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Phonon scattering limits charge-carrier mobilities and governs emission line broadening in hybrid metal halide perovskites. Establishing how charge carriers interact with phonons in these materials is therefore essential for the development of high-efficiency perovskite photovoltaics and low-cost lasers. Here we investigate the temperature dependence of emission line broadening in the four commonly studied formamidinium and methylammonium perovskites, HC(NH 2 ) 2 PbI 3 , HC(NH 2 ) 2 PbBr 3 , CH 3 NH 3 PbI 3 and CH 3 NH 3 PbBr 3 , and discover that scattering from longitudinal optical phonons via the Fröhlich interaction is the dominant source of electron–phonon coupling near room temperature, with scattering off acoustic phonons negligible. We determine energies for the interacting longitudinal optical phonon modes to be 11.5 and 15.3 meV, and Fröhlich coupling constants of ∼40 and 60 meV for the lead iodide and bromide perovskites, respectively. Our findings correlate well with first-principles calculations based on many-body perturbation theory, which underlines the suitability of an electronic band-structure picture for describing charge carriers in hybrid perovskites. Phonon scattering limits charge transport in perovskite solar cells, yet the interactions involved are still poorly understood. Here, Wright et al . show by photoluminescence measurements and first-principles calculations that longitudinal optical phonons dominate the electron-phonon coupling at room temperature.

Photovoltaic devices based on metal halide perovskites are rapidly improving in efficiency. Once the Shockley–Queisser limit is reached, charge-carrier extraction will be limited only by radiative bimolecular recombination of electrons with holes. Yet, this fundamental process, and its link with material stoichiometry, is still poorly understood. Here we show that bimolecular charge-carrier recombination in methylammonium lead triiodide perovskite can be fully explained as the inverse process of absorption. By correctly accounting for contributions to the absorption from excitons and electron-hole continuum states, we are able to utilise the van Roosbroeck–Shockley relation to determine bimolecular recombination rate constants from absorption spectra. We show that the sharpening of photon, electron and hole distribution functions significantly enhances bimolecular charge recombination as the temperature is lowered, mirroring trends in transient spectroscopy. Our findings provide vital understanding of band-to-band recombination processes in this hybrid perovskite, which comprise direct, fully radiative transitions between thermalized electrons and holes. Radiative bimolecular processes will dominate charge-carrier recombination in hybrid perovskite solar cells operating near the Shockley-Queisser limit. Here, the authors show that such processes are the inverse of absorption and increase as distribution functions sharpen towards lower temperatures.

Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4(+) T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4(+) T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A(+) CD4(+) T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF(+)/IL-17A(+) co-producing CD4(+) memory T-cells (p<0.01); IFNγ(+) CD4(+) memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4(+) memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = -0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4(+) memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans.

•We developed HyPER: Regional hypersampling of fMRI to resolve three physiological pulsations—systemic low-frequency oscillations (LFOs), respiratory, and cardiac—in four key brain regions: major cerebral arteries, superior sagittal sinus (SSS), gray matter (GM), and white matter (WM).•HyPER was validated on a local fast fMRI dataset and applied to the Human Connectome Project-Aging (HCP-A) data, increasing the resolvable frequency range by ninefold (0.625 Hz to 5.625 Hz).•Hypersampling HCP-A data revealed an age-related increase in cardiac and respiratory pulsations and decreased LFO power.•HyPER can be broadly applied to existing fMRI datasets to uncover hidden physiological pulsations and advance our understanding of brain physiology in health and disease. Resting-state functional MRI (fMRI) signals capture physiological processes, including systemic low-frequency oscillations (LFOs), respiration, and cardiac pulsations. These physiological oscillations—often treated as noise in functional connectivity analysis—reflect fundamental aspects of brain physiology and have recently been recognized as key drivers of brain waste clearance. However, these critical physiological signals are obscured in fMRI data due to slow sampling rates (typical repetition time (TR) > 0.8 s), which cause cardiac signal to alias into lower frequencies. To resolve physiological signals in fMRI datasets, we leveraged fast cross-slice sampling within each TR to hypersample the fMRI signal. A key novelty of this study is the development of a region-specific hypersampling approach, called HyPER (Hypersampling for Physiological signal Extraction in a Region-specific manner). HyPER enhances temporal resolution within coherently pulsating vascular and tissue compartments, including the major cerebral arteries, the superior sagittal sinus (SSS), gray matter (GM), and white matter (WM). This study is structured in three parts: (1) We developed and validated the HyPER approach using fast fMRI from a local dataset in four regions of interest: the major cerebral arteries, SSS, GM, and WM. (2) We applied this approach to the publicly available Human Connectome Project-Aging (HCP-A) dataset (ages 36–90 years), increasing the resolvable frequency by ninefold—from 0.625 Hz to 5.625 Hz—enabling clear separation of cardiac, respiration, and LFO oscillations. (3) We investigated how brain physiological pulsations change with age. Our findings revealed an age-related increase in cardiac and respiratory pulsations across all brain regions, likely reflecting an increased vessel stiffness and reduced dampening of high-frequency pulsations along the vascular network. In contrast, LFO pulsations generally declined with age, suggesting reduced vasomotion in the older brain. In summary, we demonstrated the feasibility and reliability of a region-specific hypersampling technique to resolve physiological pulsations in fMRI. This method can be broadly applied to existing fMRI datasets to uncover hidden physiological pulsations and advance our understanding of brain physiology and disease-related alterations.

Abstract Rationale The immunological and protective role of pneumococcal carriage in healthy adults is not known, but high rates of disease and death in the elderly are associated with low carriage prevalence. Objectives We employed an experimental human pneumococcal carriage model to investigate the immunizing effect of a single carriage episode. Methods Seventy healthy adults were challenged, and of those with carriage, 10 were rechallenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of the first carriage episode. Serum and nasal wash antibody responses were measured before and after each challenge. Measurements and Main Results A total of 29 subjects were experimentally colonized. No subjects were colonized by experimental rechallenge, demonstrating the protective effect of initial carriage against subsequent infection. Carriage increased both mucosal and serum IgG levels to pneumococcal proteins and polysaccharide, resulting in a fourfold increase in opsonophagocytic activity. Importantly, passive transfer of postcarriage sera from colonized subjects conferred 70% protection against lethal challenge by a heterologous strain in a murine model of invasive pneumococcal pneumonia. These levels were significantly higher than the protection conferred by either precarriage sera (30%) or saline (10%). Conclusions Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against recolonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies may be important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.

Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke–exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.

•Brief rest boosts mental clarity, but its effect on neurofluid dynamics is unclear.•Neurofluid dynamics in 5 compartments was studied after 30-min rest using fast fMRI.•30-min rest increased low-frequency oscillations, potentially aiding waste clearance.•Cardiac power decreased post-rest, indicating cerebrovascular relaxation.•Elderly showed smaller changes, suggesting an age-related decline in benefits. Brief eyes-closed rest (e.g., 30 min) during the day promotes rejuvenation and enhances mental clarity. However, its effect on neurofluid dynamics—including cerebral hemodynamics and cerebrospinal fluid (CSF) oscillations—remains largely unexplored. These neurofluid dynamics, driven by low-frequency oscillations (LFOs), respiration, and cardiac pulsation, play a critical role in the brain’s waste clearance and may serve as a key mechanism underlying the cognitive benefits of rest. This study used fast functional MRI (TR=363msec) to assess neurofluid dynamics across three frequency bands in five key regions of interest (ROI): cerebral arteries, superior sagittal sinus, grey matter, white matter, and fourth ventricle CSF. Measurements were taken before and after 30 min of eyes-closed rest in a cohort of 38 participants aged 35–82. After rest, we observed a significant increase in LFO power across all five ROIs, suggesting that enhanced LFO may promote neurofluid clearance and contribute to the rest’s restorative effects. Concurrently, cardiac power significantly decreased across all ROIs, indicating cerebrovascular relaxation, consistent with reduced cardiovascular activity during drowsiness. Lastly, older participants exhibited significantly smaller LFO and cardiac power changes than younger individuals, reflecting an age-related decline in neurofluid modulation that may diminish the benefits of rest. By simultaneously examining arterial, venous, and parenchymal hemodynamics, this study offers a integrated view of how brief rest influences brain pulsations and how these effects change with aging.