Assessing Nonadiabatic Dynamics Methods in Long Timescales.

Nonadiabatic dynamics simulations complement time-resolved experiments by revealing ultrafast excited-state mechanistic information in photochemical reactions. Understanding the relaxation mechanisms of photoexcited molecules finds application in energy, material, and medicinal research. However, with substantial computational costs, the nonadiabatic dynamics simulations have been restricted to ultrafast timescales, typically less than a few picoseconds, thus neglecting a wide range of photoactivated processes occurring in much longer timescales.

Early exposure to farm dust in an allergic airway inflammation rabbit model: Does it affect bronchial and cough hyperresponsiveness?

Introduction: Over the past 50 years, the prevalence of allergic respiratory diseases has been increasing. The Hygiene hypothesis explains this progression by the decrease in the bio-diversity of early microbial exposure. This study aims to evaluate the effect of early-life farm exposure on airway hyperresponsiveness and cough hypersensitivity in an allergic airway inflammation rabbit model.

Newton-X Platform: New Software Developments for Surface Hopping and Nuclear Ensembles.

Newton-X is an open-source computational platform to perform nonadiabatic molecular dynamics based on surface hopping and spectrum simulations using the nuclear ensemble approach. Both are among the most common methodologies in computational chemistry for photophysical and photochemical investigations. This paper describes the main features of these methods and how they are implemented in Newton-X.

Trajectory Surface Hopping for a Polarizable Embedding QM/MM Formulation.

We present the implementation of trajectory surface-hopping nonadiabatic dynamics for a polarizable embedding QM/MM formulation. Time-dependent density functional theory was used at the quantum mechanical level of theory, whereas the molecular mechanics description involved the polarizable AMOEBA force field. This implementation has been obtained by integrating the surface-hopping program Newton-X NS with an interface between the Gaussian 16 and the Tinker suites of codes to calculate QM/AMOEBA energies and forces.

Simulations of molecular photodynamics in long timescales.

Nonadiabatic dynamics simulations in the long timescale (much longer than 10 ps) are the next challenge in computational photochemistry. This paper delimits the scope of what we expect from methods to run such simulations: they should work in full nuclear dimensionality, be general enough to tackle any type of molecule and not require unrealistic computational resources. We examine the main methodological challenges we should venture to advance the field, including the computational costs of the electronic structure calculations, stability of the integration methods, accuracy of the nonadiabatic dynamics algorithms and software optimization.

A Physical Analog to Assess Surgical Face Mask Air Flow Resistance During Tidal Ventilation.

A large variety of disposable face masks have been produced since the onset of the COVID-19 pandemic. Decreased resistance to inspiration improves adherence to the use of the mask; the so called breathability is usually estimated by the measurement of air flow across a section of the tissue under a given pressure difference. We hypothesized that the mask pressure-flow relationship studied in conditions that mimic tidal breathing could allow a more comprehensive characterization of airflow resistance, a major determinant of mask comfort.

Impact of Inhaled Corticosteroids on the Modulation of Respiratory Defensive Reflexes During Artificial Limb Exercise in Ovalbumin-Sensitized Rabbits.

Introduction: Cough is a major lower airway defense mechanism that can be triggered by exercise in asthma patients. Studies on cough reflex in experimental animal models revealed a decrease of cough reflex sensitivity during exercise in healthy animals, but a lack of desensitization in ovalbumin-sensitized rabbits. The aim of our study is to evaluate the impact of inhaled corticosteroids on cough reflex during artificial limb exercise in an animal model of eosinophilic airway inflammation.

Control of Protonated Schiff Base Excited State Decay within Visual Protein Mimics: A Unified Model for Retinal Chromophores.

Artificial biomimetic chromophore-protein complexes inspired by natural visual pigments can feature color tunability across the full visible spectrum. However, control of excited state dynamics of the retinal chromophore, which is of paramount importance for technological applications, is lacking due to its complex and subtle photophysics/photochemistry. Here, ultrafast transient absorption spectroscopy and quantum mechanics/molecular mechanics simulations are combined for the study of highly tunable rhodopsin mimics, as compared to retinal chromophores in solution.

Desensitization of the Cough Reflex Induced by Corticosteroids in Ovalbumin-Sensitized Rabbits During Artificial Limb Exercise.

Introduction: Cough is a major symptom frequently experienced during exercise, mainly in asthmatic patients. Inhaled glucocorticoids represent the keystone treatment in the management of asthma, but little is known about interactions between cough and exercise, especially in controlled patients. During exercise, cough reflex (CR) appears downregulated in healthy animal models whereas a lack of desensitization of CR has been shown in ovalbumin-sensitized animal models, mimicking asthmatic disease.

A New Benchmark Set for Excitation Energy of Charge Transfer States: Systematic Investigation of Coupled Cluster Type Methods.

The numerous existing publications on benchmarking quantum chemistry methods for excited states rarely include Charge Transfer (CT) states, although many interesting phenomena in, e.g., biochemistry and material physics involve the transfer of electrons between fragments of the system.

In Vivo Documentation of Stimulus Velocity Tuning of Mechanically Induced Reflex Cough.

In order to clear airways and lungs defensive reflexes are provoked rather by the dynamic phase of mechanical stimulus. It is speculated that provocation of defensive response depends not only on stimulus duration but also on stimulus velocity. Fourteen adult rabbits were anaesthetized and tracheotomized.

Modulation of protective reflex cough by acute immune driven inflammation of lower airways in anesthetized rabbits.

Chronic irritating cough in patients with allergic disorders may reflect behavioral or reflex response that is inappropriately matched to the stimulus present in the respiratory tract. Such dysregulated response is likely caused by sensory nerve damage driven by allergic mediators leading to cough hypersensitivity. Some indirect findings suggest that even acid-sensitive, capsaicin-insensitive A-δ fibers called "cough receptors" that are likely responsible for protective reflex cough may be modulated through immune driven inflammation.

A domain-based local pair natural orbital implementation of the equation of motion coupled cluster method for electron attached states.

This work describes a domain-based local pair natural orbital (DLPNO) implementation of the equation of motion coupled cluster method for the computation of electron affinities (EAs) including single and double excitations. Similar to our earlier work on ionization potentials (IPs), the method reported in this study uses the ground state DLPNO framework and extends it to the electron attachment problem. While full linear scaling could not be achieved as in the IP case, leaving the Fock/Koopmans' contributions in the canonical basis and using a tighter threshold for singles PNOs allows us to compute accurate EAs and retain most of the efficiency of the DLPNO technique.

Multilayer Approach to the IP-EOM-DLPNO-CCSD Method: Theory, Implementation, and Application.

We present a multilayer implementation of the EOM-CCSD for the computation of ionization potentials of atoms and molecules in the presence of their environment. The method uses local orbitals to partition the system into a number of hypothetical fragments and treat different fragments of the system at different levels of theory. This approach significantly reduces the computational cost with a systematically controllable accuracy and is equally applicable to describe the environmental effect of both bonded and nonbonded nature.

Overcoming Target Driven Fratricide for T Cell Therapy.

Chimeric Antigen Receptor (CAR) T cells expressing the fusion of the NKG2D protein with CD3ζ (NKG2D-CAR T Cells) acquire a specificity for stress-induced ligands expressed on hematological and solid cancers. However, these stress ligands are also transiently expressed by activated T cells implying that NKG2D-based T cells may undergo self-killing (fratricide) during cell manufacturing or during the freeze thaw cycle prior to infusion in patients. To avoid target-driven fratricide and enable the production of NKG2D-CAR T cells for clinical application, two distinct approaches were investigated.

A Calibration Device to Compare Body Plethysmographs Among Pediatric Lung Function Laboratories.

Multi-center studies in specific airway resistance have shown significant inter laboratory variability. Comparison of plethysmographic equipment using a lung model easily transportable from one site to another should be of help to international normative studies. A resistor made of parallel capillary tubes - insuring adequate linearity within 1 L/sec - was connected to a glass bottle.

Assessement of Awareness of, Concerns and Attitudes Towards HIV-Related Court-Case Sentences in France in a Representative Sample of People Living with HIV (ANRS VESPA2 Survey).

Some of the 12 criminal trials and sentences in France for HIV transmission in 1998-2011 attracted substantial public attention, with a possible negative impact on people living with HIV (PLWH) through reinforced stigma and discrimination. This analysis aimed to characterize PLWH enrolled in the representative ANRS-VESPA2 survey, aware of and concerned about convictions for HIV transmission. Being a migrant from Sub-Saharan Africa, having difficult socio-economic conditions, having unprotected sex with one's main partner and concealing one's HIV status were all factors statistically associated with concern about the sentences.

Modulation of defensive airway reflexes during continuous positive airway pressure in the rabbit.

Lung hyperinflation may alter the pattern of ventilatory reflexes in chronic respiratory disorders. The aim of the study was to test the effect of continuous positive airway pressure (CPAP) on ventilatory responses to mechanical stimulation of the trachea.

Fine Tuning of Retinal Photoinduced Decay in Solution.

Single methylation at position C of the all-trans retinal protonated Schiff base switches its excited-state decay in methanol from a slower picosecond into an ultrafast, protein-like subpicosecond process. QM/MM modeling in conjunction with on-the-fly excited-state dynamics provides fundamental understanding of the fine-tuning mechanics that "catalyzes" the photoinduced decay of solvated retinals. Methylation alters the interplay between the ionic S and covalent S states, reducing the excited-state lifetime by favoring the formation of a S transient fluorescent state with fully inverted bond lengths that accounts for the recorded transient spectroscopy and from which a space-saving conical intersection seam is quickly (<1 ps) reached.

Exploiting natural killer group 2D receptors for CAR T-cell therapy.

Chimeric antigen receptors (CARs) are genetically engineered proteins that combine an extracellular antigen-specific recognition domain with one or several intracellular T-cell signaling domains. When expressed in T cells, these CARs specifically trigger T-cell activation upon antigen recognition. While the clinical proof of principle of CAR T-cell therapy has been established in hematological cancers, CAR T cells are only at the early stages of being explored to tackle solid cancers.

Down-Regulation of Cough during Exercise Is Less Frequent in Healthy Children than Adults. Role of the Development and/or Atopy?

Cough is typically associated with physical activity in children with asthma, but the characteristics of the relationship between cough and exercise has not been established under physiological conditions. The aim of the study was to describe the effect of exercise on the reflex cough response elicited by a single breath of capsaicin in non-asthmatic children. A group of non-asthmatic adults was studied as reference.

Self-Reported Bothersome Symptoms Across Different Socioepidemiological Groups of People Living With HIV Attending French Hospitals: Results From the ANRS-VESPA2 Survey.

Context: Twenty years after the advent of combined antiretroviral therapies (ARTs), there is a growing need for up-to-date information about the daily experience of people living with HIV (PLWH).

Objectives: This study aimed to investigate the relationship between socioepidemiological groups and the types of bothersome symptoms reported by PLWH participating in a national survey in France.

Methods: We analyzed self-reported bothersome symptoms in a representative sample of PLWH (ANRS-VESPA2 survey), most of whom were receiving ART treatment.

Maturation of Airway Defensive Reflexes Is Related to Development of Feeding Behavior during Growth in Rabbits.

Cough and expiration reflex are major lower airway defense mechanisms that have not been studied throughout development in relation with the feeding behavior. To describe airway defense reflexes evoked by mechanical stimulation of the trachea in developing rabbit pups. Sixty one pups were allocated to 3 groups according to their feeding behavior: suckling ( = 22), weanling ( = 21) and weaning ( = 18) group.

Lack of desensitization of the cough reflex in ovalbumin-sensitized rabbits during exercise.

Introduction: Cough is a major symptom of asthma frequently experienced during exercise but little is known about interactions between cough and exercise. The goal of our study was to clarify the potential modulation of the cough reflex (CR) by exercise in a spontaneously breathing anaesthetized animal model of airway eosinophilic inflammation.

Materials & Methods: Ten ovalbumin (OVA) sensitized adult rabbits and 8 controls were studied.