The Role of CDK4 in the Pathogenesis of Pancreatic Cancer.

Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer. While the use of these agents is encouraging, their potential is yet to be fully explored. In this study we used the GLOBOCAN database to understand the most recent epidemiology of PC, Human Protein Atlas and KEGG to highlight the role, prevalence, and significance on patient survival of CDK4 in PC. We found that CDK4 cannot be used as prognostic in PC and no significant differences were observed between CDK4 expression and the patient's clinical status, though larger studies, especially concerning CDK4 protein expressions, are required for a more thorough understanding. The use of CDK4/6 inhibitors in PC is still in clinical trials. However, due to only modest improvements observed in the use of single-agent therapies, efforts have focused on combinatorial approaches

Validation of the effect of cross-calibrated GOES solar proton effective energies on derived integral fluxes by comparison with STEREO observations

The derivation of integral fluxes from instrument coincidence rates requires accurate knowledge of their effective energies. Recent cross calibrations of GOES with the high-energy-resolution Interplanetary Monitoring Platform (IMP) 8 Goddard Medium Energy Experiment (GME) (Sandberg et al., Geophys. Res. Lett, 41, 4435, 2014a) gave significantly lower effective energies than those currently used by the NOAA Space Weather Prediction Center to calculate solar proton integral fluxes from GOES rates. This implies systematically lower integral fluxes than currently produced. This paper quantifies the differences between the current and the cross-calibrated GOES integral fluxes and validates the latter. Care is taken to rule out the spectral resolution of the measurements or different integration algorithms as major contributors to differences in the magnitudes of the derived integral fluxes. The lower effective energies are validated by comparison with the independent, high-resolution observations by the STEREO Low-Energy Telescope (LET) and High-Energy Telescope (HET) during the December 2006 solar proton events. The current GOES product is similar to the >10 MeV integral fluxes recalculated by using the Sandberg et al. [2014a] effective energies but is substantially greater at higher energies. (The median ratios of the current to the recalculated fluxes are 1.1 at >10 MeV, 1.7 at >30 MeV, 2.1 at >60 MeV, and 2.9 at >100 MeV.) By virtue of this validation, the cross-calibrated GOES integral fluxes should be considered more accurate than the current NOAA product. The results of this study also demonstrate good consistency between the two long-term IMP 8 GME and STEREO LET and HET solar proton data sets

Updated Model of the Solar Energetic Proton Environment in Space

The Solar Accumulated and Peak Proton and Heavy Ion Radiation Environment (SAPPHIRE) model provides environment specification outputs for all aspects of the Solar Energetic Particle (SEP) environment. The model is based upon a thoroughly cleaned and carefully processed data set. Herein the evolution of the solar proton model is discussed with comparisons to other models and data. This paper discusses the construction of the underlying data set, the modelling methodology, optimisation of fitted flux distributions and extrapolation of model outputs to cover a range of proton energies from 0.1 MeV to 1 GeV. The model provides outputs in terms of mission cumulative fluence, maximum event fluence and peak flux for both solar maximum and solar minimum periods. A new method for describing maximum event fluence and peak flux outputs in terms of 1-in-x-year SPEs is also described. SAPPHIRE proton model outputs are compared with previous models including CREME96, ESP-PSYCHIC and the JPL model. Low energy outputs are compared to SEP data from ACE/EPAM whilst high energy outputs are compared to a new model based on GLEs detected by Neutron Monitors (NMs)

A Statistical Study of Solar Particle Events in Flux and Dose

The high-energy protons from solar energetic particle (SEP) events present a hazard to space systems: damage to science instruments/electronics/materials or to astronauts. A reliable estimate of the high-energy proton environment is critical to assure mission success. Important characteristics of an SEP event are fluence, peak flux, energy spectrum, time to reach the peak flux, time to reach peak dose, and properties of the cumulative dose profile after an event starts. All of these characteristics are important to understand in order to design space missions properly for both robotic and human missions. Because of the unpredictable and sporadic nature of SEP events, statistical models are often used to represent the SEP parameters described above. In a study by Jun et al. (2007), the statistics of event fluences, durations, and time intervals between events were investigated using the then available historical SEP dataset obtained from the instruments onboard the IMP-8 spacecraft. Since then, a more comprehensive SEP dataset based off of IMP-8 and GOES called Reference Data Set Version 2.0 (RDSv2.0) has become available covering the SEP events up to Year 2015 under a framework of the European Space Agency's (ESA's) Solar Energetic Particle Environment Modelling (SEPEM) project (Jiggens et al., 2018). The main objectives of this statistical study of SEP events are two-fold: First, the statistics of peak fluxes, event fluences, durations, and time intervals will be re-visited by using RDSv2.0; Second, the statistical analyses of flux and dose timing will be performed using the same dataset RDSv2.0. The results of this study will address the statistical properties of all key parameters for designing a spacecraft or a human mission where the SEP environment is an important consideration

Prediction of Solar Proton Event Fluence spectra from their Peak flux spectra

Solar Proton Events (SPEs) are of great importance and significance for the study of Space Weather and Heliophysics. These populations of protons are accelerated at high energies ranging from a few MeVs to hundreds of MeVs and can pose a significant hazard both to equipment on board spacecrafts as well as astronauts as they are ionizing radiation. The ongoing study of SPEs can help to understand their characteristics, relative underlying physical mechanisms, and help in the design of forecasting and nowcasting systems which provide warnings and predictions. In this work, we present a study on the relationships between the Peak Flux and Fluence spectra of SPEs. This study builds upon existing work and provides further insights into the characteristics and the relationships of SPE Peak flux and Fluence spectra. Moreover it is shown how these relationships can be quantified in a sound manner and exploited in a simple methodology with which the Fluence spectrum of an SPE can be well predicted from its given Peak spectrum across two orders of magnitude of proton energies, from 5 MeV to 200 MeV. Finally it is discussed how the methodology in this work can be easily applied to forecasting and nowcasting systems

In Situ Data and Effect Correlation During September 2017 Solar Particle Event

Solar energetic particles are one of the main sources of particle radiation seen in space. In the first part of September 2017 the most active solar period of cycle 24 produced four large X-class flares and a series of (interplanetary) coronal mass ejections, which gave rise to radiation storms seen over all energies and at the ground by neutron monitors. This paper presents comprehensive cross comparisons of in situ radiation detector data from near-Earth satellites to give an appraisal on the state of present data processing for monitors of such particles. Many of these data sets have been the target of previous cross calibrations, and this event with a hard spectrum provides the opportunity to validate these results. As a result of the excellent agreement found between these data sets and the use of neutron monitor data, this paper also presents an analytical expression for fluence spectrum for the event. Derived ionizing dose values have been computed to show that although there is a significant high-energy component, the event was not particularly concerning as regards dose effects in spacecraft electronics. Several sets of spacecraft data illustrating single event effects are presented showing a more significant impact in this regard. Such a hard event can penetrate thick shielding; human dose quantities measured inside the International Space Station and derived through modeling for aircraft altitudes are also presented. Lastly, simulation results of coronal mass ejection propagation through the heliosphere are presented along with data from Mars-orbiting spacecraft in addition to data from the Mars surface

Preface to measurement, specification and forecasting of the Solar Energetic Particle (SEP) environment and Ground Level Enhancements (GLEs)

Abstract The Sun emits energetic particles following eruptive events such as solar flares and Coronal Mass Ejections (CMEs). Solar Energetic Particles (SEPs) arrive in bursts known as Solar Particle Events (SPEs), which penetrate into the Earth’s magnetosphere. SEPs with large enough energy induce a complicated atmospheric cascade, which secondary particles lead to an enhancement of count rate of ground-based detectors e.g. Neutron Monitors (NMs). This class of SEPs is therefore referred as Ground Level Enhancements (GLEs). The characterisation of the high-energy SEPs environment with corresponding space weather effects is important for space flights, aviation, and satellite industry. In this topical issue recent developments, addressing important user needs in the space radiation environment domain are published. Some articles are relevant to the specification of the SEP environment whilst others focus on space weather prediction of SEP fluxes. Catalogues based on measurement and processing of SEPs including ground-based data, and modelling of aircrew radiation exposure during major events are also presented

Cross calibration of NOAA GOES solar proton detectors using corrected NASA IMP-8/GME data

Solar proton flux measurements onboard Geostationary Operational Environmental Satellites (GOES) are of great importance as they cover several solar cycles, increasingly contributing to the development of long-term solar proton models and to operational purposes such as now-casting and forecasting of space weather. A novel approach for the cross calibration of GOES solar proton detectors is developed using as reference energetic solar proton flux measurements of NASA IMP-8 Goddard Medium Energy Experiment (GME). The spurious behavior in a part of IMP-8/GME measurements is reduced through the derivation of a nonlinear intercalibration function. The effective energy values of GOES solar proton detectors lead to a significant reduction of the uncertainties in spectra and may be used to refine existing scientific results, available models, and data products based on measurements over the last three decades. The methods presented herein are generic and may be used for calibration processes of other data sets as well. Key Points Calibration of NOAA GOES/EPS energy proton channels Correction of NASA IMP-8/GME data set Novel generic calibration techniques are presented ©2014. American Geophysical Union. All Rights Reserved

Validation of the effect of cross-calibrated GOES solar proton effective energies on derived integral fluxes by comparison with STEREO observations

The derivation of integral fluxes from instrument coincidence rates requires accurate knowledge of their effective energies. Recent cross calibrations of GOES with the high-energy-resolution Interplanetary Monitoring Platform (IMP) 8 Goddard Medium Energy Experiment (GME) (Sandberg et al., Geophys. Res. Lett, 41, 4435, 2014a) gave significantly lower effective energies than those currently used by the NOAA Space Weather Prediction Center to calculate solar proton integral fluxes from GOES rates. This implies systematically lower integral fluxes than currently produced. This paper quantifies the differences between the current and the cross-calibrated GOES integral fluxes and validates the latter. Care is taken to rule out the spectral resolution of the measurements or different integration algorithms as major contributors to differences in the magnitudes of the derived integral fluxes. The lower effective energies are validated by comparison with the independent, high-resolution observations by the STEREO Low-Energy Telescope (LET) and High-Energy Telescope (HET) during the December 2006 solar proton events. The current GOES product is similar to the >10 MeV integral fluxes recalculated by using the Sandberg et al. [] effective energies but is substantially greater at higher energies. (The median ratios of the current to the recalculated fluxes are 1.1 at >10 MeV, 1.7 at >30 MeV, 2.1 at >60 MeV, and 2.9 at >100 MeV.) By virtue of this validation, the cross-calibrated GOES integral fluxes should be considered more accurate than the current NOAA product. The results of this study also demonstrate good consistency between the two long-term IMP 8 GME and STEREO LET and HET solar proton data sets. ©2016. The Authors

The virtual enhancements-solar proton event radiation (VESPER) model

A new probabilistic model introducing a novel paradigm for the modelling of the solar proton environment at 1 AU is presented. The virtual enhancements-solar proton event radiation model (VESPER) uses the European space agency's solar energetic particle environment modelling (SEPEM) Reference Dataset and produces virtual time-series of proton differential fluxes. In this regard it fundamentally diverges from the approach of existing SPE models that are based on probabilistic descriptions of SPE macroscopic characteristics such as peak flux and cumulative fluence. It is shown that VESPER reproduces well the dataset characteristics it uses, and further comparisons with existing models are made with respect to their results. The production of time-series as the main output of the model opens a straightforward way for the calculation of solar proton radiation effects in terms of time-series and the pairing with effects caused by trapped radiation and galactic cosmic rays. © S. Aminalragia-Giamini et al., Published by EDP Sciences 2018