Type-II strained layer superlattices (SLSs) offer a broad range of design degrees of freedom to help optimize their properties as absorber layers of infrared photon detectors. We theoretically ...examine a new class of mid-wavelength infrared (2-5 μm bandpass) Type-II structures with two-layer InGaSb/InPSb and four-layer InAs/GaSb/InAs/InPSb SLS periods. Phosphorous-containing SLSs are a promising approach to improving infrared photon detector performance due to providing a new set of material properties, including favorable valence band offsets. P-based SLSs of four-layer type InAs/GaSb/InAs/InPSb were found to be among the best 5-μm gap SLSs that we have modeled. Among the studied designs, the lowest dark current in an ideal structure is predicted for a four-layer 23.6 Å InAs/20 Å GaSb/23.6 Å InAs/60 Å InP 0.62 Sb 0.38 SLS. Its predicted ideal dark current is about 35 times lower than an n-type HgCdTe-based photodiode absorber and six times lower than a p-type HgCdTe one for the same bandgap, temperature, and dopant concentration. We also discuss a defect mitigation strategy that involves positioning the SLS gap in an energy range that avoids defect levels and show how this applies to the aforementioned P-containing SLS.
Data on students' perceptions of teacher social support, academic functioning, and social-emotional functioning were collected from a sample of 796 7th and 8th grade middle school students using the ...Child and Adolescent Social Support Scale (CASSS; Malecki, Demaray, & Elliott, 2000), Iowa Tests of Basic Skills (ITBS) and school records, and the Behavior Assessment Scale for Children, Second Edition, Adolescent Version, (BASC-2 SRP-A; Reynolds & Kamphaus, 2004). The purpose of the current study was to examine possible gender differences in perceptions of the frequency and importance of different types of teacher support and the related academic and social-emotional outcomes. Girls rated Emotional and Appraisal Support as more important than did boys. Teacher Emotional Support was significantly and positively related to grade point average (GPA) for boys and girls. For girls only, Emotional and Informational Support were significantly related to ITBS Reading scores, and Emotional, Informational, and Instrumental Support were significantly related to ITBS Math scores. Regarding social-emotional variables, Emotional Support was significantly and negatively related to School Problems, Internalizing Problems, Inattention/Hyperactivity, and overall Emotional Symptoms and positively related to Personal Adjustment for both boys and girls. Furthermore, Emotional Support from teachers was more strongly related to Inattention/Hyperactivity for girls than boys. These results emphasize the importance of providing teacher social support, especially emotional support, to students in early adolescence and recognizing gender differences in the function of specific types of teacher support.
A thorough literature review was undertaken to understand how the pathways of N-nitrosamine transformation relate to mutagenic potential and carcinogenic potency in rodents. Empirical and ...computational evidence indicates that a common radical intermediate is created by CYP-mediated hydrogen abstraction at the α-carbon; it is responsible for both activation, leading to the formation of DNA-reactive diazonium species, and deactivation by denitrosation. There are competing sites of CYP metabolism (e.g., β-carbon), and other reactive species can form following initial bioactivation, although these alternative pathways tend to decrease rather than enhance carcinogenic potency. The activation pathway, oxidative dealkylation, is a common reaction in drug metabolism and evidence indicates that the carbonyl byproduct, e.g., formaldehyde, does not contribute to the toxic properties of N-nitrosamines. Nitric oxide (NO), a side product of denitrosation, can similarly be discounted as an enhancer of N-nitrosamine toxicity based on carcinogenicity data for substances that act as NO-donors. However, not all N-nitrosamines are potent rodent carcinogens. In a significant number of cases, there is a potency overlap with non-N-nitrosamine carcinogens that are not in the Cohort of Concern (CoC; high-potency rodent carcinogens comprising aflatoxin-like-, N-nitroso-, and alkyl-azoxy compounds), while other N-nitrosamines are devoid of carcinogenic potential. In this context, mutagenicity is a useful surrogate for carcinogenicity, as proposed in the ICH M7 (R2) (2023) guidance. Thus, in the safety assessment and control of N-nitrosamines in medicines, it is important to understand those complementary attributes of mechanisms of mutagenicity and structure–activity relationships that translate to elevated potency versus those which are associated with a reduction in, or absence of, carcinogenic potency.
Cerebral deposition of amyloid-β peptide (Aβ) within neuritic plaques is a hallmark pathology of Alzheimer's disease. It is now generally believed that the development of this pathology is central to ...the pathogenesis of Alzheimer's disease. As such, inhibiting Aβ deposition or removing Aβ deposits once they are formed represent therapeutic targets for Alzheimer's disease. Aβ is derived from a precursor, the amyloid precursor protein (APP), and APP binds to the X11 family of adaptor proteins. Studies from several laboratories have now shown that X11α and X11β (the two neuronal X11s) inhibit APP processing and Aβ production. Exactly how this is achieved is not yet known but recent studies in which other X11 binding partners have been identified are beginning to reveal potential mechanisms.
Dual-task (DT) testing reflects real-world walking demands in older adults but is not always feasible to perform in clinic. Whether clinical measures that predict single-task (ST) performance also ...predict DT performance or dual-task effects (DTEs) has not been fully explored.
What are the relationships between cognitive performance, functional mobility, and self-reported physical activity and balance confidence and ST and DT Gait Speed and Cognitive Reaction Time, as well as DTEs on Gait Speed (DTEGS) and Cognitive Reaction Time (DTERT), in older adults?
Sixty-two older adults (71.5 ± 7.1 years, 17 males) completed cognitive performance, functional mobility, and self-report physical activity and balance confidence assessments. Three 1-min trials were performed: 1) ST Cognition (clock task), 2) ST Gait and 3) DT Cognition + Gait, with Cognitive Reaction Time (recorded during clock task performance via DirectRT) and Gait Speed (measured during walking trial via APDM system) recorded, and DTEGS and DTERT calculated, as the cognitive and gait outcomes. Six multivariate regressions were conducted to test whether cognitive performance, functional mobility, and self-report assessments predicted Gait Speed and Cognitive Reaction Time in ST and DT conditions and DTEs.
The Comprehensive Trail Making Test (CTMT) predicted Reaction Time in ST cognitive (β = − 0.525, p = .003) and DT (β = − 0.510, p = .006) trials. The Physical Activity Scale for the Elderly (PASE) predicted DTERT (β = − 0.397, p = .008). The 10-Meter Walk Test (10MWT) predicted Gait Speed in ST gait (β = 0.692, p < .001) and DT (β = 0.715, p < .001) trials. The Four Square Step Test (FSST) predicted ST Gait Speed (β = − 0.233, p = .034). The Montreal Cognitive Assessment (MoCA) (β = 0.293, p = .027), 10MWT (β = 0.322, p = .046), and the FSST (β = 0.378, p = .019) predicted DTEGS.
The 10MWT, CTMT, and MoCA can be easily implemented in the clinic and may be good choices to assess cognitive and functional abilities necessary for ambulation in older adults.
•Ten Meter Walk Test (10MWT) predicts single- and dual-task gait speed.•10MWT and Montreal Cognitive Assessment predict dual-task effects on gait speed.•Comprehensive Trail Making predicts single- and dual-task cognitive reaction time.•Cognitive and gait assessments should be used to assess everyday walking abilities.
Under ICH M7, impurities are assessed using the bacterial reverse mutation assay (i.e., Ames test) when predicted positive using in silico methodologies followed by expert review. N-Nitrosamines ...(NAs) have been of recent concern as impurities in pharmaceuticals, mainly because of their potential to be highly potent mutagenic carcinogens in rodent bioassays. The purpose of this analysis was to determine the sensitivity of the Ames assay to predict the carcinogenic outcome with curated proprietary Vitic (n = 131) and Leadscope (n = 70) databases. NAs were selected if they had corresponding rodent carcinogenicity assays. Overall, the sensitivity/specificity of the Ames assay was 93–97% and 55–86%, respectively. The sensitivity of the Ames assay was not significantly impacted by plate incorporation (84–89%) versus preincubation (82–89%). Sensitivity was not significantly different between use of rat and hamster liver induced S9 (80–93% versus 77–96%). The sensitivity of the Ames is high when using DMSO as a solvent (87–88%). Based on the analysis of these databases, the Ames assay conducted under OECD 471 guidelines is highly sensitive for detecting the carcinogenic hazards of NAs.
•Sensitivity analysis of the Ames assay to predict carcinogenicity of N-nitrosamines was performed on proprietary databases.•Sensitivity of the Ames assay conducted under OECD 471 guidelines was found to be high.•Plate incorporation vs preincubation, DMSO as solvent, and rat vs hamster liver induced S9 did not impact sensitivity.
Limiting the defect-mediated dark currents in type-II superlattice (T2SL) IR photodiodes remains the key challenge to focal plane arrays (FPAs) based on this material system. In spite of its larger ...effective mass to suppress tunneling and more than an order of magnitude longer Auger lifetime, the T2SL photodiode performance still lags behind that of the incumbent HgCdTe-based technology. The tunneling and generation–recombination currents can be strongly suppressed by employing a “W” T2SL structure and gradually increasing the energy gap in the depletion region. For maximum quantum efficiency, this graded-gap geometry is combined in a hybrid structure with two-constituent T2SL absorbers that exhibit roughly twice the diffusion length of the “W” structure. Finally, if the etch used to isolate neighboring pixels is stopped just beyond the junction in the graded-gap device, narrow-gap regions are not exposed and the total sidewall area is reduced by a factor of 20. We have combined all of these approaches to produce a 10.5
μm cutoff FPA with diffusion-limited performance and noise-equivalent differential temperature (NEDT) of 35
mK at 70
K.
Lhasa Limited have had a role in the in silico prediction of drug and other chemical toxicity for over 30 years. This role has always been multifaceted, both as a provider of predictive software such ...as Derek Nexus, and as an honest broker for the sharing of proprietary chemical and toxicity data. A changing regulatory environment and the drive for the Replacement, Reduction and Refinement (the 3Rs) of animal testing have led both to increased acceptance of in silico predictions and a desire for the sharing of data to reduce duplicate testing. The combination of these factors has led to Lhasa Limited providing a suite of products and coordinating numerous data-sharing consortia that do indeed facilitate a significant reduction in the testing burden that companies would otherwise be laboring under. Many of these products and consortia can be organized into workflows for specific regulatory use cases, and it is these that will be used to frame the narrative in this chapter.
The Dermal Sensitisation Thresholds (DST) are Thresholds of Toxicological Concern, which can be used to justify exposure-based waiving when conducting a skin sensitisation risk assessment. This study ...aimed to update the published DST values by expanding the size of the Local Lymph Node Assay dataset upon which they are based, whilst assigning chemical reactivity using an in silico expert system (Derek Nexus). The potency values within the expanded dataset fitted a similar gamma distribution to that observed for the original dataset. Derek Nexus was used to classify the sensitisation activity of the 1152 chemicals in the expanded dataset and to predict which chemicals belonged to a High Potency Category (HPC). This two-step classification led to three updated thresholds: a non-reactive DST of 710 μg/cm2 (based on 79 sensitisers), a reactive (non-HPC) DST of 73 μg/cm2 (based on 331 sensitisers) and an HPC DST of 1.0 μg/cm2 (based on 146 sensitisers). Despite the dataset containing twice as many sensitisers, these values are similar to the previously published thresholds, highlighting their robustness and increasing confidence in their use. By classifying reactivity in silico the updated DSTs can be applied within a skin sensitisation risk assessment in a reproducible, scalable and accessible manner.
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•An expanded dataset contains three times the amount of Local Lymph Node Assay data.•Derek Nexus can assign a skin sensitisation potency category based on reactivity.•The updated non-reactive Dermal Sensitisation Threshold is 710 μg/cm2.•The updated reactive (non-HPC) Dermal Sensitisation Threshold is 73 μg/cm2.•The updated HPC Dermal Sensitisation Threshold is 1.0 μg/cm2.
The purpose of the current study was to identify how defending behaviors in bullying overlap with bullying behaviors and victimization experiences using an empirical approach. Furthermore, an ...additional goal was to examine internalizing problems associated with these bullying role behaviors. Data on students' defending and bullying behaviors, victimization experiences, anxiety, depression, and self-esteem were collected from 700 sixth- through eighth-grade students using the Bully Participant Behaviors Questionnaire, the Screen for Child Anxiety Related Disorders-Child Version, the Center for Epidemiological Studies-Depression, and the Rosenberg Self-Esteem Scale. Results of a latent profile analysis identified the following roles: defenders, bully-victim-defenders, and students who had low involvement in bullying, victimization, and defending. Results documented significant differences in internalizing problems among the roles. Specifically, bully-victim-defenders reported higher levels of depression and anxiety and lower levels of self-esteem than did defenders and students who had low involvement with bullying scenarios.
