The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma

Contains fulltext : 208930.pdf (publisher's version ) (Open Access)BACKGROUND/AIM: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease. PATIENTS AND METHODS: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted. RESULTS: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment. CONCLUSION: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease

Active Magnetic Bearings for Energy Storage Systems for Combat Vehicles

Advanced energy storage systems for electric guns and other pulsed weapons on combat vehicles present significant challenges for rotor bearing design, Active magnetic bearings (AMBs) present one emerging bearing option with major advantages in terms of lifetime and rotational speed, and also favorably integrate into high-speed flywheel systems. The Department of Defense Combat Hybrid Power Systems (CHPS) program serves as a case study for magnetic bearing applications on combat vehicles. The University of Texas at Austin Center for Electromechanics (UT-CEM) has designed active magnetic bearing actuators for use in a 5 MW flywheel alternator with a 318 kg (700 lb), 20000 rpm rotor. To minimize CHPS flywheel size and mass, a topology was chosen in which the rotating portion of the flywheel is located outside the stationary components. Accordingly, magnetic bearing actuators are required which share this configuration. Because of inherent low loss and nearly linear force characteristics, UT-CEM has designed and analyzed permanent magnet bias bearing actuators for this application. To verify actuator performance, a nonrotating bearing test fixture was designed and built which permits measurement of static and dynamic force. An AMB control system was designed to provide robust, efficient magnetic levitation of the CHPS rotor over a wide range of operating speeds and disturbance inputs, while minimizing the occurrence of backup bearing touchdowns. This paper discusses bearing system requirements, actuator and controller design, and predicted performance; it also compares theoretical vs. measured actuator characteristicsCenter for Electromechanic

Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype

Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor

The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology

BACKGROUND: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. FINDINGS: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog. CONCLUSIONS: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney

Band structure of 235 U

Over a period of several years we have performed three separate experiments at Lawrence Berkeley National Laboratory's 88-Inch Cyclotron in which 235U (thick target) was Coulomb-excited. The program involved stand-alone experiments with Gammmasphere and with the 8pi Spectrometer using 136Xe beams at 720 MeV, and a CHICO-Gammasphere experiment with a 40Ca beam at 184 MeV. In addition to extending the known negative-parity bands to high spin, we have assigned levels in some seven positive-parity bands which are in some cases (e.g., [631]1/2, [624]7/2, and [622]5/2) strongly populated by E3 excitation. The CHICO data have been analyzed to extract E2 and E3 matrix elements from the observed yields. Additionally, many M1 matrix elements could be extracted from the γ-ray branching ratios. A number of new features have emerged, including the unexpected attenuation of magnetic transitions between states of the same Nilsson multiplet, the breakdown of Coriolis staggering at high spin, and the effect of E3 collectivity on Coriolis interactions

Reply to: Possible overestimation of isomer depletion due to contamination

We appreciate the interest of Guo et al., the points that they raise, and the opportunity that we have to provide additional details that are not included in ref. This allows us to strengthen our experimental case while, in parallel, recent developments are improving our theoretical understanding of nuclear excitation by electron capture (NEEC), such as the exploration of a substantial increase in predicted NEEC probability when considering capture by an ion in an excited state (S. Gargiulo et al., submitted) or the impact of the momentum distribution of target electrons (J.R. et al., submitted). In the accompanying Comment, Guo et al. focus on whether potential background contributions were underestimated in our analysis. As discussed below, these concerns are mostly unwarranted; aside from a small systematic uncertainty that could possibly slightly reduce our reported NEEC excitation probability of Pexc = 0.010(3), our original conclusions still stand

Isomer depletion as experimental evidence of nuclear excitation by electron capture

The atomic nucleus and its electrons are often thought of as independent systems that are held together in the atom by their mutual attraction. Their interaction, however, leads to other important effects, such as providing an additional decay mode for excited nuclear states, whereby the nucleus releases energy by ejecting an atomic electron instead of by emitting a 3-ray. This 'internal conversion' has been known for about a hundred years and can be used to study nuclei and their interaction with their electrons. In the inverse process - nuclear excitation by electron capture (NEEC) - a free electron is captured into an atomic vacancy and can excite the nucleus to a higher-energy state, provided that the kinetic energy of the free electron plus the magnitude of its binding energy once captured matches the nuclear energy difference between the two states. NEEC was predicted in 1976 and has not hitherto been observed. Here we report evidence of NEEC in molybdenum-93 and determine the probability and cross-section for the process in a beam-based experimental scenario. Our results provide a standard for the assessment of theoretical models relevant to NEEC, which predict cross-sections that span many orders of magnitude. The greatest practical effect of the NEEC process may be on the survival of nuclei in stellar environments, in which it could excite isomers (that is, long-lived nuclear states) to shorter-lived states. Such excitations may reduce the abundance of the isotope after its production. This is an example of 'isomer depletion', which has been investigated previously through other reactions, but is used here to obtain evidence for NEEC

Do precocial mammals develop at a faster rate? A comparison of rates of skull development in Sigmodon fulviventer and Mus musculus domesticus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72993/1/j.1420-9101.2003.00568.x.pd

Coulomb excitation of a 242Am isomeric target: E2 and e3 strengths, rotational alignment, and collective enhancement

A 98% pure242mAm (K = 5-, t1/2 = 141 years) isomeric target was Coulomb excited with a 170.5-MeV 40Ar beam. The selectivity of Coulomb excitation, coupled with the sensitivity of Gammasphere plus CHICO, was sufficient to identify 46 new states up to spin 18h{stroke} in at least four rotational bands; 11 of these new states lie in the isomer band, 13 in a previously unknown yrast Kπ = 6- rotational band, and 13 in a band tentatively identified as the predicted yrast Kπ = 5+ band. The rotational bands based on the Kπ = 5- isomer and the 6-bandhead were populated by Coulomb excitation with unexpectedly equal cross sections. The γ -ray yields are reproduced by Coulomb excitation calculations using a two-particle plus rotor model (PRM), implying nearly complete ΔK = 1 mixing of the two almost-degenerate rotational bands, but recovering the Alaga rule for the unperturbed states. The degeneracy of the 5- and 6- bands allows for precise determination of the mixing interaction strength V, which approaches the strong-mixing limit; this agrees with the 50% attenuation of the Coriolis matrix element assumed in the model calculations. The fractional admixture of the I πK= 6-6 state in the nominal 6-5 isomer band state is measured within the PRM as 45.6+0.3-1.1%. The E2 and M1 strengths coupling the 5- and 6- bands are enhanced significantly by the mixing, while E1 and E2 couplings to other low-K bands are not measurably enhanced. The yields of the 5+ band are reproduced by an E3 strength of ≈15 W.u., competitive with the interband E2 strength. Alignments of the identified two-particle Nilsson states in 242Am are compared with the single-particle alignments in 241Am

Rotational alignments in Np235 and the possible role of j15/2 neutrons

The role j15/2 neutron orbitals play in the transuranic region of actinides has been studied by exploring γ-ray transitions between yrast states in Np235, populated utilizing the nucleon-transfer reaction Np237(Sn116,Sn118). Two rotational sequences, presumably the two signatures of the ground-state band, have been delineated to high spin for the first time, with the α=+1/2 and α=-1/2 signature partners reaching 49/2 (tentatively 53/2+) and 47/2+ (tentatively 51/2+), respectively. Definite isotopic assignments for these in-band transitions were established through γ-ray cross correlations between Np235 and Sn118 and events where at least three γ rays corresponding to neptunium-like particles were detected. These transitions reveal clear upbends in the aligned angular momentum and kinematic moment of inertia plots; such a phenomenon could indicate a strong interaction between an aligned νj15/2 configuration crossing the ground-state band in Np235, which is based on a πi13/2 orbital. However, the lack of any signature splitting over the observed frequency range of the Np235 rotational sequences cannot remove the possibility of a πh9/2 assignment for the observed band. The role of the νj15/2 and πi13/2 alignment mechanisms in the deformed U-Pu region is discussed in light of the current spectroscopic data and in the context of the cranked-shell model