Tune Measurements in the SPS as a Multicycling Machine

Throughout the operation cycle of the SPS different particles are accelerated : High intensity protons, leptons and heavy ions. For each particle type a measurement of the betatron tunes along the acceleration cycle is required. The paper describes the different excitation and data analysis methods used in order to minimize beam blow-up during the measurements (protons) or in order to optimize the time resolution (leptons). Measurement examples are given

HIGH-FREQUENCY 3D GEOMORPHIC OBSERVATION USING HOURLY TERRESTRIAL LASER SCANNING DATA OF A SANDY BEACH

Geomorphic processes occur spatially variable and at varying magnitudes, frequencies and velocities, which poses a great challenge to current methods of topographic change analysis. For the quantification of surface change, permanent terrestrial laser scanning (TLS) can generate time series of 3D point clouds at high temporal and spatial resolution. We investigate how the temporal interval influences volume change observed on a sandy beach regarding the temporal detail of the change process and the total volume budget, on which accretion and erosion counteract. We use an hourly time series of TLS point clouds acquired over six weeks in Kijkduin, the Netherlands. A raster-based approach of elevation differencing provides the volume change over time per square meter. We compare the hourly analysis to results of a three- and six-week observation period. For the larger period, a volume increase of 0.3 m3/ m2 is missed on a forming sand bar before it disappears, which corresponds to half its volume. Generally, a strong relationship is shown between observation interval and observed volume change. An increase from weekly to daily observations leads to a five times larger volume change quantified in total. Another important finding is a temporally variable measurement uncertainty in the 3D time series, which follows the daily course of air temperature. Further experiments are required to fully understand the effect of atmospheric conditions on high-frequency TLS acquisition in beach environments. Continued research of 4D geospatial analysis methods will enable automatic identification of dynamic change and improve the understanding of geomorphic processes

Automated Classification of Airborne Laser Scanning Point Clouds

Making sense of the physical world has always been at the core of mapping. Up until recently, this has always dependent on using the human eye. Using airborne lasers, it has become possible to quickly "see" more of the world in many more dimensions. The resulting enormous point clouds serve as data sources for applications far beyond the original mapping purposes ranging from flooding protection and forestry to threat mitigation. In order to process these large quantities of data, novel methods are required. In this contribution, we develop models to automatically classify ground cover and soil types. Using the logic of machine learning, we critically review the advantages of supervised and unsupervised methods. Focusing on decision trees, we improve accuracy by including beam vector components and using a genetic algorithm. We find that our approach delivers consistently high quality classifications, surpassing classical methods

A Natural Love of Natural Products

Recent research on the chemistry of natural products from the author’s group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies with the epothilones suggest that the current tubulin-binding model needs to be modified. Examples of natural products discovery and biodiversity conservation in Suriname and Madagascar are also presented, and it is concluded that natural products chemistry will continue to make significant contributions to drug discovery. My first real exposure to natural products chemistry came in my third and final year as an undergraduate at Cambridge University, when I attended a course of lectures on the chemistry of natural products by the Nobel Prize-winning chemist Sir Alexander Todd (later to become Lord Todd). The lectures included many references to his own work in the field, with stories of his early work on the structure of cholesterol, th

Microevolution of Pandemic Vibrio parahaemolyticus Assessed by the Number of Repeat Units in Short Sequence Tandem Repeat Regions

The emergence of the pandemic strain Vibrio parahaemolyticus O3:K6 in 1996 caused a large increase of diarrhea outbreaks related to seafood consumption in Southeast Asia, and later worldwide. Isolates of this strain constitutes a clonal complex, and their effectual differentiation is possible by comparison of their variable number tandem repeats (VNTRs). The differentiation of the isolates by the differences in VNTRs will allow inferring the population dynamics and microevolution of this strain but this requires knowing the rate and mechanism of VNTRs' variation. Our study of mutants obtained after serial cultivation of clones showed that mutation rates of the six VNTRs examined are on the order of 10−4 mutant per generation and that difference increases by stepwise addition of single mutations. The single stepwise mutation (SSM) was deduced because mutants with 1, 2, 3, or more repeat unit deletions or insertions follow a geometric distribution. Plausible phylogenetic trees are obtained when, according to SSM, the genetic distance between clusters with different number of repeats is assessed by the absolute differences in repeats. Using this approach, mutants originated from different isolates of pandemic V. parahaemolyticus after serial cultivation are clustered with their parental isolates. Additionally, isolates of pandemic V. parahaemolyticus from Southeast Asia, Tokyo, and northern and southern Chile are clustered according their geographical origin. The deepest split in these four populations is observed between the Tokyo and southern Chile populations. We conclude that proper phylogenetic relations and successful tracing of pandemic V. parahaemolyticus requires measuring the differences between isolates by the absolute number of repeats in the VNTRs considered

Pretubulysin: From Hypothetical Biosynthetic Intermediate to Potential Lead in Tumor Therapy

Pretubulysin is a natural product that is found in strains of myxobacteria in only minute amounts. It represents the first enzyme-free intermediate in the biosynthesis of tubulysins and undergoes post-assembly acylation and oxidation reactions. Pretubulysin inhibits the growth of cultured mammalian cells, as do tubulysins, which are already in advanced preclinical development as anticancer and antiangiogenic agents. The mechanism of action of this highly potent compound class involves the depolymerization of microtubules, thereby inducing mitotic arrest. Supply issues with naturally occurring derivatives can now be circumvented by the total synthesis of pretubulysin, which, in contrast to tubulysin, is synthetically accessible in gram-scale quantities. We show that the simplified precursor is nearly equally potent to the parent compound. Pretubulysin induces apoptosis and inhibits cancer cell migration and tubulin assembly in vitro. Consequently, pretubulysin appears to be an ideal candidate for future development in preclinical trials and is a very promising early lead structure in cancer therapy

Machine layout and performance

The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new energy frontier for exploration in 2010, it has gathered a global user community of about 7,000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its luminosity (rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total collisions created) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this upgrade must be carefully conceived and will require about ten years to implement. The new configuration, known as High Luminosity LHC (HL-LHC), will rely on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11-12 tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 300 metre-long high-power superconducting links with negligible energy dissipation. The present document describes the technologies and components that will be used to realise the project and is intended to serve as the basis for the detailed engineering design of HL-LHC

OPERATIONAL PERFORMANCE OF THE LHC PROTON BEAMS WITH THE SPS LOW TRANSITION ENERGY OPTICS

Abstract An optics in the SPS with lower integer tunes (20 versus 26) was proposed and introduced in machine studies since 2010, as a measure for increasing transverse and longitudinal instability thresholds, especially at low energy, for the LHC proton beams. After two years of machine studies and careful optimisation, the new Q20 optics became operational in September 2012 and steadily delivered beam to the LHC until the end of the run. This paper reviews the operational performance of the Q20 optics with respect to transverse and longitudinal beam characteristics in the SPS, enabling high brightness beams injected into the LHC. Aspects of longitudinal beam stability, transmission, high-energy orbit control and beam transfer are discussed

OPERATIONAL PERFORMANCE OF THE LHC PROTON BEAMS WITH THE SPS LOW TRANSITION ENERGY OPTICS

Abstract An optics in the SPS with lower integer tunes (20 versus 26) was proposed and introduced in machine studies since 2010, as a measure for increasing transverse and longitudinal instability thresholds, especially at low energy, for the LHC proton beams. After two years of machine studies and careful optimisation, the new Q20 optics became operational in September 2012 and steadily delivered beam to the LHC until the end of the run. This paper reviews the operational performance of the Q20 optics with respect to transverse and longitudinal beam characteristics in the SPS, enabling high brightness beams injected into the LHC. Aspects of longitudinal beam stability, transmission, high-energy orbit control and beam transfer are discussed