The 13 years of TRMM Lightning Imaging Sensor: From Individual Flash Characteristics to Decadal Tendencies

How often lightning strikes the Earth has been the object of interest and research for decades. Several authors estimated different global flash rates using ground-based instruments, but it has been the satellite era that enabled us to monitor lightning thunderstorm activity on the time and place that lightning exactly occurs. Launched into space as a component of NASA s Tropical Rainfall Measuring Mission (TRMM) satellite, in November 1997, the Lighting Imaging Sensor (LIS) is still operating. LIS detects total lightning (i.e., intracloud and cloud-to-ground) from space in a low-earth orbit (35deg orbit). LIS has collected lightning measurements for 13 years (1998-2010) and here we present a fully revised and current total lightning climatology over the tropics. Our analysis includes the individual flash characteristics (number of events and groups, total radiance, area footprint, etc.), composite climatological maps, and trends for the observed total lightning during these 13 years. We have identified differences in the energetics of the flashes and/or the optical scattering properties of the storms cells due to cell-relative variations in microphysics and kinematics (i.e., convective or stratiform rainfall). On the climatological total lightning maps we found a dependency on the scale of analysis (resolution) in identifying the lightning maximums in the tropics. The analysis of total lightning trends observed by LIS from 1998 to 2010 in different temporal (annual and seasonal) and spatial (large and regional) scales, showed no systematic trends in the median to lower-end of the distributions, but most places in the tropics presented a decrease in the highest total lightning flash rates (higher-end of the distributions)

A Magnetic Transition Probed by the Ce Ion in Square-Lattice Antiferromagnet CeMnAsO

We examined the magnetic properties of the square-lattice antiferromagnets CeMnAsO and LaMnAsO and their solid solutions La1-xCexMnAsO by resistivity, magnetic susceptibility, and heat capacity measurements below room temperature. A first-order phase transition is observed at 34.1 K, below which the ground-state doublet of the Ce ion splits by 3.53 meV. It is likely that Mn moments already ordered above room temperature are reoriented at the transition, as reported for related compounds, such as NdMnAsO and PrMnSbO. This transition generates a large internal magnetic field at the Ce site in spite of the fact that simple Heisenberg interactions should be cancelled out at the Ce site owing to geometrical frustration. The transition takes place at nearly the same temperature with the substitution of La for Ce up to 90%. The Ce moment does not undergo long-range order by itself, but is parasitically induced at the transition, serving as a good probe for detecting the magnetism of Mn spins in a square lattice.Comment: 11 pages, 5 figures, to be published in J. Phys. Soc. Jp

Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells

Introduction: The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated. Methods: The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level). Results: Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 mu g/ml to 6 mu g/ml when combined with tamoxifen. At a concentration of 6 mu g/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 mu g/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir. Conclusions: The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals

RNA isolation for transcriptomics of human and mouse small skin biopsies

<p>Abstract</p> <p>Background</p> <p>Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies.</p> <p>Findings</p> <p>We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms.</p> <p>Conclusions</p> <p>Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.</p

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk.

The associations between serum concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP)-3 and risk of breast cancer were investigated in a nested case-control study involving 117 cases (70 premenopausal and 47 postmenopausal at blood collection) and 350 matched controls within a cohort of women from the island of Guernsey, UK. Women using exogenous hormones at the time of blood collection were excluded. Premenopausal women in the top vs bottom third of serum IGF-I concentration had a nonsignificantly increased risk for breast cancer after adjustment for IGFBP-3 (odds ratio (OR) 1.71; 95% confidence interval (CI): 0.74-3.95; test for linear trend, P=0.21). Serum IGFBP-3 was associated with a reduction in risk in premenopausal women after adjustment for IGF-I (top third vs the bottom third: OR 0.49; 95% CI: 0.21-1.12, P for trend=0.07). Neither IGF-I nor IGFBP-3 was associated with risk in postmenopausal women and serum IGF-II concentration was not associated with risk in pre- or postmenopausal women. These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Eerste evaluatie Jeugdwet:Na de transitie nu de transformatie

Vanaf 1 Januari 2015 is de Jeugdwet van kracht1. Het doel van de Jeugdwet wordt als volgt omschreven: “Het doel …. is om het jeugdstelsel te vereenvoudigen en het efficiënter en effectiever te maken, met het uiteindelijke doel het versterken van de eigen kracht van de jongere en van het zorgend en probleemoplossend vermogen van diens gezien en sociale omgeving”2. Daarvoor is een transformatie nodig in de hulp die aan gezinnen wordt geboden, meer gericht op preventie, het bieden van juiste, integrale, hulp op maat voor gezinnen, waarbij wordt uitgegaan van de eigen kracht van gezinnen en hun sociale omgeving en er meer ruimte is voor professionals door vermindering van de regeldruk. De bestuurlijke en financiële randvoorwaarde om dit te realiseren is de decentralisatie van alle vormen van jeugdhulp naar de gemeente, zo wordt in de memorie van toelichting gesteld 3. De Jeugdwet heeft daarnaast ook nog als doel om ieder kind te verzekeren van de bescherming en zorg die nodig zijn voor zijn of haar welzijn en toegang tot voorzieningen voor gezondheidszorg (art. 3 en 24 Internationaal verdrag inzake de rechten van het kind). Zelfs uit deze compacte beschrijving wordt al duidelijk dat de doelen van de Jeugdwet ambitieus en ook divers zijn en de ingezette veranderingen complex, met als dominante element de decentralisatie van alle vormen van jeugdhulp naar de gemeente. Artikel 12.2 van de Jeugdwet bepaalt dat binnen drie jaar na de inwerkingtreding van de wet aan de Staten-Generaal een verslag wordt gezonden over de doeltreffendheid en de effecten van deze wet in de praktijk. In een motie in de Kamer is vastgesteld dat het hierbij om een tussenevaluatie gaat. Dit verslag ligt voor u. In dit inleidende hoofdstuk gaan we, op hoofdlijnen, in op het domein waarop de Jeugdwet betrekking heeft, op de doelen van de Jeugdwet en op de assumpties achter de Jeugdwet: Wat zijn de verwachtingen van de wetgever over de werking van de Jeugdwet en de daarmee gepaard gaande decentralisatie en hoe dragen deze bij aan de gestelde doelen? Dit hoofdstuk wordt afgesloten met een beschrijving van de opzet van deze evaluatie. (aut. ref.