Bivalent single domain antibody constructs for effective neutralization of Venezuelan equine encephalitis

Venezuelan equine encephalitis virus (VEEV) is a mosquito borne alphavirus which leads to high viremia in equines followed by lethal encephalitis and lateral spread to humans. In addition to naturally occurring outbreaks, VEEV is a potential biothreat agent with no approved human vaccine or therapeutic currently available. Single domain antibodies (sdAb), also known as nanobodies, have the potential to be effective therapeutic agents. Using an immune phage display library derived from a llama immunized with an equine vaccine that included inactivated VEEV, five sdAb sequence families were identified that showed varying ability to neutralize VEEV. One of the sequence families had been identified previously in selections against chikungunya virus, a related alphavirus of public health concern. A key advantage of sdAb is the ability to optimize properties such as neutralization capacity through protein engineering. Neutralization of VEEV was improved by two orders of magnitude by genetically linking sdAb. One of the bivalent constructs showed effective neutralization of both VEEV and chikungunya virus. Several of the bivalent constructs neutralized VEEV in cell-based assays with reductions in the number of plaques by 50% at protein concentrations of 1 ng/mL or lower, making future evaluation of their therapeutic potential compelling.

Three-dimensional numerical investigation on micro-meter droplet impact and penetration into the porous media with different velocities

Droplets impacting and penetration into porous media is commonly seen in natural and engineering processes, in which the kinetics and capillary effect are of great importance to the lateral spreading and vertical penetration. In this study, a three-dimensional numerical simulation method was proposed to study the micro-meter droplet impact and penetration into the porous media. It is found that both the lateral spread and vertical penetration occur on the millisecond timescale and larger velocity will enhance the lateral spreading but have little influence on the penetration time and depth. The direct numerical method proposed in this study can be applied to predict the actual spreading and penetration status in the droplet-powder system and further insight into the droplet-powder interaction.

Predicting Early Loss of Lateral Spread Response before Decompression in Hemifacial Spasm Surgery

Recent studies have shown the evocation of lateral spread response (LSR) due to the compression of the facial nerve in hemifacial spasm (HFS). Intraoperative monitoring (IOM) of LSR could help locate neurovascular conflicts and confirm adequate micro-vascular decompression (MVD) while treatment of hemifacial spasm (HFS). However, studies on early LSR loss before decompression in HFS surgery are sparse, indicating the need to understand various perceptions on it. Therefore, we retrospectively analyzed 50 adult HFS patients who underwent MVD during the period of September 2018–June 2021. We employed IOM combining traditional LSR (tLSR) and dual LSR (dLSR). One patient was excluded owing to the lack of LSR induction throughout the surgery, while 49 were divided into groups A (n = 14) and B (n = 35), designated as with or without early LSR loss groups, respectively, and offending vessels were analyzed. The mean age of group A patients was significantly younger (47.8 ± 8.6) than that of group B (53.9 ± 10.6) (p = 0.0393). The significant predominating offending vessel in group A was the anterior inferior cerebellar artery (AICA, 78.57%). However, group B included those with AICA (28.57%), posterior inferior cerebellar artery (PICA, 22.86%), vertebral artery (VA) involved (25.71%), and combined AICA and PICA (22.86%). Group B exhibited poorer clinical outcomes with more complications. Conclusively, early LSR loss might occur in the younger population, possibly due to the AICA offending vessel. The compression severity of offending vessels may determine the occurrence of early LSR loss.

Colliding respiratory jets as a mechanism of air exchange and pathogen transport during conversations

Air exchange between people has emerged in the COVID-19 pandemic as the important vector for transmission of the SARS-CoV-2 virus. We study the airflow and exchange between two unmasked individuals conversing face-to-face at short range, which can potentially transfer a high dose of a pathogen, because the dilution is small when compared to long-range airborne transmission. We conduct flow visualization experiments and direct numerical simulations of colliding respiratory jets mimicking the initial phase of a conversation. The evolution and dynamics of the jets are affected by the vertical offset between the mouths of the speakers. At low offsets the head-on collision of jets results in a `blocking effect', temporarily shielding the susceptible speaker from the pathogen carrying jet, although, the lateral spread of the jets is enhanced. Sufficiently large offsets prevent the interaction of the jets. At intermediate offsets (8-10 cm for 1 m separation), jet entrainment and the inhaled breath assist the transport of the pathogen-loaded saliva droplets towards the susceptible speaker's mouth. Air exchange is expected, in spite of the blocking effect arising from the interaction of the respiratory jets from the two speakers.

Relative importance of region, seasonality and weed management practices effects on the functional structure of weed communities in French vineyards

Winegrowers have diversified their weed management practices over the last two decades changing the structure and the composition of weed communities. Complementary to taxonomic studies, trait-based approaches are promising ways for a better understanding of weed communities responses to environmental and agronomic filters. In the present study, the impacts of climate, soil characteristics, seasons and weed management practices (chemical weeding, tillage and mowing) were assessed on weed communities from 46 plots in three French wine-growing regions (Champagne, Languedoc and Rhone valley). These agro-environmental gradients structuring weed communities according to their combinations of traits were highlighted using multivariate analysis (RLQ). The impacts of these filters on Community Weighted Means (CWM) and Community Weighted Variance (CWV) of weed communities were analysed using mixed and null modelling. Our results showed that spatio-temporal and weed management practices variables explained from 13% to 48% of the total variance of CWM (specific leaf area, maximum height, seed mass, flowering onset and duration and lateral spread). Region, seasonality and management practices explained 53%, 28% and 19% of CWM marginal variance, respectively. Weed management impacted CWM and CWV through two main gradients: (i) a soil disturbance gradient with high mechanical disturbance of soil in tilled plots and low mechanical disturbance in chemically weeded plots and (ii) a vegetation cover gradient with high vegetation abundance in mowed plots compared to more bare soils in tilled and chemically weeded plots. In Languedoc, chemical weeding filtered weed communities with ruderal strategy trait values (low seed mass, small-stature) while mowed communities were more competitive (higher seed mass, higher stature and lower SLA). In Languedoc and Champagne, tillage favoured communities with high seed mass that increases the viability of buried seeds and high lateral spread values associated to the ability to resprout after tillage. This study demonstrated that trait-based approaches can be successfully applied to perennial cropping systems such as vineyards, in order to understand community assembly to better guide weed management practices.

High Phenotypic Plasticity in a Prominent Plant Invader along Altitudinal and Temperature Gradients

Studies on plant growth and trait variation along environmental gradients can provide important information for identifying drivers of plant invasions and for deriving management strategies. We used seeds of the annual plant invader Ambrosia artemisiifolia L. (common ragweed) collected from an agricultural site in Northern Italy (226 m. a.s.l; Mean Annual Air Temperature: 12.9 °C; precipitations: 930 mm) to determine variation in growth trajectories and plant traits when grown along a 1000-m altitudinal gradient in Northern Italy, and under different temperature conditions in the growth chamber (from 14/18 °C to 26/30 °C, night/day), using a non-liner modeling approach. Under field conditions, traits related to plant height (maximum height, stem height, number of internodes) followed a three-parameter logistic curve. In contrast, leaf traits (lateral spread, number of leaves, leaf length and width) followed non-monotonic double-Richards curves that captured the decline patterns evident in the data. Plants grew faster, reaching a higher maximum plant height, and produced more biomass when grown at intermediate elevations. Under laboratory conditions, plants exhibited the same general growth trajectory of field conditions. However, leaf width did not show the recession after the maximum value shown by plants grown in the field, although the growth trajectories of some individuals, particularly those grown at 18 °C, showed a decline at late times. In addition, the plants grown at lower temperatures exhibited the highest value of biomass and preserved reproductive performances (e.g., amount of male inflorescence, pollen weight). From our findings, common ragweed exhibits a high phenotypic plasticity of vegetative and reproductive traits in response to different altitudes and temperature conditions. Under climate warming, this plasticity may facilitate the shift of the species towards higher elevation, but also the in situ resistance and (pre)adaptation of populations currently abundant at low elevations in the invasive European range. Such results may be also relevant for projecting the species management such as the impact by possible biocontrol agents.

Local and correlated studies of humidity-mediated ferroelectric thin film surface charge dynamics

Electrochemical phenomena in ferroelectrics are of particular interest for catalysis and sensing applications, with recent studies highlighting the combined role of the ferroelectric polarisation, applied surface voltage and overall switching history. Here, we present a systematic Kelvin probe microscopy study of the effect of relative humidity and polarisation switching history on the surface charge dissipation in ferroelectric Pb(Zr0.2Ti0.8)O3 thin films. We analyse the interaction of surface charges with ferroelectric domains through the framework of physically constrained unsupervised machine learning matrix factorisation, Dictionary Learning, and reveal a complex interplay of voltage-mediated physical processes underlying the observed signal decays. Additional insight into the observed behaviours is given by a Fitzhugh–Nagumo reaction–diffusion model, highlighting the lateral spread and charge passivation process contributors within the Dictionary Learning analysis.

The novel prognostic value of postoperative follow-up lateral spread response after microvascular decompression for hemifacial spasm

OBJECTIVE The lateral spread response (LSR) is an aberrant electrophysiological response in which a stimulus on one branch of the facial nerve spills over to other branches of the nerve, which can be captured by electrodes near each branch. The authors performed this study to evaluate the prognostic value of the follow-up LSR with a sufficient time interval from intraoperative LSR (IO-LSR) after microvascular decompression (MVD) for hemifacial spasm (HFS), excluding the interference of various intraoperative situations. METHODS A total of 247 patients treated with MVD for HFS between June 2011 and March 2019 were enrolled in this study. The IO-LSR was routinely evaluated in all patients. The LSR was checked again on postoperative day (POD) 2 after surgery (POD2-LSR). A total of 228 patients (92.3%) were considered cured at the last clinical follow-up. RESULTS The IO-LSR disappeared in 189 patients (76.5%), and among them, 181 patients (95.8%) were cured 1 year after surgery. The POD2-LSR disappeared in 193 patients (78.1%), and 185 patients (95.9%) among them were cured. Among the 189 patients in which the IO-LSR disappeared, the POD2-LSR reappeared in 26 patients (13.8%). In contrast, the POD2-LSR disappeared in 30 (51.7%) of 58 patients for whom the IO-LSR continued at the end of surgery. When classified into groups according to the status of the IO-LSR and POD2-LSR, in the group of patients in whom both LSRs disappeared, the cure rate was 98.2%, which was significantly higher than that of the other 3 groups (p < 0.05, Cochran-Armitage trend test). The use of both LSRs was found to be significantly associated with better predictability (p < 0.05, McNemar’s test). CONCLUSIONS Postoperative follow-up LSR examination may be beneficial in predicting clinical outcomes after MVD for HFS, especially when considered together with IO-LSR.