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While metabolic disorders such as obesity and diabetes are costly and deadly to the current population, they are also extremely detrimental to the next generation. Much of the current literature focuses on the negative impact of poor maternal choices on offspring disease, while there is little work examining maternal behaviors that may improve offspring health. Research has shown that voluntary maternal exercise in mouse models improves metabolic function in offspring. In this study, we hypothesized that controlled maternal exercise in a mouse model will effect positive change on offspring obesity and glucose homeostasis. Female mice were separated into three groups: home cage, sedentary, and exercise. The sedentary home cage group was not removed from the home cage, while the sedentary wheel group was removed from the cage and placed in an immobile wheel apparatus. The exercise group was removed from the home cage and run on the same wheel apparatus but with the motor activated at 5–10 m/min for 1 h/d prior to and during pregnancy. Offspring were subjected to oral glucose tolerance testing and body composition analysis. There was no significant difference in offspring glucose tolerance or body composition as a consequence of the maternal exercise intervention compared to the sedentary wheel group. There were no marked negative consequences of the maternal controlled exercise intervention. Further research should clarify the potential advantages of the controlled exercise model and improve experimental techniques to facilitate translation of this research to human applications.

To evaluate the exploratory time to exceed pre-randomization seizure count (T-PSC) in the determination of efficacy of adjunctive perampanel in participants with primary generalized tonic-clonic (PGTC) seizures in generalized-onset epilepsy.In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743), participants ≥12 years of age with treatment-resistant idiopathic generalized epilepsy were randomized to receive placebo or adjunctive perampanel (≤8 mg/day) across a 17-week double-blind treatment phase (4-week titration; 13-week maintenance). We evaluated the pre-planned exploratory end point of the T-PSC using a Kaplan-Meier analysis. We also re-evaluated the correspondence of the primary end points of median percent seizure frequency change (MPC) and 50% responder rate (50RR) calculated at T-PSC and at the end of the trial.The exploratory end point of median T-PSC on placebo was 43 days and120 days on perampanel (log-rank p .001). The primary end points calculated at T-PSC did not differ significantly from the end points at the end of the trial (MPC -31% vs -42% at T-PSC; 50RR 32% vs 51% at T-PSC). After T-PSC was reached, participants had a median (interquartile range) of 5 (3-13) additional seizures on placebo and 5 (2-10) on perampanel.The exploratory end point of T-PSC demonstrated the effectiveness of perampanel despite a shorter duration of monitoring. The seizures that occurred after T-PSC did not influence the conclusions of the trial; therefore, T-PSC may be a viable alternative to traditional trial end points that reduces the risk to participants.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphate flame retardant. The primary TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), is detectable in the urine of over 90 % of Americans. Epidemiological studies show sex-specific associations between urinary BDCPP levels and metabolic syndrome, which is an established risk factor for type 2 diabetes, heart disease, and stroke. We used a mouse model to determine whether TDCPP exposure disrupts glucose homeostasis. Six-week old male and female C57BL/6J mice were given ad libitum access to diets containing vehicle (0.1 % DMSO) and TDCPP resulting in the following treatment groups: 0 mg/kg/day, 0.02 mg/kg/day, 1 mg/kg/day, or 100 mg/kg/day. After being on the experimental diet for five weeks without interruption, body composition was analyzed, glucose and insulin tolerance tests were performed, and fasting glucose and insulin levels were quantified. TDCPP at 100 mg/kg/day caused male sex-specific adiposity, fasting hyperglycemia, and insulin resistance. TDCPP-induced modulation of nuclear receptor activation was investigated using an in vitro screen to identify potential mechanisms of metabolic disruption. TDCPP activated farnesoid X receptor (FXR) and pregnane X receptor (PXR), and inhibited the androgen receptor (AR). PXR target genes, but not FXR target genes, were upregulated in livers from mice exposed to 100 mg TDCPP/kg/day. Interestingly, PXR target genes were differentially expressed in livers from both males and females. It remains to be determined whether TDCPP-induced metabolic disruption occurs via modulation of nuclear receptor activity. Taken together, these studies build upon the association of TDCPP exposure and metabolic syndrome in humans by identifying sex-specific effects of TDCPP on glucose homeostasis in mice.

Background: Acute kidney injury remains a common complication with a poor prognosis, and is a significant predictor of mortality in cirrhosis patients. We aimed to determine the percentage of acute kidney injury in decompensated cirrhosis patients and evaluate the treatment results of acute kidney injury as well as several factors related to the mortality of decompensated cirrhosis patients. Methods: A prospective study was conducted on decompensated cirrhosis patients in Can Tho City, Vietnam, from 2019 to 2020. Decompensated cirrhosis patients were found to have acute kidney injury on admission by a blood creatinine test. They were treated according to ICA 2015 standards, after which they were monitored and evaluated for treatment outcomes during hospitalization. Results: Of 250 decompensated cirrhosis patients, 64 (25.6%) had acute kidney injury and 37.5% died. Several factors were associated with mortality in decompensated cirrhosis patients, such as Child–Pugh C (p = 0.02; OR = 3, 95% CI 1.5–6.3), acute kidney injury (p < 0.0001; OR = 9.5, 95% CI 4.3–21.1), hyponatremia (p = 0.01; OR = 2.5, 95% CI 1.2–5.1), elevated total bilirubin > 51 µmol/L (p = 0.03; OR = 2.2, 95% CI 1.1–4.6), and prothrombin < 70% (p = 0.03; OR = 6.8, 95% CI 1–51.6). Hypoalbuminemia was unrelated to mortality in these patients (p = 0.8; OR = 1.2, 95% CI 0.5–2.7), but gastrointestinal bleeding significantly increased mortality in these patients up to 2.3 times (p = 0.03; OR = 2.3, 95% CI 1.1–4.9). Three independent factors regarding mortality in decompensated cirrhosis patients included acute kidney injury, hepatic encephalopathy, and gastrointestinal bleeding. The rate of acute kidney injury in patients with decompensated cirrhosis was 25.6%; the mortality rate was 37.5%. Conclusions: Acute kidney injury was a valuable predictor of mortality in Vietnamese patients with decompensated cirrhosis.

Intravenous (IV) drug administration enables treatment of epilepsy when oral administration is temporarily not feasible. Perampanel is a once-daily antiseizure medication currently available as oral formulations. Study 050 (NCT03376997) was an open-label, randomized, single-dose, crossover study to evaluate the interchangeability of oral and IV perampanel in healthy subjects (N = 48). Bioequivalence of single 12-mg doses of IV (30-, 60-, or 90-minute infusion) and oral perampanel, ≥6 weeks apart, was assessed. Analyses indicated bioequivalence of area under the plasma concentration-time curve extrapolated to infinity for 30- and 60-minute IV infusions and oral perampanel doses (geometric mean ratio [90% confidence interval], 0.93 [0.84-1.02] and 1.03 [0.97-1.09], respectively); however, IV maximum observed drug concentration (C

BackgroundWe report data from three Phase IV, observational studies (Studies 506 [US;NCT03208660], 508 [India;NCT03836924] and 501 [Italy;NCT04257604]), which assessed real-world safety and efficacy of adjunctive perampanel across different regions.MethodsStudy 506 included patients with any seizure type. Studies 508/501 included patients with focal- onset seizures.Endpoints included: retention rate (Studies 506/501), median percent reduction in seizure frequency/28 days, seizure-freedom rates and safety.ResultsIn Study 506, the 12-month retention rate was 58.5% (n=876/1498). At Months 10–12, the median percent reduction in seizure frequency/28 days was 75.0% (n=123) and the seizure-freedom rate was 30.9% (n=38/123). In Study 508, the 6-month median percent reduction in seizure frequency/28 days was 100.0% (n=174) and seizure-freedom rate was 49.4% (n=86/174). In Study 501, the 6-month median percent reduction in seizure frequency/28 days, retention rate and seizure-freedom rate were 55.4% (n=198), 72.6% (n=170/234) and 18.0% (n=36/200), respectively. Treatment-emergent adverse events occurred in 704/1703 (41.3%; Study 506), 36/199 (18.1%; Study 508) and 132/234 (56.4%; Study 501) patients; the most common was dizziness/vertigo.ConclusionsPerampanel is efficacious and well tolerated during real-world use regardless of geographi- cal region; no unexpected safety signals emerged.FundingEisai Inc., Eisai Pharmaceuticals India Pvt., Ltd., and Eisai s.r.l.

Knowledge related to the biology of inborn errors of immunity and associated laboratory testing methods continues to expand at a tremendous rate. Despite this, many patients with inborn errors of immunity suffer for prolonged periods of time before identification of their underlying condition, thereby delaying appropriate care. Understanding that test selection and optimal evaluation for patients with recurrent infections or unusual patterns of inflammation can be unclear, we present a document that distills relevant clinical features of immunologic disease due to inborn errors of immunity and related appropriate and available test options. This document is intended to serve the practicing clinical immunologist and, in turn, patients by describing best available test options for initial and expanded immunologic evaluations across the disease spectrum. Our goal is to demystify the process of evaluating patients with suspected immune dysfunction and to enable more rapid and accurate diagnosis of such individuals.

Cadmium exposure is ubiquitous and has been linked to diseases including cancers and reproductive defects. Since cadmium is nonmutagenic, it is thought to exert its gene dysregulatory effects through epigenetic reprogramming. Several studies have implicated germline exposure to cadmium in developmental reprogramming. However, most of these studies have focused on maternal exposure, while the impact on sperm fertility and disease susceptibility has received less attention. In this study, we used reduced representation bisulfite sequencing to comprehensively investigate the impact of chronic cadmium exposure on mouse spermatozoa DNA methylation. Adult male C57BL/J6 mice were provided water with or without cadmium chloride for 9 weeks. Sperm, testes, liver, and kidney tissues were collected at the end of the treatment period. Cadmium exposure was confirmed through gene expression analysis of metallothionein-1 and 2, 2 well-known cadmium-induced genes. Analysis of sperm DNA methylation changes revealed 1788 differentially methylated sites present at regulatory regions in sperm of mice exposed to cadmium compared with vehicle (control) mice. Furthermore, most of these differential methylation changes positively correlated with changes in gene expression at both the transcription initiation stage as well as the splicing levels. Interestingly, the genes targeted by cadmium exposure are involved in several critical developmental processes. Our results present a comprehensive analysis of the sperm methylome in response to chronic cadmium exposure. These data, therefore, highlight a foundational framework to study gene expression patterns that may affect fertility in the exposed individual as well as their offspring, through paternal inheritance.

Purpose This post hoc analysis assessed the effects of adjunctive perampanel on myoclonic and absence seizure outcomes in patients (aged ≥12 years) with idiopathic generalized epilepsy (IGE) and generalized tonic-clonic seizures during the double-blind (up to 8 mg/day) and open-label extension (OLEx; up to 12 mg/day) phases of Study 332. Methods Patients experiencing myoclonic and/or absence seizures during study baseline were included. Assessments for myoclonic and absence seizures included: median percent change in seizure frequency, number of seizure days and seizure-free days (all per 28 days), 50 % and 75 % responder rates, seizure-freedom rates, seizure worsening, and monitoring of treatment-emergent adverse events (TEAEs). Results During the double-blind phase, myoclonic and/or absence seizures were reported in 47/163 and 60/163 patients, respectively. Median percent reductions in seizure frequency per 28 days from study baseline were 52.5% and 24.5% (myoclonic seizures) and 7.6 % and 41.2 % (absence seizures) for placebo and perampanel, respectively; seizure-freedom rates were 13.0 % and 16.7 % (myoclonic seizures) and 12.1 % and 22.2 % (absence seizures), respectively. During the OLEx phase, 46/138 and 52/138 patients experienced myoclonic and/or absence seizures, respectively. Responses during the double-blind phase were maintained during long-term (>104 weeks) adjunctive perampanel treatment. The frequency/type of TEAEs was consistent with the known safety profile of perampanel. Conclusion In this post hoc analysis, adjunctive perampanel was not associated with any overall worsening of absence seizures. Further research is needed to investigate the effect of adjunctive perampanel in IGE patients with myoclonic and/or absence seizures.

BackgroundThis post hoc analysis assessed the efficacy and safety of adjunctive perampanel in adult/adolescent/paediatric patients with myoclonic and absence seizures during Phase II/III clinical studies.MethodsDuring Study 332 (NCT01393743), patients aged ≥12 years with generalised tonic-clonic seizures (GTCS) received placebo/adjunctive perampanel 8-mg/day. In Study 311 (NCT02849626), patients aged 4–NCT01527006), patients aged 2–ResultsOverall, 66/393 patients had myoclonic seizures (placebo, n=23; perampanel, n=43) and 72/393 had absence seizures (placebo, n=33; perampanel, n=39); patients with both seizure types are counted twice. Reductions in seizure frequency/28 days were observed with placebo and perampanel: myoclonic, 52.5% and 24.6%; absence, 7.6% and 25.1%, respectively. TEAEs with placebo and perampanel occurred in 18 (78.3%) and 36 (83.7%) patients with myoclonic seizures, and 25 (75.8%) and 34 (87.2%) patients with absence seizures, respectively; most common TEAEs with perampanel were dizziness and fatigue.ConclusionThese data suggest adjunctive perampanel does not worsen myoclonic/absence seizures in adult/adolescent/paediatric patients.FundingEisai Inc. stella_ngo@eisai.com32

BackgroundThe long-term (≤1-year) effects of adjunctive perampanel on cognition, behaviour and growth/development were assessed in paediatric patients aged 4–NCT02849626).MethodsCore Study (4-week pretreatment/23-week treatment) completers could enter the Extension (29-week maintenance/4-week follow-up). Assessments included: change from baseline at Week 52 for cognition (Aldenkamp-Baker Neuropsychological Assessment Schedule [ABNAS]), behavioural/emotional problems (Child Behaviour Checklist [CBCL]), visuomotor skills (Lafayette Grooved Pegboard Test [LGPT]) and growth/development.ResultsMean standard deviation (SD) change from baseline to Week 52 in total ABNAS score was -3.3 (16.6) (n=112). Mean (SD) change from baseline at Week 52 in CBCL total problems was -6.0 (14.0) and-1.6 (14.7) for patients aged 1.5–5 (n=17) and 6–18 years (n=102), respectively; for time to complete the LGPT, this was 5.3 (48.0) seconds for patients aged ≤8 years (n=33) and 0.4 (23.2) for patients aged >8 years (n=51). No significant impact on growth/development observed.ConclusionNo clinically significant changes were observed in cognition, behaviour or growth/devel- opment parameters following long-term (≤1 year) adjunctive perampanel in paediatric patients (aged 4–manoj_malhotra@eisai.com

BackgroundLong-term (1-year) seizure-freedom rates with adjunctive perampanel were assessed in paediatric patients aged 4–NCT02849626).MethodsSeizure-freedom rates (FOS, FBTCS, GTCS) were assessed in patients who achieved seizure freedom during the Core Study Maintenance Period and then remained seizure free for up to 12 months (calculated from the start of their seizure-free period). Data were stratified by concomitant enzyme- inducing anti-seizure medications (EIASMs) (with and without) and age (4–ResultsFor FOS, 6/11 (54.5%) patients remained seizure free for 12 months (with EIASMs, n=2/5 [40.0%]; without EIASMs, n=4/6 [66.7%]; 4–ConclusionDespite small patient numbers, seizure-freedom rates are maintained during long-term (1-year) perampanel treatment in paediatric patients, consistent with analyses in adolescents/adults.Funding.Eisai Inc. stella_ngo@eisai.com

BackgroundThe long-term efficacy and safety of adjunctive perampanel was evaluated in patients aged≥60 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures (FBTCS) who participated in open-label extension Studies 307 (NCT00735397) and 335 (NCT01618695).MethodsPatients received perampanel 2–12 mg/day during Studies 307 (16-week blinded Conversion; 256-week Maintenance) and 335 (4-week Pre-conversion; 6-week Conversion; ≥46-week Maintenance). Assessments included median per cent reduction in seizure frequency/28 days vs pre-perampanel baseline, 50% responder rates and treatment-emergent adverse events (TEAEs).ResultsThe Safety Analysis Set included 71 patients (mean age, 64.0 years). Seizure frequency reductions during Years 1 and 2 were 31.7% (n=71) and 44.5% (n=38) (total FOS), and 95.5% (n=19) and 100.0% (n=9) (FBTCS), respectively. Seizure frequency reductions were observed during Years 3/4 (low patient numbers); over one-third of patients achieved a ≥50% seizure reduction each year. During Years 1, 2, 3 and 4, TEAE incidence was 87.3% (n=62/71), 60.4% (n=29/48), 47.4% (n=9/19) and 57.1% (n=8/14), respectively; most common were dizziness and fall during Years 1/2 and 3/4, respectively.ConclusionPerampanel was associated with reductions in seizure frequency over 4 years in elderly patients. The safety profile was consistent with the overall populations.FundingEisai Inc. stella_ngo@eisai.com33

BackgroundThe long-term (≤1-year) effects of adjunctive perampanel on cognition by responder status and modal dose were assessed in paediatric patients (aged 4–NCT02849626).MethodsCore Study (4-week pretreatment/23-week treatment) completers could enter the Extension (29-week maintenance/4-week follow-up). The Aldenkamp-Baker Neuropsychological Assessment Schedule [ABNAS] was used to assess cognition (change from baseline, Weeks 23/52) by total seizure response category (ResultsMean (standard deviation) change from baseline in total ABNAS for Weeks 23 and 52 by response category was: (14.8); 100%, -1.6 (18.3) and -0.6 (20.6), respectively; and by modal dose was: -2.0 (7.2); 4 mg/day, -4.8 (22.4) and -10.4 (25.6); >4–6 mg/day, 1.3 (8.3) and -1.3 (10.2); >6–8 mg/day, -0.5(10.7) and 1.9 (9.4); >8–12 mg/day, -0.1 (12.8) and -7.4 (20.2); >12–16 mg/day, 2.2 (12.4) and 1.1 (14.8), respectively.ConclusionAdjunctive perampanel had few long-term effects on cognition in paediatric patients, regard- less of responder status and modal dose.FundingEisai Inc.11m2anoj_malhotra@eisai.com

Objective Study 311 (NCT02849626) was a global, multicenter, open‐label, single‐arm study that assessed safety, tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics of once‐daily adjunctive perampanel oral suspension in pediatric patients (aged 4 to

Study 311 (E2007-G000-311; NCT02849626) was a Phase 3, multicenter, open-label single-arm study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to12 years) with partial-onset seizures (POS) (with/without secondarily generalized tonic-clonic seizures [SGTCS]) or primary generalized tonic-clonic seizures (PGTCS). Health-related quality of life (HRQoL) was an exploratory endpoint initially analyzed through simple descriptive summaries. The aim of this post hoc analysis was to provide a more thorough assessment of HRQoL.This analysis focused on EQ-5D-Y data collected at Baseline, Week 23, and Week 52. Individual dimensions, visual analog scale (VAS) and summed misery index (MI) were evaluated at all visits and compared by seizure type (POS versus SGTCS versus PGTCS), age (4 to7 versus 7 to12), and use of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) (yes versus no). Paretian Classification of Health Change (PCHC) analysis summarized the proportion of patients who showed improvement or deterioration in HRQoL. Waterfall plots assessed changes in EQ-5D-Y scores by treatment-emergent adverse events (TEAEs) and by reduction in seizure frequency. Health state utility values associated with differing seizure frequency states were estimated using a linear mixed model.One hundred and fifteen patients completed EQ-5D-Y at relevant study visits (Seizure type: POS n = 84 [of which 21 had SGTCS], PGTCS n = 31; Age: 4 to7 years n = 30, 7 to12 years n = 85; Concomitant EIAEDs: Yes n = 35, No n = 80). Completion rates out of those expected to complete EQ-5D-Y were high at both timepoints (84.4% at Week 23 and 97.2% at Week 52). Overall, VAS/MI remained stable over time (did not exceed minimal important difference); this was similar according to seizure type, age, and EIAED usage. In patients with 'no problems' on any EQ-5D-Y dimension at Baseline, nearly all retained their full health at Week 23 (94.7%), and all retained it at Week 52 (100.0%). PCHC analysis showed fewer patients with POS experienced deterioration in EQ-5D-Y than patients with PGTCS at Week 23 (24.1% versus 42.1%). Not experiencing a TEAE, or remaining seizure-free, was associated with improvements in VAS score at Week 23 compared to those experiencing TEAEs or seizures, respectively. Health state utility values (HSUVs) were estimated as follows: seizure free (LS Mean 0.914 [95% CIs 0.587, 1.240]), ≥1 seizure per year (0.620 [0.506, 0.734]), ≥1 seizure per month (0.596 [0.338, 0.855]), ≥1 seizure per week (0.284 [-0.014, 0.582]).An in-depth analysis of EQ-5D-Y data allowed for a more nuanced exploration of HRQoL than previous descriptive summaries. Our findings provide evidence that perampanel as adjunctive therapy did not result in deterioration of patient HRQoL. The association between TEAEs or remaining seizure-free and HRQoL warrants further exploration. Increasing seizure frequency was associated with decreasing HSUVs; these can inform cost-effectiveness modeling of perampanel and other therapies aiming to reduce seizure frequency in pediatric patients.

Carbon fiber reinforced polymer (CFRP) composites are increasingly used in aerospace applications due to its superior mechanical properties and reduced weight. Adhesive bonding is commonly used to join the composite parts since it is capable of joining incompatible or dissimilar components. However, insufficient adhesive or contamination in the adhesive bonds might occur and pose as threats to the integrity of the plane during service. It is thus important to look for suitable nondestructive testing (NDT) techniques to detect and characterize the sub-surface defects within the CFRP composites. Some of the common NDT techniques include ultrasonic techniques and thermography. In this work, we report the use of the abovementioned techniques for improved interpretation of the results.

Polyurethanes are versatile elastomers but suffer from biological limitations such as poor control over cell attachment and the associated disadvantages of increased fibrosis. We address this problem by presenting a novel strategy that retains elasticity while modulating biological performance. We describe a new biomaterial that comprises a blend of synthetic and natural elastomers: the biostable polyurethane Elast-Eon and the recombinant human tropoelastin protein. We demonstrate that the hybrid constructs yield a class of coblended elastomers with unique physical properties. Hybrid constructs displayed higher elasticity and linear stress-strain responses over more than threefold strain. The hybrid materials showed increased overall porosity and swelling in comparison to polyurethane alone, facilitating enhanced cellular interactions. In vitro, human dermal fibroblasts showed enhanced proliferation, while in vivo, following subcutaneous implantation in mice, hybrid scaffolds displayed a reduced fibrotic response and tunable degradation rate. To our knowledge, this is the first example of a blend of synthetic and natural elastomers and is a promising approach for generating tailored bioactive scaffolds for tissue repair.

Dielectric-based metamaterials are proposed to be the ideal candidates for low-loss, high-efficiency devices. However, to employ dielectric nanostructures for high-power applications, the dielectric material must have a high laser-induced damaged threshold (LIDT) value. In this work, we investigated the LIDT values of dielectric nanostructures for high-power fiber laser applications. Consequently, we found that the fabricated SiO2 nanostructured lens can withstand laser fluence exceeding 100 J/cm2.

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring ( P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels ( P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams ( P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring.

Significant improvements in the performance of p-doped ten-layer InAs/InGaAs quantum dot laser are demonstrated using rapid thermal annealing at 600 °C. The annealed laser shows about 2.7 times increase in the saturated output power and external differential quantum efficiency without obvious wavelength shift. Decrease in internal loss of 2.9 cm-1 and improvement in the threshold current by 23% are achieved. Defect reduction is thought to be the most likely mechanism contributing to the improved performance according to the electroluminescence and improved characteristic temperature behavior.

Bilayer quantum dots (BQDs) are interesting structures for long wavelength emission due to its ability to tune the areal density and dot size separately. However, wide implementation of BQDs is hindered by the complicated growth procedures, which involve two sets of growth rate and temperature for the respective QD layers. We had recently reported the optical properties of the BQDs grown at constant growth rate and temperature [Appl. Phys. Lett. 95 (2009) 181913]. In this work, we investigate the effects of GaAs spacer thickness and InxGa1−xAs strain-reducing layer on the structural and optical properties of such BQDs.

We present the heterogeneous growth of InAs quantum dots (QDs) on Si platform using GaAs/Ge/Si 1− x Ge x /Si substrate. Self-assembled InAs QDs were grown on GaAs/Ge/Si 1− x Ge x /Si substrate by employing molecular beam epitaxy (MBE). The areal density, width and height of QDs were characterized using atomic force microscopy (AFM). The undulation originating from the graded Si 1− x Ge x /Si substrate causes no noticeable change in dot densities and dot dimensions across the undulated surface. The effects of V/III ratio and InAs coverage on structural properties of the QDs were investigated. The dot density increases with increasing V/III ratio and QDs with high density of 10 11 cm −2 were obtained, attributed to the reduced diffusion length of the adatoms. Lateral dimension of the QDs increases as the InAs coverage increases. The QDs coalesce at 3.0 monolayer (ML) InAs coverage. This work is beneficial to those working on III–V on Si integration.

Terahertz (THz) technology has attracted vast interests due to its wide applications. Quantum dot (QD) system is proposed to be the most suitable candidate for compact THz sources based on intraband transitions. However, transition energies of reported results still fall outside the THz range (with corresponding energy of ∼0.4–41 meV). In this study, we investigate the effect of growth temperature and monolayer coverage on the transition energies of InAs/InGaAs/GaAs QDs and InAs/GaAs bilayer QDs, respectively. Consequently, the obtained energy difference was less than 40 meV, thus demonstrating the feasibility of varying the QD growth parameters for bandgap engineering towards the THz emission range.