Temporal and Spatial Variations of Total Electron Content Enhancements During a Geomagnetic Storm on 27 and 28 September 2017

Temporal and spatial evolutions of total electron content (TEC) and electron density in the ionosphere during a geomagnetic storm that occurred on 27 and 28 September 2017 have been investigated using global TEC data obtained from many Global Navigation Satellite System stations together with the ionosonde, geomagnetic field, Jicamarca incoherent scatter and Super Dual Auroral Radar Network (SuperDARN) radar data. Our analysis results show that a clear enhancement of the ratio of the TEC difference (rTEC) first occurs from noon to afternoon at high latitudes within 1 hr after a sudden increase and expansion of the high‐latitude convection and prompt penetration of the electric field to the equator associated with the southward excursion of the interplanetary magnetic field. Approximately 1–2 hr after the onset of the hmF2 increase in the midlatitude and low‐latitude regions associated with the high‐latitude convection enhancement, the rTEC and foF2 values begin to increase and the enhanced rTEC region expands to low latitudes within 1–2 hr. This signature suggests that the ionospheric plasmas in the F2 region move at a higher altitude due to local electric field drift, where the recombination rate is smaller, and that the electron density increases due to additional production at the lower altitude in the sunlit region. Later, another rTEC enhancement related to the equatorial ionization anomaly appears in the equatorial region approximately 1 hr after the prompt penetration of the electric field to the equator and expands to higher latitudes within 3–4 hr.ファイル公開：2021-01-01journal articl

Multivariable binary logistic regression analysis of factors associated with intended monitoring frequency, referral to other healthcare providers and change in medication use (total study population, n = 1366).

Multivariable binary logistic regression analysis of factors associated with intended monitoring frequency, referral to other healthcare providers and change in medication use (total study population, n = 1366).</p

Temporal and Spatial Variations of Total Electron Content Enhancements During a Geomagnetic Storm on 27 and 28 September 2017

Temporal and spatial evolutions of total electron content (TEC) and electron density in the ionosphere during a geomagnetic storm that occurred on 27 and 28 September 2017 have been investigated using global TEC data obtained from many Global Navigation Satellite System stations together with the ionosonde, geomagnetic field, Jicamarca incoherent scatter and Super Dual Auroral Radar Network (SuperDARN) radar data. Our analysis results show that a clear enhancement of the ratio of the TEC difference (rTEC) first occurs from noon to afternoon at high latitudes within 1 hr after a sudden increase and expansion of the high‐latitude convection and prompt penetration of the electric field to the equator associated with the southward excursion of the interplanetary magnetic field. Approximately 1–2 hr after the onset of the hmF2 increase in the midlatitude and low‐latitude regions associated with the high‐latitude convection enhancement, the rTEC and foF2 values begin to increase and the enhanced rTEC region expands to low latitudes within 1–2 hr. This signature suggests that the ionospheric plasmas in the F2 region move at a higher altitude due to local electric field drift, where the recombination rate is smaller, and that the electron density increases due to additional production at the lower altitude in the sunlit region. Later, another rTEC enhancement related to the equatorial ionization anomaly appears in the equatorial region approximately 1 hr after the prompt penetration of the electric field to the equator and expands to higher latitudes within 3–4 hr.ファイル公開：2021-01-01journal articl

Patient characteristics.

Means (±SD) or percentages, unless indicated otherwise*.</p

Preferred monitoring frequency, referral to other healthcare providers and medication change after the patient-centered consultation (n, %).

Preferred monitoring frequency, referral to other healthcare providers and medication change after the patient-centered consultation (n, %).</p

Patient goals in primary (PC) and secondary care (SC) (n, %).

Patient goals in primary (PC) and secondary care (SC) (n, %).</p

Nampt and NMN potentiate glucose stimulated insulin secretion (GSIS) in human islets.

<p>GSIS from human islets cultured on extracellular matrix coated dishes and chronically (<b>A–D</b>) or acutely (E–I) exposed to NMN (100 µM) and Nampt (2.5 ng/ml). (<b>A–D</b>) Islets were chronically exposed to the treatment conditions for 72 h (<b>A,B</b>: 5.5 mM glucose; <b>C,D</b>: 5.5 mM glucose, the mixture of 22.2 mM glucose/0.5 mM palmitate or 2 ng/ml IL-1β/1000 IU IFN-γ), medium was changed and GSIS performed in the absence of the treatment conditions. Basal and stimulated insulin secretion indicate the amount secreted during 1 h incubations at 2.8 (basal) and 16.7 mM (stimulated) glucose following the 72 h culture period and normalized to insulin content. The stimulatory index was calculated (<b>B,D</b>). (<b>E,F</b>) Islets were pre-cultured for 48h and then exposed to 2.8 mM glucose for 1 h (basal), to 2.8 mM glucose including the adipocytokines for 1 h (basal+adipokine) and another subsequent hour to 16.7 mM glucose including the adipocytokines (stim+adipokine). The stimulatory index was calculated (<b>F</b>). (<b>G, H</b>) Islets were pre-cultured for 48 h and then exposed to 2.8 mM glucose for 1 h (basal), to 16.7 mM glucose for 1 h (stimulated) and another subsequent hour to 16.7 mM glucose including the adipocytokines (stim+adipokine). The stimulatory index was calculated (<b>H</b>). (<b>I</b>) Stimulatory index from human islets exposed to 2.8 mM glucose (basal) and subsequently to 1 h exposure to IBMX (100 mM)/Forskolin (10 mM) with or without Nampt or NMN was calculated. Results are means ±SEM from triplicates from three independent experiments from three donors. *p<0.05 to the respective untreated control, ⁺p<0.05 to 2.8 mM basal glucose.</p

Insulin, glucagon and type 2 diabetes susceptibility gene expression in diabetic sorted islet cells.

<p>A: Differential expression of beta cell insulin and alpha cell glucagon in non-diabetic (white bars) compared to diabetic (black bars) islet cells. B: Expression levels of type 2 diabetes susceptibility gene in diabetic alpha cells (white bars) and beta cells (black bars). C: Differential expression of <i>FTO</i> in both cell fractions from non-diabetic (white bars) compared to diabetic (black bars) islet cells. Statistical comparison of diabetic to non-diabetic samples was by unpaired T test assuming unequal variance. n = 16 non-diabetic and 3 diabetic samples.</p

Nampt and NMN increase NAD level and ameliorate NAD depletion.

<p>Human islets (A) and INS-1E cells (B) were stimulated with NMN [100 µM] or Nampt [2.5 ng/ml] for a short time (2 or 3 h) or a long time exposure (48 h). NAD level were normalised to the total protein amount in each sample. FK866 [10 nM], a specific Nampt inhibitor, was used as a positive control in INS-1E cells. * p<0.05 compared to con (serum free medium);+p<0.05 compared to FK866 treated cells.</p

The adipocytokines leptin, adiponectin, Nampt and NMN have no direct effects on beta-cell survival in INS-1E cells.

<p>INS-1E cells were kept under serum-free conditions 24 h before and during the 48 h experiment. (<b>A,B</b>) INS-1E cells were exposed to cytokines (<b>A</b>: IL-1β, IFN-γ or TNFα) or adipocytokines (<b>B</b>: adiponectin, leptin, Nampt, NMN) at the indicated concentrations for 48 h and cell viability was measured by WST-1 assay. Data are shown as means ±SEM of 3 independent experiments performed in triplicates. Statistical analyses were performed by one-way ANOVA with Bonferroni’s Multiple Comparison Test as posthoc test. <b>C,D</b>: INS-1E cells were exposed to adipocytokines (adiponectin 167 ng/ml, leptin 200 ng/ml, Nampt 2.5 ng/ml, NMN 100 µM) or a cytokine combination (10 ng/ml IL-1β+10 ng/ml IFN-γ) for 48 h. Cytotoxicity (<b>C</b>) was analyzed by measuring the release of adenylate kinase into the supernatant and (<b>D</b>) apoptosis was measured by FITC-annexinV (An) and propidium iodide (PI) staining and subsequent flow cytometric analysis of An-positive and double An/PI positive cells. Results were expressed relative to cells exposed to serum free medium (con) and as means ±SEM of three independent experiments performed in triplicates. <b>E,F</b>: INS-1E cells were exposed to a cytokine combination (IL/IF; 10 ng/ml IL-1β+10 ng/ml IFN-γ) (<b>E</b>) or 0.25 mM palmitate (pal) (<b>F</b>) for 48 h in the absence or presence of the adipocytokines (167 ng/ml adiponectin, 200 ng/ml leptin, 2.5 ng/ml Nampt) and induction of apoptosis was measured by An/PI staining and flow cytometric analysis. Data are shown as means ±SEM of triplicates of three independent experiments. Statistical analyses were performed by student´s t-test. G: INS-1E cells were exposed to the adipocytokines adiponectin (167 ng/ml), leptin (200 ng/ml) or Nampt (2.5 ng/ml) or a combination of camptothecin (2 µM) and etoposide (85 µM; CE, <b>upper and lower panel</b>) or a cytokine combination (10 ng/ml IL-1β+10 ng/ml IFN-γ, <b>middle and lower panel</b>). Western blot analyses were performed for full length and cleaved caspase-3 (<b>upper panel</b>), phospho-NF-κB p65 (Ser536) and NF-κB p65 (<b>middle panel</b>) and phospho-p53 (Ser15) (<b>lower panel</b>). GAPDH or beta-actin were used as loading control. All panels show one typical blot out of three independent experiments. *p<0.05 compared to untreated control.</p