A
bstract
We consider extensions of the Standard Model by vectorlike leptons and set limits on a new charged lepton,
e
4
±
, using the ATLAS search for anomalous production of multi-lepton events. It ...is assumed that only one Standard Model lepton, namely the muon, dominantly mixes with vectorlike leptons resulting in possible decays
e
4
±
→
W
±
ν
μ
,
e
4
±
→
Zμ
±
, and
e
4
±
→
hμ
±
. We derive generally applicable limits on the new lepton treating the branching ratios for these processes as free variables. We further interpret the general limits in two scenarios with
e
4
±
originating predominantly from either the SU(2) doublet or the SU(2) singlet. The doublet case is more constrained as a result of larger production cross-section and extra production processes
e
4
±
ν
4
and
ν
4
ν
4
in addition to
e
4
±
e
4
−
, where
ν
4
is a new neutral state accompanying
e
4
. We find that some combinations of branching ratios are poorly constrained, whereas some are constrained up to masses of more than 500 GeV. In the doublet case, assuming BR(
ν
4
→
Wμ
) = 1, all masses below about 300 GeV are ruled out. Even if this condition is relaxed and additional decay modes,
ν
4
→
Zν
μ
and
ν
4
→
hν
μ
, are allowed, below the Higgs threshold still almost all of the parameter space (of independent branching ratios) is ruled out. Nevertheless, even assuming the maximal production cross-section, which coincides with the doublet case, the new charged lepton can still be as light as the LEP-II limit allows. We discuss several possible improvements of current experimental analyses that would dramatically reduce the allowed parameter space, even with current data.
The severe acute respiratory syndrome coronavirus (SARS‐COV‐2) that causes COVID‐19 has had a devastating impact on human populations, infrastructure, and economies. The structures and systems that ...supply people with their basic needs have been stressed by the necessary changes COVID‐19 has rendered in everyday life. Here I explore the potential role of wild food provisioning in mitigating the acute impacts of COVID on food supply and its impacts more broadly on modern foodways. Wild food provisioning is a waning practice among human populations in the Global North, but recent research has shown that there are significant amounts of food produced and harvested on the landscape that go unaccounted for in food systems research. Building on this work, I theorize a framework for thinking about food systems that are inclusive of wild food provisioning practices and how said framework might increase the ability of human populations to withstand extreme disturbances such as a global pandemic.
Tolling roads to improve reliability Hall, Jonathan D.; Savage, Ian
Journal of urban economics,
September 2019, 2019-09-00, Letnik:
113
Journal Article
Recenzirano
A significant cost of traffic congestion is unreliable travel times. A major source of this unreliability is that when roads are congested, interactions between drivers can lead to capacity ...unexpectedly falling. For example, collisions can close lanes and aggressive lane changers can slow traffic. This paper analyzes how tolls should be set when accounting for such endogenous reliability. We find tolls should be higher and maximum flow lower than we might naïvely expect; and that such tolls make homogeneous drivers better off, even before the toll revenue is used. Simulations suggest the socially optimal maximum departure rate is 15% below that which maximizes expected throughput, and that tolling reduces private costs by almost 10%.
Can better methods be developed to evaluate the performance and characteristics of an artificial intelligence model for evaluating the likelihood of clinical pregnancy based on analysis of day-5 ...blastocyst-stage embryos, such that performance evaluation more closely reflects clinical use in IVF procedures, and correlations with known features of embryo quality are identified?
De-identified images were provided retrospectively or collected prospectively by IVF clinics using the artificial intelligence model in clinical practice. A total of 9359 images were provided by 18 IVF clinics across six countries, from 4709 women who underwent IVF between 2011 and 2021. Main outcome measures included clinical pregnancy outcome (fetal heartbeat at first ultrasound scan), embryo morphology score, and/or pre-implantation genetic testing for aneuploidy (PGT-A) results.
A positive linear correlation of artificial intelligence scores with pregnancy outcomes was found, and up to a 12.2% reduction in time to pregnancy (TTP) was observed when comparing the artificial intelligence model with standard morphological grading methods using a novel simulated cohort ranking method. Artificial intelligence scores were significantly correlated with known morphological features of embryo quality based on the Gardner score, and with previously unknown morphological features associated with embryo ploidy status, including chromosomal abnormalities indicative of severity when considering embryos for transfer during IVF.
Improved methods for evaluating artificial intelligence for embryo selection were developed, and advantages of the artificial intelligence model over current grading approaches were highlighted, strongly supporting the use of the artificial intelligence model in a clinical setting.
MicroRNAs (miRNAs) are short noncoding RNAs, which bind to messenger RNAs and regulate protein expression. The biosynthesis of miRNAs includes two precursors, a primary miRNA transcript (pri-miRNA) ...and a shorter pre-miRNA, both of which carry a common stem-loop bearing the mature miRNA. MiR-122 is a liver-specific miRNA with an important role in the life cycle of hepatitis C virus (HCV). It is the target of miravirsen (SPC3649), an antimiR drug candidate currently in clinical testing for treatment of HCV infections. Miravirsen is composed of locked nucleic acid (LNAs) ribonucleotides interspaced throughout a DNA phosphorothioate sequence complementary to mature miR-122. The LNA modifications endow the drug with high affinity for its target and provide resistance to nuclease degradation. While miravirsen is thought to work mainly by hybridizing to mature miR-122 and blocking its interaction with HCV RNA, its target sequence is also present in pri- and pre-miR-122. Using new in vitro and cellular assays specifically developed to discover ligands that suppress biogenesis of miR-122, we show that miravirsen binds to the stem-loop structure of pri- and pre-miR-122 with nanomolar affinity, and inhibits both Dicer- and Drosha-mediated processing of miR-122 precursors. This inhibition may contribute to the pharmacological activity of the drug in man.
Macrophages are conventionally classified as pro-inflammatory (M1) and anti-inflammatory (M2) functional types. There is evidence for a predominance of macrophages with an inflammatory phenotype (M1) ...in the rheumatoid arthritis (RA) synovium. MicroRNAs (miRs) play a pivotal role in regulating the inflammatory response in innate immune cells and are found at dysregulated levels in RA patients. Here we explored miRs that tune the inflammatory function of M2-macrophages.
Expression profiles of miR-221-3p and miR-155-5p were analyzed in clinical samples from RA, other inflammatory arthritis (OIA), osteoarthritis (OA), and healthy donors (HD) by qPCR.
generated macrophages were transfected with miR-mimics and inhibitors. Transcriptome profiling through RNA-sequencing was performed on M2-macrophages overexpressing miR-221-3p mimic with or without LPS treatment. Secretion of IL-6, IL-10, IL-12, IL-8, and CXCL13 was measured in M1- and M2-macrophages upon TLR2/TLR3/TLR4-stimulation using ELISA. Inflammatory pathways including NF-κB, IRF3, MAPKs, and JAK3/STAT3 were evaluated by immunoblotting. Direct target interaction of miR-221-3p and predicted target sites in 3'UTR of JAK3 were examined by luciferase reporter gene assay.
miR-221-3p in synovial tissue and fluid was increased in RA vs. OA or OIA. Endogenous expression levels of miR-221-3p and miR-155-5p were higher in M1- than M2-macrophages derived from RA patients or HD. TLR4-stimulation of M1- and M2-macrophages resulted in downregulation of miR-221-3p, but upregulation of miR-155-5p. M2-macrophages transfected with miR-221-3p mimics secreted less IL-10 and CXCL13 but more IL-6 and IL-8, exhibited downregulation of JAK3 protein and decreased pSTAT3 activation. JAK3 was identified as new direct target of miR-221-3p in macrophages. Co-transfection of miR-221-3p/miR-155-5p mimics in M2-macrophages increased M1-specific IL-12 secretion.
miR-221-3p acts as a regulator of TLR4-induced inflammatory M2-macrophage function by directly targeting JAK3. Dysregulated miR-221-3p expression, as seen in synovium of RA patients, leads to a diminished anti-inflammatory response and drives M2-macrophages to exhibit a M1-cytokine profile.
Splicing modifiers promoting SMN2 exon 7 inclusion have the potential to treat spinal muscular atrophy, the leading genetic cause of infantile death. These small molecules are SMN2 exon 7 selective ...and act during the early stages of spliceosome assembly. Here, we show at atomic resolution how the drug selectively promotes the recognition of the weak 5' splice site of SMN2 exon 7 by U1 snRNP. The solution structure of the RNA duplex formed following 5' splice site recognition in the presence of the splicing modifier revealed that the drug specifically stabilizes a bulged adenine at this exon-intron junction and converts the weak 5' splice site of SMN2 exon 7 into a stronger one. The small molecule acts as a specific splicing enhancer cooperatively with the splicing regulatory network. Our investigations uncovered a novel concept for gene-specific alternative splicing correction that we coined 5' splice site bulge repair.
Progress in the calculation of the electromagnetic properties of baryon excitations in lattice QCD presents new challenges in the determination of sea-quark loop contributions to matrix elements. A ...reliable estimation of the sea-quark loop contributions represents a pressing issue in the accurate comparison of lattice QCD results with experiment. In this article, an extension of the graded symmetry approach to partially quenched QCD is presented, which builds on previous theory by explicitly including flavor-singlet baryons in its construction. The formalism takes into account the interactions among both octet and singlet baryons, octet mesons, and their ghost counterparts; the latter enables the isolation of the quark-flow disconnected sea-quark loop contributions. The introduction of flavor-singlet states enables systematic studies of the internal structure of Λ-baryon excitations in lattice QCD, including the topical Λ(1405).
For Bakhtin "dialogism" is the basis of consciousness and its potential for change. But it can also be the scene of a struggle to prevent change. The unconscious is produced out of this repressive ...struggle to achieve or maintain hegemony.
How does war shape human altruism? Some find warfare increases generosity within groups only. Others maintain that war's prosocial effects extend to outgroup members as well. To make sense of these ...disparate findings, we offer a theoretical framework that highlights the role of threat sensitivity in altruism. Refugees from Syria and Iraq (N = 1521) completed a welfare tradeoff task and threat perceptions scale where the other's group identity, gender and age were experimentally varied. We found that individuals belonging to social categories associated with more threat (outgroup members, males, and younger individuals) were afforded less altruism compared to individuals belonging to non-threatening social categories (ingroup members, females and the elderly). War exposure enhanced bias against threatening social categories through increased threat-sensitivity. Our results have implications for understanding how warfare shapes altruism and welfare tradeoffs in light of cross-cutting social categories and for policies promoting post-conflict cooperation.
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