High Lifetime Research Articles

Highly Efficient Light-Emitting Diodes based on Self-Assembled Colloidal Quantum Wells.

Nanocrystal-based light-emitting diodes (Nc-LEDs) have immense potential for next-generation high-definition displays and lighting applications. They offer numerous advantages, such as low cost, high luminous efficiency, narrow emission, and long lifetime. However, the external quantum efficiency (EQE) of Nc-LEDs, typically employing isotropic nanocrystals, has been limited by the out-coupling factor. Here we demonstrate efficient, bright, and long lifetime red Nc-LEDs based on anisotropic nanocrystals of colloidal quantum wells (CQWs). Through modification of the substrate's surface properties and control of the interactions among CQWs, we successfully spin-coated a self-assembled layer with an exceptionally high distribution of in-plane transitions dipole moment (TDM) of 95%, resulting in an out-coupling factor of 37%. Our devices exhibit a remarkable peak external quantum efficiency (EQE) of 26.9%, accompanied by a maximum brightness of 55,754cd m-2 and a long operational lifetime (T95 @100cd m-2 ) over 15,000h. These achievements represent a significant advancement compared to previous studies on Nc-LEDs incorporating anisotropic nanocrystals. We expect our work to provide a general self-assembly strategy for enhancing the light extraction efficiency of Nc-LEDs based on anisotropic nanocrystals. This article is protected by copyright. All rights reserved.

Post traumatic stress disorder in African American men exposed to violent trauma

Research has shown strong association between exposures to violence resulting in post traumatic stress symptoms. Despite the high lifetime prevalence of post traumatic stress disorder (PTSD) and exposure to violence among African American men, research outcomes are limited and inconsistent. African American youth who live in low-income urban areas routinely face various contextual specific risks factors that leave them susceptible to loss and trauma in their lifetime resulting in persistent PTSD over time. Personas of resilience found in African American men exposed to chronic violence often mask trauma symptoms raising concerns on the evaluation of PTSD symptomology among African American men as well as the process of resilience and coping methods within this population. Limitations to research include convenience sampling limited to specific cities and exclusion of incarcerated African American men. In addition, there is a lack of longitudinal studies detailing the physiological and psychological course of PTSD and rates of recovery in African Americans. Health care systems and providers must be equipped, informed, and prepared to responding to mental health needs of African American men. The understanding of the expression and presence of PTSD among African American men will result in improvements of healthcare professionals' ability to evaluate, diagnose, and provide treatment for PTSD among this group whose symptoms of trauma may be misinterpreted or overlooked.

Mn4+-doped organometallic hafnium hexafluoride phosphors: Achieving near-unity quantum yield to elevate LED performance

Mn4+-activated fluoride phosphors with high luminous efficacy and short decay lifetimes are essential in realizing high-quality warm white-light-emitting diode (WLED) lighting. In this work, Mn4+-activated narrow-band red (∼630 nm) phosphor [(CH3)4N]2HfF6 was successfully synthesized by introducing an organic cationic group (tetramethylammonium) into the [HfF6]2- system using a mild chemical co-precipitation method. The sample structure was confirmed using various characterization techniques such as scanning electron microscopy, X-ray diffraction and Raman spectroscopy. Powder particles with diameters ranging from 10 to 20 um and double pyramidal structures were prepared by adjusting the anti-solvent temperature to control the crystal growth rate. The investigation of the morphology, structure and photoluminescence properties of Mn4+-doped [(CH3)4N]2HfF6 phosphors at different anti-solvent temperatures deepened our understanding of the correlation between structure and luminescence. Ultimately, phosphors with optimal performance (external quantum efficiency, ∼92.2%, and decay lifetime, ∼3.6 ms) were obtained. The samples were mixed with polydimethylsiloxane organosilicon to prepare a red light-conversion flexible film, and the (TMA)2HfF6:Mn4+ red phosphor and commercially available YAG:Ce3+ yellow-green phosphor was thoroughly mixed with transparent silica to form a stable paste, and then coated on a blue LED bead to prepare warm white LEDs, which significantly optimized the performance of the white LEDs (correlated color temperature, ∼5564 K). These experimental results indicate that the materials prepared by the mild solution method have important applications in the domains of display and lighting.

Sociodemographic and health-related differences in undiagnosed hypertension in the health survey for England 2015–2019: a cross-sectional cohort study

Hypertension is a leading cause of morbidity and mortality worldwide, yet a substantial proportion of cases are undiagnosed. Understanding the scale of undiagnosed hypertension and identifying groups most at risk is important to inform approaches to detection. In this cross-sectional cohort study, we used data from the 2015 to 2019 Health Survey for England, an annual, cross-sectional, nationally representative survey. The survey follows a multi-stage stratified probability sampling design, involving a random sample of primary sampling units based on postcode sectors, followed by a random sample of postal addresses within these units. Within each selected household, all adults (aged ≥16 years) and up to four children, were eligible for participation. For the current study, individuals aged 16 years and over who were not pregnant and had valid blood pressure data were included in the analysis. The primary outcome was undiagnosed hypertension, defined by a measured blood pressure of 140/90mmHg or above but no history of diagnosis. Age-adjusted prevalence of undiagnosed hypertension was estimated across sociodemographic and health-related characteristics, including ethnicity, region, rural-urban classification, relationship status, highest educational qualification, National Statistics Socio-Economic Classification (NS-SEC), Body Mass Index (BMI), self-reported general health, and smoking status. To assess the independent association between undiagnosed hypertension and each characteristic, we fitted a logistic regression model adjusted for sociodemographic factors. The sample included 21,476 individuals, of whom 55.8% were female and 89.3% reported a White ethnic background. An estimated 30.7% (95% confidence interval 29.0-32.4) of men with hypertension and 27.6% (26.1-29.1) of women with hypertension were undiagnosed. Younger age, lower BMI, and better self-reported general health were associated with an increased likelihood of hypertension being undiagnosed for men and women. Living in rural areas and in regions outside of London and the East of England were also associated with an increased likelihood of hypertension being undiagnosed for men, as were being married or in a civil partnership and having higher educational qualifications for women. Hypertension is commonly undiagnosed, and some of the groups that are at the lowest risk of hypertension are the most likely to be undiagnosed. Given the high lifetime risk of hypertension and its strong links with morbidity and mortality, our findings suggest a need for greater awareness of the potential for undiagnosed hypertension, including among those typically considered 'low risk'. Further research is needed to assess the impact of extending hypertension screening to lower-risk groups. None.

Aggressive sexual fantasy frequency outperforms other characteristics in cross-sectionally predicting self-reported sexual aggression in 4 samples.

Aggressive sexual fantasies (ASFs) have consistently been associated with sexual aggression measures. ASF frequency has mostly been used to indicate ASF, but other ASF characteristics may be important to explain the apparent gap between alleged high lifetime prevalence rates of ASF and lower sexual aggression rates-that is, why ASFs are only sometimes put into action. The present study therefore examined whether additional ASF characteristics show associations with sexual aggression measures above and beyond ASF frequency to identify the most relevant ASF characteristics. The present study is based on cross-sectional survey data from 4 independent mostly community samples with 448, 131, 758, and 415 participants to examine whether ASF elaboration, intrusion, preoccupation, context, and consent were associated with self-reported sexual aggression measures beyond ASF frequency. Self-reported sexual aggression measures included presumably consensual and nonconsensual sexual sadism, self-reports on acting on ASF, sexual harassment, use of coercive strategies, and rape proclivity. The results showed positive correlations among all ASF characteristics. ASF frequency was the most consistent and often strongest predictor of sexual aggression across samples and outcome measures. ASF elaboration and/or its interaction with ASF frequency added to this prediction in study 1 but not in study 2. All other ASF characteristics in studies 1 to 4 either did not add to the predictions or yielded results contrary to expectations, mostly suggesting suppressor effects. Sexual medicine and forensic sexology researchers may want to consider ASF frequency in diagnostics and develop and refine interventions to reduce it in cases of clearly elevated levels. The strengths of the present study include considering 4 independent samples as well as a large number of ASF characteristics and sexual aggression measures. Its limitations include the reliance on cross-sectional data and not being able to examine the potential influences of all ASF characteristics in a single model. ASF frequency seems the most valid and reliable indicator of ASF and the most important associate of sexual aggression. It should be considered the main indicator of ASF by future research and in prevention efforts and risk assessment.

Prevalence, correlates, and trends of intimate partner violence against women in Sierra Leone: findings from 2013 and 2019 demographic and health surveys.

Intimate partner violence (IPV) is a globally pervasive public health and medical problem in addition to being a serious violation of women's rights. The two-fold objectives of this study were to compute the lifetime prevalence and correlates of IPV perpetrated by current/former husbands/partners of ever-married women aged 15-49 years using the nationally representative Sierra Leone Demographic and Health Survey (DHS) conducted in 2019; ethnicity-based levels and trends of IPV were also computed using the data from the DHS conducted in 2013 along with the 2019 DHS. Twelve IPV correlates pertaining to socio-demographic, attitudinal, and experiential attributes were analyzed using logistic regression models for bivariate and multivariable analysis. IPV was computed as a composite variable comprising of physical, emotional, and/or sexual IPV. Lifetime prevalence of experiencing any kind of IPV was a staggering 60.81%, whereas emotional, physical, and sexual IPV prevalence were reported by 45.90%, 49.81%, and 8.14% of the respondents, respectively. No ethnicity reported a statistically significant decrease in any type of IPV during the intervening period between the two surveys. Five out of nine ethnicities reported a statistically significant increase in emotional IPV, while few ethnicities reported a statistically significant increase in one or more types of IPV. The high lifetime prevalence of IPV is alarming and points to the need for targeted health promotion campaigns to reverse the tide of IPV in Sierra Leone, including focusing on changes in cultural and ethnicity-based norms and mores to ensure women's human rights are respected and upheld.

Effects of second-stage active phase shifter on the inter-stage refrigeration capacity of a Stirling/pulse tube cryocooler

The Stirling/pulse tube cryocooler (SPC) is one of the most promising cryocoolers for space applications due to its advantages like high efficiency and long lifetime. The second pulse tube stage is coaxial pneumatically coupled in series with the first Stirling stage. The SPC possesses a distinctive capability to dynamically adjust the inter-stage refrigeration capacity by actively controlling the Stirling displacer in the first stage. This enables the SPC to effectively cater to varying heat loads over time. Nevertheless, the investigation into the regulation mechanism of the second-stage phase shifter on inter-stage refrigeration capacity shift is hindered by the presence of the second-stage passive phase shifter. This manuscript proposes an SPC with a second-stage active phase shifter (APS), which can actively control the phase difference between the pressure wave and mass flow at the second-stage hot end of the pulse tube in real time. The effect of the APS phase and amplitude on the inter-stage refrigeration capacity shift is analyzed using the theoretical and numerical model proven by the experiment. The first experimentally reported SPC with a second-stage APS demonstrates a refrigeration capacity of 0.22 W at 20 K plus 3.11 W at 70 K, requiring a compressor electrical power of 220 W. The SPC achieves a no-load minimum temperature of 13.5 K.

A Population-Based Family Case-Control Study of Sun Exposure and Follicular Lymphoma Risk.

Epidemiologic evidence suggests an inverse association between sun exposure and follicular lymphoma risk. We conducted an Australian population-based family case-control study based on 666 cases and 459 controls (288 related, 171 unrelated). Participants completed a lifetime residence and work calendar and recalled outdoor hours on weekdays, weekends, and holidays in the warmer and cooler months at ages 10, 20, 30, and 40 years, and clothing types worn in the warmer months. We used a group-based trajectory modeling approach to identify outdoor hour trajectories over time and examined associations with follicular lymphoma risk using logistic regression. We observed an inverse association between follicular lymphoma risk and several measures of high lifetime sun exposure, particularly intermittent exposure (weekends, holidays). Associations included reduced risk with increasing time outdoors on holidays in the warmer months [highest category OR = 0.56; 95% confidence interval (CI), 0.42-0.76; Ptrend < 0.01], high outdoor hours on weekends in the warmer months (highest category OR = 0.71; 95% CI, 0.52-0.96), and increasing time outdoors in the warmer and cooler months combined (highest category OR = 0.66; 95% CI, 0.50-0.91; Ptrend 0.01). Risk was reduced for high outdoor hour maintainers in the warmer months across the decade years (OR = 0.71; 95% CI, 0.53-0.96). High total and intermittent sun exposure, particularly in the warmer months, may be protective against the development of follicular lymphoma. Although sun exposure is not recommended as a cancer control policy, confirming this association may provide insights regarding the future control of this intractable malignancy.

Long‐Persistent Circularly Polarized Luminescence from a Host‐Guest System Regulated by the Multiple Roles of a Gold(I)‐Carbene Motif

AbstractThe promotion of intersystem crossing (ISC) is critical for achieving a high‐efficiency long‐persistent luminescence (LPL) from organic materials. However, the use of a transition‐metal complex for LPL materials has not been explored because it can also shorten the emission lifetime by accelerating the phosphorescence decay. Here, we report a new class of LPL materials by doping a monovalent Au‐carbene complex into a boron‐embedded molecular host. The donor‐acceptor systems exhibit photoluminescence with both high efficiencies (&gt;57 %) and long lifetimes (ca. 40 ms) at room temperature. It is revealed that the Au atom promotes the population of low‐lying triplet excited states of the host aggregate (T1*) which can be converted into the charge‐transfer (CT) state, thereby resulting in afterglow luminescence. Moreover, the use of a chirality unit on the guest molecule results in the LPL being circularly polarized. This work illustrates that transition‐metal complexes can be used for developing organic afterglow systems by exquisite control over the excited state mechanism.

Long-Persistent Circularly Polarized Luminescence from a Host-Guest System Regulated by the Multiple Roles of a Gold(I)-Carbene Motif.

The promotion of intersystem crossing (ISC) is critical for achieving a high-efficiency long-persistent luminescence (LPL) from organic materials. However, the use of a transition-metal complex for LPL materials has not been explored because it can also shorten the emission lifetime by accelerating the phosphorescence decay. Here, we report a new class of LPL materials by doping a monovalent Au-carbene complex into a boron-embedded molecular host. The donor-acceptor systems exhibit photoluminescence with both high efficiencies (>57 %) and long lifetimes (ca. 40 ms) at room temperature. It is revealed that the Au atom promotes the population of low-lying triplet excited states of the host aggregate (T1 *) which can be converted into the charge-transfer (CT) state, thereby resulting in afterglow luminescence. Moreover, the use of a chirality unit on the guest molecule results in the LPL being circularly polarized. This work illustrates that transition-metal complexes can be used for developing organic afterglow systems by exquisite control over the excited state mechanism.

High Lifetime Blast Exposure Using the Blast Exposure Threshold Survey Is Associated With Worse Warfighter Brain Health Following Mild Traumatic Brain Injury.

The purpose of this study was to extend previous research by examining the relationship between lifetime blast exposure and neurobehavioral functioning after mild TBI (MTBI) by (a) using a comprehensive measure of lifetime blast exposure, and (b) controlling for the influence of post-traumatic stress disorder (PTSD). Participants were 103 United States service members and veterans (SMVs) with a medically documented diagnosis of MTBI, recruited from three military treatment facilities (74.8%) and community-based recruitment initiatives (25.2%, e.g., social media, flyers). Participants completed a battery of neurobehavioral measures 12 or more months post-injury (Neurobehavioral Symptom Inventory, PTSD-Checklist PCLC, TBI-Quality of Life), including the Blast Exposure Threshold Survey (BETS). The sample was classified into two lifetime blast exposure (LBE) groups: High (n = 57) and Low (n = 46) LBE. In addition, the sample was classified into four LBE/PTSD subgroups: High PTSD/High LBE (n = 38); High PTSD/Low LBE (n = 19); Low PTSD/High LBE (n = 19); and Low PTSD/Low LBE (n = 27). The High LBE group had consistently worse scores on all neurobehavioral measures compared with the Low LBE group. When controlling for the influence of PTSD (using ANCOVA), however, only a handful of group differences remained. When comparing measures across the four LBE/PTSD subgroups, in the absence of clinically meaningful PTSD symptoms (i.e., Low PTSD), participants with High LBE had worse scores on the majority of neurobehavioral measures (e.g., post-concussion symptoms, sleep, fatigue). When examining the total number of clinically elevated measures, the High LBE subgroup consistently had a greater number of clinically elevated scores compared with the Low LBE subgroup for the majority of comparisons (i.e., four to 15 or more elevated symptoms). In contrast, in the presence of clinically meaningful PTSD symptoms (i.e., High PTSD), there were no differences between High versus Low LBE subgroups for all measures. When examining the total number of clinically elevated measures, however, there were meaningful differences between High versus Low LBE subgroups for those comparisons that included a high number of clinically elevated scores (i.e., six to 10 or more), but not for a low number of clinically elevated scores (i.e., one to five or more). High LBE, as quantified using a more comprehensive measure than utilized in past research (i.e., BETS), was associated with worse overall neurobehavioral functioning after MTBI. This study extends existing literature showing that lifetime blast exposure, that is largely subconcussive, may negatively impact warfighter brain health and readiness beyond diagnosable brain injury.

Terahertz wave emission with 1.5 μm pump from photoconductive antenna using stacked Er-doped-InAs quantum dot layers with ultrafast carrier relaxation

We fabricated a photoconductive antenna (PCA) with Er-doped InAs quantum dot (QD) layers on a GaAs substrate and demonstrated THz wave generation with 1.5 μm pump. In terahertz time-domain spectroscopy (THz-TDS), PCAs require high mobility and short lifetimes of photocarriers since the carriers need to respond rapidly to optical pulses for broad THz generation and detection with a high time resolution. In this study, to achieve PCA operation at an optical communication wavelength band of 1.5 μm, a substrate for a PCA was fabricated using stacked Er-doped-InAs QD layers. Then, photocurrent measurements were performed to observe optical absorption in the 1.5 μm band. The results indicated the high capability of the PCA for THz wave generation and detection, in fact, which enabled us to generate the THz wave in the 1.5 μm band optical system.

Dual-discriminator Conditional Generative Adversarial Network Optimized with Hybrid Momentum Search Algorithm and Giza Pyramids Construction Algorithm for Cluster-based Routing in WSN Assisted IoT

Wireless sensor network (WSN) efficiently sends and receives the data on the internet of things (IoT) environment. As a large-scale WSN's nodes are powered by batteries, it is essential to create an energy-efficient system to decrease energy consumption and increase the network's lifespan. The existing methods not present effectual cluster head (CH) selection and trust node computation. Therefore, dual-discriminator conditional generative adversarial network optimized with a hybrid Momentum search algorithm and Giza Pyramids Construction algorithm for Cluster Based Routing in WSN Assisted IoT is proposed in this manuscript, for securing data transmission by identifying the optimum CH in the network (DDcGAN-MSA-GPCA-CBR-WSN-IoT). Initially, the proposed method is acting routing process via cluster head. Therefore, Dual-Discriminator conditional Generative Adversarial Network (DDcGAN) is considered to select the CH depending on multi-objective fitness function. The multi-objective fitness function, such as energy, delay, throughput, distance among the nodes, cluster density, capacity, collision, traffic rate, and cluster density. Based on fitness function, CH is selected. After cluster head selection, a malicious node depends on three parameters: trust, delay, and distance. These three parameters are optimized by hyb MSA-GPCA for ideal trust path selection. The proposed DDcGAN-MSA-GPCA-WSN-IoT technique is activated in PYTHON and network simulator (NS2) tool. Its effectiveness is analyzed under performance metrics, such as number of alive nodes, dead nodes, delay, energy consumption, packet delivery ratio, a lifetime of sensor nodes, and total residual energy. The simulation outcomes display that the proposed method attains lower delay, higher packet delivery ratio and high network lifetime when comparing to the existing models.

MXene Lubricated Tribovoltaic Nanogenerator with High Current Output and Long Lifetime

HighlightsSuccessfully solves the key issue of tribovoltaic nanogenerators (TVNGs) lifetime (90,000 cycles) and improves its output current density (754 mA m−2) simultaneously.Conductive polar liquid with MXene as additive is proposed as the dominant factor in enhancing the electrical output performance and durability of TVNG simultaneously.The mechanism of lubricated TVNG with enhanced output performance is explained from the perspective of solution polarity at the first time.Mxene solution exhibits universality in different types of semiconductor systems (Cu and P-type Si, and Cu and N-GaAs as material pairs).

Persistent Room‐Temperature Phosphorescent Triazole Derivatives with High Quantum Yields and Long Lifetimes

AbstractPure organic persistent room‐temperature phosphorescence (p‐RTP) materials have attracted rapidly growing attention due to their unique photophysical properties and wide potential practical applications. However, most of the reported pure organic p‐RTP materials have low quantum yields and short lifetimes, and many p‐RTP compounds contain large π‐conjugated structures, which are difficult and complex to synthesize. Herein, a series of triazole derivatives with efficient p‐RTP emissions is reported. 2H‐1,2,3‐triazole‐4,5‐dicarboxylic acid (TDAc) is first found to exhibit green RTP under 312 nm excitation. Then, a series of ionized products of TDAc and their isomers with red‐shifted RTP emissions are further obtained by ionization of TDAc. Among them, the sodium 2H‐1,2,3‐triazole‐4‐carboxy‐5‐carboxylate can emit RTP with an ultra‐long phosphorescence lifetime (3.25 s) and high photoluminescence (PL) and p‐RTP quantum yields of 31.3% and 14.2%, respectively, as well as mechanorochromic behavior. Experimental results and theoretical calculations prove that strong intra‐/intermolecular interactions including hydrogen bonding and ionic bonding promote the overlap of molecular orbitals to form effective through‐space conjugation (TSC) and greatly stabilize the conformations, thus achieving efficient p‐RTP emissions. This work provides a simple and efficient strategy for designing p‐RTP compounds with high quantum yields.

Thermally stable 3D cross-linked fluorinated polyimide/PVDF-HFP hybrid separator for lithium battery applications

Commercial Celgard 2325 separators suffer from poor flexibility, poor electrolyte wettability, and thermal instability, which can cause internal short circuits and thermal runaway in lithium rechargeable batteries. A novel 3D cross-linked and thermotolerant fluorinated polyimide (PI) / PVDF-HFP (PV) hybrid nanofiber separator rich in polar functional groups was fabricated using an electrospinning technique. PI and PV polymers are joined by a hydrogen bond through their exposed amide (–NH) and fluorinated (-CF) functional groups to build a supramolecular polymer cross-linked system. The separator exhibited high porosity (75 %), outstanding electrolyte uptake ability (775 %), strong mechanical properties (15.7 MPa), excellent thermal stability, and flexibility. As a result, the separator showed excellent Li+-conductivity (3.3 mS cm−1) and high Li+-transference number (tLi+ = 0.7) and maintained a proper-contacted electrolyte/electrode interaction for stable Li plating/stripping. Furthermore, when the PI/PV hybrid separator was applied in anode-free Li-metal batteries (a protocol of Cu/NMC cell), or Li-ion (MCMB /NMC) batteries, the cells achieved a high capacity and long lifetime. Remarkably, the Cu/NMC cell fabricated with a PI/PV hybrid separator is more robust and continues to function even after being heated at a high temperature of 140 °C for 1 h.

NIR FRET Luminescence in Rhenium Complex and Dye Co‐Loaded Polymer Nanoparticles

AbstractPhotoactive transition‐metal complexes are luminophores combining high photostability and long luminescence lifetimes. However, reduced optical performance in aqueous solutions has limited their use in biological systems. Herein, the physicochemical and photophysical properties and bioimaging compatibility of Re diimine complexes and near‐infrared (NIR) emitting Cy5 dyes coencapsulated in polymer nanoparticles (NPs) are investigated. By varying the polymers, NPs with sizes from 20 to 70 nm and encapsulating ≤ 40 wt.% of Re complexes, i.e., ≈11 000 Re complexes per NP, are obtained. The photoluminescence (PL) quantum yields of the Re complexes increase eightfold to ≈50% upon encapsulation (vs 6–7% in acetonitrile), resulting in PL brightness up to 108 m−1 cm−1 and PL lifetimes of 3–4 µs. Coencapsulation of Cy5 yields very bright NIR emission upon Re complex excitation. Very close Re‐to‐Cy5 donor–acceptor distances down to ≤2 nm and FRET efficiencies over 90% are confirmed by PL lifetime measurements. The Re‐Cy5 NPs enter mammalian cells for high‐contrast PL imaging in both visible and NIR. This detailed characterization provides a better understanding of the photophysical properties of the transition‐metal‐dye FRET NPs and presents a vital step toward the efficient design of a new class of bright luminescent NP probes.

Promoting Empathy and Affiliation in Relationships (PEAR) study: protocol for a longitudinal study investigating the development of early childhood callous-unemotional traits

IntroductionChildren with callous-unemotional (CU) traits are at high lifetime risk of antisocial behaviour. Low affiliation (ie, social bonding difficulties) and fearlessness (ie, low threat sensitivity) are proposed risk factors for...

Rational design and experimental evaluation of peptide ligands for the purification of adeno-associated viruses via affinity chromatography.

Adeno-associated viruses (AAVs) have acquired a central role in modern medicine as delivery agents for gene therapies targeting rare diseases. While new AAVs with improved tissue targeting, potency, and safety are being introduced, their biomanufacturing technology is lagging. In particular, the AAV purification pipeline hinges on protein ligands for the affinity-based capture step. While featuring excellent AAV binding capacity and selectivity, these ligands require strong acid (pH <3) elution conditions, which can compromise the product's activity and stability. Additionally, their high cost and limited lifetime has a significant impact on the price tag of AAV-based therapies. Seeking to introduce a more robust and affordable affinity technology, this study introduces a cohort of peptide ligands that (i) mimic the biorecognition activity of the AAV receptor (AAVR) and anti-AAV antibody A20, (ii) enable product elution under near-physiological conditions (pH 6.0), and (iii) grant extended reusability by withstanding multiple regenerations. A20-mimetic CYIHFSGYTNYNPSLKSC and AAVR-mimetic CVIDGSQSTDDDKIC demonstrated excellent capture of serotypes belonging to distinct clones/clades - namely, AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. This corroborates the in silico models documenting their ability to target regions of the viral capsid that are conserved across all serotypes. CVIDGSQSTDDDKIC-Toyopearl resin features binding capacity (≈1014 vp mL-1 ) and product yields (≈60%-80%) on par with commercial adsorbents, and purifies AAV2 from HEK293 and Sf9 cell lysates with high recovery (up to 78%), reduction of host cell proteins (up to 700-fold), and high transduction activity (up to 65%).

Maternal steroids during pregnancy and their associations with exposure to lifetime stressful life events, prenatal stress appraisal and psychological functioning

BackgroundDuring pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied. AimTo assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22–40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334). MethodsSerum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects. ResultsHigh prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [β (95%CI): androgens: −0.13 (−0.25;−0.01); estrogens: −0.16 (−0.31;−0.01)], particularly among women carrying males [androgens: −0.22 (−0.39;−0.05); estrogens: −0.28 (−0.50;−0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite—5alpha-androstan-3alpha,17alpha-diol disulfate—negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males. ConclusionsIncreased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.