Quantification Of Efficiency Research Articles

Phenotyping heart failure by echocardiography: imaging of ventricular function and haemodynamics at rest and exercise.

Traditionally, congestive heart failure (HF) was phenotyped by echocardiography or other imaging techniques according to left ventricular (LV) ejection fraction (LVEF). The more recent echocardiographic modality speckle tracking strain is complementary to LVEF, as it is more sensitive to diagnose mild systolic dysfunction. Furthermore, when LV systolic dysfunction is associated with a small, hypertrophic ventricle, EF is often normal or supernormal, whereas LV global longitudinal strain can reveal reduced contractility. In addition, segmental strain patterns may be used to identify specific cardiomyopathies, which in some cases can be treated with patient-specific medicine. In HF with preserved EF (HFpEF), a diagnostic hallmark is elevated LV filling pressure, which can be diagnosed with good accuracy by applying a set of echocardiographic parameters. Patients with HFpEF often have normal filling pressure at rest, and a non-invasive or invasive diastolic stress test may be used to identify abnormal elevation of filling pressure during exercise. The novel parameter LV work index, which incorporates afterload, is a promising tool for quantification of LV contractile function and efficiency. Another novel modality is shear wave imaging for diagnosing stiff ventricles, but clinical utility remains to be determined. In conclusion, echocardiographic imaging of cardiac function should include LV strain as a supplementary method to LVEF. Echocardiographic parameters can identify elevated LV filling pressure with good accuracy and may be applied in the diagnostic workup of patients suspected of HFpEF.

Multi-UAV Roundup Inspired by Hierarchical Cognition Consistency Learning Based on an Interaction Mechanism

This paper is concerned with the problem of multi-UAV roundup inspired by hierarchical cognition consistency learning based on an interaction mechanism. First, a dynamic communication model is constructed to address the interactions among multiple agents. This model includes a simplification of the communication graph relationships and a quantification of information efficiency. Then, a hierarchical cognition consistency learning method is proposed to improve the efficiency and success rate of roundup. At the same time, an opponent graph reasoning network is proposed to address the prediction of targets. Compared with existing multi-agent reinforcement learning (MARL) methods, the method developed in this paper possesses the distinctive feature that target assignment and target prediction are carried out simultaneously. Finally, to verify the effectiveness of the proposed method, we present extensive experiments conducted in the scenario of multi-target roundup. The experimental results show that the proposed architecture outperforms the conventional approach with respect to the roundup success rate and verify the validity of the proposed model.

A Cell-Based Double Reporter Gene Splicing Assay for Therapeutic Screening in Myotonic Dystrophy

Abstract The study has developed a model splicing construct assay system based on splicing misregulation, one of the major molecular features associated with myotonic dystrophy. The splicing construct assay has double reporters for intron 2 splicing in chloride channel (CLCN1). The CLCN1 transgene splicing construct assay was used to transfect wild type and DM fibroblast cell lines and the clones generated showed that it enabled quantification of splicing efficiency in transgene construct. Validation of the DM fibroblasts containing transgene splicing construct was performed by differentiating the DM fibroblasts into myoblasts which exhibited a switch in CLCN1 splicing construct which was consistent with that associated with myotonic dystrophy (DM) condition. The myoblast derived from fibroblasts cell-based gene-splicing assay was subsequently applied in therapeutic screening in small throughput screens of 113 compounds which identified Protein Kinase C inhibitors- hypericin and Ro-31-8220 as potential therapeutic agents. The CLCN1 gene-splicing assay is a good model system for application in therapeutic screening in myotonic dystrophy because its double reporters facilitated quantification of effect putative drug on correction of misregulated splicing.

On the Determinants of the Bank Efficiency in the Republic of Serbia: Two-Stage Dea Approach

Abstract The important role of the banking sector in the economic development of the country imposes the need for continuous measurement and monitoring of bank efficiency. Besides, identifying industry-specific and macroeconomic factors that affect the achieved efficiency is an important task in order to detect potential disruptions, as well as to provide adequate guidelines to improve the efficiency. Therefore, the main goal of this paper is to quantify the achieved efficiency and uncover its determinants. The study is conducted in two stages. In the first stage, using the DEA method, the efficiency of banks for the period from 2005 to 2022 will be assessed, while in the second stage, the factors of efficiency will be determined by applying Tobit regression. The results indicate that when it comes to industry-specific factors, greater market concentration unfavourably affects the efficiency of banks. Regarding the macroeconomic factors, the growth of gross domestic product, inflation rate and global financial crisis have a significant influence on the achieved level of bank efficiency in the Republic of Serbia. In addition to expanding the existing knowledge on quantification of efficiency and defining the determinants of efficiency on the example of banks in the Republic of Serbia, the results in this paper also hold relevance to policymakers and practitioners.

Escinosome thermosensitive gel optimizes efficacy of CAI-CORM in a rat model of rheumatoid arthritis.

Rheumatoid arthritis is among the most common disabling diseases associated with chronic inflammation. The efficacy of the current therapeutic strategies is limited; therefore, new pharmacological agents and formulation approaches are urgently needed. In this work, we developed a thermosensitive gel incorporating escinosomes, innovative nanovesicles made of escin, stabilized with 10% of tween 20 and loaded with a Carbonic Anhydrase Inhibitor (CAI) bearing a Carbon Monoxide Releasing Moiety (CORM) (i.e., CAI-CORM 1), previously synthesized by some of the authors as a new potent pain-relieving agent. The light scattering analysis of the developed formulation showed optimal physical parameters, while the chromatographic analysis allowed the quantification of the encapsulation efficiency (90.1 ± 5.91 and 91.6 ± 8.46 for CAI-CORM 1 and escin, respectively). The thermosensitive gel, formulated using 23% w/v of poloxamer 407, had a sol-gel transition time of 40 s and good syringeability. Its stability in simulated synovial fluid (SSF) was morphologically evaluated by electron microscopy. Nanovesicles were physically stable in contact with the medium for two weeks, maintaining their original dimensions and spherical shape. The viscosity increased by about 30- to 100-fold with the temperature change from 25 °C to 37 °C. The gel erosion in SSF occurred within 9 h (88.2 ± 0.743%), and the drug's passive diffusion from escinosomes lasted 72 h, allowing a potential sustained therapeutic effect. The efficacy of a single intra-articular injection of the gel containing escinosomes loaded with CAI-CORM 1 (3 mg/mL; 30 μL, CAI-CORM 1 formulation) and the gel containing unloaded escinosomes (30 μL, blank formulation) was evaluated in a rat model of Complete Freund's Adjuvant (CFA)-induced rheumatoid arthritis. CAI-CORM 1 formulation was assessed to counteract mechanical hyperalgesia, spontaneous pain, and motor impairments on days 7 and 14 after treatment. The histological evaluation of the joints stressed the improvement of several morphological parameters in CFA + CAI-CORM 1 formulation-treated rats. In conclusion, the hybrid molecule CAI-CORM 1 formulated in escinosome-based thermosensitive gel could represent a new valid approach for managing rheumatoid arthritis.

PO-02-242 AAV6-CTNT-HCN2/SKM1 GENE TRANSFER ENABLES A TRANSIENT BIOLOGICAL PACEMAKER ACTIVITY IN A PORCINE MODEL OF CAVB

In an effort to develop hardware-free pacemakers, we have engaged into the development of gene therapy-based biological pacemakers by means of ion channel overexpression. To this end, we report our progress with regard to Hcn2/SkM1 gene delivery mediated by adeno associated virus (AAV), in an attempt to generate long-term biological pacing. To assess the long-term efficacy of biological pacing based on AAV-mediated gene transfer of Hcn2/SkM1. Functional biological pacemaker studies were conducted in a porcine model of radiofrequency ablation-induced complete atrioventricular block. Four weeks after the ablation, animals were distributed in four different groups: non-injected, saline, and AAV6-Hcn2/SkM1 with or without immunosuppression. All animals were followed for another four to six weeks to evaluate in vivo biological pacemaker performance and then hearts were harvested to assess transduction efficiency. One week after gene transfer, Hcn2/SkM1-transduced animals displayed a notable increase in maximal beating rates above 100 beats/min (Figure A), mean heart rates only modestly trended up, yet a remarkable reduction of electronically paced beats was evident with a backup pacing of less than 60% (Figure B). Quantification of gene transfer efficiency in the injection sites showed considerable expression levels of both transgenes (Hcn2 and SkM1; not shown) in transduced animals at four- and six-weeks post-injection. AAV6-mediated Hcn2/SkM1 gene transfer in CAVB pigs resulted in transient biological pacemaker activity in the first week after injection, which reemerged four to six weeks after injection in animals that receive immunosuppression.

Fundamental and State-of-the-Art Technologies In Retinal Studies and Disease Repair

ARTICLES DISCUSSED: Ma, Y., Li., T. Monitoring dynamic growth of retinal vessels in oxygen-induced retinopathy mouse model. Journal of Visualized Experiments. (170), e62410 (2021). Guan, Y., Xie, B. Zhong, X. Retinal organoid induction system for derivation of 3D retinal tissues from human pluripotent stem cells. Journal of Visualized Experiments. (170), e62435 (2021). Rose, K., Lokappa, S. Chen, J. Two peeling methods for the isolation of photoreceptor cell compartments in the mouse retina for protein analysis. Journal of Visualized Experiments. (178), e62977 (2021). Ye., Q. et al. In vivo methods to assess retinal ganglion cell and optic nerve function and structure in large animals. Journal of Visualized Experiments. (180), e62879 (2022). Abbas, F., Vinberg, F., Becker, S. Optimizing the setup and conditions for ex vivo electroretinogram to study retina function in small and large eyes. Journal of Visualized Experiments. (184), e62763 (2022). Okan, I., Ahmadian, M., Tutuncu, Y., Altay, H., Agca, C. Digital droplet PCR method for the quantification of AAV transduction efficiency in murine retina. Journal of Visualized Experiments. (178), e63038 (2021).

Performance analysis of bauxite beneficiation process in Juruti Mine. Part 2: Simulation and optimization alternatives

The simulation process was applied to the industrial circuit of the Juruti Bauxite Mine using mathematical models calibrated for the equipment and based on information from industrial sampling. The sampling campaign, mass balance routines and quantification of the process efficiency were discussed in Part I of this study and the model calibration and simulations process were the Part II objective. Simulation scenarios were defined considering the possible particle size curves for feeding the plant. Based on the simulated results, it was possible to observe which operations may be impacted by the increase in production, impacting the percentage of contaminants in the final product, indicating the necessity of equipment interventions to support increases in capacity. Another group of scenarios were established with the objective to evaluate the possibility of increasing the mass recovery and improving the quality of the fine product, by variations in the opening diameters of the apex and vortex finder of the five cyclone stages. Considering the simulated scenarios, the points of attention identified in the simulations were: (a) the washing efficiency could be reduced, in view of a consequent reduction in residence time connected to the change in characteristics of the ore fed to the plant; (b) increase capacity of the primary and secondary screens need to be done; (c) to keep the classification efficiencies, it is necessary install more cyclone units; and (d) changes in the apex diameter and vortex finder could generate results in terms of mass recovery and product quality.

In-line inspection technology of oil and gas long-distance pipeline based on alternating current field measurement

Abstract Alternating current field measurement (ACFM) has advantages of fast inspection speed, high efficiency, sensitive inspection, and easy quantification. In this study, a probe based on ACFM has been carried out, trying to inspect cracks on the inner wall of pipeline with high precision. An inspection tool which is working according to ACFM is developed in order to determine the stress corrosion cracking. The lift-off distance and excitation frequency parameters are optimized, and the influence of uneven magnetic permeability of the pipeline on the test results is analyzed. In addition, experiments are carried out to test the practicality of the tool. The minimum axial crack length that the probe can detect is 15 mm and the minimal depth is 1 mm. The research results show that the probe has the ability to quantitatively evaluate the axial cracks on the inner surface of the pipeline, which has certain guiding significance for the design and development of the AC electromagnetic field inspection probe.

Quantification of capture efficiency, purity, and single-cell isolation in the recovery of circulating melanoma cells from peripheral blood by dielectrophoresis.

This paper describes a dielectrophoretic method for selection of circulating melanoma cells (CMCs), which lack reliable identifying surface antigens and are extremely rare in blood. This platform captures CMCs individually by dielectrophoresis (DEP) at an array of wireless bipolar electrodes (BPEs) aligned to overlying nanoliter-scale chambers, which isolate each cell for subsequent on-chip single-cell analysis. To determine the best conditions to employ for CMC isolation in this DEP-BPE platform, the static and dynamic dielectrophoretic response of established melanoma cell lines, melanoma cells from patient-derived xenografts (PDX) and peripheral blood mononuclear cells (PBMCs) were evaluated as a function of frequency using two established DEP platforms. Further, PBMCs derived from patients with advanced melanoma were compared with those from healthy controls. The results of this evaluation reveal that each DEP method requires a distinct frequency to achieve capture of melanoma cells and that the distribution of dielectric properties of PBMCs is more broadly varied in and among patients versus healthy controls. Based on this evaluation, we conclude that 50 kHz provides the highest capture efficiency on our DEP-BPE platform while maintaining a low rate of capture of unwanted PBMCs. We further quantified the efficiency of single-cell capture on the DEP-BPE platform and found that the efficiency diminished beyond around 25% chamber occupancy, thereby informing the minimum array size that is required. Importantly, the capture efficiency of the DEP-BPE platform for melanoma cells when using optimized conditions matched the performance predicted by our analysis. Finally, isolation of melanoma cells from contrived (spike-in) and clinical samples on our platform using optimized conditions was demonstrated. The capture and individual isolation of CMCs, confirmed by post-capture labeling, from patient-derived samples suggests the potential of this platform for clinical application.

Mechanistic Insights into the Superior DNA Delivery Efficiency of Multicomponent Lipid Nanoparticles: An In Vitro and In Vivo Study.

Lipid nanoparticles (LNPs) are currently having an increasing impact on nanomedicines as delivery agents, among others, of RNA molecules (e.g., short interfering RNA for the treatment of hereditary diseases or messenger RNA for the development of COVID-19 vaccines). Despite this, the delivery of plasmid DNA (pDNA) by LNPs in preclinical studies is still unsatisfactory, mainly due to the lack of systematic structural and functional studies on DNA-loaded LNPs. To tackle this issue, we developed, characterized, and tested a library of 16 multicomponent DNA-loaded LNPs which were prepared by microfluidics and differed in lipid composition, surface functionalization, and manufacturing factors. 8 out of 16 formulations exhibited proper size and zeta potential and passed to the validation step, that is, the simultaneous quantification of transfection efficiency and cell viability in human embryonic kidney cells (HEK-293). The most efficient formulation (LNP15) was then successfully validated both in vitro, in an immortalized adult keratinocyte cell line (HaCaT) and in an epidermoid cervical cancer cell line (CaSki), and in vivo as a nanocarrier to deliver a cancer vaccine against the benchmark target tyrosine-kinase receptor HER2 in C57BL/6 mice. Finally, by a combination of confocal microscopy, transmission electron microscopy and synchrotron small-angle X-ray scattering, we were able to show that the superior efficiency of LNP15 can be linked to its disordered nanostructure consisting of small-size unoriented layers of pDNA sandwiched between closely apposed lipid membranes that undergo massive destabilization upon interaction with cellular lipids. Our results provide new insights into the structure-activity relationship of pDNA-loaded LNPs and pave the way to the clinical translation of this gene delivery technology.

Quantification of some ARVs' removal efficiency from wastewater using a moving bed biofilm reactor.

To date, in South Africa alone, there are an estimated 4.5 million people receiving antiretroviral (ARV) therapy. This places South Africa as the country with the largest ARV therapy programme in the world. As a result, there are an increasing number of reports on the occurrence of ARVs in South African waters. Achieving efficient and bio-friendly methods for the removal of these pollutants is considered as a concern for environmental researchers. This study aims at studying the efficiency of a moving bed biofilm reactor (MBBR) system for removing ARVs from wastewater. A continuous-flow laboratory scale system was designed, built, installed, and operated at a carrier filling rate of 30%, an organic loading rate of 0.6 kg COD/m3.d-1 OLR, a hydraulic retention time of 18h, and a 27.8 mL/min flow rate. The systems were monitored over time for the elimination of conventional wastewater parameters i.e., Biological Oxygen Demand, Chemical Oxygen Demand, and nutrients. The results showed that the MBBR system as a bio-friendly method has high efficiency in removing Nevirapine, Tenofovir, Efavirenz, Ritonavir and Emtricitabine from the synthetic influent sample with an average removal of 62%, 74%, 94%, 94% and 95%, respectively, after 10 days of operation.

Disentangling Aerosol and Cloud Effects on Dimming and Brightening in Observations and CMIP6

AbstractPeriods of dimming and brightening have been recorded in observational datasets of surface solar radiation (SSR) between the mid‐20th century and present day. Atmospheric components affect SSR, including aerosols and clouds, though studies disagree somewhat about the relative effect of each component in different regions. Current Earth system models (ESMs) are unable to simulate observed trends in SSR. This study includes an investigation into observed SSR variations between 1961 and 2014 and an evaluation of the effects of cloud cover variations and impacts of aerosol extinction, using timeseries of SSR and cloud cover from in‐situ measurements. Historical simulations by 42 ESMs participating in the Coupled Model Intercomparison Project phase 6 (CMIP6) have also been studied and compared to observations. The observational study indicates that cloud cover has had a dampening effect on the variations of SSR and that emissions of aerosol and aerosol precursors are the main cause of the general trends in observed SSR in four regions—China, Japan, Europe, and the United States—during 1961–2014. The study of simulated SSR in CMIP6 yields the conclusion that current ESMs remain unable to simulate the magnitude of observed dimming and brightening in China, Japan, and the United States, but that the European SSR trends between 1961 and 2014 are fairly well reproduced in the ESMs. A rough quantification of the regional surface radiation extinction efficiency of aerosol and precursor emissions in the simulations is found to agree with observed values in Europe, but not in the other three regions.

Urban road network resilience metrics and their relationship: Some experimental findings

Resilience is a complex term, bearing multiple definitions and resilience-related metrics. The most commonly utilized metrics are network efficiency and criticality that examine the impact that the removal of a structural element of a graph/ network has on its operation. Efficiency examines this term from a pure topological aspect and takes into account the shortest paths between the nodes whereas, on the other hand, criticality takes into account transportation-related variables like travel demand. In the present research, the interrelation between efficiency and criticality is further examined through a series of simulation experiments on the Athens city-center urban road network. For the quantification of efficiency, vulnerability, and criticality an iterative approach is used where, per iteration, one link of the network was removed. The outputs of the experiments are, then, statistically analyzed, using unsupervised and supervised techniques. Findings reveal that a polynomial relationship between the ratio of criticality and efficiency, and traffic flow exists. Finally, the implications of these findings to traffic and network management are discussed.

Detection and Discrimination of Single Nucleotide Polymorphisms by Quantification of CRISPR-Cas Catalytic Efficiency.

The specificity of CRISPR-Cas12 assays is attractive for the detection of single nucleotide polymorphisms (SNPs) implicated in, e.g., cancer and SARS-CoV-2 variants. Such assays often employ endpoint measurements of SNP or wild type (WT) activated Cas12 trans-cleavage activity; however, the fundamental kinetic effects of SNP versus WT activation remain unknown. We here show that endpoint-based assays are limited by arbitrary experimental choices (like used reporter concentration and assay duration) and work best for known target concentrations. More importantly, we show that SNP (versus WT) activation results in measurable kinetic shifts in the Cas12 trans-cleavage substrate affinity (KM) and apparent catalytic efficiency (kcat*/KM). To address endpoint-based assay limitations, we then develop an assay based on the quantification of Michaelis-Menten parameters and apply this assay to a 20 base pair WT target of the SARS-CoV-2 E gene. We find that the kcat*/KM measured for WT is 130-fold greater than the lowest kcat*/KM among all 60 measured SNPs (compared to a 4.8-fold for endpoint fluorescence of the same SNP). KM also offers a strong ability to distinguish SNPs, varies 27-fold over all the cases, and, importantly, is insensitive to the target concentration. Last, we point out trends among kinetic rates and SNP base and location within the CRISPR-Cas12 targeted region.

S1480 Clinical Burden of Electronic Health Record Use Amongst Gastroenterology Providers Associated With Differences in Sex, Provider Subspecialty, and Provider Training

Introduction: The electronic health record (EHR) has increased time spent outside of face-to-face encounters, with higher EHR burden associated with differences in provider sex, specialty, and rates of burnout. However, the EHR burden specific to gastroenterology (GI) providers is not fully understood. Methods: Measures of EHR use calculated through Epic Systems were retrospectively collected for GI providers from a tertiary referral center during a 6-month period starting January 1, 2021. Primary measures used to characterize EHR use included time spent performing clinical review, documentation, and in-basket management as well as quantification of efficiency, messaging, and time logged into the EHR, including time outside regularly scheduled hours (5:30 p.m. to 7:00 a.m. and weekends). EHR use patterns were compared across provider sex, sub-specialty (inflammatory bowel disease [IBD], motility/irritable bowel syndrome, advanced endoscopy [AE], and esophagus [ESO]), and training (physician vs non-physician provider [NPP]). Data was analyzed in aggregate using t-tests and analysis of variance with post-hoc Boniferri correction. Results: Data from 33 providers compromising 3,743 clinic days and 16,572 appointments was collected. Overall, 69.7% (23/33) were physicians, 30.3% (10/33) NPPs and 48.5% (16/33) were women, with women comprising all NPPs. Comparing EHR burden across sexes, women spent more daily time in clinical review than men (42.4 minutes vs 26.0, P = 0.02), though this result lost statistical significance when excluding NPPs. Comparing sub-specialties, IBD specialists spent more daily time in clinical review per appointment than AEs or ESOs (13.7 minutes vs 3.9 and 3.7, respectively; P < 0.001) yet had higher efficiency scores compared to these sub-specialties (P < 0.001). Compared to AEs, IBD specialists spent more overall daily time in the EHR (131.5 minutes vs 39.7, P < 0.005) as well as more daily time outside of regular work hours (60.0 minutes vs 8.9, P < 0.01). Comparing provider training, NPPs spent more daily time in the in-basket (P = 0.03), clinical review (P = 0.02), and overall EHR (P < 0.001) than physicians. Additionally, NPPs received more patient medical advice request messages per day than physicians (P = 0.03). Conclusion: IBD specialists and NPPs have an increased EHR burden. More work is needed to better understand sex, sub-specialty, and training-based differences in workload to combat factors contributing to provider burnout.

Estimating energy costs and greenhouse gas emissions efficiency in the provision of domestic water: An empirical application for England and wales

• Specific efficiency sores for energy costs and greenhouse gas emissions were estimated. • English and Welsh water companies could save 35.6% of the current energy costs. • Efficiency on greenhouse gas emissions was estimated at 41.5% level. Reducing greenhouse gas (GHG) emissions and energy costs has been one of the main challenges faced by the water sector. This study provides a quantification of energy costs and GHG emissions efficiency of a sample of the English and the Welsh water companies over the period of 2013-2018. In doing so, the multi-directional data envelopment analysis (DEA) method was employed, which allows the quantification of the potential savings in energy costs and GHG emissions, i.e. defining the targets to be set by the water regulators. In the second stage of the analysis, bootstrap techniques were applied to identify environmental variables influencing the performance of water companies. The results indicate that the efficiency of the English and the Welsh water companies was low since the average efficiency scores for energy costs and GHG emissions were 0.644 and 0.415, respectively. It reveals that the water sector might save 35.6% and 58.6% of the current energy costs and GHG emissions. The study's findings demonstrated that the source of raw water, the treatment required to produce drinking water and population density were the environmental variables influencing the efficiency of these water companies in terms of energy costs and GHG emissions. The evidence provided by this study is of great interest to water regulators and water companies to implement policies and measures towards a low-carbon urban water cycle.

Quantitative Cell Proteomic Atlas: Pathway-Scale Targeted Mass Spectrometry for High-Resolution Functional Profiling of Cell Signaling.

In spite of extensive studies of cellular signaling, many fundamental processes such as pathway integration, cross-talk, and feedback remain poorly understood. To enable integrated and quantitative measurements of cellular biochemical activities, we have developed the Quantitative Cell Proteomics Atlas (QCPA). QCPA consists of panels of targeted mass spectrometry assays to determine the abundance and stoichiometry of regulatory post-translational modifications of sentinel proteins from most known physiologic and pathogenic signaling pathways in human cells. QCPA currently profiles 1 913 peptides from 469 effectors of cell surface signaling, apoptosis, stress response, gene expression, quiescence, and proliferation. For each protein, QCPA includes triplets of isotopically labeled peptides covering known post-translational regulatory sites to determine their stoichiometries and unmodified protein regions to measure total protein abundance. The QCPA framework incorporates analytes to control for technical variability of sample preparation and mass spectrometric analysis, including TrypQuant, a synthetic substrate for accurate quantification of proteolysis efficiency for proteins containing chemically modified residues. The ability to precisely and accurately quantify most known signaling pathways should enable improved chemoproteomic approaches for the comprehensive analysis of cell signaling and clinical proteomics of diagnostic specimens. QCPA is openly available at https://qcpa.mskcc.org.

Repurposing of HIV/HCV protease inhibitors against SARS-CoV-2 3CLpro

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that caused the global COVID-19 outbreak. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a key role in virus replication and has become an ideal target for antiviral drug design. In this work, we have employed bioluminescence resonance energy transfer (BRET) technology to establish a cell-based assay for screening inhibitors against SARS-CoV-2 3CLpro, and then applied the assay to screen a collection of known HIV/HCV protease inhibitors. Our results showed that the assay is capable of quantification of the cleavage efficiency of 3CLpro with good reproducibility (Z′ factor is 0.59). Using the assay, we found that 9 of 26 protease inhibitors effectively inhibited the activity of SARS-CoV-2 3CLpro in a dose-dependent manner. Among them, four compounds exhibited the ability to bind to 3CLproin vitro. HCV protease inhibitor simeprevir showed the most potency against 3CLpro with an EC50 vale of 2.6 μM, bound to the active site pocket of 3CLpro in a predicted model, and importantly, exhibited a similar activity against the protease containing the mutations P132H in Omicron variants. Taken together, this work demonstrates the feasibility of using the cell-based BRET assay for screening 3CLpro inhibitors and supports the potential of simeprevir for the development of 3CLpro inhibitors.

An Efficient and Uncertainty-Aware Decision Support System for Disaster Response Using Aerial Imagery

Efficient and robust search and rescue actions are always required when natural or technical disasters occur. Empowered by remote sensing techniques, building damage assessment can be achieved by fusing aerial images of pre- and post-disaster environments through computational models. Existing methods pay over-attention to assessment accuracy without considering model efficiency and uncertainty quantification in such a life-critical application. Thus, this article proposes an efficient and uncertain-aware decision support system (EUDSS) that evolves the recent computational models into an efficient decision support system, realizing the uncertainty during building damage assessment (BDA). Specifically, a new efficient and uncertain-aware BDA integrates the recent advances in computational models such as Fourier attention and Monte Carlo Dropout for uncertainty quantification efficiently. Meanwhile, a robust operation (RO) procedure is designed to invite experts for manual reviews if the uncertainty is high due to external factors such as cloud clutter and poor illumination. This procedure can prevent rescue teams from missing damaged houses during operations. The effectiveness of the proposed system is demonstrated on a public dataset from both quantitative and qualitative perspectives. The solution won the first place award in International Overhead Imagery Hackathon.