107 research outputs found
Evaluating Future Nanotechnology: The Net Societal Impacts of Atomically Precise Manufacturing
Atomically precise manufacturing (APM) is the assembly of materials with atomic precision. APM does not currently exist, and may not be feasible, but if it is feasible, then the societal impacts could be dramatic. This paper assesses the net societal impacts of APM across the full range of important APM sectors: general material wealth, environmental issues, military affairs, surveillance, artificial intelligence, and space travel. Positive effects were found for material wealth, the environment, military affairs (specifically nuclear disarmament), and space travel. Negative effects were found for military affairs (specifically rogue actor violence and AI. The net effect for surveillance was ambiguous. The effects for the environment, military affairs, and AI appear to be the largest, with the environment perhaps being the largest of these, suggesting that APM would be net beneficial to society. However, these factors are not well quantified and no definitive conclusion can be made. One conclusion that can be reached is that if APM R&D is pursued, it should go hand-in-hand with effective governance strategies to increase the benefits and reduce the harms
The Benefits and Harms of Transmitting Into Space
Deliberate and unintentional radio transmissions from Earth propagate into
space. These transmissions could be detected by extraterrestrial watchers over
interstellar distances. Here, we analyze the harms and benefits of deliberate
and unintentional transmissions relevant to Earth and humanity. Comparing the
magnitude of deliberate radio broadcasts intended for messaging to
extraterrestrial intelligence (METI) with the background radio spectrum of
Earth, we find that METI attempts to date have much lower detectability than
emissions from current radio communication technologies on Earth. METI
broadcasts are usually transient and several orders of magnitude less powerful
than other terrestrial sources such as astronomical and military radars, which
provide the strongest detectable signals. The benefits of radio communication
on Earth likely outweigh the potential harms of detection by extraterrestrial
watchers; however, the uncertainty regarding the outcome of contact with
extraterrestrial beings creates difficulty in assessing whether or not to
engage in long-term and large-scale METI.Comment: Published in Space Polic
Long-Term Trajectories of Human Civilization
Purpose
This paper aims to formalize long-term trajectories of human civilization as a scientific and ethical field of study. The long-term trajectory of human civilization can be defined as the path that human civilization takes during the entire future time period in which human civilization could continue to exist.
Design/methodology/approach
This paper focuses on four types of trajectories: status quo trajectories, in which human civilization persists in a state broadly similar to its current state into the distant future; catastrophe trajectories, in which one or more events cause significant harm to human civilization; technological transformation trajectories, in which radical technological breakthroughs put human civilization on a fundamentally different course; and astronomical trajectories, in which human civilization expands beyond its home planet and into the accessible portions of the cosmos.
Findings
Status quo trajectories appear unlikely to persist into the distant future, especially in light of long-term astronomical processes. Several catastrophe, technological transformation and astronomical trajectories appear possible.
Originality/value
Some current actions may be able to affect the long-term trajectory. Whether these actions should be pursued depends on a mix of empirical and ethical factors. For some ethical frameworks, these actions may be especially important to pursue
Would contact with extraterrestrials benefit or harm humanity? A scenario analysis
While humanity has not yet observed any extraterrestrial intelligence (ETI),
contact with ETI remains possible. Contact could occur through a broad range of
scenarios that have varying consequences for humanity. However, many
discussions of this question assume that contact will follow a particular
scenario that derives from the hopes and fears of the author. In this paper, we
analyze a broad range of contact scenarios in terms of whether contact with ETI
would benefit or harm humanity. This type of broad analysis can help us prepare
for actual contact with ETI even if the details of contact do not fully
resemble any specific scenario.Comment: 33 Pages, 1 Figure, PDF Fil
Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry
Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. Epub 2023 Jun 1.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227232/Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a βreal-worldβ setting. Untreated lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.Dr Martin is supported by grants/contracts from the American Heart Association (20SFRN35380046, 20SFRN35490003, 878924, and 882415), PatientβCentered Outcomes Research Institute (PCORI) (MEβ2019C1β15328), National Institutes of Health (NIH) (R01AG071032 and P01 HL108800), the David and June Trone Family Foundation, Pollin Digital Health Innovation Fund, and Sandra and Larry Small; Dr Knowles is supported by the NIH through grants P30 DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236; and by a grant from the Bilateral Science Foundation. Dr Linton is supported by NIH grants P01HL116263, HL148137, HL159487, and HL146134.info:eu-repo/semantics/publishedVersio
Distinct in vitro binding properties of the anti-CD20 small modular immunopharmaceutical 2LM20-4 result in profound and sustained in vivo potency in cynomolgus monkeys
Objectives. To characterize the in vitro binding and effector function properties of CD20-directed small modular immunopharmaceutical (SMIP) 2LM20-4, and to compare its in vivo B-cell depletion activity with the mutated 2LM20-4 P331S [no in vitro complement-dependent cytotoxicity (CDC)] and rituximab in cynomolgus monkeys
Stochastic Expression of the Interferon-Ξ² Gene
The analysis of stochastic interferon-beta gene expression in virus-infected mammalian cells reveals that the levels of components required for virtually every step in the virus induction pathway are limiting
The 3β² Untranslated Regions of Influenza Genomic Sequences Are 5β²PPP-Independent Ligands for RIG-I
Retinoic acid inducible gene-I (RIG-I) is a key regulator of antiviral immunity. RIG-I is generally thought to be activated by ssRNA species containing a 5β²-triphosphate (PPP) group or by unphosphorylated dsRNA up to βΌ300 bp in length. However, it is not yet clear how changes in the length, nucleotide sequence, secondary structure, and 5β² end modification affect the abilities of these ligands to bind and activate RIG-I. To further investigate these parameters in the context of naturally occurring ligands, we examined RNA sequences derived from the 5β² and 3β² untranslated regions (UTR) of the influenza virus NS1 gene segment. As expected, RIG-I-dependent interferon-Ξ² (IFN-Ξ²) induction by sequences from the 5β² UTR of the influenza cRNA or its complement (26 nt in length) required the presence of a 5β²PPP group. In contrast, activation of RIG-I by the 3β² UTR cRNA sequence or its complement (172 nt) exhibited only a partial 5β²PPP-dependence, as capping the 5β² end or treatment with CIP showed a modest reduction in RIG-I activation. Furthermore, induction of IFN-Ξ² by a smaller, U/A-rich region within the 3β² UTR was completely 5β²PPP-independent. Our findings demonstrated that RNA sequence, length, and secondary structure all contributed to whether or not the 5β²PPP moiety is needed for interferon induction by RIG-I
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