The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community ...has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic continues to pose a significant worldwide threat to human health, as emerging SARS-CoV-2 Omicron variants exhibit resistance to therapeutic antibodies and the ability to evade ...vaccination-induced antibodies. Here, we aimed to identify human antibodies (hAbs) from convalescent patients that are potent and broadly neutralizing toward Omicron sublineages.
Using a single B-cell cloning approach, we isolated BA.5 specific human antibodies. We further examined the neutralizing activities of the most promising neutralizing hAbs toward different variants of concern (VOCs) with pseudotyped virus.
Sixteen hAbs showed strong neutralizing activities against Omicron BA.5 with low IC
values (IC
< 20 ng/mL). Among four of the most promising neutralizing hAbs (RBD-hAb-B22, -B23, -B25 and -B34), RBD-hAb-B22 exhibited the most potent and broad neutralization profiles across Omicron subvariant pseudoviruses, with low IC
values (7.7-41.6 ng/mL) and a low PRNT
value (3.8 ng/mL) in plaque assays with authentic BA.5. It also showed potent therapeutic effects in BA.5-infected K18-hACE2 mice.
Thus, our efficient screening of BA.5-specific neutralizing hAbs from breakthrough infectious convalescent donors successfully yielded hAbs with potent therapeutic potential against multiple SARS-CoV-2 variants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This research paper outlines a method for automatically classifying wakefulness and deep sleep stage (N3) based on the American Academy of Sleep Medicine (AASM) standards. The study employed a ...single-channel EEG signal, leveraging the Wigner-Ville Distribution (WVD) for time-frequency analysis to determine EEG energy per second in specific frequency bands (δ, θ, α, and entire band). Particle Swarm Optimization (PSO) was used to optimize thresholds for distinguishing between wakefulness and stage N3. This process aims to mimic a sleep technician's visual scoring but in an automated fashion, with features and thresholds extracted to classify epochs into correct sleep stages. The study's methodology was validated using overnight PSG recordings from 20 subjects, which were evaluated by a technician. The PSG setup followed the 10-20 standard system with varying sampling rates from different hospitals. Two baselines, T1 for the wake stage and T2 for the N3 stage, were calculated using PSO to ascertain the best thresholds, which were then used to classify EEG epochs. The results showed high sensitivity, accuracy, and kappa coefficient, indicating the effectiveness of the classification algorithm. They suggest that the proposed method can reliably determine sleep stages, being aligned closely with the AASM standards and offering an intuitive approach. The paper highlights the strengths of the proposed method over traditional classifiers and expresses the intentions to extend the algorithm to classify all sleep stages in the future.
Students often face challenges while learning computer programming because programming languages' logic and visual presentations differ from human thought processes. If the course content does not ...closely match learners' skill level, the learner cannot follow the learning process, resulting in frustration, low learning motivation, or abandonment. This research proposes a web programming learning recommendation system to provide students with personalized guidance and step-by-step learning planning. The system contains front-end and back-end web development instructions. It can create personalized learning paths to help learners achieve a sense of accomplishment. The system can help learners build self-confidence and improve learning effectiveness. In study 1, the recommendation system was developed based on the personal data and feedback of 41 professional web design engineers. The system uses C4.5 decision tree methods to develop a programming learning recommendation model to provide appropriate learning recommendations and establish personalized learning paths. The test group included 13 beginner programmers. After 4 weeks' programming instructions in front-end and back-end web development, the learners were interviewed to understand their preferences and learning effectiveness. The results show that the effectiveness of the recommendation system is acceptable. In study 2, online real-time feedback and adaptive instruction platform is developed, which is different from the past adaptive curriculums mainly using the Internet platform and only the submitted assignments to determine the newly recommended learning process for students. The study found that the students' learning performance in the adaptive instruction group is better than those in the fixed instruction group.
Abstract
We used light to irradiate skin-derived stem cells and tried to find any cellular protein alterations 24 h after illumination. A 266-nm laser with four intensities was used, and of the nine ...cell markers that were surveyed in our trials, only CD90 was downregulated at an intensity of 20 μJ for 10 s. Repeated illuminations from the 266-nm laser at seven intensities revealed that CD90 expression was downregulated 14.6–28.8%, depending on light intensity. The maximal effect was noted at an intensity of 30 μJ for 2 s. This innovative finding reveals that a 266-nm laser can regulate protein expression in skin-derivative stem cells.
This paper describes a video coding technology proposal submitted by MediaTek in April 2018 in response to a joint call for proposals (CfP) issued by ITU-T VCEG and ISO/IEC MPEG. The proposal uses ...the conventional block-based hybrid coding approach with a breakthrough design of block structure, substantial improvements of coding tools, and new inventions of loop filtering techniques. First, the block structure is designed using a highly flexible partitioning scheme, where each coding tree unit in a picture is split into multiple coding units (CUs) by a recursive quaternary tree followed by a recursive binary-ternary tree. The prediction unit (PU) and transform unit (TU) concepts are unified with the CU concept, i.e., PU and TU are basically the same as CU. Moreover, inter prediction, intra prediction, transform, quantization, in-loop filtering, and entropy coding are all improved. Finally, new loop filtering techniques are invented, where the proposed convolutional neural network loop filtering is of particular interest. The proposed video codec achieves 43.81% average bit rate savings based on objective measures compared to the High Efficiency Video Coding (HEVC) anchors and is among the best-performing CfP responses both objectively and subjectively. It has been partially adopted into the working draft of the Versatile Video Coding (VVC) standard.
Typhoon (TY) Koppu (2015) brought intensive small horizontal-scale rainfall at Baguio, Philippines. This study examines the applicability of the TWRF model (based on the Weather Research and ...Forecasting model, https://www.mmm.ucar. edu/weather-research-and-forecasting-model, specifically for the TY prediction) of the Central Weather Bureau, Taiwan in the rainfall prediction of Koppu. Moreover, it aims to improve the understanding of the mountainous terrain effect on the rainfall and structural changes of TY Koppu. The TWRF-predicted rainfall initiated at 1200 UTC 17 October is compared with the surface observed rainfall and the passive microwave rainfall product, and the TWRF-simulated TY Koppu structure is verified against satellite infrared cloud imagery. Verifying available best tracks, the largest predicted track error within 72 hours of prediction is 145 km. Rainfall similar to that at Baguio can also be obtained by the TWRF, except that the location of the maximum rainfall is to the south of the observation. Modeling results show that heavy rainfall was caused by the outer rain band of TY Koppu, which gradually reorganized over the western coastal area when Koppu weakened after landing. Results also show that the high terrain located south of the TY center enhanced the rain band. However, the dry air in the lee side and downstream of the high mountains located north of the TY center weakened and pushed the band southward. TY Koppu and the rain band then moved northward. The formation and intensification, the weakening and southward shifting, and then the northward approaching and passing of the rain band resulted in the extreme rainfall at Baguio.
•Ensemble forecast of typhoon tracks has a comparable skill to operational centers.•Ensemble forecast has better performance for rainfall than a deterministic forecast.•Ensemble prediction provides ...useful probabilistic information.•Runoff forecast over mountainous watershed is sensitive to rainfall forecast.
In this study, an ensemble meteorological modeling system is one-way coupled with a hydrological model to predict typhoon rainfall and flood responses in a mountainous watershed in Taiwan. This ensemble meteorological model framework includes perturbations of the initial conditions, data analysis methods, and physical parameterizations. The predicted rainfall from the ensemble meteorological modeling system is then used to drive a physically distributed hydrological model for flood responses in the Lanyang basin during the landfall of Typhoon Nanmadol (2011). The ensemble forecast provides track forecasts that are comparable to the operational center track forecasts and provides a more accurate rainfall forecast than a single deterministic prediction. The runoff forecast, which is driven by the ensemble rainfall prediction, can provide uncertainties for the runoff forecasts during typhoon landfall. Thus, the ensemble prediction system provides useful probability information for rainfall and runoff forecasting.
Typhoon WRF (TWRF) based on the Advanced Research Weather Research and Forecasting Model (ARW WRF) was operational at the Central Weather Bureau (CWB) for tropical cyclone (TC) predictions since 2010 ...(named TWRF V1). CWB has committed to improve this regional model, aiming to increase the model predictability toward typhoons over East Asia. In 2016, an upgraded version designed to replace TWRF V1 became operational (named TWRF V2). Compared with V1, which has triple-nested meshes with coarser resolution (45/15/5 km), V2 increased the model resolution to 15/3 km. Since V1 and V2 were maintained in parallel from 2016 to 2018, this study utilized the real-time forecasts to investigate the impact of model resolution on TC prediction. Statistical measures pointed out the superiority of the high-resolution model on TC prediction. The forecast performance was also found competitive with that of two leading global models. The case study further pointed out, with the higher resolution, the model not only advanced the prediction on the TC track and inner core structure but also improved the representativeness of the complex terrain. Overall, the high-resolution model can better handle the so-called terrain phase-lock effect and, therefore, improve the TC quantitative precipitation forecast over the complex Taiwanese terrain.
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