Diffractive triangulation of radiative point sources

We describe a general method to determine the location of a point source of waves relative to a twodimensional single-crystalline active pixel detector. Based on the inherent structural sensitivity of crystalline sensor materials, characteristic detector diffraction patterns can be used to triangulate the location of a wave emitter. The principle described here can be applied to various types of waves, provided that the detector elements are suitably structured. As a prototypical practical application of the general detection principle, a digital hybrid pixel detector is used to localize a source of electrons for Kikuchi diffraction pattern measurements in the scanning electron microscope. This approach provides a promising alternative method to calibrate Kikuchi patterns for accurate measurements of microstructural crystal orientations, strains, and phase distributions

Perspectives on the chemical etiology of breast cancer.

Multiple factors, known and unknown, contribute to human breast cancer. Hereditary, hormonal, and reproductive factors are associated with risk of breast cancer. Environmental agents, including chemical carcinogens, are modifiable risk factors to which over 70% of breast cancers have been attributed. Polymorphisms of drug-metabolizing enzymes may influence risk of breast cancer from environmental chemicals, dietary agents, and endogenous steroids. The environmental factors discussed in this review include pollutants, occupational exposures, tobacco smoke, alcohol, and diet. Aromatic amines are discussed as potential mammary carcinogens, with a focus on heterocyclic amine food pyrolysis products. These compounds are excreted into the urine after consumption of meals containing cooked meats and have recently been detected in the breast milk of lactating women

Urinary Metabolites of the Dietary Carcinogen PhIP are Predictive of Colon DNA Adducts After a Low Dose Exposure in Humans

Epidemiologic evidence indicates that exposure to heterocyclic amines (HAs) in the diet is an important risk factor for the development of colon cancer. Well-done cooked meats contain significant levels of HAs which have been shown to cause cancer in laboratory animals. To better understand the mechanisms of HA bioactivation in humans, the most mass abundant HA, 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was used to assess the relationship between PhIP metabolism and DNA adduct formation. Ten human volunteers were administered a dietary relevant dose of [{sup 14}C]PhIP 48-72 h prior to surgery to remove colon tumors. Urine was collected for 24 h after dosing for metabolite analysis, and DNA was extracted from colon tissue and analyzed by accelerator mass spectrometry for DNA adducts. All ten subjects were phenotyped for CYP1A2, NAT2, and SULT1A1 enzyme activity. Twelve PhIP metabolites were detected in the urine samples. The most abundant metabolite in all volunteers was N-hydroxy-PhIP-N{sup 2}-glucuronide. Metabolite levels varied significantly between the volunteers. Interindividual differences in colon DNA adducts levels were observed between each individual. The data showed that individuals with a rapid CYP1A2 phenotype and high levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide, had the lowest level of colon PhIP-DNA adducts. This suggests that glucuronidation plays a significant role in detoxifying N-hydroxy-PhIP. The levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide were negatively correlated to colon DNA adduct levels. Although it is difficult to make definite conclusions from a small data set, the results from this pilot study have encouraged further investigations using a much larger study group

Applications and perspectives of ultrasonic multi-gas analysis with simultaneous flowmetry

We have developed ultrasonic instrumentation for simultaneous flow and composition measurement in a variety of gas mixtures. Flow and composition are respectively derived from measurements of the difference and average of sound transit times in opposite directions in a flowing process gas. We have developed a sound velocity-based algorithm to compensate for the effects of additional gases, allowing the concentrations of a pair of gases of primary interest to be acoustically measured on top of a varying baseline from ‘third party’ gases whose concentrations in the multi-gas mixture are measured by other means. Several instruments are used in the CERN ATLAS experiment. Three monitor C3F8, (R218), and CO2 coolant leaks into N2-purged environmental envelopes. Precision in molar concentration of better than 2 × 10−5 is routinely seen in mixtures of C3F8 in N2 in the presence of varying known concentrations of CO2. Further instruments monitor air ingress and C3F8 vapor flow (at high mass flows around 1.1 kg s−1) in the 60 kW thermosiphon C3F8 evaporative cooling recirculator. This instrumentation and analysis technique, targeting binary pairs of gases of interest in multi-gas mixtures, is promising for mixtures of anesthetic gases, particularly in the developing area of xenon anesthesia.</jats:p

Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations

Limited sensitivity of existing assays has prevented investigation of whether Adriamycin–DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin–DNA adducts/104 bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin–DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [14C]Adriamycin–DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin–DNA adducts at clinically-relevant Adriamycin concentrations. [14C]Adriamycin treatment (25 nM) resulted in 4.4 ± 1.0 adducts/107 bp (∼1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin–DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin–DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues

4D Imaging and Diffraction Dynamics of Single-Particle Phase Transition in Heterogeneous Ensembles

In this Letter, we introduce conical-scanning dark-field imaging in four-dimensional (4D) ultrafast electron microscopy to visualize single-particle dynamics of a polycrystalline ensemble undergoing phase transitions. Specifically, the ultrafast metal–insulator phase transition of vanadium dioxide is induced using laser excitation and followed by taking electron-pulsed, time-resolved images and diffraction patterns. The single-particle selectivity is achieved by identifying the origin of all constituent Bragg spots on Debye–Scherrer rings from the ensemble. Orientation mapping and dynamic scattering simulation of the electron diffraction patterns in the monoclinic and tetragonal phase during the transition confirm the observed behavior of Bragg spots change with time. We found that the threshold temperature for phase recovery increases with increasing particle sizes and we quantified the observation through a theoretical model developed for single-particle phase transitions. The reported methodology of conical scanning, orientation mapping in 4D imaging promises to be powerful for heterogeneous ensemble, as it enables imaging and diffraction at a given time with a full archive of structural information for each particle, for example, size, morphology, and orientation while minimizing radiation damage to the specimen