Structural and Functional Consequences of HIV-1 Viral Protein Tat and Morphine Co-Exposure at the Blood-Brain Barrier

According to UNAIDS 2016, over 37 million people worldwide were infected with human immunodeficiency virus (HIV) in 2016, with over 1.2 million people living with HIV in the United States. Of those, approximately one half will suffer from HIV-associated neurocognitive disorders (HAND), which is a spectrum of neurocognitive disorders ranging from asymptomatic neurocognitive impairment, to mild neurocognitive disorder, to HIV-associated dementia. While combination antiretroviral therapy (cART) has decreased the incidence of the most severe forms of HAND in patients with HIV, milder forms of HAND still persist. These defects can include decreased motor skills, cognitive abilities, memory, and attention. While patients with HIV are living longer thanks to cART, there are few to no long-term options for managing the neurocognitive defects caused by the chronic disease of HAND. Additionally, opiate abuse can increase both the incidence and severity of HAND. HAND may result due to poor antiretroviral drug (ARV) penetration across the blood-brain barrier (BBB). Thus, a better understanding of the effects of HIV and opiates on the BBB may result in improved therapies for HAND. The Tat transgenic model was used to evaluate the effects of the HIV-1 viral protein Tat and morphine on blood-brain barrier leakiness using varied-sized paracellular compounds. Secondly, antiretroviral drug accumulation in the brain of Tat transgenic mice under Tat and/or morphine co-exposure was measured. Specifically, the single tablet regimen of Triumeq® (abacavir/lamivudine/dolutegravir) was studied in these mice and antiretroviral drug measured in both striatum and hippocampus brain regions and plasma via LC-MS/MS. Additionally, morphine and its metabolites were also measured via LC-MS/MS. Lastly, macrophage turnover within the caudate/putamen and phagocytic macrophage/microglia accumulation in the brain was measured in Tat transgenic mice under Tat and/or morphine conditions. Perivascular and parenchymal spaces were distinguished within the caudate/putamen, while overall phagocytic activity was measured in all other brain regions, including the nucleus accumbens, anterior cingulate cortex, primary motor cortex, somatosensory cortex, agranular insular cortex, and piriform cortex

Digital contact tracing/notification for SARS-CoV-2: navigating six points of failure

Digital contact tracing/notification was initially hailed as a promising strategy to combat SARS-CoV-2, but in most jurisdictions it did not live up to its promise. To avert a given transmission event, both parties must have adopted the tech, it must detect the contact, the primary case must be promptly diagnosed, notifications must be triggered, and the secondary case must change their behavior to avoid the focal tertiary transmission event. If we approximate these as independent events, achieving a 26% reduction in R(t) would require 80% success rates at each of these six points of failure. Here we review the six failure rates experienced by a variety of digital contact tracing/notification schemes, including Singapore's TraceTogether, India's Aarogya Setu, and leading implementations of the Google Apple Exposure Notification system. This leads to a number of recommendations, e.g. that tracing/notification apps be multi-functional and integrated with testing, manual contact tracing, and the gathering of critical scientific data, and that the narrative be framed in terms of user autonomy rather than user privacy

Structure and Rotation of the Solar Interior: Initial Results from the MDI Medium-L Program

The medium-l program of the Michelson Doppler Imager instrument on board SOHO provides continuous observations of oscillation modes of angular degree, l, from 0 to approximately 300. The data for the program are partly processed on board because only about 3% of MDI observations can be transmitted continuously to the ground. The on-board data processing, the main component of which is Gaussian-weighted binning, has been optimized to reduce the negative influence of spatial aliasing of the high-degree oscillation modes. The data processing is completed in a data analysis pipeline at the SOI Stanford Support Center to determine the mean multiplet frequencies and splitting coefficients. The initial results show that the noise in the medium-l oscillation power spectrum is substantially lower than in ground-based measurements. This enables us to detect lower amplitude modes and, thus, to extend the range of measured mode frequencies. This is important for inferring the Sun's internal structure and rotation. The MDI observations also reveal the asymmetry of oscillation spectral lines. The line asymmetries agree with the theory of mode excitation by acoustic sources localized in the upper convective boundary layer. The sound-speed profile inferred from the mean frequencies gives evidence for a sharp variation at the edge of the energy-generating core. The results also confirm the previous finding by the GONG (Gough et al., 1996) that, in a thin layer just beneath the convection zone, helium appears to be less abundant than predicted by theory. Inverting the multiplet frequency splittings from MDI, we detect significant rotational shear in this thin layer. This layer is likely to be the place where the solar dynamo operates. In order to understand how the Sun works, it is extremely important to observe the evolution of this transition layer throughout the 11-year activity cycle

Les courants politiques critiques vis-à-vis de l'état actuel du projet européen

info:eu-repo/semantics/publishe