MSWEP : 3-hourly 0.25° global gridded precipitation (1979-2015) by merging gauge, satellite, and reanalysis data

Current global precipitation (P) datasets do not take full advantage of the complementary nature of satellite and reanalysis data. Here, we present Multi-Source Weighted-Ensemble Precipitation (MSWEP) version 1.1, a global P dataset for the period 1979-2015 with a 3hourly temporal and 0.25 degrees ffi spatial resolution, specifically designed for hydrological modeling. The design philosophy of MSWEP was to optimally merge the highest quality P data sources available as a function of timescale and location. The long-term mean of MSWEP was based on the CHPclim dataset but replaced with more accurate regional datasets where available. A correction for gauge under-catch and orographic effects was introduced by inferring catchment-average P from streamflow (Q) observations at 13 762 stations across the globe. The temporal variability of MSWEP was determined by weighted averaging of P anomalies from seven datasets; two based solely on interpolation of gauge observations (CPC Unified and GPCC), three on satellite remote sensing (CMORPH, GSMaP-MVK, and TMPA 3B42RT), and two on atmospheric model reanalysis (ERA-Interim and JRA-55). For each grid cell, the weight assigned to the gauge-based estimates was calculated from the gauge network density, while the weights assigned to the satellite-and reanalysis-based estimates were calculated from their comparative performance at the surrounding gauges. The quality of MSWEP was compared against four state-of-the-art gauge-adjusted P datasets (WFDEI-CRU, GPCP-1DD, TMPA 3B42, and CPC Unified) using independent P data from 125 FLUXNET tower stations around the globe. MSWEP obtained the highest daily correlation coefficient (R) among the five P datasets for 60.0% of the stations and a median R of 0.67 vs. 0.44-0.59 for the other datasets. We further evaluated the performance of MSWEP using hydrological modeling for 9011 catchments (< 50 000 km(2)) across the globe. Specifically, we calibrated the simple conceptual hydrological model HBV (Hydrologiska Byrans Vattenbalansavdelning) against daily Q observations with P from each of the different datasets. For the 1058 sparsely gauged catchments, representative of 83.9% of the global land surface (excluding Antarctica), MSWEP obtained a median calibration NSE of 0.52 vs. 0.29-0.39 for the other P datasets. MSWEP is available via http://www.gloh2o.org

Global-scale regionalization of hydrologic model parameters

Current state-of-the-art models typically applied at continental to global scales (hereafter called macroscale) tend to use a priori parameters, resulting in suboptimal streamflow (Q) simulation. For the first time, a scheme for regionalization of model parameters at the global scale was developed. We used data from a diverse set of 1787 small-to-medium sized catchments ( 10-10,000 km(2)) and the simple conceptual HBV model to set up and test the scheme. Each catchment was calibrated against observed daily Q, after which 674 catchments with high calibration and validation scores, and thus presumably good-quality observed Q and forcing data, were selected to serve as donor catchments. The calibrated parameter sets for the donors were subsequently transferred to 0.5 degrees grid cells with similar climatic and physiographic characteristics, resulting in parameter maps for HBV with global coverage. For each grid cell, we used the 10 most similar donor catchments, rather than the single most similar donor, and averaged the resulting simulated Q, which enhanced model performance. The 1113 catchments not used as donors were used to independently evaluate the scheme. The regionalized parameters outperformed spatially uniform (i.e., averaged calibrated) parameters for 79% of the evaluation catchments. Substantial improvements were evident for all major Koppen-Geiger climate types and even for evaluation catchments>5000 km distant from the donors. The median improvement was about half of the performance increase achieved through calibration. HBV with regionalized parameters outperformed nine state-of-the-art macroscale models, suggesting these might also benefit from the new regionalization scheme. The produced HBV parameter maps including ancillary data are available via

Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features

Background Breast cancer is a complex heterogeneous disease and is one of the leading causes of death among women. In addressing the need for treatments of this life-threatening illness, we studied 3,4-dihydropyrimidin-2(1H)-one (or thione) derivatives (DHPMs), a class of inhibitor molecules of the Eg5 motor spindle protein that shows pronounced antitumor activity against several cancer cell lines. Methods An in vitro screening was performed for identification of DHPMs with potent antitumor effects on MCF-7 and MDA-MB-231 cells and the selected DHPMs were evaluated for their inhibitory activity on Eg5 both in silico, using Molecular dynamics, and in vitro Eg5 inhibition assays. Analysis of cell death induction, proliferation, cell cycle and cancer stem cells (CSC) profile were performed by flow cytometry to assess the influence of the selected DPHMs on these important tumor features. Finally, the effects of DHPM treatment on tube formation were evaluated in vitro using HUVEC cells, and in vivo using a model on chorioallantoic membrane (CAM) of fertilized eggs. Results We identified five DHPMs with pronounced inhibitory activity on Eg5 motor protein interfering with the proper mitotic spindle assembly during cell division. These compounds impair the correct conclusion of cell cycle of the breast cancer cells and showed to be selective for tumor cells. Moreover, DHPMs modulate the CD44[superscript +]/CD24[superscript −] phenotype leading to a decrease in the CSC population in MDA-MB-231 cells, an important effect since CSC are resistant to many conventional cancer therapies and play a pivotal role in tumor initiation and maintenance. This observation was confirmed by the results which demonstrated that DHPM treated cells had impaired proliferation and were unable to sustain angiogenesis events. Finally, the DHMP treated cells were induced to apoptosis, which is one of the most pursued goals in drug development. Conclusions The results of our study strongly suggest that DHPMs inhibit important tumorigenic features of breast cancer cells leading them to death by apoptosis. These findings firmly point to DHPM molecular architecture as a promising alternative against breast cancer

Implications of Flavor Dynamics for Fermion Triplet Leptogenesis

We analyze the importance of flavor effects in models in which leptogenesis proceeds via the decay of Majorana electroweak triplets. We find that depending on the relative strengths of gauge and Yukawa reactions the $B-L$ asymmetry can be sizably enhanced, exceeding in some cases an order of magnitude level. We also discuss the impact that such effects can have for TeV-scale triplets showing that as long as the $B-L$ asymmetry is produced by the dynamics of the lightest such triplet they are negligible, but open the possibility for scenarios in which the asymmetry is generated above the TeV scale by heavier states, possibly surviving the TeV triplet related washouts. We investigate these cases and show how they can be disentangled at the LHC by using Majorana triplet collider observables and, in the case of minimal type III see-saw models even through lepton flavor violation observables.Comment: 22 pages, 9 figures, extended discussion on collider phenomenology, references added. Version matches publication in JHE

In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells

Somatostatin (SS) and its analogs exert inhibitory effects on secretive and proliferative processes of various cells via high affinity SS receptors (SS-R). SS analogs bind with different affinity to the five cloned SS-R subtypes. Octreotide, an octapeptide SS analog, binds with high affinity to the SS-R subtype 2 (sst2). SS-R have been demonstrated in vivo and in vitro on cells from endocrine and immune systems. Among the lymphatic tissues, the thymus has been shown to contain the highest amount of SS, suggesting a local functional role of the peptide. We investigated the SS distribution and SS-R expression pattern in the normal human thymus using autoradiography, membrane homogenate binding studies, and RT-PCR. In addition, the effect of SS and octreotide on growth of cultured thymic epithelial cells (TEC) was studied. By autoradiography, binding of [125I-Tyr0]-SS-28 and [125I-Tyr3]-octreotide was detected in all seven thymuses studied. Specific [125I-Tyr3]-octreotide binding was shown on membrane preparations from thymuses, while not from cultured thymocytes. RT-PCR showed the expression of sst1, sst2A and sst3 messenger RNA (mRNA) in the thymic tissue, whereas sst1 and sst2A mRNAs were found in isolated TEC. SS mRNA was present in thymic tissue and in isolated TEC. SS and octreotide significantly inhibited 3H-thymidine incorporation in 3 of 3 and 6 of 6 TEC cultures, respectively. The percent inhibition ranged from 38.8 to 66.8% for SS and from 19.1 to 59.5% for octreotide. In conclusion, SS mRNA and sst1, sst2A, and sst3 mRNAs are expressed in the normal human thymus. Cultured TEC selectively express sst1 and sst2A mRNA and respond in vitro to SS and octreotide administration with an inhibition of cell proliferation. These data suggest a paracrine/autocrine role of SS and its receptors in the regulation of cell growth in thymic microenviron

MSWEP: 3-hourly 0.25° global gridded precipitation (1979-2015) by merging gauge, satellite, and reanalysis data

Current global precipitation (P) datasets do not take full advantage of the complementary nature of satellite and reanalysis data. Here, we present Multi-Source Weighted-Ensemble Precipitation (MSWEP) version 1.1, a global P dataset for the period 1979–2015 with a 3-hourly temporal and 0.25° spatial resolution, specifically designed for hydrological modeling. The design philosophy of MSWEP was to optimally merge the highest quality P data sources available as a function of timescale and location. The long-term mean of MSWEP was based on the CHPclim dataset but replaced with more accurate regional datasets where available. A correction for gauge under-catch and orographic effects was introduced by inferring catchment-average P from streamflow (Q) observations at 13 762 stations across the globe. The temporal variability of MSWEP was determined by weighted averaging of P anomalies from seven datasets; two based solely on interpolation of gauge observations (CPC Unified and GPCC), three on satellite remote sensing (CMORPH, GSMaP-MVK, and TMPA 3B42RT), and two on atmospheric model reanalysis (ERA-Interim and JRA-55). For each grid cell, the weight assigned to the gauge-based estimates was calculated from the gauge network density, while the weights assigned to the satellite- and reanalysis-based estimates were calculated from their comparative performance at the surrounding gauges. The quality of MSWEP was compared against four state-of-the-art gauge-adjusted P datasets (WFDEI-CRU, GPCP-1DD, TMPA 3B42, and CPC Unified) using independent P data from 125 FLUXNET tower stations around the globe. MSWEP obtained the highest daily correlation coefficient (R) among the five P datasets for 60.0 % of the stations and a median R of 0.67 vs. 0.44–0.59 for the other datasets. We further evaluated the performance of MSWEP using hydrological modeling for 9011 catchments (< 50 000 km2) across the globe. Specifically, we calibrated the simple conceptual hydrological model HBV (Hydrologiska Byråns Vattenbalansavdelning) against daily Q observations with P from each of the different datasets. For the 1058 sparsely gauged catchments, representative of 83.9 % of the global land surface (excluding Antarctica), MSWEP obtained a median calibration NSE of 0.52 vs. 0.29–0.39 for the other P datasets. MSWEP is available via http://www.gloh2o.org

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Absence of influenza vaccination among high-risk older adults in Taiwan

<p>Abstract</p> <p>Background</p> <p>Older adults, who often have more than one chronic disease, are at greater risk of influenza and its complications. However, because they often see physicians for other more pressing complaints, their physicians, focusing on one condition, may forget to suggest preventive measures for other diseases such as influenza. This study investigates what major factors affect an older adult with more than one chronic condition missing a vaccination opportunity.</p> <p>Methods</p> <p>Retrospectively reviewing a nationally representative random sample of medical claims from Taiwan's National Health Insurance Research Database during the period 2004 - 2006, we first identified patients sixty-five years or older who had visited physicians. Each patient was assigned a proxy for health status, the Charlson Comorbidity Index (CCI) score. An older claimant was defined has having "absence of a vaccination" when he or she had visited a physician during an influenza season but did not receive an influenza vaccination. Multivariate logistic regression was performed to estimate how likely it would be for older adults with various CCI scores to miss a vaccination.</p> <p>Results</p> <p>Out of 200,000 randomly selected claims, 20,923 older adults were included in our final analysis. We found older adults with higher CCIs to be more likely to have an absence of vaccination (<it>p </it>< 0.01). Our multivariate logistic regression results revealed CCI to be the greatest predictor of absence of vaccination, after controlling for individual factors and medical setting. Older adults with CCI scores three or higher were nearly five times more likely to miss a vaccination than those with a CCI of zero [OR: 4.93 (95%CI, 4.47-5.42)]. Those with CCIs of one and two were 2.53 and 3.92 times more likely to miss vaccination than those with a CCI of zero [OR 2.53 (95%CI, 2.26-2.84) and OR 3.92 (95%CI, 3.51-4.38), respectively].</p> <p>Conclusions</p> <p>The greater the number of certain comorbid conditions, the greater the likelihood a flu vaccination will be missed. Physicians would be well advised to not let the presenting problems of older patients distract from other possible health problems that might also need attention, in this case influenza vaccinations.</p

KM3NeT front-end and readout electronics system: hardware, firmware, and software

[EN] The KM3NeT research infrastructure being built at the bottom of the Mediterranean Sea will host water-Cherenkov telescopes for the detection of cosmic neutrinos. The neutrino telescopes will consist of large volume three-dimensional grids of optical modules to detect the Cherenkov light from charged particles produced by neutrino-induced interactions. Each optical module houses 31 3-in. photomultiplier tubes, instrumentation for calibration of the photomultiplier signal and positioning of the optical module, and all associated electronics boards. By design, the total electrical power consumption of an optical module has been capped at seven Watts. We present an overview of the front-end and readout electronics system inside the optical module, which has been designed for a 1-ns synchronization between the clocks of all optical modules in the grid during a life time of at least 20 years.The authors acknowledge financial support from the funding agencies: Agence Nationale de la Recherche (Grant No. ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), IdEx program and UnivEarthS Labex program at Sorbonne Paris Cite (Grant Nos. ANR-10-LABX-0023 and ANR-11-IDEX-0005-02), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, Grant No. FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education, Scientific Research and Professional Training, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Plan Estatal de Investigacion [refs. FPA2015-65150-C3-1-P, -2-P and -3-P, (MINECO/FEDER)], Severo Ochoa Centre of Excellence program (MINECO), Red Consolider MultiDark (ref. FPA2017-90566-REDC, MINECO), and Prometeo and Grisolia programs (Generalitat Valenciana), "la Caixa" Foundation (ID 100010434) through the fellowship LCF/BQ/IN17/11620019, and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 713673, Spain.Aiello, S.; Ameli, F.; Andre, M.; Androulakis, G.; Anghinolfi, M.; Anton, G.; Ardid Ramírez, M.... (2019). KM3NeT front-end and readout electronics system: hardware, firmware, and software. Journal of Astronomical Telescopes, Instruments, and Systems. 5(4):1-15. https://doi.org/10.1117/1.JATIS.5.4.046001S1155