Vulnerable Sites Research Articles

Piezo-enhanced photocatalytic performance of ZnO nanorod array for pollutants degradation in dynamic water: Insight into the effect of velocity and inner flow field

The piezoelectric effect, which can promote photocatalytic degradation of pollutants, has attracted great attention. However, the effect of hydrodynamic factors on the performance is still unclear in the water-driven piezo-enhanced photocatalytic process. Herein, ZnO nanorod array on porous substrate was employed to study the effect of hydrodynamic factors on piezo-assisted photocatalysis. Flow field simulation analysis based on computational fluid dynamics (CFD) indicates that velocity notably affects the piezo-photocatalytic process. Meanwhile, the porous structure of substrate promotes the formation of micro-turbulence, which also significantly improve the piezopotential of ZnO and further enhance the catalytic performance. Density functional theory (DFT) calculations further reveal the vulnerable sites attacked by reactive species, thereby proposing the possible degradation pathway of pollutant. This study illustrates the important role of hydrodynamic factors in piezo-photocatalytic process and provides a feasible way for in-situ purification of pollutants in urban sewerage and drainage.

Accumulation and fluxes of potentially toxic elements in a large coastal lagoon (southern Gulf of Mexico) from 210Pb sediment chronologies

Three 210Pb-dated sediment cores were used to evaluate the contamination degree and flux ratios of potentially toxic elements (PTEs; As, Cd, Cr, Cu, Ni, Pb, V, and Zn) in seagrass meadows from the northern margin of Términos Lagoon (TL), southern Gulf of Mexico. The sediments displayed minor Cd, Ni, V, and Zn enrichments but moderate to strong enrichment by As. Results from a chemometric analysis revealed that: 1) salinization and grain size, along with 2) the terrigenous inputs are the major factors influencing the PTEs accumulation. The historical trends of PTEs flux ratios nearly follow the large-scale land-use changes around TL, linked to the growth of the Mexican oil industry in the area since the 1970s. Our findings showed the critical role of seagrass meadows as PTEs sinks. This information is useful for decision-makers to develop restoration projects for a vulnerable site within the largest coastal lagoon ecosystem in Mexico.

Integrating Conformational Dynamics and Perturbation-Based Network Modeling for Mutational Profiling of Binding and Allostery in the SARS-CoV-2 Spike Variant Complexes with Antibodies: Balancing Local and Global Determinants of Mutational Escape Mechanisms.

In this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the spike complexes that can affect the pattern of mutational escape. A network-based perturbation approach for mutational profiling of allosteric residue potentials revealed how antibody binding can modulate allosteric interactions and identified allosteric control points that can form vulnerable sites for mutational escape. The results show that the protein stability and binding energetics of the SARS-CoV-2 spike complexes with the panel of ultrapotent antibodies are tolerant to the effect of Omicron mutations, which may be related to their neutralization efficiency. By employing an integrated analysis of conformational dynamics, binding energetics, and allosteric interactions, we found that the antibodies that neutralize the Omicron spike variant mediate the dominant binding energy hotpots in the conserved stability centers and allosteric control points in which mutations may be restricted by the requirements of the protein folding stability and binding to the host receptor. This study suggested a mechanism in which the patterns of escape mutants for the ultrapotent antibodies may not be solely determined by the binding interaction changes but are associated with the balance and tradeoffs of multiple local and global factors, including protein stability, binding affinity, and long-range interactions.

A broad and potent neutralization epitope in SARS-related coronaviruses

Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.

From Haunted Houses to Housed Hauntings

This paper is oriented around moments of crises and kinship ambivalence within the home of a merchant family on the outskirts of a small town in central Sri Lanka. The problems explored play out in two registers. The first outlines relations between men that become problematic and result in disharmony at home and at work, while the second deals with a situation in which the house itself becomes the site of disorder and vulnerability. Bringing fractious relationships between men into conversation with an established literature on spirit possession in South Asia explores how families manage (haunted) houses in a way that centers around the ritual authority maha gedera. In so doing, it makes a case for the mutual interplay of relationality between people, houses, and ghosts that haunt. At another level, the article offers a critical reflection on kinship’s agrarian history (and political death) in Sri Lanka and considers the stylistic predilection for interpretive narratives of possession in anthropology.

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

Coronaviruses can evolve and spread rapidly to cause severe disease morbidity and mortality, as exemplified by SARS-CoV-2 variants of the COVID-19 pandemic. Although currently available vaccines remain mostly effective against SARS-CoV-2 variants, additional treatment strategies are needed. Inhibitors that target essential viral enzymes, such as proteases and polymerases, represent key classes of antivirals. However, clinical use of antiviral therapies inevitably leads to emergence of drug resistance. In this study we implemented a strategy to pre-emptively address drug resistance to protease inhibitors targeting the main protease (Mpro) of SARS-CoV-2, an essential enzyme that promotes viral maturation. We solved nine high-resolution cocrystal structures of SARS-CoV-2 Mpro bound to substrate peptides and six structures with cleavage products. These structures enabled us to define the substrate envelope of Mpro, map the critical recognition elements, and identify evolutionarily vulnerable sites that may be susceptible to resistance mutations that would compromise binding of the newly developed Mpro inhibitors. Our results suggest strategies for developing robust inhibitors against SARS-CoV-2 that will retain longer-lasting efficacy against this evolving viral pathogen.

The Plug-Type Patch Results in Immediate and Postoperative Advantages in Graft-to-Bone Integration for Bridging Massive Rotator Cuff Tears in a Chronic Rabbit Model

Background: Various patches have been used to bridge massive rotator cuff tears (MRCTs) by reconnecting the cuff tendons to the humeral head, but the outcomes continue to be suboptimal. Notably, the graft-bone junction is a vulnerable site for failure, which requires optimization in patch design and techniques to enhance initial and postoperative fixation strength at the graft-bone interface. Hypothesis: The plug-type patch (Plug-Pat) through intratunnel fixation would optimize mechanical characteristics in initial graft-to-bone fixation and subsequently improve postoperative biomechanical and histological properties in graft-to-bone healing when compared with the routine rectangular patch (Rect-Pat). Study Design: Controlled laboratory study. Methods: A total of 60 mature male New Zealand White rabbits underwent acute rotator cuff defects to create chronic models with MRCTs. The fascia lata autograft was then harvested to prepare a Plug-Pat, which was distally rooted in the bone tunnel and proximally sutured to native tendons in a horizontal mattress fashion to reconnect the humeral head and cuff tendons. The control group was repaired with a routine Rect-Pat that was secured onto the bone surface for graft-bone fixation. After surgery, the cuff-graft-bone complexes of rabbits in both groups were harvested immediately (0 weeks) for time-zero initial fixation strength and refreshed contact area assessment, and at 6 or 12 weeks for postoperative biomechanical and histological evaluation. Results: The Plug-Pat significantly enhanced initial fixation strength in comparison with the Rect-Pat (mean ± SD; failure load, 36.79 ± 4.53 N vs 24.15 ± 2.76 N; P < .001) and decreased failure at the graft-bone interface of the construct at 0 weeks, with a significantly increased refreshed bone bed contact area (52.63 ± 2.97 mm2 vs 18.28 ± 1.60 mm2; P < .001) between the graft and bone. At 6 and 12 weeks postoperatively, the Plug-Pat similarly resulted in greater failure load (43.15 ± 4.53 N vs 33.74 ± 2.58 N at 6 weeks; P = .001; 76.65 ± 5.04 N vs 58.17 ± 5.06 N at 12 weeks; P < .001) and stiffness (10.77 ± 2.67 N/mm vs 8.43 ± 0.86 N/mm at 6 weeks; P = .066; 16.98 ± 2.47 N/mm vs 13.21 ± 1.66 N/mm at 12 weeks; P = .011), with less specimen failure at the graft-bone interface than the Rect-Pat. In histological analyses, the Plug-Pat had a higher postoperative graft-bone integration score than the Rect-Pat, showing a more mature intratunnel healing interface with fibrocartilage tidemark formation, improved collagen properties, and more oriented cells when compared with those at the surface healing interface in the Rect-Pat. Conclusion: The Plug-Pat enhanced initial fixation strength and enlarged the refreshed contact area for graft-bone connection at time zero and subsequently improved postoperative biomechanical properties and graft-bone integration at the graft-bone healing interface when compared with the Rect-Pat. Clinical Relevance: The Plug-Pat using intratunnel fixation may be a promising strategy for patch design to optimize its initial and postoperative graft-bone connection for bridging reconstruction of MRCTs.

Confirmation of the Applicability of Skeletochronology and Estimating the Age Structure of Kaloula borealis (Microhylidae: Anura) at Lake Sihwa, South Korea.

Simple SummaryAge determination is very important for observing life history traits, evaluating vulnerable life stages, and setting proper management and conservation strategies. Age determination in animals has always been tricky. Among other approaches, skeletochronology, an age determination method that involves counting the lines of arrested growth (LAGs) produced during inactive periods, similar to plant year rings, is well-practiced in many animal groups. However, the applicability of this method remains questioned for many species, including amphibians, because of concerns around the scarcity of information on confirmed numbers of annual LAGs (e.g., once or twice in a year), chances of the disappearance of LAGs over time, and which lines exactly to count. Herein, we tested its applicability to Kaloula borealis, a class II endangered amphibian in South Korea, by rearing juveniles in the laboratory for more than one year and comparing the results with the wild population at Lake Sihwa. This study confirmed the formation of one LAG each year and no disappearance of LAGs over time in this species. Furthermore, we were also able to determine the age structure of this wild population accurately. Hence, our study validates using skeletochronology in this species and recommends it for others that show similar growth patterns.Despite having some limitations, the use of skeletochronology—age determination by counting lines of arrested growth (LAGs)—in amphibians is increasing. The main limitation of using skeletochronology is identifying the innermost visible line (IVL) and counting the exact number of LAGs. Thus, we tested its applicability to Kaloula borealis, a class II endangered amphibian in South Korea. We reared juveniles in the lab to investigate the process of bone formation. This confirmed the development of one LAG each year. Hence, our study validates skeletochronology for the age determination of this species and recommends it for others that show similar growth patterns. Furthermore, the comparison of threshold diameters with the IVL of wild individuals confirmed no LAG1 resorption. The average age of males and females in this population was 2.75 ± 1.05 and 3.64 ± 3 years, respectively. We estimated sexual maturity at 2 years with rapid growth up to that stage in both sexes. We found a female-dominated sexual size dimorphism. This study offers accurate information on the life history traits and age structure of K. borealis that may help to evaluate population dynamics in other areas, identify vulnerable life stages and sites, assess the causes of population decline, and set conservation priorities.

Community profiling to support inclusive urban community-based climate adaptation: experiences of a survey-based approach in urban informal settlements in Honiara, Solomon Islands

ABSTRACT Urban centres in the Pacific region are fast growing, with cities presenting as complex sites of risk and vulnerability. Within these cities, urban informal settlement communities are often some of the most vulnerable to climate change and impacts and urban climate planning needs to explicitly consider the priority needs of these often-marginalized communities if strategies are to be equitable. Hence, inclusive urban community-based adaptation is now a critical component of overall adaptation. In support of this important urban agenda, this paper describes a community profiling method that was developed to elicit key contextual data in support of locally appropriate climate action planning for informal settlements in Honiara, the capital city of Solomon Islands. The paper details the methodology that was developed, and uses a sample dataset to demonstrate the breadth and richness of the constructed community profile and the insights it reveals about community vulnerabilities. The paper argues that the proposed community profiling method offers organizations and practitioners invested in local engagement a practical tool to inform locally driven, climate resilient urban planning and development and can be translated for use in other Global South contexts.

An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer.

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (“supersite”) on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2–neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2–transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability.

An Effective Method to Identify Microarchitectural Vulnerabilities in GPUs

Graphics Processing Units (GPUs) are increasingly adopted in several domains where reliability is fundamental, such as self-driving cars and autonomous systems. Unfortunately, GPU devices have been shown to have a high error rate, while the constraints imposed by real-time safety-critical applications make traditional (and costly) replication-based hardening solutions inadequate. This work proposes an effective methodology to identify the architectural vulnerable sites in GPUs modules, i.e., the locations that, if corrupted, most affect the correct instructions execution. We first identify, through an innovative method based on Register-Transfer Level (RTL) fault injection experiments, the architectural vulnerabilities of a GPU model. Then, we mitigate the fault impact via selective hardening applied to the flip-flops that have been identified as critical. We evaluate three hardening strategies: Triple Modular Redundancy (TMR), Triple Modular Redundancy against SETs ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\Delta $ </tex-math></inline-formula> TMR), and Dual Interlocked Storage Cells (Dice flip-flops). The results gathered on a publicly available GPU Model (FlexGripPlus) considering functional units, pipeline registers, and warp scheduler controller show that our method can tolerate from 85% to 99% of faults in the pipeline registers, from 50% to 100% of faults in the functional units and up to 10% of faults in the warp scheduler, with a reduced hardware overhead (in the range of 58% to 94% when compared with traditional TMR). Finally, we adapt the methodology to perform a complementary evaluation targeting permanent faults and identify critical sites prone to propagate fault effects across the GPU. We found that a considerable percentage (65% to 98%) of flip-flops that are critical for transient faults are also critical for permanent faults.

The role of emotion labor in English language teacher identity construction: An activity theory perspective

Current scholarship on language teacher emotions and identity construction emphasizes the substantial role of contextual discourses and power relations in shaping teachers' professionalism. In line with this scholarship, the present study examined the role of emotion labor in Iranian English language teachers' identity construction. Grounded in activity theory as the conceptual underpinning, the study shows how institutional work functions as a regulatory mechanism for teachers' emotion labor and their multi-faceted identities. Data analyses indicated that the teachers' emotion labor and identity construction are shaped by institutional particularities in three dimensions: (1) emotion labor of managing conflicts in subjectivity and adopted identities, (2) emotion labor of dealing with tensions in caring for students and assigned identities, and (3) emotion labor of aligning agency with resisted identities. The findings reveal how the teachers engaged in and interpreted emotion labor in light of tools, goals, division of labor, and communities of practice that come to shape their multi-faceted identities. Based on the findings, we argue that gradual policy adaptation accounting for emotions and identities, rather than policy overhauls that may create resistance, would reduce institutional clashes and transform teachers’ management of emotions into a site of mutual emotionality, rather than a site of vulnerability.

Three-dimensional, biomimetic electrospun scaffolds reinforced with carbon nanotubes for temporomandibular joint disc regeneration

Temporomandibular disorder (TMD) remained a huge clinical challenge, with high prevalence but limited, unstable, and only palliative therapeutic methods available. As one of the most vulnerable sites implicated in TMD, the temporomandibular joint disc (TMJD) displayed a complicated microstructure, region-specific fibrocartilaginous distribution, and poor regenerative property, which all further hindered its functional regeneration. To address the problem, with versatile and relatively simple electrospinning (ELS) technique, our study successfully fabricated a biomimetic, three-dimensional poly (ϵ-caprolactone) (PCL)/polylactide (PLA)/carbon nanotubes (CNTs) disc scaffold, whose biconcave gross anatomy and regionally anisotropic microstructure recapitulating those of the native disc. As in vitro results validated the superior mechanical, bioactive, and regenerative properties of the biomimetic scaffolds with optimal CNTs reinforcement, we further performed in vivo experiments. After verifying its biocompatibility and ectopic fibrochondrogenicity in nude mice subcutaneous implantation models, the scaffolds guided disc regeneration and subchondral bone protection were also confirmed orthotopically in rabbits TMJD defected areas, implying the pivotal role of morphological cues in contact-guided tissue regeneration. In conclusion, our work represents a significant advancement in complex, inhomogeneous tissue engineering, providing promising clinical solutions to intractable TMD ailments. Statement of significanceComplex tissue regeneration remains a huge scientific and clinical challenge. Although frequently implicated in temporomandibular joint disorder (TMD), functional regeneration of injured temporomandibular joint disc (TMJD) is extremely hard to achieve, mainly because of the complex anatomy and microstructure with regionally variant, anisotropic fiber alignments in the native disc. In this study, we developed the biomimetic electrospun scaffold with optimal CNTs reinforcement and regionally anisotropic fiber orientations. The excellent mechanical and bioactive properties were confirmed both in vitro and in vivo, effectively promoting defected discs regeneration in rabbits. Besides demonstrating the crucial role of morphological biomimicry in tissue engineering, our work also presents a feasible clinical solution for complex tissue regeneration.

Experimental and theoretical study on Fe(VI) oxidative degradation of dichlorophen in water: Kinetics and reaction mechanisms.

Dichlorophenol (DCP), a commonly used fungicide and insecticide, is widely found in waters and wastewaters. Herein, the degradation of DCP by Ferrate (Fe(VI)) in different matrices was comprehensively investigated. In pure water, a complete removal of DCP was achieved in 300 s at [Fe(VI)]:[DCP] molar ratio of 2:1. The presence of HA (10 mg L−1) inhibited DCP degradation to a certain extent. A total of twenty degradation products were identified by HPLC/MS analysis. Based on these products, reaction pathways including the cleavage of C–C bridge bond, hydroxylation, and radical coupling were proposed. These reaction mechanisms were further rationalized by theoretical calculations. The analyses of Wiberg bond orders and transition state indicated that C7–C8 bond was the most vulnerable site for cleavage, and C12 site was the most likely site for hydroxyl addition. Mulliken atomic spin densities distribution suggested that self-coupling products was easily generated via C–O–C coupling ways. Finally, the feasibility of applying Fe(VI) to degrade DCP (20 μM) in a municipal wastewater effluent and a lake water was evaluated and verified. The findings in this study are of relevance in designing Fe(VI)-based treatment strategy for chlorine-containing persistent pesticides.

Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening.

The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a heterodimer that drives virus-host membrane fusion. Here, we analyze the role of each amino acid in E1E2 function, expressing 545 individual alanine mutants of E1E2 in human cells, incorporating them into infectious viral pseudoparticles, and testing them against 37 different monoclonal antibodies (MAbs) to ascertain full-length translation, folding, heterodimer assembly, CD81 binding, viral pseudoparticle incorporation, and infectivity. We propose a model describing the role of each critical residue in E1E2 functionality and use it to examine how MAbs neutralize infection by exploiting functionally critical sites of vulnerability on E1E2. Our results suggest that E1E2 is a surprisingly fragile protein complex where even a single alanine mutation at 92% of positions disrupts its function. The amino-acid-level targets identified are highly conserved and functionally critical and can be exploited for improved therapies and vaccines.

Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies.

SUMMARYLassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for cell entry. Neutralizing antibodies against GP are rare and principally target quaternary epitopes displayed only on the metastable, pre-fusion conformation of GP. Currently, the structural features of the neutralizing GPC-A antibody competition group are understudied. Structures of two GPC-A antibodies presented here demonstrate that they bind the side of the pre-fusion GP trimer, bridging the GP1 and GP2 subunits. Complementary biochemical analyses indicate that antibody 25.10C, which is broadly specific, neutralizes by inhibiting binding of the endosomal receptor LAMP1 and also by blocking membrane fusion. The other GPC-A antibody, 36.1F, which is lineage-specific, prevents LAMP1 association only. These data illuminate a site of vulnerability on LASV GP and will guide efforts to elicit broadly reactive therapeutics and vaccines.

PO-709-03 THE APPLICATION OF THE RE-ENTRY VULNERABILITY INDEX TO DETERMINE VENTRICULAR TACHYCARDIA EXIT FROM DIFFERENT PACING LOCATIONS, IN A PORCINE INFARCT MODEL

The application of high-density electroanatomic (EA) and functional mapping strategies is a new frontier in ventricular tachycardia (VT) ablation. There is no definitive method to identify arrhythmogenic substrate, and ablation outcomes remain suboptimal. The re-entry vulnerability index (RVI) integrates unipolar activation and repolarisation timing, and low RVI values correlate with vulnerable sites of re-entrant VT origin.

Structural characterization of the homotropic cooperative binding of azamulin to human cytochrome P450 3A5

Cytochrome P450 3A4 and 3A5 catalyze the metabolic clearance of a large portion of therapeutic drugs. Azamulin is used as a selective inhibitor for 3A4 and 3A5 to define their roles in metabolism of new chemical entities during drug development. In contrast to 3A4, 3A5 exhibits homotropic cooperativity for the sequential binding of two azamulin molecules at concentrations used for inhibition. To define the underlying sites and mechanisms for cooperativity, an X-ray crystal structure of 3A5 was determined with two azamulin molecules in the active site that are stacked in an antiparallel orientation. One azamulin resides proximal to the heme in a pose similar to the 3A4–azamulin complex. Comparison to the 3A5 apo structure indicates that the distal azamulin in 3A5 ternary complex causes a significant induced fit that excludes water from the hydrophobic surfaces of binding cavity and the distal azamulin, which is augmented by the stacking interaction with the proximal azamulin. Homotropic cooperativity was not observed for the binding of related pleuromutilin antibiotics, tiamulin, retapamulin, and lefamulin, to 3A5, which are larger and unlikely to bind in the distal site in a stacked orientation. Formation of the 3A5 complex with two azamulin molecules may prevent time-dependent inhibition that is seen for 3A4 by restricting alternate product formation and/or access of reactive intermediates to vulnerable protein sites. These results also contribute to a better understanding of sites for cooperative binding and the differential structural plasticity of 3A5 and 3A4 that contribute to differential substrate and inhibitor binding.

Identifying highly vulnerable mosquito breeding sites using machine learning and drone based aerial survey

This study deals with Drone based Aerial Survey in analyzing and identification of highly vulnerable mosquito breeding sites at Buckingham canal Chepauk, Chennai. It is small section of Buckingham canal studied using the drone for capturing the images and furtherly images were processed for identifying the sites prone to breeding of mosquitos. Approach used here of capturing images and classifying the vulnerable sites, using a machine learning approach in for extracting features using the algorithm and later generating a Support Vector Machine to train and classify the images. Tensorflow object detection algorithm was used to detect the object and also generate the probability level. Tensorflow based supervised classification involves stacking multiple layers of neural network for a classification. Methods like back propagation invoked in the neural networks ensures the classification accuracy are increased. In this algorithm Single shot multi box detector (SSD) has been used which provides fast detection. Single shot multi box detector (SSD) method is based on a feed-forward convolutional network, followed by a non-maximum suppression step to produce final detections. The accuracy constraint of 70% was kept for qualifying as a potential site to negate ambiguities arising due to processing errors.

Optimization of Anti-SARS-CoV-2 Neutralizing Antibody Therapies: Roadmap to Improve Clinical Effectiveness and Implementation.

One of the major breakthroughs to combat the current Coronavirus Disease 2019 (COVID-19) pandemic has been the development of highly effective vaccines against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Still, alternatives are needed for individuals who are at high risk of developing severe COVID-19 and are not protected by vaccination. Monoclonal antibodies against the spike protein of SARS-CoV-2 have been shown to be effective as prophylaxis and treatment against COVID-19. However, the emergence of variants of concern (VOCs) challenges the efficacy of antibody therapies. This review describes the neutralization resistance of the clinically-approved monoclonal antibody therapies against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2), and the Omicron (B.1.1.529) variants. To guide the development of monoclonal antibody therapies and to anticipate on the continuous evolution of SARS-CoV-2, we highlight different strategies to broaden the antibody activity by targeting more conserved epitopes and/or simultaneously targeting multiple sites of vulnerability of the virus. This review further describes the contribution of antibody Fc effector functions to optimize the antibody efficacy. In addition, the main route of SARS-CoV-2 antibody administration is currently intravenously and dictates a monthly injection when used as prophylactic. Therefore, we discusses the concept of long-acting antibodies (LAABs) and non-intravenously routes of antibody administration in order to broaden the clinical applicability of antibody therapies.