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In the extreme space environment, spacecraft endure dramatic temperature variations that can impair their functionality. A VO2-based smart radiator device (SRD) offers an effective solution by adaptively adjusting its radiative properties. However, current research on VO2-based thermochromic films mainly focuses on optimizing the emissivity tunability (Δε) of single-cycle sandwich structures. Although multi-cycle structures have shown increased Δε compared to single-cycle sandwich structures, there have been few systematic studies to find the optimal cycle structure. This paper theoretically discusses the influence of material properties and cyclic structure on SRD performance using Finite-Difference Time-Domain (FDTD) software, which is a rigorous and powerful tool for modeling nano-scale optical devices. An optimal structural model with maximum emissivity tunability is proposed. The BaF2 obtained through optimization is used as the dielectric material to further optimize the cyclic resonator. The results indicate that the tunability of emissivity can reach as high as 0.7917 when the BaF2/VO2 structure is arranged in three periods. Furthermore, to ensure a longer lifespan for SRD under harsh space conditions, the effects of HfO2 and TiO2 protective layers on the optical performance of composite films are investigated. The results show that when TiO2 is used as the protective layer with a thickness of 0.1 µm, the maximum emissivity tunability reaches 0.7932. Finally, electric field analysis is conducted to prove that the physical mechanism of the smart radiator device is the combination of stacked Fabry–Perot resonance and multiple solar reflections. This work not only validates the effectiveness of the proposed structure in enhancing spacecraft thermal control performance but also provides theoretical guidance for the design and optimization of SRDs for space applications.

In recent years, smart windows have attracted widespread attention due to their ability to respond to external stimuli such as light, heat, and electricity, thereby intelligently adjusting the ultraviolet, visible, and near-infrared light in solar radiation. VO2(M) undergoes a reversible phase transition from an insulating phase (monoclinic, M) to a metallic phase (rutile, R) at a critical temperature of 68 °C, resulting in a significant difference in near-infrared transmittance, which is particularly suitable for use in energy-saving smart windows. However, due to the multiple valence states of vanadium ions and the multiphase characteristics of VO2, there are still challenges in preparing pure-phase VO2(M). Machine learning (ML) can learn and generate models capable of predicting unknown data from vast datasets, thereby avoiding the wastage of experimental resources and reducing time costs associated with material preparation optimization. Hence, in this paper, four ML algorithms, namely multi-layer perceptron (MLP), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB), were employed to explore the parameters for the successful preparation of VO2(M) films via magnetron sputtering. A comprehensive performance evaluation was conducted on these four models. The results indicated that XGB was the top-performing model, achieving a prediction accuracy of up to 88.52%. A feature importance analysis using the SHAP method revealed that substrate temperature had an essential impact on the preparation of VO2(M). Furthermore, characteristic parameters such as sputtering power, substrate temperature, and substrate type were optimized to obtain pure-phase VO2(M) films. Finally, it was experimentally verified that VO2(M) films can be successfully prepared using optimized parameters. These findings suggest that ML-assisted material preparation is highly feasible, substantially reducing resource wastage resulting from experimental trial and error, thereby promoting research on material preparation optimization.

Electrochromic smart windows can achieve controllable modulation of color and transmittance under an external electric field with active light and thermal control capabilities, which helps reduce energy consumption caused by building cooling and heating. However, electrochromic smart windows often rely on external power circuits, which greatly affects the independence and portability of smart windows. Based on this, an electrochromic smart window driven by temperature-difference power generation was designed and implemented. This smart window provides automatic and manual control of the reversible cycle of electrochromic glass from light blue to dark blue according to user requirements and changes in the surrounding environment, achieving adaptive adjustment of visual comfort and reducing energy consumption. The infrared radiation rejection (from 780 to 2500 nm) of the electrochromic smart window is as high as 77.3%, and its transmittance (from 380 to 780 nm) fluctuates between 39.2% and 56.4% with changes in working state. Furthermore, the temperature in the indoor simulation device with electrochromic glass as the window was 15 °C lower than that with ordinary glass as the window after heating with a 250 W Philips infrared lamp for ten minutes. After 2000 cycles of testing, the performance of the smart window was basically maintained at its initial values, and it has broad application prospects in buildings, vehicles, and high-speed rail systems.

This study attempts to determine whether there is a spatial correlation between electricity generation and economic scale promoting coordinated development in Africa. We explore the spatial similarity and gray correlation degree between electricity generation and economic scale in Africa since the 21st century by adopting barycenter coupling and Gray Correlation Analysis method. We argue that there is a strong correlation between electricity generation and economic scale. Our findings indicate a significant spatial difference in electricity generation, mainly concentrated in Northern and Southern Africa. Furthermore, spatial pattern remains largely consistent over time, mirroring trends observed at the economic scale. Electricity generation and economic scale were concentrated in six countries- South Africa, Egypt, Algeria, Nigeria, Morocco, and Libya- and did not change significantly over time. A correlation analysis between electricity generation and the economic scale further confirmed this, with a linear coefficient of 0.907. Both the gravity centers of economic scale and electricity generation in Africa move farther in the north-south direction than in the East-West direction, with the former showing a Southwest-Northeast-Southwest track feature and the latter a Northeast-Southwest track feature. The spatial distribution of the gravity centers of electricity generation and the gravity centers of the economic scale in Africa are highly consistent; electricity generation highly correlates with the economic scale, consistent with the research conclusion obtained by the Gray Correlation Analysis method. This study suggests the coordinated development of electricity generation and economic scales in various African countries.

Testing and verifying applications (Apps) are essential for a software-driven intelligent building system. Traditional methods connect App programs to hardware devices for debugging and testing on the engineering site. However, App bugs can hardly be found out before they are being deployed and thus always require an extended debugging cycle. To address this issue, we propose a cyber–physical simulation and verification platform named AppSimV, which enables the testing and verification of Apps in a mimic real scene. Taking swarm intelligence building as an example, this paper focuses on the cyber–physical architecture of AppSimV and its implementation mechanisms, including the standardized encapsulation of software components for the building physics model, a multitask scheduling simulation engine, a cyber–physical interaction interface, and the visual monitoring of the simulation process. The implementation mechanisms not only accurately simulate actual engineering scenarios but also facilitate the early detection and correction of issues that may arise during the App’s runtime, thus reducing the debugging time required for the App. With 1200 intelligent physical nodes connected in a swarm hardware system, AppSimV was validated by conducting the strict testing and verification of a set of Apps for an intelligent building. The results show that AppSimV is sound and reliable.

Acoustic emission (AE) testing is a widely used nondestructive testing method for the early detection of failures in materials and structures. In this paper, an AE detection sensor combining optical fiber sensing with laser self-mixing interference (SMI) technology is proposed. A multi-coil optical fiber ring wound round a cylindrical acrylic skeleton was designed in order to sense the deformation caused by AE elastic waves, which was then demodulated using self-mixing interference technology. Finite element analyses were conducted in order to investigate the deformation of fiber under acoustic sources. AE signals induced via ball-dropping impact experiments were successfully detected by the proposed experimental system. The proposed SMI optical fiber AE sensing system has the advantages of being free from electromagnetic interference and having a simple structure, low implementation cost and high measurement resolution and sensitivity.

Molybdenum disulfide (MoS2) is a layered transition metal-sulfur compound semiconductor that shows promising prospects for applications in optoelectronics and integrated circuits because of its low preparation cost, good stability and excellent physicochemical, biological and mechanical properties. MoS2 with high quality, large size and outstanding performance can be prepared via chemical vapor deposition (CVD). However, its preparation process is complex, and the area of MoS2 obtained is difficult to control. Machine learning (ML), as a powerful tool, has been widely applied in materials science. Based on this, in this paper, a ML Gaussian regression model was constructed to explore the growth mechanism of MoS2 material prepared with the CVD method. The parameters of the regression model were evaluated by combining the four indicators of goodness of fit (r2), mean squared error (MSE), Pearson correlation coefficient (p) and p-value (p_val) of Pearson’s correlation coefficient. After comprehensive comparison, it was found that the performance of the model was optimal when the number of iterations was 15. Additionally, feature importance analysis was conducted on the growth parameters using the established model. The results showed that the carrier gas flow rate (Fr), molybdenum sulfur ratio (R) and reaction temperature (T) had a crucial impact on the CVD growth of MoS2 materials. The optimal model was used to predict the size of molybdenum disulfide synthesis under 185,900 experimental conditions in the simulation dataset so as to select the optimal range for the synthesis of large-size molybdenum disulfide. Furthermore, the model prediction results were verified through literature and experimental results. It was found that the relative error between the prediction results and the literature and experimental results was small. These findings provide an effective solution to the preparation of MoS2 materials with a reduction in the time and cost of trial and error.

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

Thermochromic smart windows are optical devices that can regulate their optical properties actively in response to external temperature changes. Due to their simple structures and as they do not require other additional energy supply devices, they have great potential in building energy-saving. However, conventional thermochromic smart windows generally have problems with high response temperatures and low response rates. Owing to their great effect in photothermal conversion, photothermal materials are often used in smart windows to assist phase transition so that they can quickly achieve the dual regulation of light and heat at room temperature. Based on this, research progress on the phase transition of photothermal material-assisted thermochromic smart windows is summarized. In this paper, the phase transition mechanisms of several thermochromic materials (VO2, liquid crystals, and hydrogels) commonly used in the field of smart windows are introduced. Additionally, the applications of carbon-based nanomaterials, noble metal nanoparticles, and semiconductor (metal oxygen/sulfide) nanomaterials in thermochromic smart windows are summarized. The current challenges and solutions are further indicated and future research directions are also proposed.

Abstract In this paper, we consider a predator-prey model with prey impulsive diffusion and dispersal delay. By utilizing the dynamical properties of a single-species model with diffusion and dispersal delay between two patches and the comparison principle of impulsive differential equations, we establish the sufficient conditions on the global attractivity of predator-extinction periodic solution and the permanence of species for the model.

External optical feedback (EOF) has great impacts on the properties of lasers. It influences the stable operation of lasers. However, various applications based on lasers with EOF have been developed. One typical example is self-mixing interferometry technology, where modulated steady-state laser intensity is utilized for sensing and measurement. Other works show that laser dynamics can also be used for sensing, and the laser in this case is more sensitive to EOF. This paper reviews the sensing technology that uses the dynamics of lasers with EOF. We firstly introduce the basic operating principles of a laser with EOF and discuss the noise properties of and intensity modification in lasers induced by EOF. Then, sensing applications using laser dynamics are categorized and presented, including sensing by frequency-shifted optical feedback, relaxation oscillation frequency, and dynamics with self-mixing interferometry signals and laser optical chaos. Lastly, we present an analysis of the transient response waveform and spectrum of a laser with EOF, showing its potential for sensing.

Attractions of overseas high-level returned talents have become a widely practiced talent policy, and the spatial structures of city-related interactions are drawing the attention of researchers from various fields. China is particularly an interesting case in point, as it has moved toward an innovation-oriented economy. Based on the movement trajectories of 2,846 returnees in a program entitled “Young Thousand Talents Plan” during 2011–2016, this paper identifies three city types in China: national core city, regional excellent city, and regional special city. Subsequently, this paper employs spatial visualization and qualitative interviews. This paper also goes on to show that the national core cities that possess dense research resources that coincide with premium life conditions and have objectively more favorable conditions, wider opportunities for attracting highly qualified specialists. Moreover, the backflow pattern can be divided into circle route and linear route, which is driven by social proximity and innovation context.

Since the 2008 global food crisis, food security vulnerability has been a prominent topic in the food policy debate. However, vulnerability is inherently difficult to conceptualize and is more challenging to operationalize and measure. This study constructs a mathematical model and takes China as a case study to measure the vulnerability and sensitivity of China with its partners in the international grain trade. The results show that 1) the degree of interdependence between China and its grain trading partners is asymmetric, which generates trade vulnerability or economic power; 2) the vulnerability of China’s food trade shows a high spatiotemporal heterogeneity among countries: the higher vulnerability zones are concentrated in North America and Northeast Asia, and the scope of the higher vulnerability zones tends to expand; 3) Our results also reveal that China also has different sensitivities to fluctuations in grain markets from different countries, and the higher sensitive zones of the grain trade in China are mainly distributed in America, Europe, and Oceania. The main contribution of this paper is the development of a methodology for food trade vulnerability assessment and examines the influence of international food trade on food security in importing countries, measured using the vulnerability index and sensitivity index. Nevertheless, the conclusions of this study can be considered preliminary, and there remains great potential for future studies to deepen and broaden our analyses further.

Thermochromic smart windows can automatically control solar radiation according to the ambient temperature. Compared with photochromic and electrochromic smart windows, they have a stronger applicability and lower energy consumption, and have a wide range of application prospects in the field of building energy efficiency. At present, aiming at the challenge of the high transition temperature of thermochromic smart windows, a large amount of innovative research has been carried out via the principle that thermochromic materials can be driven to change their optical performance by photothermal or electrothermal effects at room temperature. Based on this, the research progress of photo- and electro-driven thermochromic smart windows is summarized from VO2-based composites, hydrogels and liquid crystals, and it is pointed out that there are two main development trends of photo-/electro-driven thermochromic smart windows. One is exploring the diversified combination methods of photothermal materials and thermochromic materials, and the other is developing low-cost large-area heating electrodes.

The Young’s modulus and internal friction are two important parameters of materials. Self-mixing interferometry (SMI) is an emerging non-destructive sensing method that has been employed for various applications because of its advantages of simple structure, ease of alignment and high resolution. Some recent works have proposed the use of SMI technology to measure the Young’s moduli and/or internal frictions by measuring the resonance frequencies and damping factors of specimen vibrations induced by impulse excitation. However, the measurement results may be affected by frequencies of SMI fringes, and the implementation requires extra signal processing on SMI fringes. In this work, we developed an all-fiber SMI system without SMI fringes to measure the Young’s modulus and internal friction simultaneously. Simulations and experiments were carried out to verify the feasibility of the proposed method. Two specimens of brass and aluminum were tested. The experimental results show that the standard deviations of Young’s moduli for brass and aluminum are 0.20 GPa and 0.14 GPa, and the standard deviations of internal frictions are 4.0×10−5 and 5.4×10−5, respectively. This method eliminates the influences of the SMI fringe frequency on the resonant frequency and requires no signal processing on SMI fringes, contributing to its simplicity as a method for the measurement of the Young’s modulus and internal friction.

Abstract Luminescent solar concentrators (LSCs) have attracted significant attention as promising solar energy conversion devices for building integrated photovoltaic (PV) systems due to their simple architecture and cost‐effective fabrication. Conventional LSCs are generally comprised of an optical waveguide slab with embedded emissive species and coupled PV cells. Colloidal semiconductor quantum dots (QDs) have been demonstrated as efficient emissive species for high‐performance LSCs because of their outstanding optical properties including tunable absorption and emission spectra covering the ultraviolet/visible to near‐infrared region, high photoluminescence quantum yield, large absorption cross sections, and considerable photostability. However, current commonly used QDs for high‐performance LSCs consist of highly toxic heavy metals (i.e., cadmium and lead), which are fatal to human health and the environment. In this regard, it is highly desired that heavy metal‐free and environmentally friendly QD‐based LSCs are comprehensively studied. Here, notable advances and developments of LSCs based on unary, binary, and ternary eco‐friendly QDs are presented. The synthetic approaches, optical properties of these eco‐friendly QDs, and consequent device performance of QD‐based LSCs are discussed in detail. A brief outlook pointing out the existing challenges and prospective developments of eco‐friendly QD‐based LSCs is provided, offering guidelines for future device optimizations and commercialization.

To investigate Lamb waves in thin films made of functionally graded viscoelastic material, we deduce the governing equation with respect to the displacement component and solve these partial differential equations with complex variable coefficients based on a power series method. To solve the transcendental equations in the form of a series with complex coefficients, we propose and optimize the minimum module approximation (MMA) method. The power series solution agrees well with the exact analytical solution when the material varies along its thickness following the same exponential function. When material parameters vary with thickness with the same function, the effect of the gradient properties on the wave velocity is limited and that on the wave structure is obvious. The influence of the gradient parameter on the dispersion property and the damping coefficient are discussed. The results should provide nondestructive evaluation for viscoelastic material and the MMA method is suggested for obtaining numerical results of the asymptotic solution for attenuated waves, including waves in viscoelastic structures, piezoelectric semiconductor structures, and so on.

Functionalized iron oxide nanoparticles (IONPs) are of great interest due to wide range applications, especially in nanomedicine. However, they face challenges preventing their further applications such as rapid agglomeration, oxidation, etc. Appropriate surface modification of IONPs can conquer these barriers with improved physicochemical properties. This review summarizes recent advances in the surface modification of IONPs with small organic molecules, polymers and inorganic materials. The preparation methods, mechanisms and applications of surface-modified IONPs with different materials are discussed. Finally, the technical barriers of IONPs and their limitations in practical applications are pointed out, and the development trends and prospects are discussed.

Circulating avian influenza viruses pose a significant threat, with human infections occurring infrequently but with potentially severe consequences. To examine the dynamics and locale of the adaptation process of avian influenza viruses when introduced to a mammalian host, we infected ferrets with H5N1 viruses. As expected, all ferrets infected with the human H5N1 isolate A/Vietnam/1203/2004 showed severe disease and virus replication outside the respiratory tract in multiple organs including the brain. In contrast infection of ferrets with the avian H5N1 virus A/Chicken/Laos/Xaythiani26/2006 showed a different collective pattern of infection; many ferrets developed and cleared a mild respiratory infection but a subset (25-50%), showed extended replication in the upper respiratory tract and developed infection in distal sites. Virus from these severely infected ferrets was commonly found in tissues that included liver and small intestine. In most instances the virus had acquired the common virulence substitution PB2 E627K but, in one case, a previously unidentified combination of two amino acid substitutions at PB2 S489P and NP V408I, which enhanced polymerase activity, was found. We noted that virus with high pathogenicity adaptations could be dominant in an extra-respiratory site without being equally represented in the nasal wash. Further ferret passage of these mutated viruses resulted in high pathogenicity in all ferrets. These findings illustrate the remarkable ability of avian influenza viruses that avoid clearance in the respiratory tract, to mutate towards a high pathogenicity phenotype during just a single passage in ferrets and also indicate a window of less than 5 days in which treatment may curtail systemic infection., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Aim: Current therapies against avian influenza (H5N1) provide limited clinical benefit. FBF-001 is a highly purified equine polyclonal immunoglobulin fragment against H5N1., Methods: Using a ferret model of severe acute H5N1 infection, we assessed FBF-001 when administered on the same day or 1 day after viral challenge, in comparison with oseltamivir therapy., Results: Untreated animals died 2-3 days after challenge. FBF-001 prevented most severe illness and reduced nasal viral load, with best efficacy when administered on the day of viral challenge. Oseltamivir and FBF-001 had synergistic impact on survival., Conclusion: FBF-001 prevented severe consequences of lethal H5N1 challenge in ferrets by controlling viral replication, an effect synergistic to oseltamivir. FBF-001 has recently been granted EMA orphan drug status.

We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. The alpacas shed virus at challenge but were refractory to further shedding at rechallenge on day 21. The trial indicates that alpacas may be suitable models for infection and shedding dynamics of this virus.

Unlabelled: Although avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease., Importance: Risks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus could spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower after exposure to virus by this route than when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection, such as viremia, could help prioritize antiviral treatments for patients most at risk of succumbing to infection., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Bats have been found to harbour a number of new emerging viruses with zoonotic potential, and there has been a great deal of interest in identifying novel bat pathogens to determine the risk to human and animal health. Many groups have identified novel viruses in bats by detection of viral nucleic acid; however, virus isolation is still a challenge, and there are few reports of viral isolates from bats. In recent years, our group has developed optimized procedures for virus isolation from bat urine, including the use of primary bat cells. In previous reports, we have described the isolation of Hendra virus, Menangle virus and Cedar virus in Queensland, Australia. Here, we report the isolation of four additional novel bat paramyxoviruses from urine collected from beneath pteropid bat (flying fox) colonies in Queensland and New South Wales during 2009-2011., (© 2015 The Authors.)

Objectives: The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting., Methods: A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets., Results: Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis., Conclusions: Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.

Background: Nipah virus (NiV) is a zoonotic virus belonging to the henipavirus genus in the family Paramyxoviridae. Since NiV was first identified in 1999, outbreaks have continued to occur in humans in Bangladesh and India on an almost annual basis with case fatality rates reported between 40% and 100%., Methods: Ferrets were vaccinated with 4, 20 or 100 μg HeVsG formulated with the human use approved adjuvant, CpG, in a prime-boost regime. One half of the ferrets were exposed to NiV at 20 days post boost vaccination and the other at 434 days post vaccination. The presence of virus or viral genome was assessed in ferret fluids and tissues using real-time PCR, virus isolation, histopathology, and immunohistochemistry; serology was also carried out. Non-immunised ferrets were also exposed to virus to confirm the pathogenicity of the inoculum., Results: Ferrets exposed to Nipah virus 20 days post vaccination remained clinically healthy. Virus or viral genome was not detected in any tissues or fluids of the vaccinated ferrets; lesions and antigen were not identified on immunohistological examination of tissues; and there was no increase in antibody titre during the observation period, consistent with failure of virus replication. Of the ferrets challenged 434 days post vaccination, all five remained well throughout the study period; viral genome - but not virus - was recovered from nasal secretions of one ferret given 20 μg HeVsG and bronchial lymph nodes of the other. There was no increase in antibody titre during the observation period, consistent with lack of stimulation of a humoral memory response., Conclusions: We have previously shown that ferrets vaccinated with 4, 20 or 100 μg HeVsG formulated with CpG adjuvant, which is currently in several human clinical trials, were protected from HeV disease. Here we show, under similar conditions of use, that the vaccine also provides protection against NiV-induced disease. Such protection persists for at least 12 months post-vaccination, with data supporting only localised and self-limiting virus replication in 2 of 5 animals. These results augur well for acceptability of the vaccine to industry.

Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-κB-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-κB activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-κB activity aids Hendra virus replication. Furthermore, overexpression of the IκB superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease.

Human infections with Nipah virus in Malaysia and Bangladesh are associated with markedly different patterns of transmission and pathogenicity. To compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus. Viral shedding and tissue tropism were compared between the 2 groups. Over the course of infection, significantly higher levels of viral RNA were recovered from oral secretions of ferrets infected with the Bangladesh strain. Higher levels of oral shedding of the Bangladesh strain of Nipah virus might be a key factor in onward transmission in outbreaks among humans.

Human infections with highly pathogenic avian influenza (HPAI) H5N1 have been associated with central nervous system involvement. The purpose of this study was to examine the route of invasion of wild-type HPAI H5N1 virus into the central nervous system (CNS) using a ferret model of infection. Sixteen ferrets were exposed by the intranasal route to 10(6) TCID(50) of A/Vietnam/1203/04, a Clade 1 strain originally isolated from a fatal human case. The ferrets were euthanased for histological and virological analysis at intervals after challenge at 1, 3, 5, 6 and 7 days post-inoculation (dpi). From 5 dpi encephalitis was seen in all examined ferrets. The detection of antigen in the olfactory epithelium, the olfactory bulb, and related nuclei, in that temporal sequence, supported the contention that this is a major infection route for this virus strain. The detection of antigen in the epithelial cells in the Eustachian tube on 1 dpi, followed by the cochlea and vestibulocochlear nerve on 5 dpi is consistent with a second anterograde route of invasion, namely the vestibulocochlear pathway. There was also antigen in the lining of the ventricles and central canal indicating spread via the cerebrospinal fluid. However, evidence for haematogenous dissemination in the form of antigen in the brain parenchyma surrounding blood vessels was not found. This study provides support to the contention that wild-type HPAI H5N1 virus strains may enter the CNS via cranial nerve pathways and that the ferret is an appropriate model to study preventive and therapeutic procedures involving neural infection with these viruses by this route.

Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus harbored by Australian flying foxes with sporadic spillovers directly to horses. Although the mode and critical control points of HeV spillover to horses from flying foxes, and the risk for transmission from infected horses to other horses and humans, are poorly understood, we successfully established systemic HeV disease in 3 horses exposed to Hendra virus/Australia/Horse/2008/Redlands by the oronasal route, a plausible route for natural infection. In 2 of the 3 animals, HeV RNA was detected continually in nasal swabs from as early as 2 days postexposure, indicating that systemic spread of the virus may be preceded by local viral replication in the nasal cavity or nasopharynx. Our data suggest that a critical factor for reducing HeV exposure risk to humans includes early consideration of HeV in the differential diagnosis and institution of appropriate infection control procedures.

In 2008, Reston ebolavirus (REBOV) was isolated from pigs during a disease investigation in the Philippines. Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV-2) infections were also confirmed in affected herds and the contribution of REBOV to the disease outbreak remains uncertain. We have conducted experimental challenge studies in 5-week-old pigs, with exposure of animals to 10(6) TCID(50) of a 2008 swine isolate of REBOV via either the oronasal or subcutaneous route. Replication of virus in internal organs and viral shedding from the nasopharynx were documented in the absence of clinical signs of disease in infected pigs. These observations confirm not only that asymptomatic infection of pigs with REBOV occurs, but that animals so affected pose a transmission risk to farm, veterinary, and abattoir workers.

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A canine model simulating both cervical spondylosis and its results in delayed progressive myelopathy is presented. This model allowed control of compression, an ongoing assessment of neurological deficits, and evaluation using diagnostic images, frequent electrophysiological tests, local blood flow measurements, and postmortem histological examinations. Subclinical cervical cord compression was achieved in 14 dogs by placing a Teflon washer posteriorly and a Teflon screw anteriorly, producing an average of 29% stenosis of the spinal canal. Four dogs undergoing sham operations were designated as controls. Twelve of the animals undergoing compression developed delayed and progressive clinical signs of myelopathy, with a mean latent period to onset of myelopathy of 7 months. Spinal cord blood flow studies using the hydrogen clearance method showed a significant transient increase in blood flow immediately after compression and a decrease before sacrifice. Somatosensory evoked potential studies indicated progressive deterioration during the period of compression. Magnetic resonance images revealed intramedullary changes. Histological studies showed abnormalities overwhelmingly within the gray matter, including changes in vascular morphology, loss of large motor neurons, necrosis, and cavitation. Axonal degeneration and obvious demyelination were rarely seen. The most profound morphological changes occurred at the site of greatest compression. It is proposed that a momentary arrest of microcirculation occurs during extension of the neck because of loss of the reserve space in the compromised spinal canal. This microcirculatory disturbance is predominant in the watershed area of the cord and mainly affects the highly vulnerable anterior horn cells, leading to neuronal death, necrosis, and eventual cavitation at the junction of the dorsal and anterior horns. Additional supportive evidence of this hypothesis was derived from the literature.

The hydrogen (H2) electrode technique has been applied to the measurement of local skeletal muscle blood flow (LSMBF) in experimental animals (rats, rabbits, and monkeys). LSMBF was measured during resting and postexercise states, following epinephrine injections and during CO2 inhalation. Among the limited sites studied and/or measurements obtained, significant differences in LSMBF were found in only a few instances. During hypercapnia, LSMBF was found to be increased in some muscles in rats and monkeys. The present study demonstrates that the H2 electrode technique is a simple and reliable method for measuring resting and postexercise LSMBF in anesthetized animals. This method provides measurements at discrete loci, is easily reproducible, and causes little trauma.

The hydrogen (H2) electrode technique was adapted to the measurement of local skeletal muscle blood flow (LSMBF) in humans. Thirty-five normal volunteers were utilized to study the biceps, deltoid, gastrocnemius, and quadriceps muscles at rest and following exercise. Results indicated statistically significant increases (P < 0.05) in postexercise compared with resting blood flows within the muscles. The highest mean value for LSMBF was found in deltoid muscle and the lowest in biceps. This study demonstrates the potential superiority of the H2 electrode technique over previous techniques for measuring absolute muscle blood flow at individual sites. It is suggested that measurements by means of the H2 electrode technique represent the most definitive values for skeletal muscle blood flow at this time, and its application could be especially important in various neuromuscular disorders in which some question remains concerning the role of abnormalities of the skeletal muscle vasculature.

Histoimmunological, histochemical, and histological studies were conducted on cerebral arteries from four living patients with a recent aneurysmal subarachnoid haemorrhage. There appeared to be a correlation between the severity of vasospasm and the magnitude of pathological findings. Large myofibroblast cells and type V collagen within the medial layer were abundant in arteries showing marked vasospasm, but were less conspicuous in those showing milder involvement. Intracranial arteries from patients who died from non-cerebral causes did not demonstrate these changes. In ruptured vessels, there was also a positive fluorescence for actin-myosin filaments in layers of the arterial wall other than the media. It is postulated that the intimal and adventitial actin-myosin, myofibroblasts and type V collagen may contribute to cerebral vasospasm by holding the damaged vessel in a contracted phase during the healing period.