Comparative Validation of Realtime Solar Wind Forecasting Using the UCSD Heliospheric Tomography Model

The University of California, San Diego 3D Heliospheric Tomography Model reconstructs the evolution of heliospheric structures, and can make forecasts of solar wind density and velocity up to 72 hours in the future. The latest model version, installed and running in realtime at the Community Coordinated Modeling Center(CCMC), analyzes scintillations of meter wavelength radio point sources recorded by the Solar-Terrestrial Environment Laboratory(STELab) together with realtime measurements of solar wind speed and density recorded by the Advanced Composition Explorer(ACE) Solar Wind Electron Proton Alpha Monitor(SWEPAM).The solution is reconstructed using tomographic techniques and a simple kinematic wind model. Since installation, the CCMC has been recording the model forecasts and comparing them with ACE measurements, and with forecasts made using other heliospheric models hosted by the CCMC. We report the preliminary results of this validation work and comparison with alternative models

Timing of Resource Availability Drives Divergent Social Systems and Home Range Dynamics in Ecologically Similar Tree Squirrels

Intraspecific variation in home range size has important implications for the distribution of animals across landscapes and the spatial structuring of population, community, and ecosystem processes. Among species of similar trophic guild and body mass, differences in home range size can reflect extrinsic variables that exert divergent selective forces upon spacing behavior and social organization. We tested predictions about how resource availability and timing influence social system, home range size, and territoriality in two tree squirrel species of similar size and ecological niches but that differ in foraging strategy and social organization. We estimated home range size and intraspecific home range core overlap in the Mt. Graham red squirrel (Tamiasciurus fremonti grahamensis; Arizona USA; MGRS) and the Eurasian red squirrel (Sciurus vulgaris; Alps, Italy; ERS) as functions of species, sex, season, and individual's body mass. However, body mass did not explain differences found between the two species. We found MGRS home ranges being three times smaller with higher core area exclusivity compared to ERS in all seasons. In fact, territorial MGRS evolved in a system of brief resource pulses and are larder hoarders, whereas ERS experience prolonged resource availability and are non-territorial. Only male MGRSs increased their home range during the breeding season, reflecting interspecific differences in social organization and mating behavior. Male ERS home ranges always overlap with several females to enhance mating success although male and female MGRS maintain nearly exclusive territories throughout the year. Only during spring and summer do males temporarily leave their food-based territory to increase mating opportunities with neighboring estrus females. Home range comparisons between ecologically similar species emphasize the importance of divergent extrinsic factors in shaping variability in body size–home range size scaling relationships. Timing in resource availability influenced the social structure and space use in tree squirrels of similar body size, highlighting how the coevolution of arboreal squirrels with conifer tree species has shaped their natural history

Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors

Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance

Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion

Conventional cytotoxic chemotherapy is highly effective in certain cancers, but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise (‘exhaustion’), which limits the use of chemotherapy and success of cancer therapy. Here, we show that the co-administration of G1T28 (trilaciclib), a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil (5FU) treatment model. Consistent with a cell intrinsic effect, we show directly preserved HSC function resulting in a more rapid recovery of peripheral blood counts, enhanced serial transplantation capacity and reduced myeloid skewing. When administered to healthy human volunteers, G1T28 demonstrated excellent in vivo pharmacology and transiently inhibited bone marrow (BM) HSPC proliferation. These findings suggest that the combination of CDK4/6 inhibitors (CDK4/6i) with cytotoxic chemotherapy should provide a means to attenuate therapy-induced BM exhaustion in patients with cancer

Neutrino astronomy with the MACRO detector

High energy gamma ray astronomy is now a well established field and several sources have been discovered in the region from a few GeV up to several TeV. If sources involving hadronic processes exist, the production of photons would be accompanied by neutrinos too. Other possible neutrino sources could be related to the annihilation of WIMPs at the center of galaxies with black holes. We present the results of a search for point-like sources using 1100 upward-going muons produced by neutrino interactions in the rock below and inside the MACRO detector in the underground Gran Sasso Laboratory. These data show no evidence for a possible neutrino point-like source or for possible correlations between gamma ray bursts and neutrinos. They have been used to set flux upper limits for candidate point-like sources which are in the range 10^-14-10^-15 cm-2 s-1.Comment: 37 pages, 15 figures, replacement due to a typo in tab. 6, AASLaTex, submitted to Ap

The Murchison Widefield Array: The Square Kilometre Array Precursor at Low Radio Frequencies

The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised