Global gene expression of histologically normal primary skin cells from BCNS subjects reveals "single-hit" effects that are influenced by rapamycin

Studies of dominantly heritable cancers enabled insights about tumor progression. BCNS is a dominantly inherited disorder that is characterized by developmental abnormalities and postnatal neoplasms, principally BCCs. We performed an exploratory gene expression profiling of primary cell cultures derived from clinically unaffected skin biopsies of BCNS gene-carriers (PTCH1 +/-) and normal individuals. PCA and HC of untreated keratinocytes or fibroblasts failed to clearly distinguish BCNS samples from controls. These results are presumably due to the common suppression of canonical HH signaling in vitro. We then used a relaxed threshold (p-value <0.05, no FDR cut-off; FC 1.3) that identified a total of 585 and 857 genes differentially expressed in BCNS keratinocytes and fibroblasts samples, respectively. A GSEA identified pancreatic β cell hallmark and mTOR signaling genes in BCNS keratinocytes, whereas analyses of BCNS fibroblasts identified gene signatures regulating pluripotency of stem cells, including WNT pathway. Significantly, rapamycin treatment (FDR<0.05), affected a total of 1411 and 4959 genes in BCNS keratinocytes and BCNS fibroblasts, respectively. In contrast, rapamycin treatment affected a total of 3214 and 4797 genes in normal keratinocytes and normal fibroblasts, respectively. The differential response of BCNS cells to rapamycin involved 599 and 1463 unique probe sets in keratinocytes and fibroblasts, respectively. An IPA of these genes in the presence of rapamycin pointed to hepatic fibrosis/stellate cell activation, and HIPPO signaling in BCNS keratinocytes, whereas mitochondrial dysfunction and AGRN expression were uniquely enriched in BCNS fibroblasts. The gene expression changes seen here are likely involved in the etiology of BCCs and they may represent biomarkers/targets for early intervention

A complexity approach to defining urban energy systems

Urban energy systems have been commonly considered to be socio-technical systems within the boundaries of an urban area. However, recent literature challenges this notion in that it urges researchers to look at the wider interactions and influences of urban energy systems wherein the socio-technical sphere is expanded to political, environmental and economic realms as well. In addition to the inter-sectoral linkages, the diverse agents and multilevel governance trends of energy sustainability in the dynamic environment of cities make the urban energy landscape a complex one. There is a strong case then for establishing a new conceptualisation of urban energy systems that builds upon these contemporary understandings of such systems. We argue that the complex systems approach can be suitable for this. In this paper, we propose a pilot framework for understanding urban energy systems using complex systems theory as an integrating plane. We review the multiple streams of urban energy literature to identify the contemporary discussions and construct this framework that can serve as a common ontological understanding for the different scholarships studying urban energy systems. We conclude the paper by highlighting the ways in which the framework can serve some of the relevant communities

Feminist phenomenology and the woman in the running body

Modern phenomenology, with its roots in Husserlian philosophy, has been taken up and utilised in a myriad of ways within different disciplines, but until recently has remained relatively under-used within sports studies. A corpus of sociological-phenomenological work is now beginning to develop in this domain, alongside a longer standing literature in feminist phenomenology. These specific social-phenomenological forms explore the situatedness of lived-body experience within a particular social structure. After providing a brief overview of key strands of phenomenology, this article considers some of the ways in which sociological, and particularly feminist phenomenology, might be used to analyse female sporting embodiment. For illustrative purposes, data from an autophenomenographic project on female distance running are also included, in order briefly to demonstrate the application of phenomenology within sociology, as both theoretical framework and methodological approach

Solar Energetic Particles Produced by a Slow Coronal Mass Ejection at ∼0.25 au

We present an analysis of Parker Solar Probe (PSP) IS⊙IS observations of ~30–300 keV n⁻¹ ions on 2018 November 11 when PSP was about 0.25 au from the Sun. Five hours before the onset of a solar energetic particle (SEP) event, a coronal mass ejection (CME) was observed by STEREO-A/COR2, which crossed PSP about a day later. No shock was observed locally at PSP, but the CME may have driven a weak shock earlier. The SEP event was dispersive, with higher energy ions arriving before the lower energy ones. Timing suggests the particles originated at the CME when it was at ~7.4R_⊙. SEP intensities increased gradually from their onset over a few hours, reaching a peak, and then decreased gradually before the CME arrived at PSP. The event was weak, having a very soft energy spectrum (−4 to −5 spectral index). The earliest arriving particles were anisotropic, moving outward from the Sun, but later, the distribution was observed to be more isotropic. We present numerical solutions of the Parker transport equation for the transport of 30–300 keV n⁻¹ ions assuming a source comoving with the CME. Our model agrees well with the observations. The SEP event is consistent with ion acceleration at a weak shock driven briefly by the CME close to the Sun, which later dissipated before arriving at PSP, followed by the transport of ions in the interplanetary magnetic field

Observations of the 2019 April 4 Solar Energetic Particle Event at the Parker Solar Probe

A solar energetic particle event was detected by the Integrated Science Investigation of the Sun (IS⊙IS) instrument suite on Parker Solar Probe (PSP) on 2019 April 4 when the spacecraft was inside of 0.17 au and less than 1 day before its second perihelion, providing an opportunity to study solar particle acceleration and transport unprecedentedly close to the source. The event was very small, with peak 1 MeV proton intensities of ~0.3 particles (cm² sr s MeV)⁻¹, and was undetectable above background levels at energies above 10 MeV or in particle detectors at 1 au. It was strongly anisotropic, with intensities flowing outward from the Sun up to 30 times greater than those flowing inward persisting throughout the event. Temporal association between particle increases and small brightness surges in the extreme-ultraviolet observed by the Solar TErrestrial RElations Observatory, which were also accompanied by type III radio emission seen by the Electromagnetic Fields Investigation on PSP, indicates that the source of this event was an active region nearly 80° east of the nominal PSP magnetic footpoint. This suggests that the field lines expanded over a wide longitudinal range between the active region in the photosphere and the corona

Energetic Particle Increases Associated with Stream Interaction Regions

The Parker Solar Probe was launched on 2018 August 12 and completed its second orbit on 2019 June 19 with perihelion of 35.7 solar radii. During this time, the Energetic Particle Instrument-Hi (EPI-Hi, one of the two energetic particle instruments comprising the Integrated Science Investigation of the Sun, IS⊙IS) measured seven proton intensity increases associated with stream interaction regions (SIRs), two of which appear to be occurring in the same region corotating with the Sun. The events are relatively weak, with observed proton spectra extending to only a few MeV and lasting for a few days. The proton spectra are best characterized by power laws with indices ranging from −4.3 to −6.5, generally softer than events associated with SIRs observed at 1 au and beyond. Helium spectra were also obtained with similar indices, allowing He/H abundance ratios to be calculated for each event. We find values of 0.016–0.031, which are consistent with ratios obtained previously for corotating interaction region events with fast solar wind ≤ 600 km s⁻¹. Using the observed solar wind data combined with solar wind simulations, we study the solar wind structures associated with these events and identify additional spacecraft near 1 au appropriately positioned to observe the same structures after some corotation. Examination of the energetic particle observations from these spacecraft yields two events that may correspond to the energetic particle increases seen by EPI-Hi earlier

Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma.

Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under the age of 40 years. Pigment-related characteristics are associated with BCC in older populations, but epidemiologic studies among younger individuals and analyses of phenotype-genotype interactions are limited. We examined self-reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions (n=390) under the age of 40 years were identified through Yale's Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for 1 hour (severe sunburn vs. tan odds ratio (OR)=12.27, 95% confidence interval (CI)=4.08-36.94) and skin color (very fair vs. olive OR=11.06, 95% CI=5.90-20.74). Individuals with two or more MC1R non-synonymous variants were 3.59 times (95% CI=2.37-5.43) more likely to have BCC than those without non-synonymous variants. All host characteristics and MC1R were more strongly associated with multiple BCC case status (37% of cases) than a single BCC case status. MC1R, number of moles, skin reaction to first summer sun for 1 hour, and hair and skin color were independently associated with BCC. BCC risk conferred by MC1R tended to be stronger among those with darker pigment phenotypes, traditionally considered to be at low risk of skin cancer

CME -Associated Energetic Ions at 0.23 AU -- Consideration of the Auroral Pressure Cooker Mechanism Operating in the Low Corona as a Possible Energization Process

We draw a comparison between a solar energetic particle event associated with the release of a slow coronal mass ejection close to the sun, and the energetic particle population produced in high current density field-aligned current structures associated with auroral phenomena in planetary magnetospheres. We suggest that this process is common in CME development and lift-off in the corona, and may account for the electron populations that generate Type III radio bursts, as well as for the prompt energetic ion and electron populations typically observed in interplanetary space.Comment: Accepted for publication Ap

Properties of Suprathermal-through-energetic He Ions Associated with Stream Interaction Regions Observed over the Parker Solar Probe’s First Two Orbits

The Integrated Science Investigation of the Sun (IS⊙IS) suite on board NASA's Parker Solar Probe (PSP) observed six distinct enhancements in the intensities of suprathermal-through-energetic (~0.03–3 MeV nucleon⁻¹) He ions associated with corotating or stream interaction regions (CIR or SIR) during its first two orbits. Our results from a survey of the time histories of the He intensities, spectral slopes, and anisotropies and the event-averaged energy spectra during these events show the following: (1) In the two strongest enhancements, seen at 0.35 and 0.85 au, the higher-energy ions arrive and maximize later than those at lower energies. In the event seen at 0.35 au, the He ions arrive when PSP was away from the SIR trailing edge and entered the rarefaction region in the high-speed stream. (2) The He intensities either are isotropic or show sunward anisotropies in the spacecraft frame. (3) In all events, the energy spectra between ~0.2 and 1 MeV nucleon⁻¹ are power laws of the form ∝E⁻². In the two strongest events, the energy spectra are well represented by flat power laws between ~0.03 and 0.4 MeV nucleon⁻¹ modulated by exponential rollovers between ~0.4 and 3 MeV nucleon⁻¹. We conclude that the SIR-associated He ions originate from sources or shocks beyond PSP's location rather than from acceleration processes occurring at nearby portions of local compression regions. Our results also suggest that rarefaction regions that typically follow the SIRs facilitate easier particle transport throughout the inner heliosphere such that low-energy ions do not undergo significant energy loss due to adiabatic deceleration, contrary to predictions of existing models