Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.

The effect of aquaporin-4 mis-localization on Aß deposition in mice.

The reduced clearance of amyloid-ß (Aß) is thought to contribute to the development of the pathology associated with Alzheimer's disease (AD), which is characterized by the deposition of Aß plaques. Previous studies have shown that Aß is cleared via the glymphatic system, a brain-wide network of perivascular pathways that supports the exchange between cerebrospinal fluid and interstitial fluid within the brain. Such exchange is dependent upon the water channel aquaporin-4 (AQP4), localized at astrocytic endfeet. While prior studies have shown that both the loss and mislocalization of AQP4 slow Aß clearance and promote Aß plaque formation, the relative impact of the loss or mislocalization of AQP4 on Aß deposition has never been directly compared. In this study, we evaluated how the deposition of Aß plaques within the 5XFAD mouse line is impacted by either Aqp4 gene deletion or the loss of AQP4 localization in the α-syntrophin (Snta1) knockout mouse. We observed that both the absence (Aqp4 KO) and mislocalization (Snta1 KO) of AQP4 significantly increases the parenchymal Aß plaque and microvascular Aß deposition across the brain, when compared with 5XFAD littermate controls. Further, the mislocalization of AQP4 had a more pronounced impact on Aß plaque deposition than did global Aqp4 gene deletion, perhaps pointing to a key role that mislocalization of perivascular AQP4 plays in AD pathogenesis.

Control of the Bright-Dark Exciton Splitting Using the Lamb Shift in a Two-Dimensional Semiconductor.

We investigate the exciton fine structure in atomically thin WSe_{2}-based van der Waals heterostructures where the density of optical modes at the location of the semiconductor monolayer can be tuned. The energy splitting Δ between the bright and dark exciton is measured by photoluminescence spectroscopy. We demonstrate that Δ can be tuned by a few meV as a result of a significant Lamb shift of the optically active exciton that arises from emission and absorption of virtual photons triggered by the vacuum fluctuations of the electromagnetic field. We also measure strong variations of the bright exciton radiative linewidth as a result of the Purcell effect. All these experimental results illustrate the strong sensitivity of the excitons to local vacuum field fluctuations. We find a very good agreement with a model that demonstrates the equivalence, for our system, of a classical electrodynamical transfer matrix formalism and quantum-electrodynamical approach. The bright-dark splitting control we demonstrate here in the weak light-matter coupling regime should apply to any semiconductor structures.

Optically Active Spin Defects in Few-Layer Thick Hexagonal Boron Nitride.

Optically active spin defects in hexagonal boron nitride (hBN) are promising quantum systems for the design of two-dimensional quantum sensing units offering optimal proximity to the sample being probed. In this Letter, we first demonstrate that the electron spin resonance frequencies of boron vacancy centers (V_{B}^{-}) can be detected optically in the limit of few-atomic-layer thick hBN flakes despite the nanoscale proximity of the crystal surface that often leads to a degradation of the stability of solid-state spin defects. We then analyze the variations of the electronic spin properties of V_{B}^{-} centers with the hBN thickness with a focus on (i) the zero-field splitting parameters, (ii) the optically induced spin polarization rate and (iii) the longitudinal spin relaxation time. This Letter provides important insights into the properties of V_{B}^{-} centers embedded in ultrathin hBN flakes, which are valuable for future developments of foil-based quantum sensing technologies.

Isotopic Control of the Boron-Vacancy Spin Defect in Hexagonal Boron Nitride.

We report on electron spin resonance (ESR) spectroscopy of boron-vacancy (V_{B}^{-}) centers hosted in isotopically engineered hexagonal boron nitride (hBN) crystals. We first show that isotopic purification of hBN with ^{15}N yields a simplified and well-resolved hyperfine structure of V_{B}^{-} centers, while purification with ^{10}B leads to narrower ESR linewidths. These results establish isotopically purified h^{10}B^{15}N crystals as the optimal host material for future use of V_{B}^{-} spin defects in quantum technologies. Capitalizing on these findings, we then demonstrate optically induced polarization of ^{15}N nuclei in h^{10}B^{15}N, whose mechanism relies on electron-nuclear spin mixing in the V_{B}^{-} ground state. This work opens up new prospects for future developments of spin-based quantum sensors and simulators on a two-dimensional material platform.

Optical Detection of Long Electron Spin Transport Lengths in a Monolayer Semiconductor.

Using a spatially resolved optical pump-probe experiment, we measure the lateral transport of spin-valley polarized electrons over very long distances (tens of micrometers) in a single WSe_{2} monolayer. By locally pumping the Fermi sea of 2D electrons to a high degree of spin-valley polarization (up to 75%) using circularly polarized light, the lateral diffusion of the electron polarization can be mapped out via the photoluminescence induced by a spatially separated and linearly polarized probe laser. Up to 25% spin-valley polarization is observed at pump-probe separations up to 20 µm. Characteristic spin-valley diffusion lengths of 18±3 µm are revealed at low temperatures. The dependence on temperature, pump helicity, pump intensity, and electron density highlight the key roles played by spin relaxation time and pumping efficiency on polarized electron transport in monolayer semiconductors possessing spin-valley locking.

Measurement of Conduction and Valence Bands g-Factors in a Transition Metal Dichalcogenide Monolayer.

The electron valley and spin degree of freedom in monolayer transition-metal dichalcogenides can be manipulated in optical and transport measurements performed in magnetic fields. The key parameter for determining the Zeeman splitting, namely, the separate contribution of the electron and hole g factor, is inaccessible in most measurements. Here we present an original method that gives access to the respective contribution of the conduction and valence band to the measured Zeeman splitting. It exploits the optical selection rules of exciton complexes, in particular the ones involving intervalley phonons, avoiding strong renormalization effects that compromise single particle g-factor determination in transport experiments. These studies yield a direct determination of single band g factors. We measure g_{c1}=0.86±0.1, g_{c2}=3.84±0.1 for the bottom (top) conduction bands and g_{v}=6.1±0.1 for the valence band of monolayer WSe_{2}. These measurements are helpful for quantitative interpretation of optical and transport measurements performed in magnetic fields. In addition, the measured g factors are valuable input parameters for optimizing band structure calculations of these 2D materials.

Control of the Exciton Radiative Lifetime in van der Waals Heterostructures.

Optical properties of atomically thin transition metal dichalcogenides are controlled by robust excitons characterized by a very large oscillator strengths. Encapsulation of monolayers such as MoSe_{2} in hexagonal boron nitride (hBN) yields narrow optical transitions approaching the homogenous exciton linewidth. We demonstrate that the exciton radiative rate in these van der Waals heterostructures can be tailored by a simple change of the hBN encapsulation layer thickness as a consequence of the Purcell effect. The time-resolved photoluminescence measurements show that the neutral exciton spontaneous emission time can be tuned by one order of magnitude depending on the thickness of the surrounding hBN layers. The inhibition of the radiative recombination can yield spontaneous emission time up to 10 ps. These results are in very good agreement with the calculated recombination rate in the weak exciton-photon coupling regime. The analysis shows that we are also able to observe a sizable enhancement of the exciton radiative decay rate. Understanding the role of these electrodynamical effects allows us to elucidate the complex dynamics of relaxation and recombination for both neutral and charged excitons.

Characteristics of Frequent Users of Emergency Medical Services in Singapore.

OBJECTIVES: This study aims to describe frequent users of Emergency Medical Services (EMS) conveyed to a Singapore tertiary hospital, focusing on a comparison between younger users (age <65) and older users in diagnoses and admission rates. METHODS: All patients conveyed by EMS to a tertiary hospital 4 times or more over a 1-year period in 2015 had their EMS ambulance charts and Emergency Department (ED) electronic records retrospectively analyzed (n = 243), with admission the primary outcome. RESULTS: The 243 frequent users were analyzed with a combined total of 1,705 visits, out of a total of 10,183 patients with 12,839 visits conveyed by EMS to Singapore General Hospital (SGH) in 2015. Younger frequent users (<65 years age) were found to be predominantly male (79.6%, p = 0.001) and were on average responsible for more visits than elderly frequent users (8.6 vs. 5.7, p = 0.004). Medical co-morbidities were significantly more prevalent in older users. Younger frequent users were more likely to be smokers (60.2% vs. 22.3%), heavy drinkers (51.3% vs. 8.5%), substance abusers (12.4% vs. 0.8%), and bad debtors (49.6% vs. 20.0%, p < 0.001). A larger proportion presented with altered mental states (11.7% vs. 5.4%, p < 0.001) and alcohol related diagnoses (34.7% vs. 5.3%, p < 0.001). Many were picked up from public areas (45.5% vs. 19.6%, p < 0.001), and had lower acuity triage scores at both EMS (p < 0.001) and ED (p = 0.001). They had lower admission rates (40.5% vs. 78.7%, p < 0.001) and shorter length of stay (4.3 vs. 5.9 days, p < 0.001). Univariable and multivariable analysis showed alcohol related diagnoses, history of alcohol abuse and lower triage scores were less likely to require admissions. CONCLUSION: Frequent EMS users consume a disproportionate amount of healthcare resources. Two broad subgroups of patients were identified: younger patients with social issues and older patients with multiple medical conditions. EMS usage by older patients was significantly associated with higher rates of admission.

Gate-Controlled Spin-Valley Locking of Resident Carriers in WSe_{2} Monolayers.

Using time-resolved Kerr rotation, we measure the spin-valley dynamics of resident electrons and holes in single charge-tunable monolayers of the archetypal transition-metal dichalcogenide (TMD) semiconductor WSe_{2}. In the n-type regime, we observe long (∼130 ns) polarization relaxation of electrons that is sensitive to in-plane magnetic fields B_{y}, indicating spin relaxation. In marked contrast, extraordinarily long (∼2 µs) polarization relaxation of holes is revealed in the p-type regime, which is unaffected by B_{y}, directly confirming long-standing expectations of strong spin-valley locking of holes in the valence band of monolayer TMDs. Supported by continuous-wave Kerr spectroscopy and Hanle measurements, these studies provide a unified picture of carrier polarization dynamics in monolayer TMDs, which can guide design principles for future valleytronic devices.

In-Plane Propagation of Light in Transition Metal Dichalcogenide Monolayers: Optical Selection Rules.

The optical selection rules for interband transitions in WSe_{2}, WS_{2}, and MoSe_{2} transition metal dichalcogenide monolayers are investigated by polarization-resolved photoluminescence experiments with a signal collection from the sample edge. These measurements reveal a strong polarization dependence of the emission lines. We see clear signatures of the emitted light with the electric field oriented perpendicular to the monolayer plane, corresponding to an interband optical transition forbidden at normal incidence used in standard optical spectroscopy measurements. The experimental results are in agreement with the optical selection rules deduced from group theory analysis, highlighting the key role played by the different symmetries of the conduction and valence bands split by the spin-orbit interaction. These studies yield a direct determination of the bright-dark exciton splitting, for which we measure 40±1 meV and 55±2 meV in WSe_{2} and WS_{2} monolayer, respectively.

Control of Exciton Valley Coherence in Transition Metal Dichalcogenide Monolayers.

The direct gap interband transitions in transition metal dichalcogenide monolayers are governed by chiral optical selection rules. Determined by laser helicity, optical transitions in either the K^{+} or K^{-} valley in momentum space are induced. Linearly polarized laser excitation prepares a coherent superposition of valley states. Here, we demonstrate the control of the exciton valley coherence in monolayer WSe_{2} by tuning the applied magnetic field perpendicular to the monolayer plane. We show rotation of this coherent superposition of valley states by angles as large as 30° in applied fields up to 9 T. This exciton valley coherence control on the ps time scale could be an important step towards complete control of qubits based on the valley degree of freedom.

Double resonant Raman scattering and valley coherence generation in monolayer WSe_{2}.

The electronic states at the direct band gap of monolayer transition metal dichalcogenides such as WSe_{2} at the K^{+} and K^{-} valleys are related by time reversal and may be viewed as pseudospins. The corresponding optical interband transitions are governed by robust excitons. Excitation with linearly polarized light yields the coherent superposition of exciton pseudospin states, referred to as coherent valley states. Here, we uncover how and why valley coherence can be generated efficiently. In double resonant Raman spectroscopy, we show that the optically generated 2s exciton state differs from the 1s state by exactly the energy of the combination of several prominent phonons. Superimposed on the exciton photoluminescence (PL), we observe the double resonant Raman signal. This spectrally narrow peak shifts with the excitation laser energy as incoming photons match the 2s and outgoing photons the 1s exciton transition. The multiphonon resonance has important consequences: following linearly polarized excitation of the 2s exciton, a superposition of valley states is efficiently transferred from the 2s to 1s state. This explains the high degree of valley coherence measured for the 1s exciton PL.

Giant enhancement of the optical second-harmonic emission of WSe(2) monolayers by laser excitation at exciton resonances.

We show that the light-matter interaction in monolayer WSe_{2} is strongly enhanced when the incoming electromagnetic wave is in resonance with the energy of the exciton states of strongly Coulomb bound electron-hole pairs below the electronic band gap. We perform second harmonic generation (SHG) spectroscopy as a function of laser energy and polarization at T=4 K. At the exciton resonance energies we record an enhancement by up to 3 orders of magnitude of the SHG efficiency, due to the unusual combination of electric dipole and magnetic dipole transitions. The energy and parity of the exciton states showing the strong resonance effects are identified in 1- and 2-photon photoluminescence excitation experiments, corroborated by first principles calculations. Targeting the identified exciton states in resonant 2-photon excitation allows us to maximize k-valley coherence and polarization.

Carrier and polarization dynamics in monolayer MoS2.

In monolayer MoS2, optical transitions across the direct band gap are governed by chiral selection rules, allowing optical valley initialization. In time-resolved photoluminescence (PL) experiments, we find that both the polarization and emission dynamics do not change from 4 to 300 K within our time resolution. We measure a high polarization and show that under pulsed excitation the emission polarization significantly decreases with increasing laser power. We find a fast exciton emission decay time on the order of 4 ps. The absence of a clear PL polarization decay within our time resolution suggests that the initially injected polarization dominates the steady-state PL polarization. The observed decrease of the initial polarization with increasing pump photon energy hints at a possible ultrafast intervalley relaxation beyond the experimental ps time resolution. By compensating the temperature-induced change in band gap energy with the excitation laser energy, an emission polarization of 40% is recovered at 300 K, close to the maximum emission polarization for this sample at 4 K.

Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus.

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e') velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44 ± 10 years; mean disease duration 14 ± 6 years). About 61 % of patients had normal diastolic function (E/e' ≤ 8), and 5 % of patients had definite diastolic dysfunction with E/e' > 13 (mean 7.1 ± 2.9). FMD% was associated with E/e' (regression coefficient ß = -0.35; 95 % CI -0.62 to -0.08; p = 0.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.

Instability in longitudinal sleep duration predicts cognitive impairment in aged participants of the Seattle Longitudinal Study.

Importance: Sleep disturbances and clinical sleep disorders are associated with all-cause dementia and neurodegenerative conditions. It remains unclear how longitudinal changes in sleep impact the incidence of cognitive impairment. Objective: To evaluate how longitudinal sleep patterns contribute to age-related changes in cognitive function in healthy adults. Design Setting Participants: This study utilizes retrospective longitudinal analyses of a community-based study within Seattle, evaluating self-reported sleep (1993-2012) and cognitive performance (1997-2020) in aged adults. Main Outcomes and Measures: The main outcome is cognitive impairment as defined by sub-threshold performance on 2 of 4 neuropsychological batteries: Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Trail Making Test, and Wechsler Adult Intelligent Scale (Revised). Sleep duration was defined through self-report of 'average nightly sleep duration over the last week' and assessed longitudinally. Median sleep duration, change in sleep duration (slope), variability in sleep duration (standard deviation, Sleep Variability), and sleep phenotype ("Short Sleep" median ≤7hrs.; "Medium Sleep" median = 7hrs; "Long Sleep" median ≥7hrs.). Results: A total of 822 individuals (mean age of 76.2 years [11.8]; 466 women [56.7%]; 216 APOE allele positive [26.3%]) were included in the study. Analysis using a Cox Proportional Hazard Regression model (concordance 0.70) showed that increased Sleep Variability (95% CI [1.27,3.86]) was significantly associated with the incidence of cognitive impairment. Further analysis using linear regression prediction analysis (R2=0.201, F (10, 168)=6.010, p=2.67E-07) showed that high Sleep Variability (ß=0.3491; p=0.048) was a significant predictor of cognitive impairment over a 10-year period. Conclusions and Relevance: High variability in longitudinal sleep duration was significantly associated with the incidence of cognitive impairment and predictive of decline in cognitive performance ten years later. These data highlight that instability in longitudinal sleep duration may contribute to age-related cognitive decline.

Longitudinal Sleep Patterns and Cognitive Impairment in Older Adults.

Importance: Sleep disturbances and clinical sleep disorders are associated with all-cause dementia and neurodegenerative conditions, but it remains unclear how longitudinal changes in sleep impact the incidence of cognitive impairment. Objective: To evaluate the association of longitudinal sleep patterns with age-related changes in cognitive function in healthy older adults. Design, Setting, and Participants: This cross-sectional study is a retrospective longitudinal analyses of the Seattle Longitudinal Study (SLS), which evaluated self-reported sleep duration (1993-2012) and cognitive performance (1997-2020) in older adults. Participants within the SLS were enrolled as part of a community-based cohort from the Group Health Cooperative of Puget Sound and Health Maintenance Organization of Washington between 1956 and 2020. Data analysis was performed from September 2020 to May 2023. Main Outcomes and Measures: The main outcome for this study was cognitive impairment, as defined by subthreshold performance on both the Mini-Mental State Examination and the Mattis Dementia Rating Scale. Sleep duration was defined by self-report of median nightly sleep duration over the last week and was assessed longitudinally over multiple time points. Median sleep duration, sleep phenotype (short sleep, median ≤7 hours; medium sleep, median = 7 hour; long sleep, median ≥7 hours), change in sleep duration (slope), and variability in sleep duration (SD of median sleep duration, or sleep variability) were evaluated. Results: Of the participants enrolled in SLS, only 1104 participants who were administered both the Health Behavior Questionnaire and the neuropsychologic battery were included for analysis in this study. A total of 826 individuals (mean [SD] age, 76.3 [11.8] years; 468 women [56.7%]; 217 apolipoprotein E ε4 allele carriers [26.3%]) had complete demographic information and were included in the study. Analysis using a Cox proportional hazard regression model (concordance, 0.76) showed that status as a short sleeper (hazard ratio, 3.67; 95% CI, 1.59-8.50) and higher sleep variability (hazard ratio, 3.06; 95% CI, 1.14-5.49) were significantly associated with the incidence of cognitive impairment. Conclusions and Relevance: In this community-based longitudinal study of the association between sleep patterns and cognitive performance, the short sleep phenotype was significantly associated with impaired cognitive performance. Furthermore, high sleep variability in longitudinal sleep duration was significantly associated with the incidence of cognitive impairment, highlighting the possibility that instability in sleep duration over long periods of time may impact cognitive decline in older adults.

Surfactant-free CZTS nanoparticles as building blocks for low-cost solar cell absorbers.

A process route for the fabrication of solvent-redispersible, surfactant-free Cu2ZnSnS4 (CZTS) nanoparticles has been designed with the objective to have the benefit of a simple sulfide source which advantageously acts as (i) a complexing agent inhibiting crystallite growth, (ii) a surface additive providing redispersion in low ionic strength polar solvents and (iii) a transient ligand easily replaced by an carbon-free surface additive. This multifunctional use of the sulfide source has been achieved through a fine tuning of ((Cu²âº)(a)(Zn²âº)(b)(Sn4⁺)(c)(Tu)(d)(OH⁻)(e))(t⁺), Tu = thiourea) oligomers, leading after temperature polycondensation and S²â» exchange to highly concentrated (c > 100 g l⁻¹), stable, ethanolic CZTS dispersions. The good electronic properties and low-defect concentration of the sintered, crack-free CZTSe films resulting from these building blocks was shown by photoluminescence investigation, making these building blocks interesting for low-cost, high-performance CZTSe solar cells.

Full electrical control of the electron spin relaxation in GaAs quantum wells.

The electron spin dynamics in (111)-oriented GaAs/AlGaAs quantum wells is studied by time-resolved photoluminescence spectroscopy. By applying an external electric field of 50 kV/cm a two-order of magnitude increase of the spin relaxation time can be observed reaching values larger than 30 ns; this is a consequence of the electric field tuning of the spin-orbit conduction band splitting which can almost vanish when the Rashba term compensates exactly the Dresselhaus one. The measurements under a transverse magnetic field demonstrate that the electron spin relaxation time for the three space directions can be tuned simultaneously with the applied electric field.