Electromagnetic atmosphere-plasma coupling: the global atmospheric electric circuit

A description is given of the global atmospheric electric circuit operating between the Earth’s surface and the ionosphere. Attention is drawn to the huge range of horizontal and vertical spatial scales, ranging from 10−9 m to 1012 m, concerned with the many important processes at work. A similarly enormous range of time scales is involved from 10−6 s to 109 s, in the physical effects and different phenomena that need to be considered. The current flowing in the global circuit is generated by disturbed weather such as thunderstorms and electrified rain/shower clouds, mostly occurring over the Earth’s land surface. The profile of electrical conductivity up through the atmosphere, determined mainly by galactic cosmic ray ionization, is a crucial parameter of the circuit. Model simulation results on the variation of the ionospheric potential, ∼250 kV positive with respect to the Earth’s potential, following lightning discharges and sprites are summarized. Experimental results comparing global circuit variations with the neutron rate recorded at Climax, Colorado, are then discussed. Within the return (load) part of the circuit in the fair weather regions remote from the generators, charge layers exist on the upper and lower edges of extensive layer clouds; new experimental evidence for these charge layers is also reviewed. Finally, some directions for future research in the subject are suggested

Changing the Waveform of Circadian Rhythms: Considerations for Shift-Work

Circadian disruption in shift-work is common and has deleterious effects on health and performance. Current efforts to mitigate these harms reasonably focus on the phase of the circadian pacemaker, which unfortunately in humans, shifts slowly and often incompletely. Temporal reorganization of rhythmic waveform (i.e., the shape of its 24 h oscillation), rather than phase, however, may better match performance demands of shift-workers and can be quickly and feasibly implemented in animals. In fact, a bifurcated pacemaker waveform may permit stable entrainment of a bimodal sleep/wake rhythm promoting alertness in both night and daylight hours. Although bifurcation has yet to be formally assessed in humans, evidence of conserved properties of circadian organization and plasticity predict its occurrence: humans respond to conventional manipulations of waveform (e.g., photoperiodism); behaviorally, the sleep/wake rhythm is adaptable; and finally, the human circadian system likely derives from the same multiple cellular oscillators that permit waveform flexibility in the rodent pacemaker. In short, investigation into untried manipulations of waveform in humans to facilitate adjustment to challenging schedules is justified

Quantitative upper bounds on the Gromov-Hausdorff distance between spheres

The Gromov-Hausdorff distance between two metric spaces measures how far the spaces are from being isometric. It has played an important and longstanding role in geometry and shape comparison. More recently, it has been discovered that the Gromov-Hausdorff distance between unit spheres equipped with the geodesic metric has important connections to Borsuk-Ulam theorems and Vietoris-Rips complexes. We develop a discrete framework for obtaining upper bounds on the Gromov-Hausdorff distance between spheres, and provide the first quantitative bounds that apply to spheres of all possible pairs of dimensions. As a special case, we determine the exact Gromov-Hausdorff distance between the circle and any even-dimensional sphere, and determine the asymptotic behavior of the distance from the 2-sphere to the $k$-sphere up to constants.Comment: 13 pages, 3 figure

Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos.

The regulation of transcription requires the coordination of numerous activities on DNA, yet how transcription factors mediate these activities remains poorly understood. Here, we use lattice light-sheet microscopy to integrate single-molecule and high-speed 4D imaging in developing Drosophila embryos to study the nuclear organization and interactions of the key transcription factors Zelda and Bicoid. In contrast to previous studies suggesting stable, cooperative binding, we show that both factors interact with DNA with surprisingly high off-rates. We find that both factors form dynamic subnuclear hubs, and that Bicoid binding is enriched within Zelda hubs. Remarkably, these hubs are both short lived and interact only transiently with sites of active Bicoid-dependent transcription. Based on our observations, we hypothesize that, beyond simply forming bridges between DNA and the transcription machinery, transcription factors can organize other proteins into hubs that transiently drive multiple activities at their gene targets.Editorial noteThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)

STIMULUS-RESPONSE IN THE MIXED LYMPHOCYTE REACTION

Mixed lymphocyte reactions occur when mouse spleen cell populations depleted of thymus-derived (T) lymphocytes are cultured with allogeneic target cells inactivated by mitomycin C or X irradiation, and when F1 hybrid responder cells are cultured with inactivated parental target cells. These responses might be interpreted as indicating that T lymphocytes are not required for responsiveness and that F1 lymphocytes recognize parental alloantigens. Data reported here indicate that the more likely explanation for these surprising results is that inactivated target cells recognize the "responding" cells and this recognition leads to the response observed

Extraordinary behavioral entrainment following circadian rhythm bifurcation in mice.

The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24 h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturnal illumination (<0.1 lux), rather than completely dark nights, permits expression of an altered circadian waveform wherein mice in light/dark/light/dark (LDLD) cycles "bifurcate" their rhythms into two rest and activity intervals per 24 h. Secondly, this bifurcated state enables mice to adopt stable activity rhythms under 15 or 30 h days (LDLD T15/T30), well beyond conventional limits of entrainment. Continuation of dim light is unnecessary for T15/30 behavioral entrainment following bifurcation. Finally, neither dim light alone nor a shortened night is sufficient for the extraordinary entrainment observed under bifurcation. Thus, we demonstrate in a non-pharmacological, non-genetic manipulation that the circadian system is far more flexible than previously thought. These findings challenge the current conception of entrainment and its underlying principles, and reveal new potential targets for circadian interventions

Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC)

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ RESULTS: Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. CONCLUSIONS: AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients