The DX center and other tin-related defects in AlGaAs semiconductors

Al _x Ga_1-xAs semiconductors doped with both natural and enriched¹¹⁹Sn have been studied by Mössbauer spectroscopy (MS) to help to determine the atomic-scale nature of a deleterious, deep-level defect known as the DX center. Spectra have been acquired in the dark at 76 K and under sub-bandgap illumination at 4 or 10 K to distinguish the DX center from the substitutional shallow donor defect. Although electrical differences are clearly detected in these two states, no difference in the Mössbauer spectra are observed. Unexpected high Sn contents, determined by quantitative MS, demonstrate a large non-electrically active Sn fraction in some samples and this may be obscuring the observation of the DX center by both X-ray absorption spectroscopy and MS. Grinding the single-crystal layers into fine powders leads to an Sn defect that is attributed to a surface-oxidized site.     

Passively mode-locked ytterbium fiber laser utilizing chirped-fiber-Bragg-gratings for dispersion control

A robust, self-starting picosecond pulse source based on ytterbium (Yb³⁺) doped fiber laser is described. Utilizing a chirped-fiber-Bragg-grating (C-FBG) for dispersion control, solitary mode-locking is obtained without bulk dispersion compensation elements. A semiconductor saturable absorber (SESAM) is used for stable self-starting. 3.6 ps pulses are produced, with 45 MHz basic repetition-rate and mW scale average output power at 1060 nm. Detailed numerical simulations based on the modified nonlinear Schrödinger equation agree well with the experimental results and are used as a design tool for the solitary mode-locked picosecond laser. The presented design can be simply employed in an all-fiber environmentally-stable system.     

Tandem mass spectrometry of coprogen and deferoxamine hydroxamic siderophores

Mechanisms of fragmentation of hydroxamic siderophores are proposed comparing deuterated and nondeuterated samples. Standard siderophores (e.g. deferoxamine and coprogen) were directly injected into both ion trap and linear quadrupole mass spectrometers with electrospray ionization (ESI). Four and two fragmentation steps were carried out for deferoxamine and coprogen (analyzed by positive and negative ESI, respectively). Deferoxamine cleavages occurred in both peptide and hydroxamic bonds while the coprogen fragmentation pattern is more elaborate, since it contains Fe(III) in its structure.     

Prediction of biological targets for compounds using multiple-category Bayesian models trained on chemogenomics databases

Target identification is a critical step following the discovery of small molecules that elicit a biological phenotype. The present work seeks to provide an in silico correlate of experimental target fishing technologies in order to rapidly fish out potential targets for compounds on the basis of chemical structure alone. A multiple-category Laplacian-modified na?ve Bayesian model was trained on extended-connectivity fingerprints of compounds from 964 target classes in the WOMBAT (World Of Molecular BioAcTivity) chemogenomics database. The model was employed to predict the top three most likely protein targets for all MDDR (MDL Drug Database Report) database compounds. On average, the correct target was found 77% of the time for compounds from 10 MDDR activity classes with known targets. For MDDR compounds annotated with only therapeutic or generic activities such as "antineoplastic", "kinase inhibitor", or "anti-inflammatory", the model was able to systematically deconvolute the generic activities to specific targets associated with the therapeutic effect. Examples of successful deconvolution are given, demonstrating the usefulness of the tool for improving knowledge in chemogenomics databases and for predicting new targets for orphan compounds.     

Understanding false positives in reporter gene assays: in silico chemogenomics approaches to prioritize cell-based HTS data

High throughput screening (HTS) data is often noisy, containing both false positives and negatives. Thus, careful triaging and prioritization of the primary hit list can save time and money by identifying potential false positives before incurring the expense of followup. Of particular concern are cell-based reporter gene assays (RGAs) where the number of hits may be prohibitively high to be scrutinized manually for weeding out erroneous data. Based on statistical models built from chemical structures of 650 000 compounds tested in RGAs, we created "frequent hitter" models that make it possible to prioritize potential false positives. Furthermore, we followed up the frequent hitter evaluation with chemical structure based in silico target predictions to hypothesize a mechanism for the observed "off target" response. It was observed that the predicted cellular targets for the frequent hitters were known to be associated with undesirable effects such as cytotoxicity. More specifically, the most frequently predicted targets relate to apoptosis and cell differentiation, including kinases, topoisomerases, and protein phosphatases. The mechanism-based frequent hitter hypothesis was tested using 160 additional druglike compounds predicted by the model to be nonspecific actives in RGAs. This validation was successful (showing a 50% hit rate compared to a normal hit rate as low as 2%), and it demonstrates the power of computational models toward understanding complex relations between chemical structure and biological function.     

Understanding Gas Phase Modifier Interactions in Rapid Analysis by Differential Mobility-Tandem Mass Spectrometry

A systematic study involving the use and optimization of gas-phase modifiers in quantitative differential mobility-mass spectrometry (DMS-MS) analysis is presented using nucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes, and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 10⁶ normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab initio thermochemical results, we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry, but at lower temperatures, multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.      

Phase Space Portraits of an Unresolved Gravitational Maxwell Demon

In 1885, during initial discussions of J. C. Maxwell's celebrated thermodynamic demon, Whiting ⁽¹⁾ observed that the demon-like velocity selection of molecules can occur in a gravitationally bound gas. Recently, a gravitational Maxwell demon has been proposed which makes use of this observation [D. P. Sheehan, J. Glick, and J. D. Means, Found. Phys. 30, 1227 (2000)]. Here we report on numerical simulations that detail its microscopic phase space structure. Results verify the previously hypothesized mechanism of its paradoxical behavior. This system appears to be the only example of a fully classical mechanical Maxwell demon that has not been resolved in favor of the second law of thermodynamics.