On the behavior of micro-spheres in a hydrogen pellet target

A pellet target produces micro-spheres of different materials, which are used as an internal target for nuclear and particle physics studies. We will describe the pellet hydrogen behavior by means of fluid dynamics and thermodynamics. In particular one aim is to theoretically understand the cooling effect in order to find an effective method to optimize the working conditions of a pellet target. During the droplet formation the evaporative cooling is best described by a multi-droplet diffusion-controlled model, while in vacuum, the evaporation follows the (revised) Hertz-Knudsen formula. Experimental observations compared with calculations clearly indicated the presence of supercooling, the effect of which is discussed as well.Comment: 22 pages, 8 figures (of which two are significantly compressed for easier download

Pressurized rf cavities in ionizing beams

A muon collider or Higgs factory requires significant reduction of the six dimensional emittance of the beam prior to acceleration. One method to accomplish this involves building a cooling channel using high pressure gas filled radio frequency cavities. The performance of such a cavity when subjected to an intense particle beam must be investigated before this technology can be validated. To this end, a high pressure gas filled radio frequency (rf) test cell was built and placed in a 400 MeV beam line from the Fermilab linac to study the plasma evolution and its effect on the cavity. Hydrogen, deuterium, helium and nitrogen gases were studied. Additionally, sulfur hexafluoride and dry air were used as dopants to aid in the removal of plasma electrons. Measurements were made using a variety of beam intensities, gas pressures, dopant concentrations, and cavity rf electric fields, both with and without a 3 T external solenoidal magnetic field. Energy dissipation per electron-ion pair, electron-ion recombination rates, ion-ion recombination rates, and electron attachment times to SF6 and O-2 were measured.ope

Virtual screening for inhibitors of the human TSLP:TSLPR interaction

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

Estimated refractive index and solid density of DT, with application to hollow-microsphere laser targets

The literature values for the 0.55-$mu$m refractive index N of liquid and gaseous H$sub 2$ and D$sub 2$ are combined to yield the equation (N - 1) = [(3.15 +- 0.12) x 10$sup -6$]rho, where rho is the density in moles per cubic meter. This equation can be extrapolated to 300$sup 0$K for use on DT in solid, liquid, and gas phases. The equation is based on a review of solid-hydrogen densities measured in bulk and also by diffraction methods. By extrapolation, the estimated densities and 0.55-$mu$m refractive indices for DT are given. Radiation-induced point defects could possibly cause optical absorption and a resulting increased refractive index in solid DT and T$sub 2$. The effect of the DT refractive index in measuring glass and cryogenic DT laser targets is also described. (auth

Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia

Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL

Kinetic Modeling of Slow Energy Release in Non-Ideal Carbon Rich Explosives

We present here the first self-consistent kinetic based model for long time-scale energy release in detonation waves in the non-ideal explosive LX-17. Non-ideal, insensitive carbon rich explosives, such as those based on TATB, are believed to have significant late-time slow release in energy. One proposed source of this energy is diffusion-limited growth of carbon clusters. In this paper we consider the late-time energy release problem in detonation waves using the thermochemical code CHEETAH linked to a multidimensional ALE hydrodynamics model. The linked CHEETAH-ALE model dimensional treats slowly reacting chemical species using kinetic rate laws, with chemical equilibrium assumed for species coupled via fast time-scale reactions. In the model presented here we include separate rate equations for the transformation of the un-reacted explosive to product gases and for the growth of a small particulate form of condensed graphite to a large particulate form. The small particulate graphite is assumed to be in chemical equilibrium with the gaseous species allowing for coupling between the instantaneous thermodynamic state and the production of graphite clusters. For the explosive burn rate a pressure dependent rate law was used. Low pressure freezing of the gas species mass fractions was also included to account for regions where the kinetic coupling rates become longer than the hydrodynamic time-scales. The model rate parameters were calibrated using cylinder and rate-stick experimental data. Excellent long time agreement and size effect results were achieved

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Estimated refractive index and solid density of DT, with application to hollow-microsphere laser targets

The literature values for the 0.55-$mu$m refractive index N of liquid and gaseous H$sub 2$ and D$sub 2$ are combined to yield the equation (N - 1) = [(3.15 +- 0.12) x 10$sup -6$]rho, where rho is the density in moles per cubic meter. This equation can be extrapolated to 300$sup 0$K for use on DT in solid, liquid, and gas phases. The equation is based on a review of solid-hydrogen densities measured in bulk and also by diffraction methods. By extrapolation, the estimated densities and 0.55-$mu$m refractive indices for DT are given. Radiation-induced point defects could possibly cause optical absorption and a resulting increased refractive index in solid DT and T$sub 2$. The effect of the DT refractive index in measuring glass and cryogenic DT laser targets is also described. (auth

Differential cross sections for muonic atom scattering in solid hydrogenic targets

The differential cross sections for low-energy muonic hydrogen atom scattering in solid molecular H$_2$, D$_2$ and T$_2$ targets under low pressure have been calculated for various temperatures. The polycrystalline fcc and hcp structure of the solid hydrogenic targets are considered. The Bragg and phonon scattering processes are described using the Debye model of a solid. The calculated cross sections are used for Monte Carlo simulations of the muonic atom slowing down in these targets. They have been successfully applied for a description of the production of the muonic atom beams in the multilayer hydrogenic crystals.Comment: 23 pages, 19 figures, 2 table