Over the past decade, pharmaceutical companies have seen a decline in the number of drug candidates successfully passing through clinical trials, though billions are still spent on drug development. ...Poor aqueous solubility leads to low bio-availability, reducing pharmaceutical effectiveness. The human cost of inefficient drug candidate testing is of great medical concern, with fewer drugs making it to the production line, slowing the development of new treatments. In biochemistry and biophysics, water mediated reactions and interactions within active sites and protein pockets are an active area of research, in which methods for modelling solvated systems are continually pushed to their limits. Here, we discuss a multitude of methods aimed towards solvent modelling and solubility prediction, aiming to inform the reader of the options available, and outlining the various advantages and disadvantages of each approach.
Abstract High-energy neutral solar radiation in the form of γ -rays and neutrons is produced as secondary products in solar flares. The characteristics of this emission can provide key information ...regarding the energization of charged particles, particularly when primary particles remain trapped in the corona. The Integrated Science Investigation of the Sun (IS⊙IS) suite on Parker Solar Probe is composed of instruments primarily intended to measure energetic charged particles. However, the High Energy Telescope (HET) in IS⊙IS was also designed with a supplementary neutral mode intended to measure γ -rays and neutrons. HET observed its first clear solar γ -ray event in connection with a hard X-ray flare, the eruption of a coronal mass ejection, and a solar energetic particle event on 2022 September 5. The X-ray spectral shape was observed to harden over the course of the event, culminating with the observation of γ -rays by HET. A coincident enhancement in the lower-energy Energetic Particle Instrument (EPI-Lo) was also observed, likely produced by incident solar γ -rays despite the EPI-Lo instrument not having any special neutral measurement capabilities. We use Monte Carlo modeling to reconstruct the incident γ -ray spectrum based on the measured spectrum to demonstrate that the combination of IS⊙IS instruments can measure hard X-rays and γ -rays from ∼60 keV–7 MeV. Despite the fact that this is a supplemental science goal of the mission, the capability of the IS⊙IS instruments to measure γ -rays is important for the study of this population due to the very limited instruments currently observing the Sun in γ -rays.
Abstract On 2022 September 5, Parker Solar Probe (Parker) observed a large solar energetic particle (SEP) event at the unprecedented distance of only 15 R S from the Sun. The observations from the ...Integrated Science Investigation of the Sun (IS⊙IS) obtained over the course of this event are remarkably rich, and an overview is presented here. IS⊙IS is capable of measuring ions from 20 keV to over 100 MeV nuc −1 and electrons from 30 keV to 6 MeV; here, we primarily focus on the proton and helium measurements above 80 keV. Among the surprising results are evidence of inverse velocity dispersion at energies above 1 MeV during the onset of the event, a sharp decrease in the energetic particle intensities at all energies at the interplanetary shock crossing, and repeated short durations of highly anisotropic sunward flow. Many changes in the SEP intensities, anisotropy, and spectral steepness are coincident with solar wind structure boundaries identified using the Parker solar wind magnetic field and plasma data. However, there are significant changes that are not correlated with any clearly visible solar wind variation. The observations presented here serve as an introduction to a complex event with numerous opportunities for future, more in-depth studies.
The Integrated Science Investigation of the Sun (ISIS) is a complete science investigation on the Solar Probe Plus (SPP) mission, which flies to within nine solar radii of the Sun’s surface. ISIS ...comprises a two-instrument suite to measure energetic particles over a very broad energy range, as well as coordinated management, science operations, data processing, and scientific analysis. Together, ISIS observations allow us to explore the mechanisms of energetic particles dynamics, including their: (1) Origins—defining the seed populations and physical conditions necessary for energetic particle acceleration; (2) Acceleration—determining the roles of shocks, reconnection, waves, and turbulence in accelerating energetic particles; and (3) Transport—revealing how energetic particles propagate from the corona out into the heliosphere. The two ISIS Energetic Particle Instruments measure lower (EPI-Lo) and higher (EPI-Hi) energy particles. EPI-Lo measures ions and ion composition from ∼20 keV/nucleon–15 MeV total energy and electrons from ∼25–1000 keV. EPI-Hi measures ions from ∼1–200 MeV/nucleon and electrons from ∼0.5–6 MeV. EPI-Lo comprises 80 tiny apertures with fields-of-view (FOVs) that sample over nearly a complete hemisphere, while EPI-Hi combines three telescopes that together provide five large-FOV apertures. ISIS observes continuously inside of 0.25 AU with a high data collection rate and burst data (EPI-Lo) coordinated with the rest of the SPP payload; outside of 0.25 AU, ISIS runs in low-rate science mode whenever feasible to capture as complete a record as possible of the solar energetic particle environment and provide calibration and continuity for measurements closer in to the Sun. The ISIS Science Operations Center plans and executes commanding, receives and analyzes all ISIS data, and coordinates science observations and analyses with the rest of the SPP science investigations. Together, ISIS’ unique observations on SPP will enable the discovery, untangling, and understanding of the important physical processes that govern energetic particles in the innermost regions of our heliosphere, for the first time. This paper summarizes the ISIS investigation at the time of the SPP mission Preliminary Design Review in January 2014.
Abstract
Energetic charged particles are pervasive throughout the heliosphere with contributions from solar energetic particle events, stream and corotating interaction regions, galactic cosmic rays, ...anomalous cosmic rays, and suprathermal ions. The Integrated Science Investigation of the Sun (IS⊙IS) on board the Parker Solar Probe is a suite of energetic particle detectors covering the energy range ∼20 keV–200 MeV nuc
−1
. IS⊙IS measures energetic particles closer to the Sun than any instrument suite in history, providing a singular view of the energetic particle population in a previously unexplored region. To enable the global research community to efficiently use IS⊙IS data, we have developed an online living catalog of energetic particle enhancements observed by the IS⊙IS instruments. Event identification methodology, information on accessing the catalog, highlights of several events, and a summary of the overall trends are presented. Also included is a summary Event Catalog showing many of the key event parameters for IS⊙IS events to the time of writing.
Abstract
We present analyses of 0.05–2 MeV ions from the 2022 February 16 energetic storm particle event observed by Parker Solar Probe's (PSP) IS⊙IS/EPI-Lo instrument at 0.35 au from the Sun. This ...event was characterized by an enhancement in ion fluxes from a quiet background, increasing gradually with time with a nearly flat spectrum, rising sharply near the arrival of the coronal mass ejection (CME)–driven shock, becoming nearly a power-law spectrum, then decaying exponentially afterward, with a rate that was independent of energy. From the observed fluxes, we determine diffusion coefficients, finding that far upstream of the shock the diffusion coefficients are nearly independent of energy, with a value of 10
20
cm
2
s
−1
. Near the shock, the diffusion coefficients are more than 1 order of magnitude smaller and increase nearly linearly with energy. We also determine the source of energetic particles, by comparing ratios of the intensities at the shock to estimates of the quiet-time intensity to predictions from diffusive shock acceleration theory. We conclude that the source of energetic ions is mostly the solar wind for this event. We also present potential interpretations of the near-exponential decay of the intensity behind the shock. One possibility we suggest is that the shock was overexpanding when it crossed PSP and the energetic particle intensity decreased behind the shock to fill the expanding volume. Overexpanding CMEs could well be more common closer to the Sun, and this is an example of such a case.
Chronic inflammation generated by the tumor microenvironment is known to drive cancer initiation, proliferation, progression, metastasis, and therapeutic resistance. The tumor microenvironment ...promotes the secretion of diverse cytokines, in different types and stages of cancers. These cytokines may inhibit tumor development but alternatively may contribute to chronic inflammation that supports tumor growth in both autocrine and paracrine manners and have been linked to poor cancer outcomes. Such distinct sets of cytokines from the tumor microenvironment can be detected in the circulation and are thus potentially useful as biomarkers to detect cancers, predict disease outcomes and manage therapeutic choices. Indeed, analyses of circulating cytokines in combination with cancer-specific biomarkers have been proposed to simplify and improve cancer detection and prognosis, especially from minimally-invasive liquid biopsies, such as blood. Additionally, the cytokine signaling signatures of the peripheral immune cells, even from patients with localized tumors, are recently found altered in cancer, and may also prove applicable as cancer biomarkers. Here we review cytokines induced by the tumor microenvironment, their roles in various stages of cancer development, and their potential use in diagnostics and prognostics. We further discuss the established and emerging diagnostic approaches that can be used to detect cancers from liquid biopsies, and additionally the technological advancement required for their use in clinical settings.
With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, ...analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (
www.spedas.org
), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have “crib-sheets,” user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer’s Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its “modes of use” with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans.
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