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"Long, T."
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Returns of war : South Vietnam and the price of refugee memory
\"Returns of War\" critically examines the Vietnam War and its implications for the lives and memories of Vietnamese refugees in the U.S.\"-- Provided by publisher.
Book
Enhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection
The CRISPR-Cas12a RNA-guided complexes have tremendous potential for nucleic acid detection but are limited to the picomolar detection limit without an amplification step. Here, we develop a platform with engineered crRNAs and optimized conditions that enabled us to detect various clinically relevant nucleic acid targets with higher sensitivity, achieving a limit of detection in the femtomolar range without any target pre-amplification step. By extending the 3′- or 5′-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discover a self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA and with significant improvement in specificity for target recognition. Particularly, the 7-mer DNA extension to crRNA is determined to be universal and spacer-independent for enhancing the sensitivity and specificity of LbCas12a-mediated nucleic acid detection. We perform a detailed characterization of our engineered ENHANCE system with various crRNA modifications, target types, reporters, and divalent cations. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs are incorporated in a paper-based lateral flow assay that can detect the target with up to 23-fold higher sensitivity within 40–60 min.
CRISPR-Cas12a based detection systems can be sensitive down to the picomolar range. Here the authors modify the 3′- and 5′-ends of the crRNA and show this enhances trans-cleavage for improved sensitivity.
Journal Article
Programmable RNA detection with CRISPR-Cas12a
Cas12a, a CRISPR-associated protein complex, has an inherent ability to cleave DNA substrates and is utilized in diagnostic tools to identify DNA molecules. We demonstrate that multiple orthologs of Cas12a activate trans-cleavage in the presence of split activators. Specifically, the PAM-distal region of the crRNA recognizes RNA targets provided that the PAM-proximal seed region has a DNA target. Our method, Split Activator for Highly Accessible RNA Analysis (SAHARA), detects picomolar concentrations of RNA without sample amplification, reverse-transcription, or strand-displacement by simply supplying a short DNA sequence complementary to the seed region. Beyond RNA detection, SAHARA outperforms wild-type CRISPR-Cas12a in specificity towards point-mutations and can detect multiple RNA and DNA targets in pooled crRNA/Cas12a arrays via distinct PAM-proximal seed DNAs. In conclusion, SAHARA is a simple, yet powerful nucleic acid detection platform based on Cas12a that can be applied in a multiplexed fashion and potentially be expanded to other CRISPR-Cas enzymes.
Cas12a is widely used in diagnostic platforms. Here the authors show that Cas12a can be programmed to directly detect RNA substrates, this is due to the 3’-end of the crRNA tolerating both RNA and DNA substrates: they use this to report a method, SAHARA, to detect RNA sequences.
Journal Article
Opportunities and Challenges for the Sustainability of Lakes and Reservoirs in Relation to the Sustainable Development Goals (SDGs)
Emerging global threats, such as biological invasions, climate change, land use intensification, and water depletion, endanger the sustainable future of lakes and reservoirs. To deal with these threats, a multidimensional view on the protection and exploitation of lakes and reservoirs is needed. The holistic approach needs to contain not just the development of economy and society but also take into account the negative impacts of this growth on the environment, from that, the balance between the three dimensions can be sustained to reach a sustainable future. As such, this paper provides a comprehensive review on future opportunities and challenges for the sustainable development of lakes and reservoirs via a critical analysis on their contribution to individual and subsets of the Sustainable Development Goals (SDGs). Currently, lakes and reservoirs are key freshwater resources. They play crucial roles in human societies for drinking water provision, food production (via fisheries, aquaculture, and the irrigation of agricultural lands), recreation, energy provision (via hydropower dams), wastewater treatment, and flood and drought control. Because of the (mostly) recent intensive exploitations, many lakes and reservoirs are severely deteriorated. In recent years, physical (habitat) degradation has become very important while eutrophication remains the main issue for many lakes and ponds worldwide. Besides constant threats from anthropogenic activities, such as urbanization, industry, aquaculture, and watercourse alterations, climate change and emerging contaminants, such as microplastics and antimicrobial resistance, can generate a global problem for the sustainability of lakes and reservoirs. In relation to the SDGs, the actions for achieving the sustainability of lakes and reservoirs have positive links with the SDGs related to environmental dimensions (Goals 6, 13, 14, and 15) as they are mutually reinforcing each other. On the other hand, these actions have direct potential conflicts with the SDGs related to social and economic dimensions (Goals 1, 2, 3 and 8). From these interlinkages, we propose 22 indicators that can be used by decision makers for monitoring and assessing the sustainable development of lakes and reservoirs.
Journal Article
Studying the Safety Impact of Autonomous Vehicles Using Simulation-Based Surrogate Safety Measures
Autonomous vehicle (AV) technology has advanced rapidly in recent years with some automated features already available in vehicles on the market. AVs are expected to reduce traffic crashes as the majority of crashes are related to driver errors, fatigue, alcohol, or drugs. However, very little research has been conducted to estimate the safety impact of AVs. This paper aims to investigate the safety impacts of AVs using a simulation-based surrogate safety measure approach. To this end, safety impacts are explored through the number of conflicts extracted from the VISSIM traffic microsimulator using the Surrogate Safety Assessment Model (SSAM). Behaviours of human-driven vehicles (HVs) and AVs (level 4 automation) are modelled within the VISSIM’s car-following model. The safety investigation is conducted for two case studies, that is, a signalised intersection and a roundabout, under various AV penetration rates. Results suggest that AVs improve safety significantly with high penetration rates, even when they travel with shorter headways to improve road capacity and reduce delay. For the signalised intersection, AVs reduce the number of conflicts by 20% to 65% with the AV penetration rates of between 50% and 100% (statistically significant at p<0.05). For the roundabout, the number of conflicts is reduced by 29% to 64% with the 100% AV penetration rate (statistically significant at p<0.05).
Journal Article
Host DNases prevent vascular occlusion by neutrophil extracellular traps
Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia. In the absence of both DNases, intravascular NETs formed clots that obstructed blood vessels and caused organ damage. Vascular occlusions in patients with severe bacterial infections were associated with a defect to degrade NETs ex vivo and the formation of intravascular NET clots. DNase1 and DNase1-like 3 are independently expressed and thus provide dual host protection against deleterious effects of intravascular NETs.
Journal Article
The Vietnam-Corona Quagmire: Rescripting Forever Wars in a Time of Chronic Crisis
This essay considers the legacies of the Viet Nam-American War through the lens of contemporary events of global scale such as the COVID-19 pandemic. The fiftieth anniversary since the end of that conflict occurs right after the cessation (but not end) of the worst socio-health crisis facing the planet and humanity in recent times. As a frame for remembering militarized Cold War histories in the face of ongoing crises and political quagmires, I consider how the Cold War specter of Viet Nam has been marshalled against biopolitical threats in the twenty-first century. That cultural and ideological rescripting reinforces racial, colonial, capitalist, and imperialist logics of control that simultaneously invite us to revisit and refashion that infamous war’s meaning. I approach the “war on coronavirus” through the prism of “Vietnam” to conceptualize what I am designating as “corona-quagmire.” By looping conflicts of the past into the cascading crises of the present future, corona-quagmire presents critical opportunities for rethinking the fraught global relations among society, self, subjects and states. From the spread of disinformation to America’s mishandling of the new coronavirus to Viet Nam’s martial response to the problem, the “Vietnam-sized” language mobilized against COVID-19 presents a means to analyze the dialectics of permanent wars, as they are reproduced within an era of endless violence. Corona-quagmire in the end shines light for scholars seeking to disentangle ongoing processes of militarization, nationalism, and empire.
Journal Article