SARS-CoV-2 aerosol transmission in schools: the effectiveness of different interventions.

BACKGROUND: Indoor aerosol transmission of SARS-CoV-2 has been widely recognised, especially in schools where children remain in closed indoor spaces and largely unvaccinated. Measures such as strategic natural ventilation and high efficiency particulate air (HEPA) filtration remain poorly implemented and mask mandates are often progressively lifted as vaccination rollout is enhanced. METHODS: We adapted a previously developed aerosol transmission model to study the effect of interventions (natural ventilation, face masks, HEPA filtration and their combinations) on the concentration of virus particles in a classroom of 160 m3 containing one infectious individual. The cumulative dose of viruses absorbed by exposed occupants was calculated. RESULTS: In the absence of interventions, the cumulative dose absorbed was 1.5 times higher in winter than in spring/summer, increasing chances of indoor airborne transmission in winter. However, natural ventilation was more effective in winter, leading to up to a 20-fold decrease in cumulative dose when six windows were fully open at all times. In winter, partly opening two windows all day or fully opening six windows at the end of each class was effective as well (2.7- to 3-fold decrease). In summer, good ventilation levels could be achieved through the opening of windows all day long (2- to 7-fold decrease depending on the number of windows open). Opening windows only during yard and lunch breaks had minimal effect (≤1.5-fold decrease). One HEPA filter was as effective as two windows partly open all day in winter (3-fold decrease) whereas two filters were more effective (5-fold decrease). Surgical face masks were very effective independently of the season (8-fold decrease). Combined interventions (i.e., natural ventilation, masks, and HEPA filtration) were the most effective (≥25-fold decrease) and remained highly effective in the presence of a super-spreader. INTERPRETATION: Natural ventilation, face masks, and HEPA filtration are effective interventions to reduce SARS-CoV-2 aerosol transmission. These measures should be combined and complemented by additional interventions (e.g., physical distancing, hygiene, testing, contact tracing and vaccination) to maximise benefit.

Modelling airborne transmission of SARS-CoV-2 using CARA: risk assessment for enclosed spaces.

The COVID-19 pandemic has highlighted the need for a proper risk assessment of respiratory pathogens in indoor settings. This paper documents the COVID Airborne Risk Assessment methodology, to assess the potential exposure of airborne SARS-CoV-2 viruses, with an emphasis on virological and immunological factors in the quantification of the risk. The model results from a multidisciplinary approach linking physical, mechanical and biological domains, enabling decision makers or facility managers to assess their indoor setting. The model was benchmarked against clinical data, as well as two real-life outbreaks, showing good agreement. A probability of infection is computed in several everyday-life settings and with various mitigation measures. The importance of super-emitters in airborne transmission is confirmed: 20% of infected hosts can emit approximately two orders of magnitude more viral-containing particles. The use of masks provides a fivefold reduction in viral emissions. Natural ventilation strategies are very effective to decrease the concentration of virions, although periodic venting strategies are not ideal in certain settings. Although vaccination is an effective measure against hospitalization, their effectiveness against transmission is not optimal, hence non-pharmaceutical interventions (ventilation, masks) should be actively supported. We also propose a critical threshold to define an acceptable risk level.

The HEV Ventilator: at the interface between particle physics and biomedical engineering.

A high-quality, low-cost ventilator, dubbed HEV, has been developed by the particle physics community working together with biomedical engineers and physicians around the world. The HEV design is suitable for use both in and out of hospital intensive care units, provides a variety of modes and is capable of supporting spontaneous breathing and supplying oxygen-enriched air. An external air supply can be combined with the unit for use in situations where compressed air is not readily available. HEV supports remote training and post market surveillance via a Web interface and data logging to complement standard touch screen operation, making it suitable for a wide range of geographical deployment. The HEV design places emphasis on the ventilation performance, especially the quality and accuracy of the pressure curves, reactivity of the trigger, measurement of delivered volume and control of oxygen mixing, delivering a global performance which will be applicable to ventilator needs beyond the COVID-19 pandemic. This article describes the conceptual design and presents the prototype units together with a performance evaluation.

Using gradient Forest to predict climate response and adaptation in Cork oak.

Climate change is impacting locally adapted species such as the keystone tree species cork oak (Quercus suber L.). Quantifying the importance of environmental variables in explaining the species distribution can help build resilient populations in restoration projects and design forest management strategies. Using landscape genomics, we investigated the population structure and ecological adaptation of this tree species across the Mediterranean Basin. We applied genotyping by sequencing and derived 2,583 single nucleotide polymorphism markers genotyped from 81 individuals across 17 sites in the studied region. We implemented an approach based on the nearest neighbour haplotype 'coancestry' and uncovered a weak population structure along an east-west climatic gradient across the Mediterranean region. We identified genomic regions potentially involved in local adaptation and predicted differences in the genetic composition across the landscape under current and future climates. Variants associated with temperature and precipitation variables were detected, and we applied a nonlinear multivariate association method, gradient forest, to project these gene-environment relationships across space. The model allowed the identification of geographic areas within the western Mediterranean region most sensitive to climate change: south-western Iberia and northern Morocco. Our findings provide a preliminary assessment towards a potential management strategy for the conservation of cork oak in the Mediterranean Basin.

Assessing the Molecular Basis of the Fuel Octane Scale: A Detailed Investigation on the Rate Controlling Steps of the Autoignition of Heptane and Isooctane.

N-Heptane and 2,2,4-trimethylpentane (isooctane) are the key species in the modeling of ignition of hydrocarbon-based fuel formulations. Isooctane is knock-resistant whereas n-heptane is a very knock-prone hydrocarbon. It has been suggested that interconversion of their associated alkylperoxy and hydroperoxyalkyl species via hydrogen-transfer isomerization reaction is the key step to understand their different knocking behavior. In this work, the kinetics of unimolecular hydrogen-transfer reactions of n-heptylperoxy and isooctylperoxy are determined using canonical variational transition-state theory and multidimensional small curvature tunneling. Internal rotation of involved molecules is taken explicitly into account in the molecular partition function. The rate coefficients are calculated in the temperature range 300-900 K, relevant to low-temperature autoignition. The concerted HO2 elimination is an important reaction that competes with some H-transfer and is associated with chain termination. Thus, the branching ratio between these reaction channels is analyzed. We show that variational and multidimensional tunneling effects cannot be neglected for the H-transfer reaction. In particular, the pre-exponential Arrhenius fitting parameter derived from our rate constants shows a strong dependence on the temperature, because tunneling increases quickly at temperatures below 500 K. On the basis of our results, the existing qualitative model for the reasons for different knock behavior observed for n-heptane and isooctane is quantitatively validated at the molecular level.

What Chern-Simons theory assigns to a point.

We answer the questions, "What does Chern-Simons theory assign to a point?" and "What kind of mathematical object does Chern-Simons theory assign to a point?" Our answer to the first question is representations of the based loop group. More precisely, we identify a certain class of projective unitary representations of the based loop group [Formula: see text] We define the fusion product of such representations, and we prove that, modulo certain conjectures, the Drinfel'd center of that representation category of [Formula: see text] is equivalent to the category of positive energy representations of the free loop group [Formula: see text]† The abovementioned conjectures are known to hold when the gauge group is abelian or of type [Formula: see text] Our answer to the second question is bicommutant categories. The latter are higher categorical analogs of von Neumann algebras: They are tensor categories that are equivalent to their bicommutant inside [Formula: see text], the category of bimodules over a hyperfinite [Formula: see text] factor. We prove that, modulo certain conjectures, the category of representations of the based loop group is a bicommutant category. The relevant conjectures are known to hold when the gauge group is abelian or of type [Formula: see text].

Candida glabrata drug:H+ antiporter CgTpo3 (ORF CAGL0I10384g): role in azole drug resistance and polyamine homeostasis.

OBJECTIVES: The ability of opportunistic pathogenic Candida species to persist and invade specific niches in the human host depends on their resistance to natural growth inhibitors and antifungal therapy. This work describes the role of the Candida glabrata drug:H(+) antiporter CgTpo3 (ORF CAGL0I10384g) in this context. METHODS: Deletion and cloning of CgTPO3 was achieved using molecular biology tools. C. glabrata strain susceptibility was assayed based on growth in liquid and solid media and through MIC determination. Radiolabelled compound accumulation or HPLC were used for the assessment of the role of CgTpo3 as a drug or polyamine transporter. Quantitative RT-PCR was used for expression analysis. RESULTS: CgTpo3 was found to confer resistance to azole drugs in C. glabrata. This protein was found to be localized to the plasma membrane and to decrease the intracellular accumulation of [(3)H]clotrimazole, playing a direct role in its extrusion from pre-loaded C. glabrata cells. CgTPO3 was further found to confer resistance to spermine, complementing the susceptibility phenotypes exhibited by the deletion of its Saccharomyces cerevisiae homologue, TPO3. In spermine-stressed C. glabrata cells, CgTPO3 is transcriptionally activated in a CgPdr1-dependent manner, contributing to a decrease in the intracellular concentration of this polyamine. Clotrimazole exposure was found to lead to the intracellular accumulation of spermine, and pre-exposure to this polyamine was found consistently to lead to increased clotrimazole resistance. CONCLUSIONS: Altogether, these results point to a significant role for CgTpo3 in azole drug resistance and in the tolerance to high polyamine concentrations, such as those found in the urogenital tract.

The dual role of candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance.

Opportunistic Candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. Given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms. In this study, the drug:H(+) antiporter CgAqr1 (ORF CAGL0J09944g), from Candida glabrata, was identified as a determinant of resistance to acetic acid, and also to the antifungal agents flucytosine and, less significantly, clotrimazole. These antifungals were found to act synergistically with acetic acid against this pathogen. The action of CgAqr1 in this phenomenon was analyzed. Using a green fluorescent protein fusion, CgAqr1 was found to localize to the plasma membrane and to membrane vesicles when expressed in C. glabrata or, heterologously, in Saccharomyces cerevisiae. Given its ability to complement the susceptibility phenotype of its S. cerevisiae homolog, ScAqr1, CgAqr1 was proposed to play a similar role in mediating the extrusion of chemical compounds. Significantly, the expression of this gene was found to reduce the intracellular accumulation of (3)H-flucytosine and, to a moderate extent, of (3)H-clotrimazole, consistent with a direct role in antifungal drug efflux. Interestingly, no effect of CgAQR1 deletion could be found on the intracellular accumulation of (14)C-acetic acid, suggesting that its role in acetic acid resistance may be indirect, presumably through the transport of a still unidentified physiological substrate. Although neither of the tested chemicals induces changes in CgAQR1 expression, pre-exposure to flucytosine or clotrimazole was found to make C. glabrata cells more sensitive to acetic acid stress. Results from this study show that CgAqr1 is an antifungal drug resistance determinant and raise the hypothesis that it may play a role in C. glabrata persistent colonization and multidrug resistance.

Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives.

Recently, many efforts have been made to develop N-methyl-D-aspartic acid receptor antagonists for treating different pathological conditions such as thrombo-embolic stroke, traumatic head injury, Huntington's, Parkinson's, and Alzheimer's diseases). However, as side-effects limit the use of most antagonists, new drugs are still required. In this work, we performed a (quantitative) structure-activity relationship analysis of 17 phenyl-amidine derivatives (1a-1q), reported as N-methyl-D-aspartic acid receptor antagonists, and used this data to rationally design the triazolyl-amidines. The best (quantitative) structure-activity relationship model constructed by multiple linear regression analysis presented high data fitting (R = 0.914) was able to explain 83.6% of the biological data variance (R(2) = 0.836), presented a satisfactory internal predictive ability (Q(2) = 0.609) and contained the descriptors (E(HOMO), Ovality and cLogP). Our assays confirmed that glutamate promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected the neurons from the glutamate effect (from 77% to 27% and 45%, respectively). The results of neurotoxicity and cytotoxicity on Vero cells suggested the favorable profile of 2a and 2b. Also, the molecular modeling used to predict the activity, the interaction with the receptor and the pharmacokinetic and toxicity of the triazolyl-amidines pointed them as a promising class for further exploration as N-methyl-D-aspartic acid receptor antagonists.

Chemical bonding and the equilibrium composition of Grignard reagents in ethereal solutions.

A thorough analysis of the electronic structure and thermodynamic aspects of Grignard reagents and its associated equilibrium composition in ethereal solutions is performed. Considering methylmagnesium halides containing fluorine, chlorine, and bromine, we studied the neutral, charged, and radical species associated with their chemical equilibrium in solution. The ethereal solvents considered, tetrahydrofuran (THF) and ethyl ether (Et(2)O), were modeled using the polarizable continuum model (PCM) and also by explicit coordination to the Mg atoms in a cluster. The chemical bonding of the species that constitute the Grignard reagent is analyzed in detail with generalized valence bond (GVB) wave functions. Equilibrium constants were calculated with the DFT/M06 functional and GVB wave functions, yielding similar results. According to our calculations and existing kinetic and electrochemical evidence, the species R(•), R(-), (•)MgX, and RMgX(2)(-) must be present in low concentration in the equilibrium. We conclude that depending on the halogen, a different route must be followed to produce the relevant equilibrium species in each case. Chloride and bromide must preferably follow a "radical-based" pathway, and fluoride must follow a "carbanionic-based" pathway. These different mechanisms are contrasted against the available experimental results and are proven to be consistent with the existing thermodynamic data on the Grignard reagent equilibria.