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

Progress with the Upgrade of the SPS for the HL-LHC Era

The demanding beam performance requirements of the High Luminosity (HL-) LHC project translate into a set of requirements and upgrade paths for the LHC injector complex. In this paper the performance requirements for the SPS and the known limitations are reviewed in the light of the 2012 operational experience. The various SPS upgrades in progress and still under consideration are described, in addition to the machine studies and simulations performed in 2012. The expected machine performance reach is estimated on the basis of the present knowledge, and the remaining decisions that still need to be made concerning upgrade options are detailed.Comment: 3 p. Presented at 4th International Particle Accelerator Conference (IPAC 2013

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

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

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

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

Viewing the body modulates both pain sensations and pain responses

Viewing the body can influence pain perception, even when vision is non-informative about the noxious stimulus. Prior studies used either continuous pain rating scales or pain detection thresholds, which cannot distinguish whether viewing the body changes the discriminability of noxious heat intensities or merely shifts reported pain levels. In Experiment 1, participants discriminated two intensities of heat-pain stimulation. Noxious stimuli were delivered to the hand in darkness immediately after participants viewed either their own hand or a non-body object appearing in the same location. The visual condition varied randomly between trials. Discriminability of the noxious heat intensities (d?) was lower after viewing the hand than after viewing the object, indicating that viewing the hand reduced the information about stimulus intensity available within the nociceptive system. In Experiment 2, the hand and the object were presented in separate blocks of trials. Viewing the hand shifted perceived pain levels irrespective of actual stimulus intensity, biasing responses toward ‘high pain’ judgments. In Experiment 3, participants saw the noxious stimulus as it approached and touched their hand or the object. Seeing the pain-inducing event counteracted the reduction in discriminability found when viewing the hand alone. These findings show that viewing the body can affect both perceptual processing of pain and responses to pain, depending on the visual context. Many factors modulate pain; our study highlights the importance of distinguishing modulations of perceptual processing from modulations of response bias

Nitrogen and Carbon Isotopic Dynamics of Subarctic Soils and Plants in Southern Yukon Territory and its Implications for Paleoecological and Paleodietary Studies

We examine here the carbon and nitrogen isotopic compositions of bulk soils (8 topsoil and 7 subsoils, including two soil profiles) and five different plant parts of 79 C3 plants from two main functional groups: herbs and shrubs/subshrubs, from 18 different locations in grasslands of southern Yukon Territory, Canada (eastern shoreline of Kluane Lake and Whitehorse area). The Kluane Lake region in particular has been identified previously as an analogue for Late Pleistocene eastern Beringia. All topsoils have higher average total nitrogen δ15N and organic carbon δ13C than plants from the same sites with a positive shift occurring with depth in two soil profiles analyzed. All plants analyzed have an average whole plant δ13C of −27.5 ± 1.2 ‰ and foliar δ13C of ±28.0 ± 1.3 ‰, and average whole plant δ15N of −0.3 ± 2.2 ‰ and foliar δ15N of ±0.6 ± 2.7 ‰. Plants analyzed here showed relatively smaller variability in δ13C than δ15N. Their average δ13C after suitable corrections for the Suess effect should be suitable as baseline for interpreting diets of Late Pleistocene herbivores that lived in eastern Beringia. Water availability, nitrogen availability, spacial differences and intra-plant variability are important controls on δ15N of herbaceous plants in the study area. The wider range of δ15N, the more numerous factors that affect nitrogen isotopic composition and their likely differences in the past, however, limit use of the modern N isotopic baseline for vegetation in paleodietary models for such ecosystems. That said, the positive correlation between foliar δ15N and N content shown for the modern plants could support use of plant δ15N as an index for plant N content and therefore forage quality. The modern N isotopic baseline cannot be applied directly to the past, but it is prerequisite to future efforts to detect shifts in N cycling and forage quality since the Late Pleistocene through comparison with fossil plants from the same region