This study used the National Longitudinal Transition Study–2 (NLTS2) data set to determine the effects of expectations and transition planning goals on the postsecondary education enrollment of deaf youth.
Harold Javitz
SRI Author
Antiviral T-cell Biofactory platform for SARS-CoV-2
Vaccines help reduce new infections, but interventions that can prevent the disease from transitioning to a severe stage are rather limited. Dysregulated IFN kinetics are mostly exploited by pathogenic viruses, including SARS-CoV-2.
NK-Cell Biofactory as an Off-the-Shelf Cell-based Vector for Targeted In Situ Synthesis of Engineered Proteins
NK-cell Biofactory is an off-the-shelf allogeneic platform for cell-based synthesis of desired protein following recognition of a target cell while conserving the cytolytic activity. The molecular specificity of the platform can be redirected for treating a broad range of diseases.
The NK-92MI, a fast-growing cytolytic cell line with a track record of exerting clinical efficacy, is transformed into a vector for synthesizing calibrated amounts of desired engineered proteins at our disease site, that is, NK-cell Biofactory. This provides an allogeneic option to the previously published T-cell-based living vector that is limited by high manufacturing cost and product variability. The modularity of this pathway, which combines a “target” receptor with an “effector” function, enables reprogramming of the NK-cell Biofactory to target diseases with specific molecular biomarkers, such as cancer, viral infections, or auto-immune disorders, and overcome barriers that may affect the advancement of NK-cell therapies.
Effect of accessing supports on higher education persistence of students with disabilities
SRI Authors: Lynn Newman, Harold Javitz Abstract This study examined the effect of accessing supports available to the general student body and disability-related supports on college perseverance for students with disabilities. This secondary analysis of a nationally representative longitudinal dataset included a sample of approximately 2,330 college students with disabilities who had been identified as […]
Impact of evening alcohol consumption on nocturnal autonomic and cardiovascular function in adult men and women: A dose–response laboratory investigation
Study Objectives: To investigate the dose-dependent impact of moderate alcohol intake on sleep-related cardiovascular (CV) function, in adult men and women.
Methods: A total of 26 healthy adults (30–60 years; 11 women) underwent 3 nights of laboratory polysomnographic (PSG) recordings in which different doses of alcohol (low: 1 standard drink for women and 2 drinks for men; high: 3 standard drinks for women and 4 drinks for men; placebo: no alcohol) were administered in counterbalanced order before bedtime. These led to bedtime average breath alcohol levels of up to 0.02% for the low doses and around 0.05% for the high doses. Autonomic and CV function were evaluated using electrocardiography, impedance cardiography, and beat-to-beat blood pressure monitoring.
Results: Presleep alcohol ingestion resulted in an overall increase in nocturnal heart rate (HR), suppressed total and high-frequency (vagal) HR variability, reduced baroreflex sensitivity, and increased sympathetic activity, with effects pronounced after high-dose alcohol ingestion (p’s < 0.05); these changes followed different dose- and measure-dependent nocturnal patterns in men and women. Systolic blood pressure showed greater increases during the morning hours of the high-alcohol dose night compared to the low-alcohol dose night and placebo, in women only (p’s < 0.05).
Conclusions: Acute evening alcohol consumption, even at moderate doses, has marked dose- and time-dependent effects on sleep CV regulation in adult men and women. Further studies are needed to evaluate the potential CV risk of repeated alcohol-related alterations in nighttime CV restoration in healthy individuals and in those at high risk for CV diseases, considering sex and alcohol dose and time effects.
Lentivirus Manufacturing Process for Primary T‐Cell Biofactory Production
A process for maximizing the titer of lentivirus particles, deemed to be a necessity for transducing primary cells, is developed. Lentivirus particles, with a set of transgenes encoding an artificial cell‐signaling pathway, are used to transform primary T cells as vectors for calibrated synthesis of desired proteins in situ, that is, T‐cell biofactory cells. The process is also used to generate primary T cells expressing antigen‐specific chimeric antigen receptors, that is, CAR T cells. The two differently engineered primary T cells are expanded and validated for their respective functions, that is, calibrated synthesis of desired proteins upon engaging the target cells, which is specific for the T‐cell biofactory cells, and cytolysis of the target cells common to both types of cells. The process is compliant with current Good Manufacturing Practices and can be used to support the scale‐up for clinical translation.
Sleep Disturbance Predicts Depression Symptoms in Early Adolescence: Initial Findings From the Adolescent Brain Cognitive Development Study
Purpose: The aim of the study was to investigate associations between sleep disturbances and mental health in adolescents.
Methods: Data are from a national sample of 11,670 U.S. participants (5,594 females, aged 9-10 years, 63.5% white) in the Adolescent Brain Cognitive Development study. Initial longitudinal analyses were conducted for a subset of the sample (n = 4,951). Measures of youth sleep disturbance (disorders of initiating and maintaining sleep, sleep-wake transition disorders, and disorders of excessive somnolence) and “typical” total sleep time (number of hours slept on most nights in the past 6 months) were obtained from the parent-report Sleep Disturbance Scale (Data Release 2.0). Parent-report measures of youth mental health (depression, internalizing, and externalizing behaviors) from the Child Behavior Checklist and typical screen time were included.
Results: At baseline, greater sleep disturbance and shorter total sleep time were associated with greater internalizing, externalizing, and depression scores. After controlling for baseline mental health symptoms, baseline sleep disturbance significantly predicted depression and internalizing and externalizing scores at 1-year follow-up. A significant interaction with sex indicated that the association between disorders of excessive somnolence and depression 1 year later was steeper for girls, compared with boys (p < .001; 95% confidence interval 1.04-3.45).
Conclusions: Sleep disturbances predicted future mental health, particularly depression in this young sample, highlighting the potential to harness sleep as a tool to mitigate the persistence of depression across early adolescence and potentially prevent an adolescent onset of major depressive disorder.
Engineered Ovarian Cancer Cell Lines for Validation of CAR T Cell Function
A set of genetically engineered isogenic cell lines is developed to express either folate receptor alpha or mesothelin, and a control cell line negative for both antigens. These cell lines also express fluorescent and bioluminescent reporter transgenes. The cell lines are used to authenticate specificity and function of a T‐cell biofactory, a living vector that is developed to express proportionate amounts of engineered proteins upon engaging with disease cells through their specific antigenic biomarkers. The engineered cell lines are also used to assess the cytolytic function and specificity of primary T cells engineered with chimeric antigen receptors; and the specificity of monoclonal antibodies. The strategy described can be used to generate other cell lines to present different disease‐specific biomarkers for use as quality control tools.
Modular Antigen-Specific T-cell Biofactories for Calibrated In Vivo Synthesis of Engineered Proteins
An artificial cell-signaling pathway is developed that capitalizes on the T-cell’s innate extravasation ability and transforms it into a vector (T-cell Biofactory) for synthesizing calibrated amounts of engineered proteins in vivo. The modularity of this pathway enables reprogramming of the T-cell Biofactory to target biomarkers on different disease cells, e.g. cancer, viral infections, autoimmune disorders. It can be expected that the T-cell Biofactory leads to a “living drug” that extravasates to the disease sites, assesses the disease burden, synthesizes the calibrated amount of engineered therapeutic proteins upon stimulation by the diseased cells, and reduces targeting of normal cells.
