Look up: probing the vertical profile of new particle formation and growth in the planetary boundary layer with models and observations

2022 Summer.Includes bibliographical references.The processes of new particle formation (NPF) and growth are important contributors to cloud condensation nuclei (CCN) concentrations, and CCN are important for climate from their impact on planetary radiative forcing. While the general ubiquity and importance of NPF is understood, the vertical extent and governing mechanisms of NPF and growth in the lower troposphere are uncertain. We present a two-part analysis of the vertical profile of NPF during the HI-SCALE field campaign at the Southern Great Plains observatory in Oklahoma, USA. Firstly, we analyzed airborne and ground-based observations of four NPF events. Secondly, we used a column aerosol chemistry and microphysics model, along with the observations, to probe factors that influence the vertical profile of NPF. During HI-SCALE, we found several instances of enhanced NPF occurring several hundred meters above the surface; however, the spatio-temporal characteristics of the observed NPF made comparisons between airborne- and ground-based observations difficult. For six unique events, the model represented the observed NPF (or lack of NPF) and particle growth at the surface to within 10 nm. The model predicted enhanced NPF rates in the upper mixed layer, and this enhancement is primarily due to the temperature dependence in the NPF schemes. The simulations were sensitive to the initial vertical profile of gas-phase species from HI-SCALE, such that vertical mixing in the model either enhanced or suppressed NPF rates, aerosol number concentrations, and particle growth rates at the surface. Finally, our analysis provides insights for future field campaigns and modeling efforts investigating the vertical profile of NPF

Compositional Policy Priors

This paper describes a probabilistic framework for incorporating structured inductive biases into reinforcement learning. These inductive biases arise from policy priors, probability distributions over optimal policies. Borrowing recent ideas from computational linguistics and Bayesian nonparametrics, we define several families of policy priors that express compositional, abstract structure in a domain. Compositionality is expressed using probabilistic context-free grammars, enabling a compact representation of hierarchically organized sub-tasks. Useful sequences of sub-tasks can be cached and reused by extending the grammars nonparametrically using Fragment Grammars. We present Monte Carlo methods for performing inference, and show how structured policy priors lead to substantially faster learning in complex domains compared to methods without inductive biases.This work was supported by AFOSR FA9550-07-1-0075 and ONR N00014-07-1-0937. SJG was supported by a Graduate Research Fellowship from the NSF

Reading Peer Review

This Element presents the background contexts and histories of peer review, the data-handling sensitivities of this type of research, the typical properties of reports in the journal to which the authors had access, a taxonomy of the reports, and their sentiment arcs. This title is also available as Open Access on Cambridge Core

Molecular Identification of a Malaria Merozoite Surface Sheddase

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface “sheddase,” but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite

Does impaired O-2 delivery during exercise accentuate central and peripheral fatigue in patients with coexistent COPD-CHF?

Impairment in oxygen (O-2) delivery to the central nervous system (brain) and skeletal locomotor muscle during exercise has been associated with central and peripheral neuromuscular fatigue in healthy humans. From a clinical perspective, impaired tissue O-2 transport is a key pathophysiological mechanism shared by cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). in addition to arterial hypoxemic conditions in COPD, there is growing evidence that cerebral and muscle blood flow and oxygenation can be reduced during exercise in both isolated COPD and CHF. Compromised cardiac output due to impaired cardiopulmonary function/interactions and blood flow redistribution to the overloaded respiratory muscles (i.e., up arrow work of breathing) may underpin these abnormalities. Unfortunately, COPD and CHF coexist in almost a third of elderly patients making these mechanisms potentially more relevant to exercise intolerance. in this context, it remains unknown whether decreased O-2 delivery accentuates neuromuscular manifestations of central and peripheral fatigue in coexistent COPD-CHF If this holds true, it is conceivable that delivering a low-density gas mixture (heliox) through non-invasive positive pressure ventilation could ameliorate cardiopulmonary function/interactions and reduce the work of breathing during exercise in these patients. the major consequence would be increased O-2 delivery to the brain and active muscles with potential benefits to exercise capacity (i.e.,,central and peripheral neuromuscular fatigue, respectively). We therefore hypothesize that patients with coexistent COPD-CHF stop exercising prematurely due to impaired central motor drive and muscle contractility as the cardiorespiratory system fails to deliver sufficient O-2 to simultaneously attend the metabolic demands of the brain and the active limb muscles.Universidade Federal de São Paulo, Dept Med, Pulm Funct & Clin Exercise Physiol Unit SEFICE, Resp Div,Sch Med,UNIFESP, São Paulo, BrazilQueens Univ, Dept Med, Lab Clin Exercise Physiol, Div Resp & Crit Care Med, Kingston, ON K7L 3N6, CanadaQueens Univ, Dept Med, Resp Invest Unit, Div Resp & Crit Care Med, Kingston, ON K7L 3N6, CanadaGrenoble Alpes Univ, Lab HP2, Grenoble, FranceUniversidade Federal de São Paulo, Dept Med, Pulm Funct & Clin Exercise Physiol Unit SEFICE, Resp Div,Sch Med,UNIFESP, São Paulo, BrazilWeb of Scienc

Explaining Myanmar's Regime Transition: The Periphery is Central

In 2010, Myanmar (Burma) held its first elections after 22 years of direct military rule. Few compelling explanations for this regime transition have emerged. This article critiques popular accounts and potential explanations generated by theories of authoritarian ‘regime breakdown’ and ‘regime maintenance’. It returns instead to the classical literature on military intervention and withdrawal. Military regimes, when not terminated by internal factionalism or external unrest, typically liberalise once they feel they have sufficiently addressed the crises that prompted their seizure of power. This was the case in Myanmar. The military intervened for fear that political unrest and ethnic-minority separatist insurgencies would destroy Myanmar’s always-fragile territorial integrity and sovereignty. Far from suddenly liberalising in 2010, the regime sought to create a ‘disciplined democracy’ to safeguard its preferred social and political order twice before, but was thwarted by societal opposition. Its success in 2010 stemmed from a strategy of coercive state-building and economic incorporation via ‘ceasefire capitalism’, which weakened and co-opted much of the opposition. Having altered the balance of forces in its favour, the regime felt sufficiently confident to impose its preferred settlement. However, the transition neither reflected total ‘victory’ for the military nor secured a genuine or lasting peace

Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes

Daily rhythms in behaviour, physiology, and molecular processes are expected to enable organisms to appropriately schedule activities according to consequences of the daily rotation of the Earth. For parasites, this includes capitalizing on periodicity in transmission opportunities and for hosts/vectors, this may select for rhythms in immune defence. We examine rhythms in the density and infectivity of transmission forms (gametocytes) of rodent malaria parasites in the host’s blood, parasite development inside mosquito vectors, and potential for onwards transmission. Furthermore, we simultaneously test whether mosquitoes exhibit rhythms in susceptibility. We reveal that at night, gametocytes are twice as infective, despite being less numerous in the blood. Enhanced infectiousness at night interacts with mosquito rhythms to increase sporozoite burdens four-fold when mosquitoes feed during their rest phase. Thus, changes in mosquito biting time (due to bed nets) may render gametocytes less infective, but this is compensated for by the greater mosquito susceptibility

IL-36 signalling enhances a pro-tumorigenic phenotype in colon cancer cells with cancer cell growth restricted by administration of the IL-36R antagonist.

The IL-36 cytokines are a recently described subset of the IL-1 family of cytokines, shown to play a role in the pathogenesis of intestinal diseases such as Inflammatory Bowel Disease (IBD). Given the link between IBD and colitis -associated cancer, as well as the involvement of other IL-1 family members in intestinal tumorigenesis, the aim of this work was to investigate whether IL-36 cytokines play a role in the pathogenesis of colon cancer. Whilst research to date has focused on the role of IL-36 family members in augmenting the immune response to induce tumour rejection, very little remains known about IL-36R signalling in tumour cells in this context. In this study we demonstrate that expression of IL-36 family member mRNA and protein are significantly increased in colorectal cancer tissue compared to adjacent non-tumour. In vitro assays showed stimulation of colon cancer cell lines with IL-36R agonists resulted in the activation of the pro-tumorigenic phenotypes of increased cellular migration, invasion and proliferation in both 2D and 3D models. In addition, the IL-36 cytokines induced strong expression of pro-inflammatory chemokines in both human and murine cell lines. Intraperitoneal injection of IL-36Ra significantly reduced tumour burden using the subcutaneous CT26 tumour model in syngeneic Balb/mice, and this was associated with a decrease in Ki-67 expression by tumour cells in the IL-36Ra- treated group relative to untreated, suggesting the inhibition of the pro-proliferative signalling of IL-36 agonists resulted in the decreased tumour size. Moreover, colon cancer cells lacking the IL-36R also showed reduced tumour growth and reduced Ki-67 expression in vivo. Taken together, this data suggests that targeting IL-36R signalling may be a useful targeted therapy for colorectal cancer patients with IL-36R+ tumour cells