Since their discovery, SOCS have been characterised as regulatory cornerstones of intracellular signalling. While classically controlling the JAK/STAT pathway, their inhibitory effects are documented ...across several cascades, underpinning their essential role in homeostatic maintenance and disease. After 20 years of extensive research, SOCS3 has emerged as arguably the most important family member, through its regulation of both cytokine- and pathogen-induced cascades. In fact, low expression of SOCS3 is associated with autoimmunity and oncogenesis, while high expression is linked to diabetes and pathogenic immune evasion. The induction of SOCS3 by both viruses and bacteria and its impact upon inflammatory disorders, underscores this protein’s increasing clinical potential. Therefore, with the aim of highlighting SOCS3 as a therapeutic target for future development, this review revisits its multi-faceted immune regulatory functions and summarises its role in a broad ranges of diseases.
Neonatal seizures are a common emergency in the neonatal intensive care unit (NICU). There are many questions yet to be answered regarding the temporal/spatial characteristics of seizures from ...different pathologies, response to medication, effects on neurodevelopment and optimal detection. The dataset presented in this descriptor contains EEG recordings from human neonates, the visual interpretation of the EEG by the human experts, supporting clinical data and codes to assist access. Multi-channel EEG was recorded from 79 term neonates admitted to the NICU at the Helsinki University Hospital. The median recording duration was 74 min (IQR: 64 to 96 min). The presence of seizures in the EEGs was annotated independently by three experts. An average of 460 seizures were annotated per expert in the dataset; 39 neonates had seizures and 22 were seizure free, by consensus. The dataset can be used as a reference set of neonatal seizures, in studies of inter-observer agreement and for the development of automated methods of seizure detection and other EEG analyses.
The relationship between an inner-core (r < 100 km) lightning outbreak and the subsequent rapid intensification (RI) of Hurricane Earl (2010) is examined using lightning strikes recorded by the World ...Wide Lightning Location Network (WWLLN) and in situ observations from various aircraft missions. Moderate (8.4 m s super(-1)) northeasterly deep-layer (850-200 hPa) vertical wind shear, caused by outflow from Hurricane Danielle, existed over Earl at the beginning of a prolonged period of RI. Over 70% of the lightning strikes within a 500-km radius occurred downshear, with a preference toward downshear right in the outer rainbands, in agreement with previous studies. The location of inner-core strikes in Earl differed markedly from previous studies. The inner-core lightning activity precessed from left of shear to upshear, an extremely rare event, beginning just prior to the onset of RI. Diagnosis of the vortex tilt midway through the lightning precession showed this convection was occurring downtilt in the upshear-left quadrant; however, limited observations could not confirm if the vortex tilt was precessing with the lightning. Elevated values of low-level relative humidity and CAPE were also found upshear and supported the inner-core convection, which was found to occur within the radius of maximum wind (RMW). Previous studies have shown that convection located inside the RMW promotes intensification. It is hypothesized that intensification may have occurred in part because the vertical wind shear acted to reduce the upshear tilt, and the occurrence of convection inside the RMW helped to enhance the warm core.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Every year there are > 33 million cases of Respiratory Syncytial Virus (RSV)-related respiratory infection in children under the age of five, making RSV the leading cause of lower respiratory tract ...infection (LRTI) in infants. RSV is a global infection, but 99% of related mortality is in low/middle-income countries. Unbelievably, 62 years after its identification, there remains no effective treatment nor vaccine for this deadly virus, leaving infants, elderly and immunocompromised patients at high risk. The success of all pathogens depends on their ability to evade and modulate the host immune response. RSV has a complex and intricate relationship with our immune systems, but a clearer understanding of these interactions is essential in the development of effective medicines. Therefore, in a bid to update and focus our research community’s understanding of RSV’s interaction with immune defences, this review aims to discuss how our current knowledgebase could be used to combat this global viral threat.
The structural evolution of the inner core and near-environment throughout the life cycle of Hurricane Edouard (2014) is examined using a synthesis of airborne and satellite measurements. This study ...specifically focuses on differences in the distribution of deep convection during two periods: when Edouard intensified toward hurricane status, and when Edouard peaked in intensity and began to weaken. While both periods saw precipitation maximized in the downshear-left and upshear-left quadrants, deep convection was only seen from the aircraft during the intensifying period.
Deep convection was located farther inside the radius of maximum winds (RMW) during the intensifying period than the weakening period. This convection is traced to strong updrafts inside the RMW in the downshear-right quadrant, tied to strong low-level convergence and high convective available potential energy (CAPE) as the storm remained over warm water in a moist environment. Strong updrafts persisted upshear left and were collocated with high inertial stability in the inner core. During weakening, no deep convection was present, and the precipitation that was observed was associated with weaker convergence downshear right at larger radii, as CAPE was reduced from lower sea surface temperatures, reduced humidity from subsidence, and a stronger warm core. Weak updrafts were seen upshear left, with little coincidence with the high inertial stability of the inner core.
These results highlight the importance of the azimuthal coverage of precipitation and the radial location of deep convection for intensification. A more symmetrical coverage can occur despite the presence of shear-driven azimuthal asymmetries in both the forcing and the local environment of the precipitation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a ...fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (∼40-60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ∼3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50-100 ms level. In addition, transient fine synchrony occurred primarily during the initial ∼20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (∼80 Hz) gamma-band and during high-frequency oscillations (∼130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons.
The structural evolution of the inner core and near environment throughout the life cycle of Hurricane Edouard (2014) is examined using a synthesis of airborne and satellite measurements. This study ...specifically focuses on the precipitation evolution and thermodynamic changes that occur on the vortex scale during four periods: when Edouard was a slowly intensifying tropical storm, another while a rapidly intensifying hurricane, during the initial stages of weakening after reaching peak intensity, and later while experiencing moderate weakening in the midlatitudes. Results suggest that, in a shear-relative framework, a wavenumber-1 asymmetry exists whereby the downshear quadrants consistently exhibit the greatest precipitation coverage and highest relative humidity, while the upshear quadrants (especially upshear right) exhibit relatively less precipitation coverage and lower humidity, particularly in the midtroposphere. Whether dynamically or precipitation driven, the relatively dry layers upshear appear to be ubiquitously caused by subsidence. The precipitation and thermodynamic asymmetry is observed throughout the intensification and later weakening stages, while a consistently more symmetric distribution is only observed when Edouard reaches peak intensity. The precipitation distribution, which is also discussed in the context of the boundary layer thermodynamic properties, is intimately linked to the thermodynamic symmetry, which becomes greater as the frequency, areal coverage, and, in particular, rainfall rate increases upshear. Although shear is generally believed to be detrimental to intensification, observations in Edouard also indicate that subsidence warming from mesoscale downdrafts in the low- to midtroposphere very near the center may have contributed favorably to organization early in the intensification stage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Highlights • Automated analysis of the EEG provides a widely accessible, noninvasive and continuous assessment of brain activity. • We developed an automated measure of EEG maturational age in the ...very and extremely premature neonate. • Automated estimates of EEG maturational age are correlated with gestational age.