presented and verified during the wave energy using process. The design principles of the wave energy converter are given according to wave motion characteristics. Based on the principles, a novel wave energy converter with 4UPS/UP parallel mechanism is designed, which includes the design of the parallel mechanism, hydraulic cylinders, oil circuit, and converter integration. Then the kinematics model and statics model of the wave energy converter with 4UPS/UP parallel mechanism are derived by MATLAB and ADAMS; with these two methods, we found that the errors of rod length, velocity, and acceleration were 1.13 mm, 0.04 mm/s, and 0.38 mm/s2, respectively. Maximum stress error and maximum constraint moment errors were 1.52 N and 0.57 N·mm. So the correctness of the models is verified. This article can not only provide a reference for other types of parallel mechanisms applied to the wave energy converter, but also provide a theoretical foundation for the experimental prototype and practical application of the wave energy converter.
High-entropy alloys (HEAs) have garnered significant attention across various fields owing to their unique design incorporating multi-principal elements and remarkable comprehensive performance. ...Nevertheless, the enormous composition design space of HEAs makes conventional alloy design methods appear to be costly and inefficient. Recently, computer simulation technologies such as multi-scale simulation and machine learning have emerged as an efficient way to explore the composition design, structure, and performance simulation of HEAs.This review introduces the commonly used multi-scale simulation methods such as first-principles calculation, molecular dynamics simulation, Monte Carlo simulation, CALPHAD, finite element simulation, and machine learning. These methods not only simulate the microstructure and deformation behavior of HEAs but also predict crucial material properties like mechanical and physicochemical properties, thereby facilitating the design of HEAs. The current state-of-the-art advancements in multi-scale simulation and machine learning techniques for studying HEAs are summarized, encompassing their practical applications and potential limitations. The utilization of machine learning and multi-scale computation in materials science, as well as the future prospects are ultimately proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This case series examines patients with coronavirus disease 2019 (COVID-19) who were discharged from the hospital and had recurrent positive reverse transcriptase–polymerase chain reaction (RT-PCR) ...results.
•The multidose Sabin strain-based inactivated polio vaccine (sIPV) showed good lot-to-lot consistency in immunogenicity.•The multidose sIPV met the noninferiority criteria of immunogenicity.•The ...multidose sIPV demonstrated a favorable safety profile.•No vaccine-related serious adverse events occurred.
To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation.
Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed.
Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05).
The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Sabin-strain-based inactivated poliovirus vaccine (sIPV) plays an important role in poliomyelitis eradication in developing countries. As part of the phase III clinical development program, this ...study aimed to evaluate the safety, immunogenicity and lot-to-lot consistency of the sIPV in 2-month-old infants.
We conducted a phase III, randomized, double-blind, positive-controlled trial in which 1300 healthy infants were randomly assigned to four groups in a 1:1:1:1 ratio to receive one of the three lots of the sIPV or the control IPV at 2, 3 and 4 months of age. Serum samples were collected before the first dose and 30 days after the third dose of vaccination to assess the immunogenicity. Solicited local and systemic reactions were recorded within 7 days and unsolicited adverse events within 30 days after each vaccination.
Of the 1300 randomized infants, 1190 infants completed the study and were included in the per-protocol population. The seroconversion rates in the three lots of the sIPV were 95.67%, 97.03% and 95.59%, respectively, for type 1; 94.33%, 93.73% and 92.88%, respectively, for type 2; and 98.67%, 99.67% and 99.32%, respectively, for type 3. The ratios of GMTs for poliovirus types 1, 2 and 3 of each pair of lots were all between 0.67 and 1.50, therefore meeting the predefined immunological equivalence criteria. For the seroconversion rate of poliovirus types 1, 2 and 3, the pooled sIPV group was non-inferior to the IPV group. The incidence of solicited and unsolicited adverse reactions (ARs) was similar in the pooled sIPV lots and the IPV group, and most of them were mild to moderate in severity. Non-vaccine-related serious adverse events (SAEs) were reported.
Three consecutive lots of sIPV demonstrated robust and consistent immunogenicity. The safety and tolerability of the sIPV was acceptable and similar to that of the IPV.
Demand response plays a significant role in peak load shifting, storage capacity configuration and renewable energy utilization. A bi-level planning method for energy storage system of integrated ...community energy system considering the demand response is proposed in this paper. In the upper level, the investment cost of electrical energy storage and thermal energy storage, operation and maintenance cost and fuel cost of the integrated community energy system, as well as the compensation cost to the energy consumer, are considered; in the lower level, the responded demand of the energy consumer is taken into consideration to minimize the energy bill of the energy consumer. An actual planning for energy storage system of integrated community energy system shows the effectiveness of the proposed method.
Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, ...and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older.
In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18–59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574.
540 (90%) of 600 participants aged 18–59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 95% CI 3·1–5·0) and for cohort 2b-28d-8m (n=49; 6·8 5·2–8·8). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9–190·4) for cohort 1b-14d-8m and 143·1 (110·8–184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3–27·6) on day 28 after the second dose to 45·8 (35·7–58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4–51·1) to 49·7 (39·9–61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1–12·0) in cohort 1a-14d-2m and 10·0 (7·3–13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 87% of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0–59·4) on day 28 after the second dose to 158·5 (96·6–259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m.
A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses.
National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China.
For the Mandarin translation of the abstract see Supplementary Materials section.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Media milling facilitated acid-induced pea protein gel formation.•The minimum gelation concentration of PPI pretreated by SMM was decreased from 9 % to 4 %.•SMM treatment improved ...the resistance to deformation of pea protein gel.•Reducing protein particle size to 180 nm increased gel strength.
This study explored the effect of stirred media mill (SMM) processing on the acid-induced gelling properties of pea protein. Results showed that SMM treatment enhanced the gel strength from 75.06 g to 183.89 g and increased the water holding capacity from 46.64 % to 73.50 %. The minimum gelation concentration achieved for SMM-treated pea protein was 4 %, significantly lower than that of heat-pretreated pea protein (9 %). SMM decreased protein aggregate size from 104 μm to 180 nm. Microscopy analysis revealed that the small aggregates facilitated the formation of uniform gel networks with tight connections. Linear rheology indicated that small protein aggregates resulted in slower gelation rates with a higher Gʹ for the formed gels. The SMM-pretreated protein gel showed strain hardening, shear thinning behaviors, and satisfactory stability to withstand large-amplitude oscillatory shear. Overall, SMM emerges as a promising technology for producing protein gel products with strong mechanical attributes and customizable rheological properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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