At solar minimum, the solar wind is observed at high solar latitudes as a predominantly fast (> 500 km/s), highly Alfvenic, rarefied stream of plasma originating deep within coronal holes, while near ...the ecliptic plane it is interspersed with a more variable slow (< 500 kms) wind. The precise origins of the slow wind streams are less certain, with theories and observations supporting sources from the tips of helmet streamers, interchange reconnection near coronal hole boundaries, and origins within coronal holes with highly diverging magnetic fields. The heating mechanism required to drive the solar wind is also an open question and candidate mechanisms include Alfven wave turbulence, heating by reconnection in nanoflares, ion cyclotron wave heating and acceleration by thermal gradients1. At 1 au, the wind is mixed and evolved and much of the diagnostic structure of these sources and processes has been lost. Here we present new measurements from Parker Solar Probe at 36 to 54 solar radii that show clear evidence of slow, Alfvenic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals associated with jets of plasma and enhanced Poynting flux and interspersed in a smoother and less turbulent flow with near-radial magnetic field. Furthermore, plasma wave measurements suggest electron and ion velocity-space micro-instabilities that have been identified with plasma heating and thermalization processes. Our measurements suggest an impulsive mechanism associated with solar wind energization and a heating role for micro-instabilities and provide strong evidence for low latitude coronal holes as a significant contribution to the source of the slow solar wind.
Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest in identifying BAT activators for metabolic benefits. Of particular interest are cytokines capable of ...fat browning. Irisin, derived from FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in murine white fat. Here we explored whether cold exposure is an afferent signal for irisin secretion in humans and compared it with FGF21, a brown adipokine in rodents. Cold exposure increased circulating irisin and FGF21. We found an induction of irisin secretion proportional to shivering intensity, in magnitude similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment upregulated human adipocyte brown fat gene/protein expression and thermogenesis in a depot-specific manner. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine axis that is exploitable in obesity therapeutics development.
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•Shivering stimulates irisin secretion in humans•Nonshivering cold exposure increases FGF21, which may be a brown adipokine•Irisin and/or FGF21 upregulates brown-fat-like program in human adipocytes•Exercise may be a shivering mimic exemplifying muscle-fat thermogenic crosstalk
Lee et al. show that, in humans, cold exposure leading to shivering stimulates production of irisin, an exercise-induced myokine, while nonshivering cold exposure increases FGF21. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21.
Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is ...thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).
We isolated a breast cancer cell population (CD44+CD24- cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.
Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.
Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.
Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 ...July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvénic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site.
We discuss methods to determine L‐M‐N coordinate systems for current sheet crossings observed by the Magnetospheric Multiscale (MMS) spacecraft mission during ongoing reconnection, where eL is the ...direction of the reconnecting component of the magnetic field, B, and eN is normal to the magnetopause. We present and test a new hybrid method, with eL estimated as the maximum variance direction of B (MVAB) and eN as the direction of maximum directional derivative of B, and then adjust these directions to be perpendicular. In the best case, only small adjustment is needed. Results from this method, applied to an MMS crossing of the dayside magnetopause at 1305:45 UT on 16 October 2015, are discussed and compared with those from other methods for which eN is obtained by other means. Each of the other evaluations can be combined with eL from MVAB in a generalized hybrid approach to provide an L‐M‐N system. The quality of the results is judged by eigenvalue ratios, constancy of directions using different data segments and methods, and expected sign and magnitude of the normal component of B. For this event, the hybrid method appears to produce eN accurate to within less than 10°. We discuss variance analysis using the electric current density, J, or the J × B force, which yield promising results, and minimum Faraday residue analysis and MVAB alone, which can be useful for other events. We also briefly discuss results from our hybrid method and MVAB alone for a few other MMS reconnection events.
Plain Language Summary
We discuss methods for determining coordinate systems in order to study magnetic reconnection events at the magnetopause, the boundary between the ionized gas in the region of space dominated by the Earth's magnetic field and the ionized gas coming from the solar wind. We introduce a new method that combines results from multiple methods in order to determine the three coordinate directions in space. We demonstrate this method by applying it to an event observed by the Magnetospheric Multiscale spacecraft on 16 October 2015 and at other times.
Key Points
Methods to determine L‐M‐N current sheet coordinates are described and tested
Quality of results is judged by eigenvalue ratios and consistency using different data intervals and methods and with the geophysical context
For the interval examined here, the uncertainty of the normal direction was at least several degrees but probably less than 10°
Plasma turbulence is investigated using unprecedented high-resolution ion velocity distribution measurements by the Magnetospheric Multiscale mission (MMS) in the Earth's magnetosheath. This novel ...observation of a highly structured particle distribution suggests a cascadelike process in velocity space. Complex velocity space structure is investigated using a three-dimensional Hermite transform, revealing, for the first time in observational data, a power-law distribution of moments. In analogy to hydrodynamics, a Kolmogorov approach leads directly to a range of predictions for this phase-space transport. The scaling theory is found to be in agreement with observations. The combined use of state-of-the-art MMS data sets, novel implementation of a Hermite transform method, and scaling theory of the velocity cascade opens new pathways to the understanding of plasma turbulence and the crucial velocity space features that lead to dissipation in plasmas.
Carbapenem-resistant
(CRE) represent a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly being highlighted as important potential ...reservoirs. We investigated a large
carbapenemase (KPC)-producing
outbreak and wider CRE incidence trends in the Central Manchester University Hospital NHS Foundation Trust (CMFT) (United Kingdom) over 8 years, to determine the impact of infection prevention and control measures. Bacteriology and patient administration data (2009 to 2017) were linked, and a subset of CMFT or regional hospital KPC-producing
isolates (
= 268) were sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (
= 184,539 screens), environmental sampling, enhanced cleaning, and ward closure and plumbing replacement. Segmented regression of time trends for CRE detections was used to evaluate the impact of interventions on CRE incidence. Genomic analysis (
= 268 isolates) identified the spread of a KPC-producing
outbreak clone (strain A, sequence type 216 ST216;
= 125) among patients and in the environment, particularly on 2 cardiac wards (wards 3 and 4), despite control measures. ST216 strain A had caused an antecedent outbreak and shared its KPC plasmids with other
lineages and
species. CRE acquisition incidence declined after closure of wards 3 and 4 and plumbing replacement, suggesting an environmental contribution. However, ward 3/ward 4 wastewater sites were rapidly recolonized with CRE and patient CRE acquisitions recurred, albeit at lower rates. Patient relocation and plumbing replacement were associated with control of a clonal KPC-producing
outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and the persistence of
in
, including pathogenic lineages, are of concern.
To review our 15-year institutional experience using intensity modulated radiation therapy (IMRT) to reirradiate patients with head and neck squamous cell carcinomas (HNSCC) and identify predictors ...of outcomes and toxicity.
We retrospectively reviewed the records of 227 patients who received head and neck reirradiation using IMRT from 1999 to 2014. Patients treated with noncurative intent were excluded. Radiation-related acute and late toxicities were recorded. Prognostic variables included performance status, disease site, disease-free interval, chemotherapy, and RT dose and volume. Correlative analyses were performed separately for surgery and nonsurgery patients.
Two hundred six patients (91%) were retreated with curative intent, and 173 had HNSCC histology; 104 (50%) underwent salvage resection, and 135 (66%) received chemotherapy. Median follow-up after reirradiation was 24.7 months. Clinical outcomes were worse for HNSCC patients, with 5-year locoregional control, progression-free survival, and overall survival rates of 53%, 22%, and 32%, respectively, compared with 74%, 59%, and 79%, respectively, for non-HNSCC patients. On multivariate analysis, concurrent chemotherapy and retreatment site were associated with tumor control, whereas performance status was associated with survival. Favorable prognostic factors specific to surgery patients were neck retreatment and lack of extracapsular extension, whereas for nonsurgery patients, these were a nasopharynx subsite and complete response to induction chemotherapy. Actuarial rates of grade ≥3 toxicity were 32% at 2 years and 48% at 5 years, with dysphagia or odynophagia being most common. Increased grade ≥3 toxicity was associated with retreatment volume >50 cm(3) and concurrent chemotherapy.
Reirradiation with IMRT either definitively or after salvage surgery can produce promising local control and survival in selected patients with head and neck cancers. Treatment-related toxicity remains significant. Prognostic factors are emerging to guide multidisciplinary treatment approaches and clinical trial design.
We present EUV solar observations showing evidence for omnipresent jetting activity driven by small-scale magnetic reconnection at the base of the solar corona. We argue that the physical mechanism ...that heats and drives the solar wind at its source is ubiquitous magnetic reconnection in the form of small-scale jetting activity (i.e., a.k.a. jetlets). This jetting activity, like the solar wind and the heating of the coronal plasma, are ubiquitous regardless of the solar cycle phase. Each event arises from small-scale reconnection of opposite polarity magnetic fields producing a short-lived jet of hot plasma and Alfv´en waves into the corona. The discrete nature of these jetlet events leads to intermittent outflows from the corona, which homogenize as they propagate away from the Sun and form the solar wind. This discovery establishes the importance of small-scale magnetic reconnection in solar and stellar atmospheres in understanding ubiquitous phenomena such as coronal heating and solar wind acceleration. Based on previous analyses linking the switchbacks to the magnetic network, we also argue that these new observations might provide the link between the magnetic activity at the base of the corona and the switchback solar wind phenomenon. These new observations need to be put in the bigger picture of the role of magnetic reconnection and the diverse form of jetting in the solar atmosphere.
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