Sunlight effects on the 3D polar current system determined from low Earth orbit measurements

Interaction between the solar wind and the Earth's magnetosphere is associated with large-scale currents in the ionosphere at polar latitudes that flow along magnetic field lines (Birkeland currents) and horizontally. These current systems are tightly linked, but their global behaviors are rarely analyzed together. In this paper, we present estimates of the average global Birkeland currents and horizontal ionospheric currents from the same set of magnetic field measurements. The magnetic field measurements, from the low Earth orbiting $\textit{Swarm}$ and CHAMP satellites, are used to co-estimate poloidal and toroidal parts of the magnetic disturbance field, represented in magnetic apex coordinates. The use of apex coordinates reduces effects of longitudinal and hemispheric variations in the Earth's main field. We present global currents from both hemispheres during different sunlight conditions. The results show that the Birkeland currents vary with the conductivity, which depends most strongly on solar EUV emissions on the dayside and on particle precipitation at pre-midnight magnetic local times. In sunlight, the horizontal equivalent current flows in two cells, resembling an opposite ionospheric convection pattern, which implies that it is dominated by Hall currents. By combining the Birkeland current maps and the equivalent current, we are able to calculate the total horizontal current, without any assumptions about the conductivity. We show that the total horizontal current is close to zero in the polar cap when it is dark. That implies that the equivalent current, which is sensed by ground magnetometers, is largely canceled by the horizontal closure of the Birkeland currents

The Stability of a Model Substrate for Topoisomerase 1-Mediated DNA Religation Depends on the Presence of Mismatched Base Pairs

Topoisomerase 1 (Top1) enzymes regulate DNA superhelicity by forming covalent cleavage complexes that undergo controlled rotation. Substitution of nucleoside analogs at the +1 position of the DNA duplex relative to the Top1 cleavage site inhibits DNA religation. The reduced efficiency for Top1-mediated religation contributes to the anticancer activity of widely used anticancer drugs including fluoropyrimidines and gemcitabine. In the present study, we report that mismatched base pairs at the +1 position destabilize the duplex DNA components for a model Top1 cleavage complex formation even though one duplex component does not directly include a mismatched base pair. Molecular dynamics simulations reveal G-dU and G-FdU mismatched base pairs, but not a G-T mismatched base pair, increase flexibility at the Top1 cleavage site, and affect coupling between the regions required for the religation reaction to occur. These results demonstrate that substitution of dT analogs into the +1 position of the non-scissile strand alters the stability and flexibility of DNA contributing to the reduced efficiency for Top1-mediated DNA religation. These effects are inherent in the DNA duplex and do not require formation of the Top1:DNA complex. These results provide a biophysical rationale for the inhibition of Top1-mediated DNA religation by nucleotide analog substitution

The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study.

BACKGROUND:Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. RESULTS:In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > - 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5-67.0) years and admission APACHE II score of 21.0 (16.0-32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10-5). CONCLUSIONS:In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM

Microstrip Coupling Algorithm Validation and Modification Based on Measurements and Numerical Modeling

In this study, mutual capacitance and inductance between two coupled traces is measured and computed to validate and simplify coupling algorithms used in an expert system software package. The algorithm\u27s applicability to common microstrip configurations is tested through comparisons between FEM based solutions, |S21| measurements and the algorithm solutions under several permutations of a test board. Adjustments to the original algorithm are proposed that reduce computation times with out significantly affecting the accuracy of the result

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Topoisomerase 1 (Top1) enzymes regulate DNA superhelicity by forming covalent cleavage complexes that undergo controlled rotation. Substitution of nucleoside analogs at the +1 position of the DNA duplex relative to the Top1 cleavage site inhibits DNA religation. The reduced efficiency for Top1-mediated religation contributes to the anticancer activity of widely used anticancer drugs including fluoropyrimidines and gemcitabine. In the present study, we report that mismatched base pairs at the +1 position destabilize the duplex DNA components for a model Top1 cleavage complex formation even though one duplex component does not directly include a mismatched base pair. Molecular dynamics simulations reveal G-dU and G-FdU mismatched base pairs, but not a G-T mismatched base pair, increase flexibility at the Top1 cleavage site, and affect coupling between the regions required for the religation reaction to occur. These results demonstrate that substitution of dT analogs into the +1 position of the non-scissile strand alters the stability and flexibility of DNA contributing to the reduced efficiency for Top1-mediated DNA religation. These effects are inherent in the DNA duplex and do not require formation of the Top1:DNA complex. These results provide a biophysical rationale for the inhibition of Top1-mediated DNA religation by nucleotide analog substitution

Lightcurves of Type Ia Supernovae from Near the Time of Explosion

We present a set of 11 type Ia supernova (SN Ia) lightcurves with dense, pre-maximum sampling. These supernovae (SNe), in galaxies behind the Large Magellanic Cloud (LMC), were discovered by the SuperMACHO survey. The SNe span a redshift range of z = 0.11 - 0.35. Our lightcurves contain some of the earliest pre-maximum observations of SNe Ia to date. We also give a functional model that describes the SN Ia lightcurve shape (in our VR-band). Our function uses the "expanding fireball" model of Goldhaber et al. (1998) to describe the rising lightcurve immediately after explosion but constrains it to smoothly join the remainder of the lightcurve. We fit this model to a composite observed VR-band lightcurve of three SNe between redshifts of 0.135 to 0.165. These SNe have not been K-corrected or adjusted to account for reddening. In this redshift range, the observed VR-band most closely matches the rest frame V-band. Using the best fit to our functional description of the lightcurve, we find the time between explosion and observed VR-band maximum to be 17.6+-1.3(stat)+-0.07(sys) rest-frame days for a SN Ia with a VR-band Delta m_{-10} of 0.52mag. For the redshifts sampled, the observed VR-band time-of-maximum brightness should be the same as the rest-frame V-band maximum to within 1.1 rest-frame days.Comment: 35 pages, 18 figures, 15 tables; Higher quality PDF available at http://ctiokw.ctio.noao.edu/~sm/sm/SNrise/index.html; AJ accepte

Kir4.1 channels contribute to astrocyte CO2/H+-sensitivity and the drive to breathe

Astrocytes in the retrotrapezoid nucleus (RTN) stimulate breathing in response to CO2/H+, however, it is not clear how these cells detect changes in CO2/H+. Considering Kir4.1/5.1 channels are CO2/H+-sensitive and important for several astrocyte-dependent processes, we consider Kir4.1/5.1 a leading candidate CO2/H+ sensor in RTN astrocytes. To address this, we show that RTN astrocytes express Kir4.1 and Kir5.1 transcripts. We also characterized respiratory function in astrocyte-specific inducible Kir4.1 knockout mice (Kir4.1 cKO); these mice breathe normally under room air conditions but show a blunted ventilatory response to high levels of CO2, which could be partly rescued by viral mediated re-expression of Kir4.1 in RTN astrocytes. At the cellular level, astrocytes in slices from astrocyte-specific inducible Kir4.1 knockout mice are less responsive to CO2/H+ and show a diminished capacity for paracrine modulation of respiratory neurons. These results suggest Kir4.1/5.1 channels in RTN astrocytes contribute to respiratory behavior

What failure in collective decision-making tells us about metacognition

Condorcet (1785) proposed that a majority vote drawn from individual, independent and fallible (but not totally uninformed) opinions provides near-perfect accuracy if the number of voters is adequately large. Research in social psychology has since then repeatedly demonstrated that collectives can and do fail more often than expected by Condorcet. Since human collective decisions often follow from exchange of opinions, these failures provide an exquisite opportunity to understand human communication of metacognitive confidence. This question can be addressed by recasting collective decision-making as an information-integration problem similar to multisensory (cross-modal) perception. Previous research in systems neuroscience shows that one brain can integrate information from multiple senses nearly optimally. Inverting the question, we ask: under what conditions can two brains integrate information about one sensory modality optimally? We review recent work that has taken this approach and report discoveries about the quantitative limits of collective perceptual decision-making, and the role of the mode of communication and feedback in collective decision-making. We propose that shared metacognitive confidence conveys the strength of an individual's opinion and its reliability inseparably. We further suggest that a functional role of shared metacognition is to provide substitute signals in situations where outcome is necessary for learning but unavailable or impossible to establish