Longwave Band-by-band Cloud Radiative Effect and its Application in GCM Evaluation

The cloud radiative effect (CRE) of each longwave (LW) absorption band of a GCM fs radiation code is uniquely valuable for GCM evaluation because (1) comparing band-by-band CRE avoids the compensating biases in the broadband CRE comparison and (2) the fractional contribution of each band to the LW broadband CRE (f(sub CRE)) is sensitive to cloud top height but largely insensitive to cloud fraction, presenting thus a diagnostic metric to separate the two macroscopic properties of clouds. Recent studies led by the first author have established methods to derive such band ]by ]band quantities from collocated AIRS and CERES observations. We present here a study that compares the observed band-by-band CRE over the tropical oceans with those simulated by three different atmospheric GCMs (GFDL AM2, NASA GEOS-5, and CCCma CanAM4) forced by observed SST. The models agree with observation on the annual ]mean LW broadband CRE over the tropical oceans within +/-1W/sq m. However, the differences among these three GCMs in some bands can be as large as or even larger than +/-1W/sq m. Observed seasonal cycles of f(sub CRE) in major bands are shown to be consistent with the seasonal cycle of cloud top pressure for both the amplitude and the phase. However, while the three simulated seasonal cycles of f(sub CRE) agree with observations on the phase, the amplitudes are underestimated. Simulated interannual anomalies from GFDL AM2 and CCCma CanAM4 are in phase with observed anomalies. The spatial distribution of f(sub CRE) highlights the discrepancies between models and observation over the low-cloud regions and the compensating biases from different bands

Citizen Engagement in Aquatics Equity: The Case of Winston Waterworks

Historically, swimming pools have been a source of inequity when it comes to the distribution of recreation services in the United States. Many of the problems that correlate with the inequitable allocation of recreation resources including public swimming pools began with ideas about race, geography, poor planning practices and faulty policymaking (Rothstein, 2017). Moreover, one of the primary outcomes of engaged, inclusive planning is equity in the provision of recreation programs and facilities. In this essay, we offer a summary of key legal cases that help address questions related resource allocation related to public swimming pools. Finally, we present a short case study on the Winston Water Works Project in Winston-Salem, North Carolina. This case illustrates the power of grassroots level advocacy, engaged community planning, and policymaking that protects the recreation infrastructure in a community and moves the needle of social justice toward equity. Our principle interest in this paper is in the equitable provision and distribution of aquatics programming and facilities

Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.

Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity-a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish

Heparan sulfate modulates neutrophil and endothelial function in antibacterial innate immunity

Recently, we showed that endothelial heparan sulfate facilitates entry of a bacterial pathogen into the central nervous system. Here, we show that normal bactericidal activity of neutrophils is influenced by the sulfation pattern of heparan sulfate. Inactivation of heparan sulfate uronyl 2-O-sulfotransferase (Hs2st) in neutrophils substantially reduced their bactericidal activity, and Hs2st deficiency rendered mice more susceptible to systemic infection with the pathogenic bacterium group B Streptococcus. Specifically, altered sulfation of heparan sulfate in mutant neutrophils affected formation of neutrophil extracellular traps while not influencing phagocytosis, production of reactive oxygen species, or secretion of granular proteases. Heparan sulfate proteoglycan(s) is present in neutrophil extracellular traps, modulates histone affinity, and modulates their microbial activity. Hs2st-deficient brain endothelial cells show enhanced binding to group B Streptococcus and are more susceptible to apoptosis, likely contributing to the observed increase in dissemination of group B Streptococcus into the brain of Hs2st-deficient mice following intravenous challenge. Taken together, our data provide strong evidence that heparan sulfate from both neutrophils and the endothelium plays important roles in modulating innate immunity

Trigger for group A streptococcal M1T1 invasive disease

The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of highly invasive human diseases. The transition from local to systemic infection occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known to express significantly less cysteine protease SpeB than M1T1 isolates from local infections. Here, we show that in comparison to the M1T1 strain 5448, the isogenic mutant ΔspeB accumulated 75‐fold more human plasmin activity on the bacterial surface following incubation in human plasma. Human plasminogen was an absolute requirement for M1T1 strain 5448 virulence following subcutaneous (s.c.) infection of humanized plasminogen transgenic mice. S. pyogenes M1T1 isolates from the blood of infected humanized plasminogen transgenic mice expressed reduced levels of SpeB in comparison with the parental 5448 used as inoculum. We propose that the human plasminogen system plays a critical role in group A streptococcal M1T1 systemic disease initiation. SpeB is required for S. pyogenes M1T1 survival at the site of local infection, however, SpeB also disrupts the interaction of S. pyogenes M1T1 with the human plasminogen activation system. Loss of SpeB activity in a subpopulation of S. pyogenes M1T1 at the site of infection results in accumulation of surface plasmin activity thus triggering systemic spread.—Cole, J. N., McArthur, J. D., McKay, F. C., Sanderson‐Smith, M. L., Cork, A. J., Ranson, M., Rohde, M., Itzek, A., Sun, H., Ginsburg, D., Kotb, M., Nizet, V., Chhatwal, G. S., Walker, M. J. Trigger for group A streptococcal M1T1 invasive disease. FASEB J. 20, E1139–E1145 (2006)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154248/1/fsb2fj065804fje.pd

Shortwave radiative forcing, rapid adjustment, and feedback to the surface by sulfate geoengineering: analysis of the Geoengineering Model Intercomparison Project G4 scenario

This study evaluates the forcing, rapid adjustment, and feedback of net shortwave radiation at the surface in the G4 experiment of the Geoengineering Model Intercomparison Project by analysing outputs from six participating models. G4 involves injection of 5 Tg yr(-1) of SO2, a sulfate aerosol precursor, into the lower stratosphere from year 2020 to 2069 against a background scenario of RCP4.5. A single-layer atmospheric model for shortwave radiative transfer is used to estimate the direct forcing of solar radiation management (SRM), and rapid adjustment and feedbacks from changes in the water vapour amount, cloud amount, and surface albedo (compared with RCP4.5). The analysis shows that the globally and temporally averaged SRM forcing ranges from -3.6 to -1.6 W m(-2), depending on the model. The sum of the rapid adjustments and feedback effects due to changes in the water vapour and cloud amounts increase the downwelling shortwave radiation at the surface by approximately 0.4 to 1.5 W m(-2) and hence weaken the effect of SRM by around 50 %. The surface albedo changes decrease the net shortwave radiation at the surface; it is locally strong (∼ −4 W m(-2)) in snow and sea ice melting regions, but minor for the global average. The analyses show that the results of the G4 experiment, which simulates sulfate geoengineering, include large inter-model variability both in the direct SRM forcing and the shortwave rapid adjustment from change in the cloud amount, and imply a high uncertainty in modelled processes of sulfate aerosols and clouds

New Models of Tetrahymena Telomerase RNA from Experimentally Derived Constraints and Modeling

The telomerase ribonucleoprotein complex ensures complete replication of eukaryotic chromosomes. Telomerase RNA, TER, provides the template for replicating the G-rich strand of telomeric DNA, provides an anchor site for telomerase-associated proteins, and participates in catalysis through several incompletely characterized mechanisms. A major impediment towards understanding its non-templating roles is the absence of high content structural information for TER within the telomerase complex. Here, we used selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) to examine the structure of Tetrahymena TER free in solution and bound to tTERT in the minimal telomerase RNP. We discovered a striking difference in the two conformations and established direct evidence for base pair triples in the tTER pseudoknot. We then used SHAPE data, previously published FRET data, and biochemical inference to model the structure of tTER using discrete molecular dynamics simulations. The resulting tTER structure was docked with a homology model of tTERT to characterize the conformational changes of tTER that attend binding to tTERT. Free in solution, tTER appears to contain four pairing regions: stems I, II, and IV, which are present in the commonly accepted structure, and stem III, a large paired region that encompasses the template and pseudoknot domains. Our interpretation of the data and subsequent modeling affords a molecular model for telomerase assemblage in which a large stem III of tTER unwinds to allow proper association of the template with the tTERT active site and formation of the pseudoknot. Additionally, analysis of our SHAPE data and previous enzymatic footpinting allows us to propose a model for stem-loop IV function in which tTERT is activated by binding stem IV in the major grove of the helix-capping loop

Pain and temperature processing in dementia: a clinical and neuroanatomical analysis

Symptoms suggesting altered processing of pain and temperature have been described in dementia diseases and may contribute importantly to clinical phenotypes, particularly in the frontotemporal lobar degeneration spectrum, but the basis for these symptoms has not been characterized in detail. Here we analysed pain and temperature symptoms using a semi-structured caregiver questionnaire recording altered behavioural responsiveness to pain or temperature for a cohort of patients with frontotemporal lobar degeneration (n = 58, 25 female, aged 52–84 years, representing the major clinical syndromes and representative pathogenic mutations in the C9orf72 and MAPT genes) and a comparison cohort of patients with amnestic Alzheimer’s disease (n = 20, eight female, aged 53–74 years). Neuroanatomical associations were assessed using blinded visual rating and voxel-based morphometry of patients’ brain magnetic resonance images. Certain syndromic signatures were identified: pain and temperature symptoms were particularly prevalent in behavioural variant frontotemporal dementia (71% of cases) and semantic dementia (65% of cases) and in association with C9orf72 mutations (6/6 cases), but also developed in Alzheimer’s disease (45% of cases) and progressive non-fluent aphasia (25% of cases). While altered temperature responsiveness was more common than altered pain responsiveness across syndromes, blunted responsiveness to pain and temperature was particularly associated with behavioural variant frontotemporal dementia (40% of symptomatic cases) and heightened responsiveness with semantic dementia (73% of symptomatic cases) and Alzheimer’s disease (78% of symptomatic cases). In the voxel-based morphometry analysis of the frontotemporal lobar degeneration cohort, pain and temperature symptoms were associated with grey matter loss in a right-lateralized network including insula (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest) and anterior temporal cortex (P < 0.001 uncorrected over whole brain) previously implicated in processing homeostatic signals. Pain and temperature symptoms accompanying C9orf72 mutations were specifically associated with posterior thalamic atrophy (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest). Together the findings suggest candidate cognitive and neuroanatomical bases for these salient but under-appreciated phenotypic features of the dementias, with wider implications for the homeostatic pathophysiology and clinical management of neurodegenerative diseases

Routine activities and proactive police activity: a macro-scale analysis of police searches in London and New York City

This paper explored how city-level changes in routine activities were associated with changes in frequencies of police searches using six years of police records from the London Metropolitan Police Service and the New York City Police Department. Routine activities were operationalised through selecting events that potentially impacted on (a) the street population, (b) the frequency of crime or (c) the level of police activity. OLS regression results indicated that routine activity variables (e.g. day of the week, periods of high demand for police service) can explain a large proportion of the variance in search frequency throughout the year. A complex set of results emerged, revealing cross-national dissimilarities and the differential impact of certain activities (e.g. public holidays). Importantly, temporal frequencies in searches are not reducible to associations between searches and recorded street crime, nor changes in on-street population. Based on the routine activity approach, a theoretical police-action model is proposed

Effects of forcing differences and initial conditions on inter-model agreement in the VolMIP volc-pinatubo-full experiment

International audienceThis paper provides initial results from a multi-model ensemble analysis based on the volc-pinatubo-full experiment performed within the Model Intercomparison Project on the climatic response to volcanic forcing (VolMIP) as part of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The volc-pinatubo-full experiment is based on ensemble of volcanic forcing-only climate simulations with the same volcanic aerosol dataset across the participating models (the 1991-1993 Pinatubo period from the CMIP6-GloSSAC dataset). The simulations are conducted within an idealized experimental design where initial states are sampled consistently across models from the CMIP6-piControl simulation providing unperturbed pre-industrial background conditions. The multi-model ensemble includes output from an initial set of six participating Earth system models (CanESM5, GISS-E2.1-G, IPSL-CM6A-LR, MIROC-E2SL, MPI-ESM1.2-LR and UKESM1).The results show overall good agreement between the different models on the global and hemispheric scale concerning the surface climate responses, thus demonstrating the overall effectiveness of VolMIP’s experimental design. However, small yet significant inter-model discrepancies are found in radiative fluxes especially in the tropics, that preliminary analyses link with minor differences in forcing implementation, model physics, notably aerosol-radiation interactions, the simulation and sampling of El Niño-Southern Oscillation (ENSO) and, possibly, the simulation of climate feedbacks operating in the tropics. We discuss the volc-pinatubo-full protocol and highlight the advantages of volcanic forcing experiments defined within a carefully designed protocol with respect to emerging modeling approaches based on large ensemble transient simulations. We identify how the VolMIP strategy could be improved in future phases of the initiative to ensure a cleaner sampling protocolwith greater focus on the evolving state of ENSO in the pre-eruption period