Urinary benzo[a]pyrene and its metabolites as molecular biomarkers of asphalt fume exposure characterized by microflow LC coupled to hybrid quadrupole time-of-flight mass spectrometry

As a step to study the health effects of asphalt fume exposure, an analytical method was developed to characterize benzo[a]pyrene and its hydroxy metabolites in the urine of asphalt fume-exposed rats. This method is based on microflow liquid chromatography (LC) coupled to hybrid quadrupole orthogonal acceleration time-of-flight mass spectrometry (Q-TOFMS). Twenty-four female Sprague-Dawley rats were used in the experiment, with 8 as controls and 16 exposed to asphalt fumes in a whole-body inhalation chamber for 10 days (4 h/day). Generated at 150 degrees C, the asphalt fume concentration in the animal exposure chamber ranged 76-117 mg/m(3). In the urine of the asphalt fume-exposed rats, benzo[a]pyrene and its metabolites of 3-hydroxybenzo[a]pyrene, benzo[a]pyrene-7,8-dihydrodiol(+/-), and benzo[a]pyrene-7,8,9,10-tetrahydrotetrol(+/-) were identified, and their concentrations were determined at 2.19 +/- 0.49, 16.17 +/- 0.3, 6.28 +/- 0.36, and 29.35 +/- 0.26 ng/100 mL, respectively. The metabolite concentrations from the controlled group, however, were either under the detection limits or at a relatively very low level (0.19 +/- 0.41 ng/100 mL for benzo[a]pyrene-7,8,9,10-tetrahydrotetrol metabolite). The results clearly indicate that the benzo[a]pyrene and its hydroxy metabolites were significantly elevated (p < 0.001) in the urine of asphalt fume-exposed rats relative to controls. The study also demonstrated that the combination of microflow LC separation and collision-induced dissociation leading to a characteristic fragmentation pattern by hybrid Q-TOFMS offers a distinct advantage for the identifications and characterizations of the benzo[a]pyrene metabolites.     

The effects of job rotation on the risk of reporting low back pain

Job rotation has been widely recommended as an administrative control to reduce the risk of developing work-related musculoskeletal disorders. However, evidence of its benefits are hard to find in the literature. The effect of job rotation on predictions for the risk of reporting low back pain was estimated using Low Back Pain Reporting (LBPR) and Time Weighted Average (TWA) approaches. Index scores calculated using the peak hand force, the peak L4/L5 shear force and the L4/L5 moment cumulated over the entire shift were used to estimate the effects of job rotation on the probability of reporting low back pain. Simulations of realistic rotations between two jobs showed that workers in low demand jobs who rotate into higher demand jobs experience a linear increase in reporting probability using the TWA approach. With the LBPR approach a step increase in reporting probability occurred because of the immediate exposure to the peak loading parameters associated with the more demanding job. With a 50-50 rotation the TWA and LBPR index scores increased by 39% and 57%, respectively. With the LBPR approach the redistribution of risk was not uniform with job rotation. The increase was greater for those who rotated into the demanding job compared to the reduction experienced by those who rotated out of the demanding job. The effects of job rotation are not easily estimated because of the complex effect that mixing jobs has on peak and cumulative tissue loading.     

Evolutionary Design Systems and Generative Processes

Design tools that aim not only to analyse and evaluate, but also to generate and explore alternative design proposals are now under development. An evolutionary paradigm is presented as a basis for creating such tools. First, the evolutionary paradigm is shown to be the only successful design system on which this new phase of design tool could be based. Secondly, any characterisation of design as a search problem is argued to be a serious misconception. Instead it is proposed that evolutionary design systems should be seen as generative processes that are able to evaluate their own output. Thirdly, a generic framework for generative evolutionary design systems is presented. Fourth, the generative process is introduced as a key element within this generic framework. The role of the environment within this process is fundamental. Finally, the direction of future research within the evolutionary design paradigm is discussed with possible short and long term goals being presented.     

Imaging the cell surface: argon sputtering to expose inner cell structures

Established microscopies such as Scanning Electron Microscopy (SEM) and more recent developments such as Atomic Force Microscopy (AFM) and X-ray Photo-Electron Emission spectroMicroscopy (X-PEEM) can only image the sample surface. We present an argon sputtering method able to progressively expose inner cell structures without apparent damage. By varying the sputtering time, the structure of cell cytoskeleton, vesicles, mitochondria, nuclear membrane, and nucleoli can be imaged. We compared images obtained with confocal fluorescence microscopy, transmission electron microscopy (TEM), SEM, and X-PEEM on similar samples after argon sputtering, then confirmed the similarity of reference intracellular structures, including cytoskeleton fibers, cell-cell and cell-substrate adhesion structures, and secretory vesicles. We conclude that the sputtering method is a new valuable tool for surface sensitive microscopies.     

The Correlation of Microchemical Properties to Antiwear (AW) Performance in Ashless Thiophosphate Oil Additives

X-ray absorption near-edge structure (XANES) spectroscopy at macro-scale (mm2) and X-ray photoelectron emissions microscopy (X-PEEM) at micro-scale (m2) have been used to investigate the chemistry and spatial distributions of chemical species in tribochemical films generated from ashless thiophosphate oil additives on steel. Two different ashless thiophosphate additives were used: a triaryl monothiophosphate (MTP) and a dialkyldithiophosphate (DTP). Atomic force microscopy (AFM) and secondary electron microscopy (SEM) were also used to investigate the thickness and the topography of the tribofilms. Macro-scale XANES analysis showed that both ashless thiophosphates reacted with the steel surface to produce short to medium chain polyphosphates as the main constituent and sulfur species as minor component. From the PEEM experiment, it was found that the DTP tribofilm was microchemically heterogeneous, with areas of varying degrees of polyphosphate chain length. Conversely, MTP formed a tribofilm microchemically homogeneous, with areas comprised of only short chain polyphosphates. From, the different areas of polyphosphate chain length within the DTP tribofilm, colour-coded polyphosphate distribution map was generated. AFM, X-PEEM and SEM revealed that the DTP film was thicker and was composed of AW pads that were wider in area than MTP. This resulted in a smaller wear scar width (WSW) value for DTP. This is the first time that all these analytical techniques have been combined to better understand the nature of the tribofilms from ashless additives. We have concluded that an ideal AW film is comprised of a thick film with pad-like structures that are wider in area and microchemically heterogeneous, with areas of varying polyphosphate chain length.     

Hybrid friction diffusion bonding of 316L stainless steel tube-to-tube sheet joints for coil-wound heat exchangers

Hybrid friction diffusion bonding (HFDB) is a solid-state bonding process first introduced by Helmholtz-Zentrum Geesthacht to join aluminum tube-to-tube sheet joints of Coil-wound heat exchangers (CWHE). This study describes how HFDB was successfully used to manufacture 316L test samples simulating tube-to-tube sheet joints of stainless steel CWHE for molten salt coolants as foreseen in several advanced nuclear- and thermal solar power plants. Engineering parameters of the test sample fabrication are presented and results from subsequent non-destructive vacuum decay leak testing and destructive tensile pull-out testing are discussed. The bonded areas of successfully fabricated samples as characterized by tube rupture during pull-out tensile testing, were further investigated using optical microscopy and scanning electron microscopy including electron backscatter diffraction.     

Chemomechanical Properties of Antiwear Films Using X-ray Absorption Microscopy and Nanoindentation Techniques

The first chemomechanical comparison between an antiwear film formed from a solution containing zinc dialkyl-dithiophophates (ZDDPs) to a solution containing ZDDP plus a detergent (ZDDPdet) has been performed. X-ray absorption near-edge structure (XANES) analysis has shown a difference in the type of polyphosphate between each film. The ZDDPdet film has been found to contain short-chain polyphosphates throughout. X-ray photoelectron emission microscopy (X-PEEM) has provided detailed spatially resolved microchemistry of the films. The large pads in the ZDDP antiwear film have long-chain polyphosphates at the surface and shorter-chain polyphosphates are found in the lower lying regions. The spatially resolved chemistry of the ZDDPdet film was found to be short-chain calcium phosphate throughout. Fiducial marks allowed for the re-location of the same areas with an imaging nanoindenter. This allowed the nanoscale mechanical properties, of selected antiwear pads, to be measured on the same length scale. The indentation modulus of the ZDDP antiwear pads were found to be heterogeneous, ~120 GPa at the center and ~90 GPa at the edges. The ZDDPdet antiwear pads were found to be more uniform and have a similar indentation modulus of ~90 GPa. A theory explaining this measured difference, which is based on the probing depths of all techniques used, sheds new insight into the structure and mechanical response of ZDDP antiwear films.     

Onset of antidepressant activity: reexamining the structure of depression and multiple actions of drugs

The question of when antidepressant drugs (AD) initiate significant clinical actions in depressed patients is still unsettled. Findings from early studies on whether there is a lag in the onset of therapeutic actions were in disagreement. More recent results with the selective serotonin reuptake inhibitors (SSRIs) and other new ADs indicate that clinical actions occur within the first 2 weeks. In this paper, evidence from efficacy studies with the ADs is reviewed and the methodologic and conceptual obstacles to achieving definitive results about the onset issue are analyzed. Depression, formerly viewed as a homogenous disorder, is now seen as heterogenous and multifaceted in structure. Such major structural components as anxiety and disturbed psychomotor functioning can be as significant to the core of the disorder as depressed mood itself. Further, the ADs have been shown to act initially on different facets of the clinical disorder which then result in multiple clinical actions, e.g., an initial reduction in anxiety followed by stimulation of motor activity. Data from the NIMH Collaborative Study of the Psychobiology of Depression are used to illustrate: (1) the componential structure of severe depressive disorder; (2) the sequence of change in the major behavioral components of the disorder associated with the tricyclic drugs; (3) the consequent "multiple" onsets of clinical actions; and (4) measurement of the clinical significance and visibility of the early behavioral changes. Recent results describing new behavioral and methodological approaches, the use of early clinical changes to predict outcome, and strategies for designing sound studies of onset are discussed.