Efficient Spread Research Articles

A conserved interaction between the effector Sca4 and host clathrin suggests additional contributions for Sca4 during rickettsial infection.

Intracellular bacterial pathogens deploy secreted effector proteins that manipulate diverse host machinery and pathways to promote infection. Although many effectors carry out a single function or interaction, there are a growing number of secreted effectors capable of interacting with multiple host factors. However, few effectors secreted by arthropod-borne obligate intracellular Rickettsia species have been linked to multiple host targets. Here, we investigated the conserved rickettsial secreted effector Sca4, which was previously shown to interact with host vinculin in donor cells to promote cell-to-cell spread in the model Rickettsia species R. parkeri. We discovered that Sca4 also binds the host cell protein clathrin heavy chain (CHC, CLTC) via a conserved segment in the Sca4 N-terminus. In mammalian host cells, ablation of CLTC expression or chemical inhibition of endocytosis reduced R. parkeri cell-to-cell spread, indicating that clathrin promotes efficient spread. Unexpectedly, the contribution of CHC to spread was independent of Sca4 and appeared restricted to the recipient host cell, suggesting that the Sca4-clathrin interaction regulates another aspect of the infectious lifecycle. Indeed, R. parkeri lacking Sca4 or expressing a Sca4 truncation unable to bind clathrin had markedly reduced burdens in tick cells, hinting at a cell type-specific function for the Sca4-clathrin interaction. Sca4 homologs from diverse Rickettsia species also bound clathrin, suggesting that the function of this novel effector-host interaction may be broadly important for rickettsial infection. We conclude that Sca4 has multiple targets during infection and that rickettsiae may manipulate host endocytic machinery to facilitate several stages of their life cycles.

Novel intercellular spread mode of respiratory syncytial virus contributes to neutralization escape

Developing widely used respiratory syncytial virus (RSV) vaccines remains a significant challenge, despite the recent authorization of two pre-F vaccines for elderly adults. Previous reports have suggested that even when vaccine-induced immunity generates high titers of potent neutralizing antibodies targeting the pre-F protein, it may not fully inhibit breakthrough of RSV infections. This incomplete inhibition of RSV breakthrough infections can lead to an increased risk of enhanced respiratory disease (ERD) in vaccinated individuals. The reasons why potent neutralizing antibodies cannot fully prevent RSV breakthrough infections are not yet clear. In an attempt to explain this phenomenon, we investigated the effect of potent neutralizing antibodies on the intercellular spread of RSV. Our findings indicated that a specific titer of potent neutralizing antibodies, such as 5C4, could block certain modes of intercellular spread, such as the diffusion of cell-free virions and the delivery of virions through filopodia. However, these antibodies did not fully inhibit the entire process of intercellular spread. Through the use of super-resolution imaging techniques, we observed a novel and efficient spread mode called the transition of viral materials through intercellular nanotubes (TVMIN), independent of virions and insensitive to the presence of antibodies. TVMIN allowed RSV-infected cells to directly transfer viral materials to neighboring cells via intercellular nanotubes that are rich in microfilaments. TVMIN began as early as 5 h post-infection (h.p.i.) and rapidly initiated infection in recipient cells. Our data provided new insights into the intercellular spread of RSV and might help explain the occurrence of breakthrough infections.

From source to sink: part 2-seasonal dispersion of microplastics discharged in the NW Mediterranean Sea by the Rhone River in southern France.

As the largest individual contributor of freshwater inflow to the basin, the Rhone River is likely to be one of the main sources of microplastics (MPs) to the Mediterranean Sea. In order to predict the fate of MPs discharged by the Rhone River, an innovative 3D Lagrangian dispersion of its particles associated with vertical velocities was modeled in Mediterranean ocean currents. Through winter and summer scenarios, the seasonal variability of transfers and the corresponding accumulation areas were depicted in the Northwestern Basin according to hydrodynamic conditions on the continental shelf of the Gulf of Lion and to the frontal dynamics from the Pyrenees to the North Balearic fronts. Our results indicated that MP transfers were driven by mesoscale and sub-mesoscale structures, resulting in steep concentration gradients across fronts during summer, while winter energetic mixing favored a more efficient and homogeneous spreading. After a year of drift, high MP retention (up to 50%) occurred in the coastal zone of the Gulf of Lion near the river mouth, with a large contribution of sinking MPs and an increase in stranding during the highest freshwater inflows of the winter season. Conversely, up to 60% of the floating MPs were exported to the Algerian Basin and then to the Eastern Mediterranean. This west-to-east transfer led to significant stranding on the islands, prevailing on the northern coasts of the Balearic Islands in winter (6% of floating inputs) and on the western coasts of Corsica and Sardinia in summer (13%). The southern Mediterranean coasts, from Algeria to Tunisia, represented also a major sink for floating debris with stranding ranging from 9 to 35% of MPs discharged in winter and in summer, respectively. We estimated that 3.5 to 5 t of the Rhone MPs remained in the surface layer at the end of the year, with high concentrations in the Ionian Sea.

Price Spread, Marketing Efficiency and Postharvest Losses in Marketing of Selected kharif Vegetables in Palghar District of Maharashtra State, India

Vegetables play an important role both in the regional and national economy of the agricultural sector. These crops are generally of short duration. The post-harvest losses in kharif vegetables due to insufficient storage, packaging, transportation, and handling technologies for perishable crops, such as vegetables, lead to significant wastage. The present study was undertaken to estimate these losses at various stages and price spread of selected vegetables in study area. The study was conducted in Palghar district of Maharashtra, involving 90 farmers, 6 commission agents, 9 wholesalers and 30 retailers, that the study involves multiple groups of stakeholders (farmers, commission agents, wholesalers, and retailers), with specific numbers from each group. The sampling technique used in this case likely purposive sampling. The important kharif vegetables were identified for the detailed analysis. In of case brinjal the total postharvest losses were 12.62 kg/q. out of which maximum postharvest losses of brinjal vegetables was observed to be highest (4.62 kg/q), at retailer level followed by (3.2 kg/q) at wholesaler level and (1.65 kg/q) at commission agent level. Similarly in case of okra, postharvest losses in kharif season was estimated to 13.52 kg /q, out of which the retailers level postharvest losses was highest at (5.12 kg/q), followed by (3.78 kg /q) at wholesaler level, (2.87 kg /q) at farmer level and (1.75 kg/q) at commission agent level .Whereas for cowpea total postharvest losses was workout to 12.73 kg/q out of which 4.12 kg /q postharvest losses was observed at retailer level, 3.65 kg /q losses at wholesaler level, 3.08 kg /q at farmer level and 1.88 kg /q postharvest losses at commission agent level. In study were identified channel-I (Producer-Commission agent-wholesaler-Retailer-Consumer), channel-II (Producer-Wholesaler-Retailer-Consumer) and channel-III(Producer-Consumer). For brinjal, the price spread was Rs. 2962.91 in Channel-I and Rs. 2634.72 in Channel II, with marketing efficiency of 1.01, 1.24, and 33.76 in Channels-I, II, and III, respectively. Channel-III exhibited the highest marketing efficiency, while Channel II had the lowest price spread. For okra, the price spread was Rs. 1939.70 in Channel-I and Rs. 1733.20 in Channel II, with marketing efficiency of 1.51, 1.85, and 28.84 in Channels-I, II, and III, respectively. Channel II demonstrated the highest marketing efficiency and lowest price spread. In the case of cowpea, the price spread was Rs. 4000 in Channel-I and Rs. 3260 in Channel-II, with marketing efficiency of 0.91, 1.76, and 29.76 in Channels -I, II, and III, respectively. Again, Channel III provided the highest efficiency, while Channel II had the lowest price spread. Channel-III emerged as the most efficient channel for all crops due to the direct sale to consumers, resulting in the highest marketing efficiency. Channel-II also showed better efficiency, especially in okra, while Channel-I consistently had the lowest efficiency across all crops.

LES investigation of a H2-fueled supersonic combustor: A two-strut injection approach

Efficient combustion schemes are increasingly vital as scramjet expansion into higher Mach numbers emerges as a leading trend. Thus, in the current work, an LES investigation on mixing improvement caused by a two-strut injector has been carried out for a Mach 2.5 model H2 fueled scramjet combustor. The research focuses on understanding the flow field, flame lift-off characteristics and combustion stabilization in the two-strut combustor. The simulation results indicate that the two-strut configuration exhibits a broader pattern of temperature fluctuation, implying a more efficient spread of combustion downstream compared to the single-strut configuration. Analysis of Fast Fourier Transform (FFT) pressure data reveals inherent instability in the combustion processes for two-strut under supersonic air inflow conditions. The findings also demonstrate the significant improvement in mixing performance achieved by the two-strut design compared to conventional struts. The primary mechanism is a two-strut's ability to create significant streamwise vorticity, which can improve the mixing of H2 fuel with supersonic air. According to the mixing and total pressure loss plots, a two-strut produces a rapid complete mixing at 0.182 m at the expense of a minute rise in total pressure loss. Finally, the entropy change plot reveals that the two-strut configuration exhibits a reduced entropy change compared to the single-strut configuration. This is mainly due to enhanced air-fuel mixing, efficient shock wave management, and enhanced flame stabilization in the two-strut setup. These factors collectively contribute to reduced irreversibilities and disorder in the flow, leading to lower entropy within the system.

Temporal Characterization of Prion Shedding in Secreta of White-Tailed Deer in Longitudinal Study of Chronic Wasting Disease, United States.

Chronic wasting disease (CWD) affects cervids in North America, Asia, and Scandinavia. CWD is unique in its efficient spread, partially because of contact with infectious prions shed in secreta. To assess temporal profiles of CWD prion shedding, we collected saliva, urine, and feces from white-tailed deer for 66 months after exposure to low oral doses of CWD-positive brain tissue or saliva. We analyzed prion seeding activity by using modified amyloid amplification assays incorporating iron oxide bead extraction, which improved CWD detection and reduced false positives. CWD prions were detected in feces, urine, and saliva as early as 6 months postinfection. More frequent and consistent shedding was observed in deer homozygous for glycine at prion protein gene codon 96 than in deer expressing alternate genotypes. Our findings demonstrate that improved amplification methods can be used to identify early antemortem CWD prion shedding, which might aid in disease surveillance of cervids.

Bank Specific Factors that Affect Credit Risk

Indonesian’s banking has taken steps to improve financial performance by managing credit risk and supporting economic recovery in 2023, efforts carried out by banks include providing credit and acting as intermediaries with very vulnerable credit risk challenges.This research has purpose to find out which bank spesific internal factor can significantly affect the credit risk in a bank. The independent variables in this study are efficiency, leverage, liquidity, ROA, ROE, solvency, banking spread, banking size, and ownership concentration. While the dependent variable is credit risk using NPL and Z-Score. The study used panel data regression models to test the data collected from 98 banks registered with OJK over three years (2020-2022). The results stated that leverage, ROA, ROE, solvency, bank size, have a positive influence on ZScore, while efficiency, liquidity, and bank spread have no influence on Zscore. The results also show that efficiency and ROA have a positive influence on NPL. Liquidity, ROE, solvency, bank spread, bank size, and ownership concentration variables have an influence on NPLs and leverage has no influence on NPL. Additionally, investors should be able to use this research's insights about company performance to get a general understanding of the credit risk associated with linked companies, which they can use to inform their investment decisions.

Efficient leather spreading operations by dual-arm robotic systems

To achieve precise grasping and spreading of irregular sheet-like soft objects (such as leather) by robots, this study addresses several challenges, including the irregularity of leather edges and the ambiguity of feature recognition points. To tackle these issues, this paper proposes an innovative method that involves alternately grasping the lowest point twice and using planar techniques to effectively spread the leather. We improved the YOLOV8 algorithm by incorporating the BIFPN network structure and the WIOU loss function, and trained a dedicated dataset for the lowest grasping points and planar grasping points, thereby achieving high-precision recognition. Additionally, we determined the optimal posture for grasping the lowest point and constructed an experimental platform, successfully conducting multiple rounds of leather grasping and spreading experiments with a success rate of 72%. Through an in-depth analysis of the failed experiments, this study reveals the limitations of the current methods and provides valuable guidance for future research.

HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages

HIV-1 Vpr promotes efficient spread of HIV-1 from macrophages to T cells by transcriptionally downmodulating restriction factors that target HIV-1 Envelope protein (Env). Here we find that Vpr induces broad transcriptomic changes by targeting PU.1, a transcription factor necessary for expression of host innate immune response genes, including those that target Env. Consistent with this, we find silencing PU.1 in infected macrophages lacking Vpr rescues Env. Vpr downmodulates PU.1 through a proteasomal degradation pathway that depends on physical interactions with PU.1 and DCAF1, a component of the Cul4A E3 ubiquitin ligase. The capacity for Vpr to target PU.1 is highly conserved across primate lentiviruses. In addition to impacting infected cells, we find that Vpr suppresses expression of innate immune response genes in uninfected bystander cells, and that virion-associated Vpr can degrade PU.1. Together, we demonstrate Vpr counteracts PU.1 in macrophages to blunt antiviral immune responses and promote viral spread.

Fishbone-like micro-textured surface for unidirectional spreading of droplets and lubricity improvement

Directional spreading of droplets on asymmetrical micro-structures surface has attract interests of researchers for its significant application potential in scientific and engineering fields. In this paper, a fishbone-like micro-textured surface (FMS) is proposed, which exhibits efficient unidirectional spreading behavior of droplets (maximum forward-backward spreading coefficient up to 3.7). The effect of geometrical characters on spreading performance are studied, thus facilitating obtainment of optimal parameters of the FMS. Such type of micro-structured surface is arranged on noncontact areas of pin-on-disk tribological system. Experimental results demonstrate the FMS has lubrication retention effect, resulting in reduction of friction and wear. The maximum reduction rate of friction coefficient is 63.3 % compared with the bare specimen.

A conserved interaction between the effector Sca4 and host endocytic machinery suggests additional roles for Sca4 during rickettsial infection.

Intracellular bacterial pathogens deploy secreted effector proteins that manipulate diverse host machinery and pathways to promote infection. Although many effectors carry out a single specific function or interaction, there are a growing number of secreted pathogen effectors capable of interacting with multiple host factors. However, few effectors secreted by obligate intracellular Rickettsia species have been linked to multiple host targets. Here, we investigated the conserved rickettsial secreted effector Sca4, which was previously shown to interact with host vinculin to promote cell-to-cell spread in the model Rickettsia species R. parkeri . We discovered that Sca4 also binds the host cell endocytic factor clathrin heavy chain (CHC, CLTC ) via a conserved segment in the Sca4 N-terminus. Ablation of CLTC expression or chemical inhibition of endocytosis reduced R. parkeri cell-to-cell spread, indicating that clathrin promotes efficient spread between mammalian cells. This activity was independent of Sca4 and appeared restricted to the recipient host cell, suggesting that the Sca4-clathrin interaction also regulates another aspect of the infectious lifecycle. Indeed, R. parkeri lacking Sca4 or expressing a Sca4 truncation unable to bind clathrin had markedly reduced burdens in tick cells, hinting at a cell-type specific function for the Sca4-clathrin interaction. Sca4 homologs from diverse Rickettsia species also bound clathrin, suggesting that the function of this novel effector-host interaction may be broadly important for rickettsial infection. We conclude that Sca4 has multiple targets during infection and that rickettsiae may manipulate host endocytic machinery to facilitate several stages of their life cycles.

Spectral Efficient Neural Network-Based M-ary Chirp Spread Spectrum Receivers for Underwater Acoustic Communication

Spectral Efficient Neural Network-Based M-ary Chirp Spread Spectrum Receivers for Underwater Acoustic Communication

Impact of pilot diesel injection timing on performance and emission characteristics of marine natural gas/diesel dual-fuel engine

In diesel-ignited natural gas marine dual-fuel engines, the pilot diesel injection timing (PDIT) determines the premixing time and ignition moment of the combustible mixture in the cylinder. The PDIT plays a crucial role in the subsequent development of natural gas flame combustion. In this paper, four PDITs (− 8 °CA, − 6 °CA, − 4 °CA, and − 2 °CA) were studied. The results show that the advancement of PDIT increased the engine's power, thermal efficiency, and natural gas flame spread velocity, and increased NO emissions and CH4 emissions of the marine engine. The PDIT affected the ignition delay period and the rapid combustion period to a greater extent than the slow combustion period and the post combustion period. With each 2 °CA advancement of PDIT, the engine's power increased by 69.87 kW, thermal efficiency increased by 0.42%, radial flame spread velocity increased by 2 m/s, axial flame spread velocity increased by 1.7 m/s, NO emissions increased by 6.1%, and CH4 emissions increased by 3.75%.

Next generation single-domain antibodies against respiratory zoonotic RNA viruses.

The global impact of zoonotic viral outbreaks underscores the pressing need for innovative antiviral strategies, particularly against respiratory zoonotic RNA viruses. These viruses possess a high potential to trigger future epidemics and pandemics due to their high mutation rate, broad host range and efficient spread through airborne transmission. Recent pandemics caused by coronaviruses and influenza A viruses underscore the importance of developing targeted antiviral strategies. Single-domain antibodies (sdAbs), originating from camelids, also known as nanobodies or VHHs (Variable Heavy domain of Heavy chain antibodies), have emerged as promising tools to combat current and impending zoonotic viral threats. Their unique structure, coupled with attributes like robustness, compact size, and cost-effectiveness, positions them as strong alternatives to traditional monoclonal antibodies. This review describes the pivotal role of sdAbs in combating respiratory zoonotic viruses, with a primary focus on enhancing sdAb antiviral potency through optimization techniques and diverse administration strategies. We discuss both the promises and challenges within this dynamically growing field.

Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population.

Innate immune response against vector-borne bunyavirus infection and viral countermeasures.

Bunyaviruses are a large group of important viral pathogens that cause significant diseases in humans and animals worldwide. Bunyaviruses are enveloped, single-stranded, negative-sense RNA viruses that infect a wide range of hosts. Upon entry into host cells, the components of viruses are recognized by host innate immune system, leading to the activation of downstream signaling cascades to induce interferons (IFNs) and other proinflammatory cytokines. IFNs bind to their receptors and upregulate the expression of hundreds of interferon-stimulated genes (ISGs). Many ISGs have antiviral activities and confer an antiviral state to host cells. For efficient replication and spread, viruses have evolved different strategies to antagonize IFN-mediated restriction. Here, we discuss recent advances in our understanding of the interactions between bunyaviruses and host innate immune response.

Targeted Suicide Gene Therapy with Retroviral Replicating Vectors for Experimental Canine Cancers.

Cancer in dogs has increased in recent years and is a leading cause of death. We have developed a retroviral replicating vector (RRV) that specifically targets cancer cells for infection and replication. RRV carrying a suicide gene induced synchronized killing of cancer cells when administered with a prodrug after infection. In this study, we evaluated two distinct RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) in canine tumor models both in vitro and in vivo. Despite low infection rates in normal canine cells, both RRVs efficiently infected and replicated within all the canine tumor cells tested. The efficient intratumoral spread of the RRVs after their intratumoral injection was also demonstrated in nude mouse models of subcutaneous canine tumor xenografts. When both RRVs encoded a yeast cytosine deaminase suicide gene, which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil, they caused tumor-cell-specific 5-FC-induced killing of the canine tumor cells in vitro. Furthermore, in the AZACF- and AZACH-cell subcutaneous tumor xenograft models, both RRVs exerted significant antitumor effects. These results suggest that RRV-mediated suicide gene therapy is a novel therapeutic approach to canine cancers.

Tumor epitope spreading by a novel multivalent therapeutic cellular vaccine targeting cancer antigens to invariant NKT-triggered dendritic cells in situ.

Cancer is categorized into two types based on the microenvironment: cold and hot tumors. The former is challenging to stimulate through immunity. The immunogenicity of cancer relies on the quality and quantity of cancer antigens, whether recognized by T cells or not. Successful cancer immunotherapy hinges on the cancer cell type, antigenicity and subsequent immune reactions. The T cell response is particularly crucial for secondary epitope spreading, although the factors affecting these mechanisms remain unknown. Prostate cancer often becomes resistant to standard therapy despite identifying several antigens, placing it among immunologically cold tumors. We aim to leverage prostate cancer antigens to investigate the potential induction of epitope spreading in cold tumors. This study specifically focuses on identifying factors involved in secondary epitope spreading based on artificial adjuvant vector cell (aAVC) therapy, a method established as invariant natural killer T (iNKT) -licensed DC therapy. We concentrated on three prostate cancer antigens (prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP)). By introducing allogeneic cells with the antigen and murine CD1d mRNA, followed by α-galactosylceramide (α-GalCer) loading, we generated five types of aAVCs, i.e, monovalent, divalent and trivalent antigen-expressing aAVCs and four types of prostate antigen-expressing cold tumors. We evaluated iNKT activation and antigen-specific CD8+ T cell responses against tumor cells prompted by the aAVCs. Our study revealed that monovalent aAVCs, expressing a single prostate antigen, primed T cells for primary tumor antigens and also induced T cells targeting additional tumor antigens by triggering a tumor antigen-spreading response. When we investigated the immune response by trivalent aAVC (aAVC-PROS), aAVC-PROS therapy elicited multiple antigen-specific CD8+ T cells simultaneously. These CD8+ T cells exhibited both preventive and therapeutic effects against tumor progression. The findings from this study highlight the promising role of tumor antigen-expressing aAVCs, in inducing efficient epitope spreading and generating robust immune responses against cancer. Our results also propose that multivalent antigen-expressing aAVCs present a promising therapeutic option and could be a more comprehensive therapy for treating cold tumors like prostate cancer.

Efficient Caching and Spreading of Traffic Videos by Optimized Topology in IoV

Efficient Caching and Spreading of Traffic Videos by Optimized Topology in IoV

Developing a Methodology to Establish Response Zones based on Travel Time for Controlling the Spread of Water Quality Incidents in Water Supply Systems

Water quality issues may arise within the water pipe network system due to external contamination from water leaks, aging pipes leading to damage, and the presence of suspended sediments resulting from changes in hydraulic direction. Promptly addressing these water quality problems during the supply process is crucial, as delays can swiftly escalate health risks for residents and cause economic damage to the region. Therefore, developing control techniques is imperative to minimize the rapid dissemination of accidents. This study aims to proactively identify and calculate the spread pattern of water quality incidents within the pipe network, utilizing residence time as a critical factor. A practical and efficient spread control zoning methodology was proposed to curtail the expansion of accidents. Applying the proposed methodology to the pipe network system in Cty A (Korea) involved quantitative analysis of newly defined areas based on the target residence time intended for practical management and control during water quality accidents. The results of the analysis demonstrate that the proposed method offers the potential to establish a novel concept of a response area for rapid reactions to water quality incidents. This facilitates the design of a zone centered around valves essential for crisis response, thereby creating an area with precise control over the spread of water quality accidents within a target response time.