Passive SOBP generation from a static proton pencil beam using 3D-printed range modulators for FLASH experiments

The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer (LETD) in water. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups

Precise Charm- and Bottom-Quark Masses: Theoretical and Experimental Uncertainties

Recent theoretical and experimental improvements in the determination of charm and bottom quark masses are discussed. A new and improved evaluation of the contribution from the gluon condensate $$ to the charm mass determination and a detailed study of potential uncertainties in the continuum cross section for $b\bar b$ production is presented, together with a study of the parametric uncertainty from the $\alpha_s$-dependence of our results. The final results, $m_c(3 \text{GeV})=986(13)$MeV and $m_b(m_b)=4163(16)$MeV, represent, together with a closely related lattice determination $m_c(3\;{\rm GeV})=986(6)$MeV, the presently most precise determinations of these two fundamental Standard Model parameters. A critical analysis of the theoretical and experimental uncertainties is presented.Comment: 12 pages, presented at Quarks~2010, 16th International Seminar of High Energy Physics, Kolomna, Russia, June 6-12, 2010; v2: references adde

Prospect of making XPS a high throughput analytical method illustrated for a CuxNi1 xOy combinatorial material library

Combinatorial material science crucially depends on robust, high throughput characterization methods. While X ray photoelectron spectroscopy XPS may provide detailed information about chemical and electronic properties, it is a time consuming technique and, therefore, is not viewed as a high throughput method. Here we present preliminary XPS data of 169 measurement spots on a combinatorial 72 72 cm2 CuxNi1 amp; 8722;xOy compositional library to explore how characterization and evaluation routines can be optimized to improve throughput in XPS for combinatorial studies. In particular, two quantification approaches are compared. We find that a simple integration of XPS peak regions approach is suited for fast evaluation of, in the example system, the [Cu] [Cu] [Ni] ratio. Complementary to that, the time consuming XPS peak fit approach provides additional insights into chemical speciation and oxidation state changes, without a large deviation of the [Cu] [Cu] [Ni] ratio. This insight suggests exploiting the fast integration approach for real time analysis during XPS data collection, paving the way for an on the fly selection of points of interest i.e., areas on the sample where sudden composition changes have been identified for detailed XPS characterization. Together with the envisioned improvements when going from laboratory to synchrotron based excitation sources, this will shorten the analysis time sufficiently for XPS to become a realistic characterization option for combinatorial material scienc

Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented

Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses

At the Biological Modeling and Simulation Frontier

We provide a rationale for and describe examples of synthetic modeling and simulation (M&S) of biological systems. We explain how synthetic methods are distinct from familiar inductive methods. Synthetic M&S is a means to better understand the mechanisms that generate normal and disease-related phenomena observed in research, and how compounds of interest interact with them to alter phenomena. An objective is to build better, working hypotheses of plausible mechanisms. A synthetic model is an extant hypothesis: execution produces an observable mechanism and phenomena. Mobile objects representing compounds carry information enabling components to distinguish between them and react accordingly when different compounds are studied simultaneously. We argue that the familiar inductive approaches contribute to the general inefficiencies being experienced by pharmaceutical R&D, and that use of synthetic approaches accelerates and improves R&D decision-making and thus the drug development process. A reason is that synthetic models encourage and facilitate abductive scientific reasoning, a primary means of knowledge creation and creative cognition. When synthetic models are executed, we observe different aspects of knowledge in action from different perspectives. These models can be tuned to reflect differences in experimental conditions and individuals, making translational research more concrete while moving us closer to personalized medicine