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  • 1
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    The Simulations Chain of the MURAVES Experiment (2023)
    Details
    Publication Date: 2023-01-25
    Description: Abstract The MUon RAdiography of VESuvius (MURAVES) project is aimed at studying the summital cone of Mt. Vesuvius, an active and hazardous volcano near Naples, Italy. A detailed Monte Carlo simulation frame- work is necessary in order to investigate the effects of the experimental constraints and to perform compar- isons with the actual observations. Our Monte Carlo setup combines a variety of Monte Carlo programs that address different aspects of cosmic muon simulation, from muon generation in the Earth’s upper at- mosphere to the response of the detector, including the interactions with the material of the volcano. We will elaborate on the rationale for our technical choices, including the trade-off between speed and accu- racy, and on the lessons learned, which are of general interest for similar use cases in muon radiography.
    Description: Published
    Description: 303
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: N/A or not JCR
    Keywords: Volcano muography
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
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    The MURAVES Experiment: A Study of the Vesuvius Great Cone with Muon Radiography (2023)
    Details
    Publication Date: 2023-02-09
    Description: The MURAVES experiment aims at the muographic imaging of the internal structure of the summit of Mt. Vesuvius, exploiting muons produced by cosmic rays. Though presently quiescent, the volcano carries a dramatic hazard in its highly populated surroundings. The challenging measurement of the rock density distribution in its summit by muography, in conjunction with data from other geophysical techniques, can help the modeling of possible eruptive dynamics. The MURAVES apparatus consists of an array of three independent and identical muon trackers, with a total sensitive area of 3 square meters. In each tracker, a sequence of 4 XY tracking planes made of plastic scintillators is complemented by a 60 cm thick lead wall inserted between the two downstream planes to improve rejection of background from low-energy muons. The apparatus is currently acquiring data. Preliminary results from the analysis of the first data sample are presented.
    Description: Published
    Description: 373
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: N/A or not JCR
    Keywords: MURAVES experiment at vesuvius
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 3
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    End-to-end simulations of the MUon RAdiography of VESuvius experiment (2023)
    IOP
    Details
    Publication Date: 2023-03-15
    Description: he MUon RAdiography of VESuvius (MURAVES) project aims at the study of the summital cone of Mt. Vesuvius, an active volcano near Naples (Italy), by measuring its density profile through muon flux attenuation. Its data, combined with those from gravimetric and seismic measurement campaigns, will be used for better defining the volcanic plug at the bottom of the crater. We report on the development of an end-to-end simulation framework, in order to perform accurate investigations of the effects of the experimental constraints and to compare simulations, under various model hypotheses, with the actual observations. The detector simulation setup is developed using GEANT4 and a study of cosmic particle generators has been conducted to identify the most suitable one for our simulation framework. To mimic the real data, GEANT4 raw hits are converted to clusters through a simulated digitization: energy deposits are first summed per scintillator bar, and then converted to number of photoelectrons with a data-driven procedure. This is followed by the same clustering algorithm and same tracking code as in real data. We also report on the study of muon transport through rock using PUMAS and GEANT4. In this paper we elaborate on the rationale for our technical choices, including trade-off between speed and accuracy. The developments reported here are of general interest in muon radiography and can be applied in similar cases.
    Description: Published
    Description: C01015
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: JCR Journal
    Keywords: Vesuvius ; muography ; Models and simulations; ; Particle tracking detectors ; 04.08. Volcanology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 4
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    Identification of a Highly Conserved Allosteric Binding Site on Mnk1 and Mnk2 [Articles] (2015)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2015-10-16
    Description: Elevated levels of phosphorylated eukaryotic initiation factor 4E (eIF4E) have been implicated in many tumor types, and mitogen activated protein kinase-interacting kinases (Mnks) are the only known kinases that phosphorylate eIF4E at Ser209. The phosphorylation of eIF4E is essential for oncogenic transformation but is of no significance to normal growth and development. Pharmacological inhibition of Mnks therefore provides a nontoxic and effective strategy for cancer therapy. However, a lack of specific Mnk inhibitors has confounded pharmacological target validation and clinical development. Herein, we report the identification of a novel series of Mnk inhibitors and their binding modes. A systematic workflow has been established to distinguish between type III and type I/II inhibitors. A selection of 66 compounds was tested for Mnk1 and Mnk2 inhibition, and 9 out of 20 active compounds showed type III interaction with an allosteric site of the proteins. Most of the type III inhibitors exhibited dual Mnk1 and Mnk2 activities and demonstrated potent antiproliferative properties against the MV4-11 acute myeloid leukemia cell line. Interestingly, ATP-/substrate-competitive inhibitors were found to be highly selective for Mnk2, with little or no activity for Mnk1. Our study suggests that Mnk1 and Mnk2 share a common structure of the allosteric inhibitory binding site but possess different structural features of the ATP catalytic domain. The findings will assist in the future design and development of Mnk targeted anticancer therapeutics.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  • 5
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    Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men (2013)
    The American Physiological Society (APS)
    Details
    Publication Date: 2013-09-06
    Description: Obese individuals are characterized by low circulating adiponectin concentrations and an increased number of macrophages in adipose tissue, which is believed to be causally associated with chronic low-grade inflammation and insulin resistance. Regular physical exercise decreases overall morbidity in obese subjects, which may be due to modulations of inflammatory pathways. In this randomized clinical trial we investigated the separate effects of endurance training-induced weight loss, diet-induced weight loss, and endurance training per se (without weight loss) on plasma adiponectin multimer composition (Western blotting) and adipose tissue macrophage content (immunohistochemistry) in young, moderately overweight men. Weight loss and endurance training per se decreased whole body fat percentage in an additive manner. No intervention-induced changes were observed for plasma total adiponectin. Surprisingly, endurance training, irrespectively of any associated weight loss, shifted the adiponectin multimer distribution toward a lower molecular weight (21% decrease in HMW/LMW, P = 0.015), whereas diet-induced weight loss shifted the distribution toward a higher molecular weight (42% increase in HMW/MMW, P 〈 0.001). Furthermore, endurance training per se increased the number of anti-inflammatory CD163 + macrophages [from 12.7 ± 2.1 (means ± SE) to 16.1 ± 3.1 CD163 + cells/100 adipocytes, P = 0.013], whereas diet-induced weight loss tended to decrease CD68 + macrophages in subcutaneous abdominal adipose tissue. Thus regular physical exercise influences systemic and adipose tissue inflammatory pathways differently than diet-induced weight loss in younger, moderately overweight men. Our data suggest that some of the health benefits of a physically active lifestyle may occur through modulations of anti- rather than pro-inflammatory pathways in young, overweight men.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
    Published by The American Physiological Society (APS)
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  • 6
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    Pharmacologic Inhibition of MNKs in Acute Myeloid Leukemia [Articles] (2015)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2015-06-26
    Description: The Ras/Raf/MAPK and PI3K/Akt/mTOR pathways are key signaling cascades involved in the regulation of cell proliferation and survival, and have been implicated in the pathogenesis of several types of cancers, including acute myeloid leukemia (AML). The oncogenic activity of eIF4E driven by the Mnk kinases is a convergent determinant of the two cascades, suggesting that targeting the Mnk/eIF4E axis may provide therapeutic opportunity for the treatment of cancer. Herein, a potent and selective Mnk2 inhibitor (MNKI-85) and a dual-specific Mnk1 and Mnk2 inhibitor (MNKI-19), both derived from a thienopyrimidinyl chemotype, were selected to explore their antileukemic properties. MNKI-19 and MNKI-85 are effective in inhibiting the growth of AML cells that possess an M5 subtype with FLT3-internal tandem duplication mutation. Further mechanistic studies show that the downstream effects with respect to the selective Mnk1/2 kinase inhibition in AML cells causes G 1 cell cycle arrest followed by induction of apoptosis. MNKI-19 and MNKI-85 demonstrate similar Mnk2 kinase activity and cellular antiproliferative activity but exhibit different time-dependent effects on cell cycle progression and apoptosis. Collectively, this study shows that pharmacologic inhibition of both Mnk1 and Mnk2 can result in a more pronounced cellular response than targeting Mnk2 alone. However, MNKI-85, a first-in-class inhibitor of Mnk2, can be used as a powerful pharmacologic tool in studying the Mnk2/eIF4E-mediated tumorigenic mechanism. In conclusion, this study provides a better understanding of the mechanism underlying the inhibition of AML cell growth by Mnk inhibitors and suggests their potential utility as a therapeutic agent for AML.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  • 7
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    Metformin and Myocardial Injury in Patients With Diabetes and ST-Segment Elevation Myocardial Infarction: A Propensity Score Matched Analysis [Heart Failure] (2015)
    American Heart Association (AHA)
    Details
    Publication Date: 2015-10-28
    Description: Background Although animal studies have documented metformin's cardioprotective effects, the impact in humans remains elusive. The study objective was to explore the association between metformin and myocardial infarct size in patients with diabetes presenting with ST-segment elevation myocardial infarction. Methods and Results Data extraction used the National Cardiovascular Data CathPCI Registry in all patients with diabetes aged 〉18 years presenting with ST-segment elevation myocardial infarction at 2 academic medical centers from January 2010 to December 2013. The exposure of interest was ongoing metformin use before the event. Propensity score matching was used for the metformin and nonmetformin groups on key prognostic variables. All matched pairs had acceptable D scores of 〈10%, confirming an efficient matching procedure. The primary outcome was myocardial infarct size, reflected by peak serum creatine kinase–myocardial band, troponin T, and hospital discharge left ventricular ejection fraction. Of all 1726 ST-segment elevation myocardial infarction cases reviewed, 493 patients had diabetes (28.5%), with 208 metformin users (42.1%) and 285 nonusers. Matched pairs analysis yielded 137 cases per group. The difference between metformin and nonmetformin groups was –18.1 ng/mL (95% CI –55.0 to 18.8; P =0.56) for total peak serum creatine kinase–myocardial band and –1.1 ng/mL (95% CI –2.8 to 0.5; P =0.41) for troponin T. Median discharge left ventricular ejection fraction in both groups was 45, and the difference between metformin and nonmetformin users was 0.7% (95% CI –2.2 to 3.6; P =0.99). Conclusions No statistically significant association of cardioprotection was found between metformin and myocardial infarct size in patients with diabetes and acute ST-segment elevation myocardial infarction.
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 8
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    The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled Trial (2017)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2017-08-30
    Description: Introduction Vitamin B 12 is crucial for normal cell division and differentiation, and necessary for the development and myelination of the central nervous system. Pregnant mothers in resource poor settings are at risk for poor vitamin B 12 status. Poor vitamin B 12 status in infancy is linked to poor growth and neurodevelopment. Brain development starts from conception, and pregnancy is a period of rapid growth and development for the brain. Methods and analysis The study is an individually randomised double-blind placebo controlled trial in 800 pregnant Nepalese women randomised in a 1:1 ratio. A daily dose of 50 µg of vitamin B 12 or placebo is given to women from early pregnancy, not later than week 15, until 6 months after birth. Weekly visits are conducted in order to record compliance, growth and morbidity. The primary outcomes are scores on the cognitive, language and motor subscales of the Bayley Scales of Infant and Toddler Development, Third Edition, measured at 6 and 12 months of age, and growth (length and weight) measured at 6 and 12 months of age. Ethics and dissemination National Health and Research Council, Nepal (NHRC 253/2016) and Regional Committee for Medical and Health Research Ethics of Western Norway (2016/1620/REK vest) have approved the study. Investigators who have contributed to the conceptualising, conducting, as well as being involved in the data analyses and manuscript writing will be eligible for authorship and be responsible to share outcomes with different stakeholders through publications and workshops. The results from this study may support new dietary guidelines for Nepalese and possibly South Asian pregnant women that can lead to improved pregnancy outcomes, neurodevelopment and cognitive functioning in children. Trial registration number Universal Trial Number: U1111-1183-4093. Trial registration: clinicaltrials.gov: NCT03071666. Protocol date: version 1.2, 1 June 2017.
    Keywords: Open access, Nutrition and metabolism
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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