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

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

Towards sustainable human space exploration—priorities for radiation research to quantify and mitigate radiation risks

Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon’s orbit, return to the Moon’s surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during their space travels. One of the important challenges to overcome, that could be a major showstopper of the space endeavor, is the exposure to the space radiation environment. There is an urgent need for quantifying, managing and limiting the detrimental health risks and electronics damage induced by space radiation exposure. Such risks raise key priority topics for space research programs. Risk limitation involves obtaining a better understanding of space weather phenomena and the complex radiation environment in spaceflight, as well as developing and applying accurate dosimetric instruments, understanding related short- and long-term health risks, and strategies for effective countermeasures to minimize both exposure to space radiation and the remaining effects post exposure. The ESA/SciSpacE Space Radiation White Paper identifies those topics and underlines priorities for future research and development, to enable safe human and robotic exploration of space beyond Low Earth Orbit

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

Space Radiation and Plasma Effects on Satellites and Aviation: Quantities and Metrics for Tracking Performance of Space Weather Environment Models.

The Community Coordinated Modeling Center has been leading community-wide space science and space weather model validation projects for many years. These efforts have been broadened and extended via the newly launched International Forum for Space Weather Modeling Capabilities Assessment (https://ccmc.gsfc.nasa.gov/assessment/). Its objective is to track space weather models' progress and performance over time, a capability that is critically needed in space weather operations and different user communities in general. The Space Radiation and Plasma Effects Working Team of the aforementioned International Forum works on one of the many focused evaluation topics and deals with five different subtopics (https://ccmc.gsfc.nasa.gov/assessment/topics/radiation-all.php) and varieties of particle populations: Surface Charging from tens of eV to 50-keV electrons and internal charging due to energetic electrons from hundreds keV to several MeVs. Single-event effects from solar energetic particles and galactic cosmic rays (several MeV to TeV), total dose due to accumulation of doses from electrons (>100 keV) and protons (>1 MeV) in a broad energy range, and radiation effects from solar energetic particles and galactic cosmic rays at aviation altitudes. A unique aspect of the Space Radiation and Plasma Effects focus area is that it bridges the space environments, engineering, and user communities. The intent of the paper is to provide an overview of the current status and to suggest a guide for how to best validate space environment models for operational/engineering use, which includes selection of essential space environment and effect quantities and appropriate metrics

Towards sustainable human space exploration-priorities for radiation research to quantify and mitigate radiation risks

Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon's orbit, return to the Moon's surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during their space travels. One of the important challenges to overcome, that could be a major showstopper of the space endeavor, is the exposure to the space radiation environment. There is an urgent need for quantifying, managing and limiting the detrimental health risks and electronics damage induced by space radiation exposure. Such risks raise key priority topics for space research programs. Risk limitation involves obtaining a better understanding of space weather phenomena and the complex radiation environment in spaceflight, as well as developing and applying accurate dosimetric instruments, understanding related short- and long-term health risks, and strategies for effective countermeasures to minimize both exposure to space radiation and the remaining effects post exposure. The ESA/SciSpacE Space Radiation White Paper identifies those topics and underlines priorities for future research and development, to enable safe human and robotic exploration of space beyond Low Earth Orbit

Assessment of Radiation and Plasma Environment Modeling Capabilities

In order to make space weather environment models more useful to engineers and the user community throughout different phases of a satellite lifecycle (mission concept/planning/design/build, launch, operation and anomaly resolution) or assessing radiation effects at aviation altitudes, it is important to track their performance over time with well-defined, user-focused metrics and to maintain active, ongoing communication channels in order to understand each other’s needs. To this end, working with experts in both science and engineering areas and the community in general, CCMC has launched the International Forum for Space Weather Modeling Capabilities Assessment (https://ccmc.gsfc.nasa.gov/assessment/). In this presentation, we will report the progress made from our Space Radiation and Plasma Effects Working Team. Two sets of metrics/physical quantities have been chosen with one set that are outputs of space environment models (constituting critical physical parameters/inputs directly relevant to effects quantification) and the other relevant to engineering models of effects. The initial results and follow-on activities will be discussed