Team One Carbon Catcher Design Report

Overview The burning of fossil fuels largely contributes to the increase of CO2 in the atmosphere. The US Department of Transportation alone contributed almost 6 million metric tons of carbon dioxide emissions in 2018 (EIA). Due to this, this report proposes recycling captured CO2 into a base for cleaner burning fuel in order to reduce emissions from the transportation industry and many others, which has the potential to impact many areas. Extraction of atmospheric CO2 is possible through a membrane filtration system based on traditional nitrogen generation. The passive filtration system autonomously separates the CO2 from other air components, thereby reducing energy consumption. The system's working sensors and actuators utilize similar energy saving strategies, such as distributing cloud-computing services over multiple servers and mainframes to reduce computing power. The movement of air is directed by a scalable fan device, which is presented as a modular design to allow customization of fan parts to specific size and installation requirements. As an integrated device, Team 1’s Carbon Catcher operates with a high efficiency in order to maximize the commercial opportunity of converting captured CO2 into cleaner fuel while also reducing CO2 emissions and the greenhouse effect. Goal The goal of Team 1’s Carbon Catcher project proposal is to design a cost-effective, scalable, and modular atmospheric carbon dioxide removal system that is capable of being utilized in a range of urban environments and may fit a variety of different customer requirements or requests

A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism

BACKGROUND: HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. METHODS AND FINDINGS: We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649) and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage site changes are associated with virological failure during PI therapy. CONCLUSIONS: HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy

Role of Minority Populations of Human Immunodeficiency Virus Type 1 in the Evolution of Viral Resistance to Protease Inhibitors

Human immunodeficiency virus type 1 (HIV-1) drug resistance results from the accumulation of mutations in the viral genes targeted by the drugs. These genetic changes, however, are commonly detected and monitored by techniques that only take into account the dominant population of plasma virus. Because HIV-1-infected patients harbor a complex and diverse mixture of virus populations, the mechanisms underlying the emergence and the evolution of resistance are not fully elucidated. Using techniques that allow the quantification of resistance mutations in minority virus species, we have monitored the evolution of resistance in plasma virus populations from patients failing protease inhibitor treatment. Minority populations with distinct resistance genotypes were detected in all patients throughout the evolution of resistance. The emergence of new dominant genotypes followed two possible mechanisms: (i) emergence of a new mutation in a currently dominant genotype and (ii) emergence of a new genotype derived from a minority virus species. In most cases, these population changes were associated with an increase in resistance at the expense of a reduction in replication capacity. Our findings provide a preliminary indication that minority viral species, which evolve independently of the majority virus population, can eventually become dominant populations, thereby serving as a reservoir of diversity and possibly accelerating the development of drug resistance