Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy

Duramycin, through binding with phosphatidylethanolamine (PE), has been shown to be a selective molecular probe for the targeting and imaging of cancer cells. Photodynamic therapy aims to bring about specific cytotoxic damage to tumours through delivery of a photosensitising agent and light irradiation. Conjugation to biological molecules that specifically target cancer has been shown to increase photosensitiser (PS) selectivity and decrease damage to surrounding normal tissue. The aim of this study was to target tumour cells with a PE-specific PS therefore duramycin was conjugated to a porphyrin based PS which was achieved via direct reaction with the ε-amino group on the lysine residue near duramycin's N-terminal. The compound was subsequently purified using RP-HPLC and confirmed using mass spectrometry. Binding of the conjugate to ovarian and pancreatic cancer cell lines was assessed by flow cytometry. Light irradiation with a light fluence of 7.5 J/cm2 was delivered to conjugate treated cancer cells and cell proliferation analysed by MTT assay. The conjugate detected PE on all 4 cancer cell lines in a concentration dependent manner and conjugate plus irradiation effectively reduced cell proliferation at concentrations ≥0.5 μM, dependent on cancer cell line. Reduction in cell proliferation by the irradiated conjugate was enhanced over unconjugated duramycin in A2780, AsPC-1 and SK-OV-3 (p b 0.05). In this study we have shown that a duramycin-porphyrin conjugate retained good binding affinity for its target and, following irradiation, reduced cell proliferation of pancreatic and ovarian cancer cell lines

SST-GATE: A dual mirror telescope for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be the world's first open observatory for very high energy gamma-rays. Around a hundred telescopes of different sizes will be used to detect the Cherenkov light that results from gamma-ray induced air showers in the atmosphere. Amongst them, a large number of Small Size Telescopes (SST), with a diameter of about 4 m, will assure an unprecedented coverage of the high energy end of the electromagnetic spectrum (above ~1TeV to beyond 100 TeV) and will open up a new window on the non-thermal sky. Several concepts for the SST design are currently being investigated with the aim of combining a large field of view (~9 degrees) with a good resolution of the shower images, as well as minimizing costs. These include a Davies-Cotton configuration with a Geiger-mode avalanche photodiode (GAPD) based camera, as pioneered by FACT, and a novel and as yet untested design based on the Schwarzschild-Couder configuration, which uses a secondary mirror to reduce the plate-scale and to allow for a wide field of view with a light-weight camera, e.g. using GAPDs or multi-anode photomultipliers. One objective of the GATE (Gamma-ray Telescope Elements) programme is to build one of the first Schwarzschild-Couder prototypes and to evaluate its performance. The construction of the SST-GATE prototype on the campus of the Paris Observatory in Meudon is under way. We report on the current status of the project and provide details of the opto-mechanical design of the prototype, the development of its control software, and simulations of its expected performance.Comment: In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223

Estimation of the atmospheric flux of nutrients and trace metals to the Eastern Tropical North Atlantic Ocean

Atmospheric deposition contributes potentially significant amounts of the nutrients iron, nitrogen and phosphorus (via mineral dust and anthropogenic aerosols) to the oligotrophic tropical North Atlantic Ocean. Transport pathways, deposition processes and source strengths contributing to this atmospheric flux are all highly variable in space and time. Atmospheric sampling was conducted during 28 research cruises through the Eastern Tropical North Atlantic (ETNA) over a 12 year period and a substantial dataset of measured concentrations of nutrients and trace metals in aerosol and rainfall over the region was acquired. This database was used to quantify (on a spatial- and seasonal-basis) the atmospheric input of ammonium, nitrate, soluble phosphorus and soluble and total iron, aluminium and manganese to the ETNA. The magnitude of atmospheric input varies strongly across the region, with high rainfall rates associated with the Inter-tropical Convergence Zone contributing to high wet deposition fluxes in the south, particularly for soluble species. Dry deposition fluxes of species associated with mineral dust exhibited strong seasonality, with highest fluxes associated with winter-time low-level transport of Saharan dust. Overall (wet plus dry) atmospheric inputs of soluble and total trace metals were used to estimate their soluble fractions. These also varied with season and were generally lower in the dry north than in the wet south. The ratio of ammonium plus nitrate to soluble iron in deposition to the ETNA was lower than the N:Fe requirement for algal growth in all cases, indicating the importance of the atmosphere as a source of excess iron

Room-temperature cycling of metal fluoride electrodes: Liquid electrolytes for high-energy fluoride ion cells

Fluoride ion batteries are potential “next-generation” electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion–conducting electrolytes are known only in the solid state. We report a liquid fluoride ion–conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper–lanthanum trifluoride (Cu@LaF_3) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion–mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology

Comparative evaluation of the tendon-bone interface contact pressure in different single- versus double-row suture anchor repair techniques

The aim of the study was to evaluate the time zero contact pressure over a defined rotator cuff footprint using different repair and stitch techniques in an established sheep model. Forty fresh-frozen sheep shoulders were randomly assigned to five repair groups: single-row repair using simple stitches (SRA-s), single-row repair using horizontal mattress stitches (SRA-m), and single-row repair using arthroscopic Mason-Allen stitches (SRA-ama). Double-row repair was either performed with a combination of simple and horizontal mattress stitches (DRA-sm) or with arthroscopic Mason-Allen/horizontal mattress stitches (DRA-amam). Investigations were performed using a pressure-sensitive film system. The average contact pressure and pressure pattern were measured for each group. Contact pressure was lowest in SRA-m followed by SRA-s. SRA-ama showed highest contact pressure of all single-row treatment groups (P < 0.05). DRA-amam presented the highest overall contact pressure (P < 0.05), whereas DRA-sm exerted contact pressure equal to that of SRA-ama. Both double-row techniques showed the most expanded pressure pattern. Average contact pressures for the more complex single- and double-row techniques utilizing arthroscopic Mason-Allen stitches were greater than were those of the repair techniques utilizing simple and horizontal mattress stitches. However, the contact pattern between the anchors could be increased by using the double-row technique, resulting in more footprint coverage compared to patterns utilizing the single-row techniques. These results support the use of the more complex arthroscopic Mason-Allen stitches and may improve the environment for healing of the repaired rotator cuff tendon

Human Gastrointestinal Juices Intended for Use in In Vitro Digestion Models

The aim of this study was to characterise the individual human gastric and duodenal juices to be used in in vitro model digestion and to examine the storage stability of the enzymes. Gastroduodenal juices were aspirated, and individual variations in enzymatic activities as well as total volumes, pH, bile acids, protein and bilirubin concentrations were recorded. Individual pepsin activity in the gastric juice varied by a factor of 10, while individual total proteolytic activity in the duodenal juice varied by a factor of 5. The duodenal amylase activity varied from 0 to 52.6 U/ml, and the bile acid concentration varied from 0.9 to 4.5 mM. Pooled gastric and duodenal juices from 18 volunteers were characterised according to pepsin activity (26.7 U/ml), total proteolytic activity (14.8 U/ml), lipase activity (951.0 U/ml), amylase activity (26.8 U/ml) and bile acids (4.5 mM). Stability of the main enzymes in two frozen batches of either gastric or duodenal juice was studied for 6 months. Pepsin activity decreased rapidly and adjusting the pH of gastric juice to 4 did not protect the pepsin from degradation. Lipase activity remained stable for 4 months, however decreased rapidly thereafter even after the addition of protease inhibitors. Glycerol only marginally stabilised the survival of the enzymatic activities. These results of compositional variations in the individual gastrointestinal juices and the effect of storage conditions on enzyme activities are useful for the design of in vitro models enabling human digestive juices to simulate physiological digestion

Determining the bubble nucleation efficiency of low-energy nuclear recoils in superheated C3_3F8_8 dark matter detectors

The bubble nucleation efficiency of low-energy nuclear recoils in superheated liquids plays a crucial role in interpreting results from direct searches for weakly interacting massive particle (WIMP) dark matter. The PICO Collaboration presents the results of the efficiencies for bubble nucleation from carbon and fluorine recoils in superheated C$_3$F$_8$ from calibration data taken with 5 distinct neutron spectra at various thermodynamic thresholds ranging from 2.1 keV to 3.9 keV. Instead of assuming any particular functional forms for the nuclear recoil efficiency, a generalized piecewise linear model is proposed with systematic errors included as nuisance parameters to minimize model-introduced uncertainties. A Markov-Chain Monte-Carlo (MCMC) routine is applied to sample the nuclear recoil efficiency for fluorine and carbon at 2.45 keV and 3.29 keV thermodynamic thresholds simultaneously. The nucleation efficiency for fluorine was found to be $\geq 50\, \%$ for nuclear recoils of 3.3 keV (3.7 keV) at a thermodynamic Seitz threshold of 2.45 keV (3.29 keV), and for carbon the efficiency was found to be $\geq 50\, \%$ for recoils of 10.6 keV (11.1 keV) at a threshold of 2.45 keV (3.29 keV). Simulated data sets are used to calculate a p-value for the fit, confirming that the model used is compatible with the data. The fit paradigm is also assessed for potential systematic biases, which although small, are corrected for. Additional steps are performed to calculate the expected interaction rates of WIMPs in the PICO-60 detector, a requirement for calculating WIMP exclusion limits.Comment: 17 pages, 22 figures, 5 table