Rapid pulsations in sub-THz solar bursts

A new solar burst emission spectral component has been found showing sub-THz fluxes increasing with frequency, spectrally separated from the well known microwave component. Rapid pulsations are found present in all events observed at the two frequencies of the solar submillimeter-wave telescope (SST): 212 and 405 GHz. They were studied in greater detail for three solar bursts exhibiting the new THz spectral component. The pulse amplitudes are of about 5-8% of the mean flux throughout the bursts durations, being comparable for both frequencies. Pulsations range from one pulse every few seconds to 8-10 per second. The pulse repetition rates (R) are linearly proportional to the mean burst fluxes (S), following the simple relationship S = k R, suggesting that the pulsations might be the response to discrete flare particle accelerator injections quantized in energy. Although this result is consistent with qualitative trends previously found in the GHz range, the pulse amplitude relative to the mean fluxes at the sub-THz frequencies appear to be nearly ten times smaller than expected from the extrapolation of the trends found in the GHz range. However there are difficulties to reconcile the nearly simultaneous GHz and THz burst emission spectrally separated components, exhibiting rapid pulsations with considerably larger relative intensities in the GHz range.Comment: 9 pages and 11 figures, submitted to Astrophys. J; Revised version accepted by ApJ on 4 March 200

Sub-terahertz, microwaves and high energy emissions during the December 6, 2006 flare, at 18:40 UT

The presence of a solar burst spectral component with flux density increasing with frequency in the sub-terahertz range, spectrally separated from the well-known microwave spectral component, bring new possibilities to explore the flaring physical processes, both observational and theoretical. The solar event of 6 December 2006, starting at about 18:30 UT, exhibited a particularly well-defined double spectral structure, with the sub-THz spectral component detected at 212 and 405 GHz by SST and microwaves (1-18 GHz) observed by the Owens Valley Solar Array (OVSA). Emissions obtained by instruments in satellites are discussed with emphasis to ultra-violet (UV) obtained by the Transition Region And Coronal Explorer (TRACE), soft X-rays from the Geostationary Operational Environmental Satellites (GOES) and X- and gamma-rays from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI). The sub-THz impulsive component had its closer temporal counterpart only in the higher energy X- and gamma-rays ranges. The spatial positions of the centers of emission at 212 GHz for the first flux enhancement were clearly displaced by more than one arc-minute from positions at the following phases. The observed sub-THz fluxes and burst source plasma parameters were found difficult to be reconciled to a purely thermal emission component. We discuss possible mechanisms to explain the double spectral components at microwaves and in the THz ranges.Comment: Accepted version for publication in Solar Physic

Launch of solar coronal mass ejections and submillimeter pulse bursts

The rapid solar spikes (100-500 ms) recently discovered at submillimeter waves bring new possibilities to investigate energetic processes near the solar surface that might have an important role in the launch and propelling of ionized mass away from the Sun. We present a study on the association between the launch time of coronal mass ejections (CMEs) observed by the LASCO instruments on the SOHO spacecraft and the onset of the new kind of rapid solar spikes (100-500 ms) observed at submillimetric waves (212 and 405 GHz) by the new Solar Submm-wave Telescope (SST). We investigated six submm-wave events, all found associated to CMEs. Seven related CME were identified. Five of them were associated with flares with large GOES class soft X-rays, presenting distinct time histories and associations at other energy ranges, and two of them were related to flares behind the solar limb, with simultaneous related activity observed in the visible solar disk. Ultraviolet images from EIT on SOHO show some kind of small or large-scale magnetic activity or brightening for all events. The extrapolation of apparent CME positions to the solar surface show that they occurred nearly coincident in time with the onset of submm-wave pulses for all six events. These results suggest that pulse bursts might be representative of an important early signature of CMEs, especially for events beginning near the center of the solar disk, sometimes identified as "halo" CMEs. They lead to several challenging questions relative to the physical nature of the pulses and its association to the launch and acceleration of coronal mass ejections. Although these evidences may favor multiple rapid energy releases at the origin near the solar surface, they require further research in order to better understand both diagnostics and model descriptions.Fil: Kaufmann, Pierre. Universidade Estadual de Campinas; Brasil. Universidade Presbiteriana Mackenzie; BrasilFil: De Castro, C. Guillermo Giménez. Universidade Presbiteriana Mackenzie; BrasilFil: Makhmutov, Vladimir S.. Universidade Presbiteriana Mackenzie; Brasil. The Russian Academy Of Sciences; RusiaFil: Raulin, Jean Pierre. Universidade Presbiteriana Mackenzie; BrasilFil: Schwenn, Rainer. Max Planck Institute For Solar System Research; AlemaniaFil: Levato, Orlando Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Rovira, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin

More than clean air and tranquillity: residential green is independently associated with decreasing mortality

Green space may improve health by enabling physical activity and recovery from stress or by decreased pollution levels. We investigated the association between residential green (greenness or green space) and mortality in adults using the Swiss National Cohort (SNC) by mutually considering air pollution and transportation noise exposure. To reflect residential green at the address level, two different metrics were derived: normalised difference vegetation index (NDVI) for greenness, and high resolution land use classification data to identify green spaces (LU-green). We used stratified Cox proportional hazard models (stratified by sex) to study the association between exposure and all natural cause mortality, respiratory and cardiovascular disease (CVD), including ischemic heart disease, stroke and hypertension related mortality. Models were adjusted for civil status, job position, education, neighbourhood socio-economic position (SEP), geographic region, area type, altitude, air pollution (PM10), and transportation noise. From the nation-wide SNC, 4.2 million adults were included providing 7.8years of follow-up and respectively 363,553, 85,314 and 232,322 natural cause, respiratory and CVD deaths. Hazard ratios (and 95%-confidence intervals) for NDVI [and LU-green] per interquartile range within 500m of residence were highly comparable: 0.94 (0.93-0.95) [0.94 (0.93-0.95)] for natural causes; 0.92 (0.91-0.94) [0.92 (0.90-0.95)] for respiratory; and 0.95 (0.94-0.96) [0.96 (0.95-0.98)] for CVD mortality. Protective effects were stronger in younger individuals and in women and, for most outcomes, in urban (vs. rural) and in the highest (vs. lowest) SEP quartile. Estimates remained virtually unchanged after incremental adjustment for air pollution and transportation noise, and mediation by these environmental factors was found to be small. We found consistent evidence that residential green reduced the risk of mortality independently from other environmental exposures. This suggests the protective effect goes beyond the absence of pollution sources. Environmental public health measures should not only aim at reducing pollutant exposure, but additionally maintain existing and increase residential green in areas where lacking

Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34+ hematopoietic stem and progenitor cells. Within the hematopoietic system, we show that HK3 is predominantly expressed in cells of myeloid origin. CRISPR/Cas9 mediated gene disruption revealed that loss of HK3 has no effect on glycolytic activity in AML cell lines while knocking out HK2 significantly reduced basal glycolysis and glycolytic capacity. Instead, loss of HK3 but not HK2 led to increased sensitivity to ATRA-induced cell death in AML cell lines. We found that HK3 knockout (HK3-null) AML cells showed an accumulation of reactive oxygen species (ROS) as well as DNA damage during ATRA-induced differentiation. RNA sequencing analysis confirmed pathway enrichment for programmed cell death, oxidative stress, and DNA damage response in HK3-null AML cells. These signatures were confirmed in ATAC sequencing, showing that loss of HK3 leads to changes in chromatin configuration and increases the accessibility of genes involved in apoptosis and stress response. Through isoform-specific pulldowns, we furthermore identified a direct interaction between HK3 and the proapoptotic BCL-2 family member BIM, which has previously been shown to shorten myeloid life span. Our findings provide evidence that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

Sub-THz and H{\alpha} activity during the preflare and main phases of a GOES class M2 event

Radio and optical observations of the evolution of flare-associated phenomena have shown an initial and rapid burst at 0.4 THz only followed subsequently by a localized chromospheric heating producing an H{\alpha} brightening with later heating of the whole active region. A major instability occurred several minutes later producing one impulsive burst at microwaves only, associated with an M2.0 GOES X-ray flare that exhibited the main H{\alpha} brightening at the same site as the first flash. The possible association between long-enduring time profiles at soft X-rays, microwaves, H{\alpha} and sub-THz wavelengths is discussed. In the decay phase the H{\alpha} movie shows a disrupting magnetic arch structure ejecting dark, presumably chromospheric, material upwards. The time sequence of events suggests genuine interdependent and possibly non-thermal instabilities triggering phenomena, with concurrent active region plasma heating and material ejection.Comment: Accepted by Astrophysical Journal, October 13, 201

Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study

BACKGROUND Progranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison. METHODS The diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset. RESULTS Plasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8-84.9, Q25-Q75) ng/ml and significantly higher than in CAP (38.0, 33.5-41.0~ng/ml, p < 0.001), SIRS (29.0, 25.0-35.0~ng/ml, p < 0.001) and the healthy state (28.7, 25.5-31.7~ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6-96.0 vs. 38.0, 33.5-41.0~ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87-0.93) for progranulin and 0.92 (CI = 0.88-0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8-1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others. CONCLUSIONS Progranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders. TRIAL REGISTRATION Clinicaltrials.gov registration number NCT03280576 Registered November 19, 2015