Search

Tunable terahertz lasers are desirable in applications in sensing and spectroscopy because many biochemical species have strong spectral fingerprints at terahertz frequencies. Conventionally, the frequency of a laser is tuned in a similar manner to a stringed musical instrument, in which pitch is varied by changing the length of the string (the longitudinal component of the wave vector) and/or its tension (the refractive index). However, such methods are difficult to implement in terahertz semiconductor lasers because of their poor outcoupling efficiencies. Here, we demonstrate a novel tuning mechanism based on a unique ‘wire laser’ device for which the transverse dimension w is ≪λ. Placing a movable object close to the wire laser manipulates a large fraction of the waveguided mode propagating outside the cavity, thereby tuning its resonant frequency. Continuous single-mode redshift and blueshift tuning is demonstrated for the same device by using either a dielectric or metallic movable object. In combination, this enables a frequency tuning of ∼137 GHz (3.6%) from a single laser device at ∼3.8 THz. [ABSTRACT FROM AUTHOR]

Biological aging is the correlated decline of multi-organ system integrity central to the etiology of many age-related diseases. A novel epigenetic measure of biological aging, DunedinPACE, is associated with cognitive dysfunction, incident dementia, and mortality. Here, we tested for associations between DunedinPACE and structural MRI phenotypes in three datasets spanning midlife to advanced age: the Dunedin Study (age=45 years), the Framingham Heart Study Offspring Cohort (mean age=63 years), and the Alzheimer's Disease Neuroimaging Initiative (mean age=75 years). We also tested four additional epigenetic measures of aging: the Horvath clock, the Hannum clock, PhenoAge, and GrimAge. Across all datasets (total N observations=3380; total N individuals=2322), faster DunedinPACE was associated with lower total brain volume, lower hippocampal volume, greater burden of white matter microlesions, and thinner cortex. Across all measures, DunedinPACE and GrimAge had the strongest and most consistent associations with brain phenotypes. Our findings suggest that single timepoint measures of multi-organ decline such as DunedinPACE could be useful for gauging nervous system health. • DunedinPACE is a novel epigenetic measure of multi-organ decline. • DunedinPACE associates with worse structural brain integrity in midlife and old age. • Association effect sizes were consistent across three large datasets. • DunedinPACE captures brain-body aging associations using a single blood sample. [ABSTRACT FROM AUTHOR]

We report a terahertz quantum-cascade vertical-external-cavity surface-emitting laser (QC-VECSEL) based upon a metasurface consisting of an array of gain-loaded resonant patch antennas. Compared with the typical ridge-based metasurfaces previously used for QC-VECSELs, the patch antenna surface can be designed with a much sparser fill factor of gain material, which allows for reduced heat dissipation and improved thermal performance. It also exhibits larger amplification thanks to enhanced interaction between the incident radiation and the QC-gain material. We demonstrate devices that produce several milliwatts of continuous-wave power in a single mode at ∼4.6 THz and dissipate less than 1 W of pump power. Use of different output couplers demonstrates the ability to optimize device performance for either high power or high operating temperature. Maximum demonstrated power is 6.7 mW at 4 K (0.67% wall-plug efficiency, WPE) and 0.8 mW at 77 K (0.06% WPE). Directive output beams are measured throughout with divergence angles of ∼5°. [ABSTRACT FROM AUTHOR]

We report a terahertz quantum-cascade vertical-external-cavity surface-emitting laser (QC-VECSEL) whose output power is scaled up to watt-level by using an amplifying metasurface designed for increased power density. The metasurface is composed of a subwavelength array of metal-metal waveguide antenna-coupled sub-cavities loaded with a terahertz quantum-cascade gain material. Unlike previously demonstrated THz QC-VECSELs, the sub-cavities operate on their third-order lateral modal resonance (TM03), instead of their first-order (TM01) resonance. This results in a metasurface with a higher spatial density of the gain material, leading to an increased output power per metasurface area. In pulsed mode operation, peak THz output powers up to 830 mW at 77 K and 1.35 W at 6 K are observed, while a single-mode spectrum and a low divergence beam pattern are maintained. In addition, piezoelectric control of the cavity length allows approximately 50 GHz of continuous, single-mode tuning without a significant effect on output power or beam quality. [ABSTRACT FROM AUTHOR]

Radiofrequency (RF) injection locking and spectral broadening of a terahertz (THz) quantum‐cascade vertical‐external‐cavity surface‐emitting laser (QC‐VECSEL) is demonstrated. An intracryostat VECSEL focusing cavity design is used to enable continuous‐wave lasing with a cavity length over 30 mm, which corresponds to a round‐trip frequency near 5 GHz. Strong RF current modulation is injected to the QC‐metasurface electrical bias to pull and lock the round‐trip frequency. The injection locking range at various RF injection powers is recorded and compared with the injection locking theory. Moreover, the lasing spectrum broadens from 14 GHz in free‐running mode to a maximum spectral width around 110 GHz with 20 dBm of injected RF power. This experimental setup is suitable for further exploration of active mode‐locking and picosecond pulse generation in THz QC‐VECSELs. [ABSTRACT FROM AUTHOR]

Objectives Individuals with more education are at lower risk of developing multiple, different age-related diseases than their less-educated peers. A reason for this might be that individuals with more education age slower. There are 2 complications in testing this hypothesis. First, there exists no definitive measure of biological aging. Second, shared genetic factors contribute toward both lower educational attainment and the development of age-related diseases. Here, we tested whether the protective effect of educational attainment was associated with the pace of aging after accounting for genetic factors. Methods We examined data from 5 studies together totaling almost 17,000 individuals with European ancestry born in different countries during different historical periods, ranging in age from 16 to 98 years old. To assess the pace of aging, we used DunedinPACE, a DNA methylation algorithm that reflects an individual's rate of aging and predicts age-related decline and Alzheimer's disease and related disorders. To assess genetic factors related to education, we created a polygenic score based on the results of a genome-wide association study of educational attainment. Results Across the 5 studies, and across the life span, higher educational attainment was associated with a slower pace of aging even after accounting for genetic factors (meta-analysis effect size = −0.20; 95% confidence interval [CI]: −0.30 to −0.10; p =.006). Further, this effect persisted after taking into account tobacco smoking (meta-analysis effect size = −0.13; 95% CI: −0.21 to −0.05; p =.01). Discussion These results indicate that higher levels of education have positive effects on the pace of aging, and that the benefits can be realized irrespective of individuals' genetics. [ABSTRACT FROM AUTHOR]

We report the demonstration of a composite right/left-handed (CRLH) metamaterial waveguide for terahertz quantum-cascade (QC) lasers. By incorporating gap capacitors (∼250 nm) in the top metallization of a metal-metal waveguide operating in a higher order lateral mode, we have realized a CRLH transmission line that supports traveling modes with negative effective phase indices (i.e., left-handed or backward-wave propagation). The CRLH metamaterial waveguide is employed as an active leaky-wave antenna for a terahertz QC-laser. Directional single-lobed beams launched in the backwards direction at angles of -4° and -63° were experimentally observed at excitation frequencies 2.59 and 2.48 THz, respectively. [ABSTRACT FROM AUTHOR]

We report continuous wave (cw) operation of a terahertz quantum-cascade vertical-external-cavity surface-emitting laser with an external cavity length of approximately 30 mm, benefited by an intra-cryostat focusing cavity. Compared to previous plano–plano cavities, an off-axis paraboloid mirror is introduced into the external cavity as a focusing element to reduce the diffraction loss and to enable cw lasing using small-area metasurfaces and long cavity lengths. The device shows lasing operation in the cw mode up to 111 K, and cw output power up to 11.5 mW at 77 K (0.5% wall-plug efficiency). A circular, directive beam pattern is collected, and free-running linewidths on the order of tens of kHz are measured over tens of seconds. [ABSTRACT FROM AUTHOR]

An active amplifying metasurface based on a quantum-cascade gain material at 2.7 THz is studied. The metasurface is first evaluated as the active component of an external cavity laser with excellent beam quality and frequency tunability from 2.55–2.8 THz. Amplification and absorption of the metasurface alone are then separately measured at a single frequency using a probe signal from a CO2-pumped gas laser operating at 2.743 THz. The metasurface reflectance vs bias is measured and compared with expectations from non-equilibrium Green's function simulations of the quantum-cascade gain material and FEM simulations of the metasurface reflectance. A peak amplification on the order of 0.3 dB is measured. Design strategies are discussed for increasing single-reflection amplification (upward of 10 dB) and reducing power dissipation. Further increased amplification could be achieved by cascading multiple metasurfaces. [ABSTRACT FROM AUTHOR]

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome). Methods: We used data from the Dunedin Study 1972-1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNAmethylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named Dunedin- PACE, in five additional datasets. Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge. Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience. [ABSTRACT FROM AUTHOR]

We compare the performance of 10 and 5 μm thick metal–metal waveguide terahertz quantum-cascade laser ridges operating around 2.7 THz and based on a 4-well phonon depopulation active region design. Thanks to reduced heat dissipation and lower thermal resistance, the 5 μm thick material shows an 18 K increase in continuous wave operating temperature compared to the 10 μm material, despite a lower maximum pulsed-mode operating temperature and a larger input power density. A maximum continuous wave operating temperature of 129 K is achieved using the 5 μm thick material and a 15 μm wide ridge waveguide, which lased up to 155 K in the pulsed mode. The use of thin active regions is likely to become increasingly important to address the increasing input power density of emerging 2- and 3-well active region designs that show the highest pulsed operating temperatures. [ABSTRACT FROM AUTHOR]

The feasibility of composite right/left-handed (CRLH) metamaterial waveguides based upon graphene plasmons is demonstrated via numerical simulation. Designs are presented that operate in the terahertz frequency range along with their various dimensions. Dispersion relations, radiative and free-carrier losses, and free-carrier based tunability are characterized. Finally, the radiative characteristics are evaluated, along with its feasibility for use as a leaky-wave antenna. While CRLH waveguides are feasible in the terahertz range, their ultimate utility will require precise nanofabrication, and excellent quality graphene to mitigate free-carrier losses. [ABSTRACT FROM AUTHOR]

An amplifying quantum-cascade (QC) metasurface, the key component of the QC vertical-external-cavity surface-emitting-laser (VECSEL), is studied as a function of injected current density using reflection-mode terahertz time domain spectroscopy. Nearly perfect absorption is measured at zero bias, which is associated with the transition from the weak to strong coupling condition between the metasurface resonance and an intersubband transition within the QC material. An increase in reflectance is observed as the device is biased, both due to reduction in intersubband loss and the presence of intersubband gain. Significant phase modulation associated with the metasurface resonance is observed via electrical control, which may be useful for electrical tuning of QC-VECSEL. These results provide insight into the interaction between the intersubband QC-gain material and the metasurface and modify the design rules for QC-VECSELs for both biased and unbiased regions. [ABSTRACT FROM AUTHOR]

To date, terahertz quantum-cascade vertical-external-cavity surface-emitting lasers (QC-VECSELs) have tended to oscillate in only one or two lasing modes at a time. This is due to the fact that the interaction between all of the longitudinal external cavity modes and the QC gain material is mediated through a single metasurface resonance, whose spatial overlap changes little with frequency; this suppresses spatial-hole-burning induced multi-mode operation. In this Letter, a VECSEL external cavity is demonstrated using an output coupler based upon a high-resistivity silicon etalon, which presents a periodic reflectance spectrum that is nearly matched with the external cavity mode spectrum. As the cavity length is varied, a systematic transition between a single/double-mode lasing regime and a multi-mode lasing regime is realized due to the Vernier effect. Up to nine modes lasing simultaneously with a free-spectral-range of approximately 21 GHz is demonstrated. This result provides a path toward the multi-mode operation necessary for eventual frequency comb operation. [ABSTRACT FROM AUTHOR]

Objective: To understand whether genetic risk for attention-deficit/hyperactivity disorder (ADHD) is associated with the course of the disorder across childhood and into young adulthood.Method: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2,232 twins. ADHD was assessed at ages 5, 7, 10, and 12 with mother- and teacher-reports and at age 18 with self-report. Polygenic risk scores (PRSs) were created using a genome-wide association study of ADHD case status. Associations with PRS were examined at multiple points in childhood and longitudinally from early childhood to adolescence. We investigated ADHD PRS and course to young adulthood, as reflected by ADHD remission, persistence, and late onset.Results: Participants with higher ADHD PRSs had increased risk for meeting ADHD diagnostic criteria (odds ratios ranging from 1.17 at age 10 to 1.54 at age 12) and for elevated symptoms at ages 5, 7, 10, and 12. Higher PRS was longitudinally associated with more hyperactivity/impulsivity (incidence rate ratio = 1.18) and inattention (incidence rate ratio = 1.14) from age 5 to age 12. In young adulthood, participants with persistent ADHD exhibited the highest PRS (mean PRS = 0.37), followed by participants with remission (mean PRS = 0.21); both groups had higher PRS than controls (mean PRS = -0.03), but did not significantly differ from one another. Participants with late-onset ADHD did not show elevated PRS for ADHD, depression, alcohol dependence, or marijuana use disorder.Conclusion: Genetic risk scores derived from case-control genome-wide association studies may have relevance not only for incidence of mental health disorders, but also for understanding the longitudinal course of mental health disorders. [ABSTRACT FROM AUTHOR]

Objective: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become "embedded" in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation.Method: The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994-1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime).Results: Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes.Conclusions: Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress. [ABSTRACT FROM AUTHOR]

A previous genome-wide association study (GWAS) of more than 100,000 individuals identified molecular-genetic predictors of educational attainment. We undertook in-depth life-course investigation of the polygenic score derived from this GWAS using the four-decade Dunedin Study (N = 918). There were five main findings. First, polygenic scores predicted adult economic outcomes even after accounting for educational attainments. Second, genes and environments were correlated: Children with higher polygenic scores were born into better-off homes. Third, children's polygenic scores predicted their adult outcomes even when analyses accounted for their social-class origins; social-mobility analysis showed that children with higher polygenic scores were more upwardly mobile than children with lower scores. Fourth, polygenic scores predicted behavior across the life course, from early acquisition of speech and reading skills through geographic mobility and mate choice and on to financial planning for retirement. Fifth, polygenic-score associations were mediated by psychological characteristics, including intelligence, self-control, and interpersonal skill. Effect sizes were small. Factors connecting DNA sequence with life outcomes may provide targets for interventions to promote population-wide positive development. [ABSTRACT FROM AUTHOR]

We report terahertz metamaterial waveguides based on the concept of composite right/left-handed transmission-lines. The waveguides are implemented in a metal-insulator-metal geometry fabricated with spin-coated Benzocyclobutene and contact photolithography. Angle-resolved reflection spectroscopy shows strong resonant absorption features corresponding to both right-handed and left-handed (backward wave) propagating modes within the leaky-wave bandwidth. Tuning of the waveguide dispersion is achieved by varying the effective lumped element series capacitance. The experimental results are in good agreement with full-wave finite element method simulations as well as an intuitive transmission-line circuit model. [ABSTRACT FROM AUTHOR]

Prism coupling and reflection spectroscopy are used to characterize bound modes within composite right/left handed terahertz metamaterial waveguides. The cavity antenna model is used to understand the polarization dependence of the radiative coupling to TM00 and TM01 waveguide modes. Furthermore, the cavity model along with transmission-line theory is used to derive a surface impedance model for a waveguide array metasurface. Qualitative agreement with the experiment is observed, including a mode splitting for p-polarized surface waves at the light line and the existence of s-polarized magnetic spoof surface plasmons. [ABSTRACT FROM AUTHOR]

We derive a density matrix (DM) theory for quantum cascade lasers (QCLs) that describes the influence of scattering on coherences through a generalized scattering superoperator. The theory enables quantitative modeling of QCLs, including localization and tunneling effects, using the well-defined energy eigenstates rather than the ad hoc localized basis states required by most previous DM models. Our microscopic approach to scattering also eliminates the need for phenomenological transition or dephasing rates. We discuss the physical interpretation and numerical implementation of the theory, presenting sets of both energy-resolved and thermally averaged equations, which can be used for detailed or compact device modeling. We illustrate the theory's applications by simulating a high performance resonant-phonon terahertz (THz) QCL design, which cannot be easily or accurately modeled using conventional DM methods. We show that the theory's inclusion of coherences is crucial for describing localization and tunneling effects consistent with experiment. [ABSTRACT FROM AUTHOR]

Ethanol is one of the most widely used drugs in the world. Ethanol induces profound physiological and behavioural responses in invertebrate model organisms, such as Caenorhabditis elegans and Drosophila melanogaster. Lumbriculus variegatus (Annelida, Oligochaete) is an aquatic worm which shows behavioural responses to common drugs and thus is potentially useful in pharmacological research. The effects of ethanol are unknown in this organism. In this study, we examine the effects of acute exposure to ethanol (0-500 mM) on the stereotypical movements and locomotor activity of L. variegatus and examine the concentration- (0-500 mM) and time-dependent (0-210 min) effects of ethanol in L. variegatus. We show that ≥250 mM ethanol reversibly reduced the ability of tactile stimulation to elicit stereotypical movements, namely body reversal and helical swimming and locomotor activity (p < 0.05, N = 8). We also found that 2 min of exposure to ≥250 mM ethanol rapidly induces steady-state hypokinesis (p < 0.05, N = 11) and confirm ethanol absorption into L. variegatus tissues. Additionally, we also observed acute ethanol tolerance after 150 min of exposure to 500 mM ethanol (p < 0.05, N = 24). This study is the first to report the behavioural effects of ethanol in L. variegatus. Our results show that this is a model organism for use in ethanol studies, providing further evidence for its utility in pharmacological research., (© 2024 The Author(s). Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

To understand how aging affects functional decline and increases disease risk, it is necessary to develop accurate and reliable measures of how fast a person is aging. Epigenetic clocks measure aging but require DNA methylation data, which many studies lack. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain MRI: the Dunedin Pace of Aging Calculated from NeuroImaging or DunedinPACNI. Exporting this measure to the Alzheimer's Disease Neuroimaging Initiative and UK Biobank neuroimaging datasets revealed that faster DunedinPACNI predicted participants' cognitive impairment, accelerated brain atrophy, and conversion to diagnosed dementia. Underscoring close links between longitudinal aging of the body and brain, faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases, and mortality in older adults. Furthermore, DunedinPACNI followed the expected socioeconomic health gradient. When compared to brain age gap, an existing MRI aging biomarker, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a "next generation" MRI measure that will be made publicly available to the research community to help accelerate aging research and evaluate the effectiveness of dementia prevention and anti-aging strategies., Competing Interests: CONFLICT OF INTEREST K. Sugden, A. Caspi, and T. E. Moffitt are listed as inventors of DunedinPACE, a Duke University and University of Otago invention licensed to TruDiagnostic for commercial uses; however, the DunedinPACE algorithm is open access for research purposes. All other authors report no conflict of interest.

The effects of optical feedback on a terahertz (THz) quantum-cascade metasurface vertical-external-cavity surface-emitting laser (QC-VECSEL) are investigated via self-mixing. A single-mode 2.80 THz QC-VECSEL operating in continuous-wave is subjected to various optical feedback conditions (i.e., feedback strength, round-trip time, and angular misalignment) while variations in its terminal voltage associated with self-mixing are monitored. Due to its large radiating aperture and near-Gaussian beam shape, we find that the QC-VECSEL is strongly susceptible to optical feedback, which is robust against misalignment of external optics. This, in addition to the use of a high-reflectance flat output coupler, results in high feedback levels associated with multiple round-trips within the external cavity-a phenomenon not typically observed for ridge-waveguide QC-lasers. Thus, a new theoretical model is established to describe self-mixing in the QC-VECSEL. The stability of the device under variable optical feedback conditions is also studied. Any mechanical instabilities of the external cavity (such as vibrations of the output coupler), are enhanced due to feedback and result in low-frequency oscillations of the terminal voltage. The work reveals how the self-mixing response differs for the QC-VECSEL architecture, informs other systems in which optical feedback is unavoidable, and paves the way for QC-VECSEL self-mixing applications.

Design strategies for improving terahertz (THz) quantum cascade lasers (QCLs) in the 5-6 THz range are investigated numerically and experimentally, with the goal of overcoming the degradation in performance that occurs as the laser frequency approaches the Reststrahlen band. Two designs aimed at 5.4 THz were selected: one optimized for lower power dissipation and one optimized for better temperature performance. The active regions exhibited broadband gain, with the strongest modes lasing in the 5.3-5.6 THz range, but with other various modes observed ranging from 4.76 to 6.03 THz. Pulsed and continuous-wave (cw) operation is observed up to temperatures of 117 K and 68 K, respectively. In cw mode, the ridge laser has modes up to 5.71 THz - the highest reported frequency for a THz QCL in cw mode. The waveguide loss associated with the doped contact layers and metallization is identified as a critical limitation to performance above 5 THz., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Genetic inheritance is not the only way parents' genes may affect children. It is also possible that parents' genes are associated with investments into children's development. We examined evidence for links between parental genetics and parental investments, from the prenatal period through to adulthood, using data from six population-based cohorts in the UK, US and New Zealand, together totalling 36,566 parents. Our findings revealed associations between parental genetics-summarized in a genome-wide polygenic score-and parental behaviour across development, from smoking in pregnancy, breastfeeding in infancy, parenting in childhood and adolescence, to leaving a wealth inheritance to adult children. Effect sizes tended to be small at any given time point, ranging from RR = 1.12 (95% confidence interval (95%CI) 1.09, 1.15) to RR = 0.76 (95%CI 0.72, 0.80) during the prenatal period and infancy; β = 0.07 (95%CI 0.04, 0.11) to β = 0.29 (95%CI 0.27, 0.32) in childhood and adolescence, and RR = 1.04 (95%CI 1.01, 1.06) to RR = 1.11 (95%CI 1.07, 1.15) in adulthood. There was evidence for accumulating effects across development, ranging from β = 0.15 (95%CI 0.11, 0.18) to β = 0.23 (95%CI 0.16, 0.29) depending on cohort. Our findings are consistent with the interpretation that parents pass on advantages to offspring not only via direct genetic transmission or purely environmental paths, but also via genetic associations with parental investment from conception to wealth inheritance., (© 2023. The Author(s).)

Optical injection locking of a metasurface quantum-cascade (QC) vertical-external-cavity surface-emitting laser (VECSEL) is demonstrated at 2.5 THz using a Schottky diode frequency multiplier chain as the injection source. The spectral properties of the source are transferred to the laser output with a locked linewidth of ∼1 Hz, as measured by a separate subharmonic diode mixer, and a locking bandwidth of ∼300 MHz is achieved. The large locking range is enabled by the microwatt power levels available from modern diode multipliers. The interplay between the injected signal and feedback from external reflections is studied and demonstrated to increase or decrease the locking bandwidth relative to the classic locking range depending on the phase of the feedback.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10 -10 ). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression r g  = 0.63, insomnia r g  = 0.47), physical health (overweight r g  = 0.19, waist-to-hip ratio r g  = 0.32), smoking (r g  = 0.54), cognitive ability (intelligence r g  = -0.40), educational attainment (years of schooling r g  = -0.46) and reproductive traits (age at first birth r g  = -0.58, father's age at death r g  = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: DNA methylation algorithms are increasingly used to estimate biological aging; however, how these proposed measures of whole-organism biological aging relate to aging in the brain is not known. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Framingham Heart Study (FHS) Offspring Cohort to test the association between blood-based DNA methylation measures of biological aging and cognitive impairment and dementia in older adults., Methods: We tested 3 "generations" of DNA methylation age algorithms (first generation: Horvath and Hannum clocks; second generation: PhenoAge and GrimAge; and third generation: DunedinPACE, Dunedin Pace of Aging Calculated from the Epigenome) against the following measures of cognitive impairment in ADNI: clinical diagnosis of dementia and mild cognitive impairment, scores on Alzheimer disease (AD) / Alzheimer disease and related dementias (ADRD) screening tests (Alzheimer's Disease Assessment Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment), and scores on cognitive tests (Rey Auditory Verbal Learning Test, Logical Memory test, and Trail Making Test). In an independent replication in the FHS Offspring Cohort, we further tested the longitudinal association between the DNA methylation algorithms and the risk of developing dementia., Results: In ADNI ( N = 649 individuals), the first-generation (Horvath and Hannum DNA methylation age clocks) and the second-generation (PhenoAge and GrimAge) DNA methylation measures of aging were not consistently associated with measures of cognitive impairment in older adults. By contrast, a third-generation measure of biological aging, DunedinPACE, was associated with clinical diagnosis of Alzheimer disease (beta [95% CI] = 0.28 [0.08-0.47]), poorer scores on Alzheimer disease/ADRD screening tests (beta [Robust SE] = -0.10 [0.04] to 0.08[0.04]), and cognitive tests (beta [Robust SE] = -0.12 [0.04] to 0.10 [0.03]). The association between faster pace of aging, as measured by DunedinPACE, and risk of developing dementia was confirmed in a longitudinal analysis of the FHS Offspring Cohort ( N = 2,264 individuals, hazard ratio [95% CI] = 1.27 [1.07-1.49])., Discussion: Third-generation blood-based DNA methylation measures of aging could prove valuable for measuring differences between individuals in the rate at which they age and in their risk for cognitive decline, and for evaluating interventions to slow aging., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

We report a terahertz quantum-cascade vertical-external-cavity surface-emitting laser (QC-VECSEL) emitting around 1.9 THz with up to 10% continuous fractional frequency tuning of a single laser mode. The device shows lasing operation in pulsed mode up to 102 K in a high-quality beam, with the maximum output power of 37 mW and slope efficiency of 295 mW/A at 77 K. Challenges for up-scaling the operating wavelength in QC metasurface VECSELs are identified.

Some humans age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between midlife biological aging and indicators of future frailty-risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants' Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years. At age 45 in 2019, participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports., Competing Interests: Competing Interests The authors declare no competing interests.

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.

Developing uncooled photodetectors at midwavelength infrared (MWIR) is critical for various applications including remote sensing, heat seeking, spectroscopy, and more. In this study, we demonstrate room-temperature operation of nanowire-based photodetectors at MWIR composed of vertical selective-area InAsSb nanowire photoabsorber arrays on large bandgap InP substrate with nanoscale plasmonic gratings. We accomplish this by significantly suppressing the nonradiative recombination at the InAsSb nanowire surfaces by introducing ex situ conformal Al 2 O 3 passivation shells. Transient simulations estimate an extremely low surface recombination velocity on the order of 10 3 cm/s. We further achieve room-temperature photoluminescence emission from InAsSb nanowires, spanning the entire MWIR regime from 3 to 5 μm. A dry-etching process is developed to expose only the top nanowire facets for metal contacts, with the sidewalls conformally covered by Al 2 O 3 shells, allowing for a higher internal quantum efficiency. Based on these techniques, we fabricate nanowire photodetectors with an optimized pitch and diameter and demonstrate room-temperature spectral response with MWIR detection signatures up to 3.4 μm. The results of this work indicate that uncooled focal plane arrays at MWIR on low-cost InP substrates can be designed with nanostructured absorbers for highly compact and fully integrated detection platforms.