Approach to wild-type gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) arise from the intestinal pacemaker cells of Cajal. Wild-type gastrointestinal stromal tumors (WT-GIST) are a unique and uncommon subtype of GISTs that lack activating mutations in the tyrosine kinase c-KIT or platelet derived growth factor receptor alpha (PDGFRA) receptors. The lack of these growth-stimulating mutations renders tyrosine kinase receptor inhibitors, such as imatinib mesylate, relatively ineffective against these tumors. WT-GIST arises most commonly due to underlying alternate proliferative signals associated with germ-line, genetic mutations. WT-GIST frequently arises in patients with BRAF mutations, Carney’s Triad or neurofibromatosis type-1 (NF-1). All patients with WT-GIST require a careful examination for germ-line mutations and very close observation for recurrent tumors. Surgery remains a mainstay therapy for these patients. This review aims to discuss the most recent data available on the diagnosis and treatment of WT-GIST

Quantum interference of electromechanically stabilized emitters in nanophotonic devices

Photon-mediated coupling between distant matter qubits may enable secure communication over long distances, the implementation of distributed quantum computing schemes, and the exploration of new regimes of many-body quantum dynamics. Nanophotonic devices coupled to solid-state quantum emitters represent a promising approach towards realization of these goals, as they combine strong light-matter interaction and high photon collection efficiencies. However, the scalability of these approaches is limited by the frequency mismatch between solid-state emitters and the instability of their optical transitions. Here we present a nano-electromechanical platform for stabilization and tuning of optical transitions of silicon-vacancy (SiV) color centers in diamond nanophotonic devices by dynamically controlling their strain environments. This strain-based tuning scheme has sufficient range and bandwidth to alleviate the spectral mismatch between individual SiV centers. Using strain, we ensure overlap between color center optical transitions and observe an entangled superradiant state by measuring correlations of photons collected from the diamond waveguide. This platform for tuning spectrally stable color centers in nanophotonic waveguides and resonators constitutes an important step towards a scalable quantum network

Adaptive Radiation Therapy (ART) Strategies and Technical Considerations: A State of the ART Review From NRG Oncology

The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided

Exploring Halo Substructure with Giant Stars XI: The Tidal Tails of the Carina Dwarf Spheroidal and the Discovery of Magellanic Cloud Stars in the Carina Foreground

A new large-area Washington M,T_2+DDO51 filter survey of more than 10 deg^2 around the Carina dSph galaxy reveals a spectroscopically confirmed power law radial density "break" population of Carina giant stars extending several degrees beyond the central King profile. Magellan telescope MIKE spectroscopy establishes the existence of Carina stars to at least 4.5 times its central King limiting radius, r_lim and primarily along Carina's major axis. To keep these stars bound to the dSph would require a global Carina mass-to-light ratio of M/L > 6,300 M/L_sun. The MIKE velocities, supplemented with ~950 additional Carina field velocities from archived VLT+GIRAFFE spectra with r<=r_lim, demonstrate a nearly constant Carina velocity dispersion to just beyond r = r_lim, and both a rising velocity dispersion and a velocity shear at still larger radii. Together, the observational evidence suggests that the discovered extended Carina population represents tidal debris from the dSph. Of 65 giant candidates at large angular radii from the Carina center for which MIKE spectra have been obtained 94% are associated either with Carina or a second, newly discovered diffuse, but strongly radial velocity-coherent (velocity dispersion of 9.8 km s^-1), foreground halo system. The fifteen stars in this second, retrograde velocity population have (1) a mean metallicity ~1 dex higher than that of Carina, and (2) colors and magnitudes consistent with the red clump of the Large Magellanic Cloud (LMC). Additional spectroscopy of giant star candidates in fields linking Carina and the LMC shows a smooth velocity gradient between the LMC and the retrograde Carina moving group. We conclude that we have found Magellanic stars almost twice as far (22 deg) from the LMC center than previously known.Comment: ApJ, in pres

Comment on "How green is blue hydrogen?"

This paper is written in response to the paper “How green is blue hydrogen?” by R. W. Howarth and M. Z. Jacobson. It aims at highlighting and discussing the method and assumptions of that paper, and thereby providing a more balanced perspective on blue hydrogen, which is in line with current best available practices and future plant specifications aiming at low CO2 emissions. More specifically, in this paper, we show that: (i) the simplified method that Howarth and Jacobson used to compute the energy balance of blue hydrogen plants leads to significant overestimation of CO2 emissions and natural gas (NG) consumption and (ii) the assumed methane leakage rate is at the high end of the estimated emissions from current NG production in the United States and cannot be considered representative of all-NG and blue hydrogen value chains globally. By starting from the detailed and rigorously calculated mass and energy balances of two blue hydrogen plants in the literature, we show the impact that methane leakage rate has on the equivalent CO2 emissions of blue hydrogen. On the basis of our analysis, we show that it is possible for blue hydrogen to have significantly lower equivalent CO2 emissions than the direct use of NG, provided that hydrogen production processes and CO2 capture technologies are implemented that ensure a high CO2 capture rate, preferably above 90%, and a low-emission NG supply chain

High ALDH Activity Identifies Chemotherapy-Resistant Ewing's Sarcoma Stem Cells That Retain Sensitivity to EWS-FLI1 Inhibition

Cancer stem cells are a chemotherapy-resistant population capable of self-renewal and of regenerating the bulk tumor, thereby causing relapse and patient death. Ewing's sarcoma, the second most common form of bone tumor in adolescents and young adults, follows a clinical pattern consistent with the Cancer Stem Cell model - remission is easily achieved, even for patients with metastatic disease, but relapse remains frequent and is usually fatal.We have isolated a subpopulation of Ewing's sarcoma cells, from both human cell lines and human xenografts grown in immune deficient mice, which express high aldehyde dehydrogenase (ALDH(high)) activity and are enriched for clonogenicity, sphere-formation, and tumor initiation. The ALDH(high) cells are resistant to chemotherapy in vitro, but this can be overcome by the ATP binding cassette transport protein inhibitor, verapamil. Importantly, these cells are not resistant to YK-4-279, a small molecule inhibitor of EWS-FLI1 that is selectively toxic to Ewing's sarcoma cells both in vitro and in vivo.Ewing's sarcoma contains an ALDH(high) stem-like population of chemotherapy-resistant cells that retain sensitivity to EWS-FLI1 inhibition. Inhibiting the EWS-FLI1 oncoprotein may prove to be an effective means of improving patient outcomes by targeting Ewing's sarcoma stem cells that survive standard chemotherapy

Strain engineering of the silicon-vacancy center in diamond

We control the electronic structure of the silicon-vacancy (SiV) color-center in diamond by changing its static strain environment with a nano-electro-mechanical system. This allows deterministic and local tuning of SiV optical and spin transition frequencies over a wide range, an essential step towards multiqubit networks. In the process, we infer the strain Hamiltonian of the SiV revealing large strain susceptibilities of order 1 PHz/strain for the electronic orbital states. We identify regimes where the spin-orbit interaction results in a large strain susceptibility of order 100 THz/strain for spin transitions, and propose an experiment where the SiV spin is strongly coupled to a nanomechanical resonator

Genome Degradation in Brucella ovis Corresponds with Narrowing of Its Host Range and Tissue Tropism

Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ovis does not cause zoonotic disease. Genomic analysis of the type strain ATCC25840 revealed a high percentage of pseudogenes and increased numbers of transposable elements compared to the zoonotic Brucella species, suggesting that genome degradation has occurred concomitant with narrowing of the host range of B. ovis. The absence of genomic island 2, encoding functions required for lipopolysaccharide biosynthesis, as well as inactivation of genes encoding urease, nutrient uptake and utilization, and outer membrane proteins may be factors contributing to the avirulence of B. ovis for humans. A 26.5 kb region of B. ovis ATCC25840 Chromosome II was absent from all the sequenced human pathogenic Brucella genomes, but was present in all of 17 B. ovis isolates tested and in three B. ceti isolates, suggesting that this DNA region may be of use for differentiating B. ovis from other Brucella spp. This is the first genomic analysis of a non-zoonotic Brucella species. The results suggest that inactivation of genes involved in nutrient acquisition and utilization, cell envelope structure and urease may have played a role in narrowing of the tissue tropism and host range of B. ovis