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Low frequency pitch and fore-and-aft oscillations arise in many modes of transport. Pitch oscillation rotates a seat through the gravity vector giving rise to a fore-and-aft acceleration in the plane of the seat: the measurement of fore-and-aft acceleration does not discriminate between the component of this acceleration arising from pitch and the component arising from horizontal acceleration in the fore-and-aft direction. The objectives of this study were to investigate whether fore-and-aft acceleration in the plane of the seat was an adequate predictor of vibration discomfort arising from low frequency oscillation in both the pitch and fore-and-aft axes, and to determine the effect of a backrest on discomfort during pitch and fore-and-aft oscillation at low frequencies. Twelve male subjects used the method of magnitude estimation to judge the discomfort produced by sinusoidal oscillations in the pitch and fore-and-aft axes at 10 frequencies between 0.2 and 1.6Hz, while seated with and without a backrest. For both pitch and fore-and-aft oscillation, the rate of growth of discomfort with increasing vibration magnitude decreased with increasing frequency of oscillation, indicating that the frequency-dependence of discomfort is magnitude-dependent. At frequencies greater than about 0.4Hz with a backrest, and at frequencies greater than about 0.8Hz without a backrest, fore-and-aft acceleration in the plane of the seat arising from pitch oscillation caused greater discomfort than the same acceleration produced by fore-and-aft oscillation. A backrest increased discomfort with pitch oscillation at frequencies greater than about 0.63Hz, but tended to decrease discomfort during fore-and-aft oscillation. The prediction of discomfort caused by low frequency pitch and fore-and-aft oscillation requires that both components are measured and assessed according to their separate effects, taking into account any beneficial and detrimental effects of a backrest. [Copyright &y& Elsevier]

Resonance frequencies evident in the apparent mass and the transmissibility of the human body decrease with increasing vibration magnitude, but the mechanisms responsible for this nonlinearity have not been established. This experiment was designed to explore the effects of body location on the nonlinearity of the body in supine postures. In a group of 12 male subjects, the apparent mass and transmissibility to the sternum, upper abdomen, and lower abdomen were measured in three postures (relaxed semi-supine, flat supine and constrained semi-supine) with vertical random vibration (0.25¿20Hz) at seven vibration magnitudes (nominally 0.0313, 0.0625, 0.125, 0.25, 0.5, 0.75, and 1.0ms¿2 rms). In all three postures, the apparent mass resonance frequencies and the primary peak frequencies in the transmissibilities to the upper and lower abdomen decreased with increases in vibration magnitude from 0.25 to 1.0ms¿2 rms. Nonlinearity generally apparent in transmissibility to the abdomen was less evident in transmissibility to the sternum and less evident in transmissibilities to the abdomen at vibration magnitudes less than 0.125ms¿2 rms. The nonlinearity was more apparent in the flat supine posture than in the semi-supine postures. The findings are consistent with the nonlinearity being associated with the response of soft tissues, more likely a consequence of passive thixotropy than muscle activity. [Copyright &y& Elsevier]

Abstract: Self-assembling complexes have potential as novel supramolecular biomaterials but domain swapped complexes have yet to investigated in this capacity. Bovine ribonuclease A (RNase A) is a useful model protein as it is able to form a range of three dimensional domain swapped structures, including dimers, trimers and tetramers that have similar catalytic ability. However, little work has been carried out investigating the physical characteristics of these complexes. In an effort to characterise the strength of these oligomeric interactions, analytical ultracentrifugation was carried out to measure the dissociation of higher order complexes, using fluorescent tags to test for dissociation at very low concentrations. Results of this work suggest that the oligomers form a very tight complex, with no evidence of dissociation down to 250pM. RNase A oligomers also had similar thermal stability to that of monomeric enzyme, suggesting that the main limiting factor in RNase A stability is the tertiary, rather than quaternary structure. Following thermal unfolding of RNase A, the protein refolded upon cooling, but returned to the monomeric state. This latter result may limit the potential of domain swapping as a means of material assembly. [Copyright &y& Elsevier]

Abstract: The apparent mass of the human body reflects gross movements caused by whole-body vibration and can be used to predict the influence of body dynamics on seat transmissibility. With vertical excitation, various models fit the measured vertical apparent mass of the human body, but experiments also show high fore-and-aft forces on the seat (the fore-and-aft cross-axis apparent mass) that have not influenced current models. This paper defines a model that predicts the vertical apparent mass and the fore-and-aft cross-axis apparent mass of the seated human body during vertical excitation. A three degree-of-freedom model with vertical, fore-and-aft and rotational (i.e. pitch) degrees of freedom has been developed with twelve model parameters (representing inertia, stiffness, damping, and geometry) optimised to the measured vertical apparent mass and the measured fore-and-aft cross-axis apparent mass of the body. The model provides close fits to the moduli and phases for both median data and the responses of 12 individual subjects. The optimum model parameters found by fitting to the median apparent mass of 12 subjects were similar to the medians of the same parameters found by fitting to the individual apparent masses of the same 12 subjects. The model suggests the seated human body undergoes fore-and-aft motion on a seat when exposed to vertical excitation, with the primary resonance frequency of the apparent mass arising from vertical motion of the body. According to the model, changes in the vertical, fore-and-aft, or rotational degree of freedom have an effect on the resonance in the fore-and-aft cross-axis apparent mass. [Copyright &y& Elsevier]

Abstract: The dynamic interaction between the human back and a backrest is complex: the forces at the back–backrest interface depend on the dynamic characteristics of both the back and the backrest, which vary with location over the backrest. This experimental study was designed to investigate the variation in the ratio of the force to acceleration (referred to as the apparent mass) at the back associated with variations in the vertical position and the magnitude of fore-and-aft vibration. Twelve male subjects were exposed to random fore-and-aft vibration in the frequency range 0.25–10Hz at five vibration magnitudes (0.1, 0.2, 0.4, 0.8 and 1.6ms−2 rms). The fore-and-aft forces were measured at five vertical locations (using a flat vertical contact area 120mm in height) and with a flat vertical backrest covering the entire back. At all locations, but not for all subjects, three resonances were observed in the fore-and-aft apparent mass of the back. The first resonance around 1–2Hz was most visible at the middle and lower back. A clearer, second resonance was exhibited between 4 and 5Hz (in the upper back) and between 5 and 8Hz (in the middle and lower back). A third resonance around 7Hz was most apparent in the middle back. The forces at the back were highly dependent on the location: the lower back produced greater forces than the middle and the upper back. The apparent mass of the entire back showed three resonances at similar frequencies: around 2Hz, between 4 and 6Hz and between 7 and 8Hz. The first and the third resonances were observed in most subjects, but not all. With the entire back, the forces were similar to those with the middle back. With variations in vibration magnitude, a nonlinearity in the apparent mass of the back was evident at all locations and with the entire back. It is concluded that biodynamic models of seated persons in contact with a backrest and excited by fore-and-aft vibration should allow for the effects of vibration magnitude and the location of excitation. [Copyright &y& Elsevier]

Abstract: We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and diacid analogues as inhibitors of bacterial dihydrodipicolinate synthase. Enzyme kinetic studies allowed the determination of second-order rate constants of inactivation; and substrate co-incubation studies have shown the inhibitors act at the active-site. Mass spectrometric analyses have further explored the enzyme–inhibitor interaction and determined the sites of enzyme alkylation. [Copyright &y& Elsevier]

We have performed experimental and computational studies to investigate the influences of phospholipids, methionine oxidation and acidic pH on amyloid fibril formation by a peptide derived from human apolipoprotein C-II (apoC-II), a known component of proteinaceous atherosclerotic plaques. Fibril growth monitored by thioflavin T fluorescence revealed inhibition under lipid-rich and oxidising conditions. We subsequently performed fully-solvated atomistic molecular dynamics (MD) simulations of the peptide monomer to study its conformations under both fibril favouring (neutral and low pH) and inhibiting (lipid-rich and oxidising) conditions. Examination of the chain topology, backbone hydrogen-bonding patterns and aromatic sidechain orientations of the peptide under different conditions reveals that, while the peptide adopts similar structures under the fibril-favouring conditions, significantly different structures are obtained under fibril-disruptive conditions. Based on our results, we advance hypotheses for the roles of peptide conformation on aggregation and fibrillisation propensities. [ABSTRACT FROM AUTHOR]

Methionine residues are linked to the pathogenicity of several amyloid diseases; however, the mechanism of this relationship is largely unknown. These diseases are characterized, in vivo, by the accumulation of insoluble proteinaceous plaques, of which the major constituents are amyloid fibrils. In vitro, methionine oxidation has been shown to modulate fibril assembly in several well-characterized amyloid systems. Human apolipoprotein (apo) C-Il contains two methionine residues (Met-9 and Met-60) and readily self-assembles in vitro to form homogeneous amyloid fibrils, thus providing a convenient system to examine the effect of methionine oxidation on amyloid fibril formation and stability. Upon oxidation of the methionine residues of apoC-II with hydrogen peroxide, fibril formation was inhibited. Oxidized apoC-Il molecules did not inhibit native apoC-II assembly, indicating that the oxidized molecules had a reduced ability to interact with the growing fibrils. Single Met-Val substitutions were performed and showed that oxidation of Met-60 had a more significant inhibitory effect than oxidation of Met-9. In addition, Met-Gln substitutions designed to mimic the effect of oxidation on side chain hydrophilicity showed that a change in hydrophobicity at position 60 within the core region of the fibril had a potent inhibitory effect. The oxidation of preformed apoC-Il fibrils caused their dissociation; however, mutants in which the Met-60 was substituted with a valine were protected from this peroxide-induced dissociation. This work highlights an important role for methionine in the formation of amyloid fibril structure and gives new insight into how oxidation affects the stability of mature fibrils. [ABSTRACT FROM AUTHOR]

In the last 20 years the notion that images overpower words, and the belief that a decreasing lexical literacy among the young has been offset by an increasing visual literacy, has been repeated often enough to become accepted wisdom. Yet the precise nature of visual literacy among the young and the relationship between visual competencies and the notion of media literacy have not been fully explored or adequately specified. Concepts of visual literacy and media literacy are unproductively conflated, and visual competencies are too often assumed on the part of those that exhibit familiarity with media culture. This essay compares and analyses notions of visual competence and media literacy and argues that: (1) a cultivated awareness of the production of visual forms and characteristics, and their implications, is necessary for what has been described in the literature as 'media literacy'; and (2) the acquisition of visual analysis skills pre-requires a broader operational context of media literacy. Through an examination of images from religious painting to news coverage the article argues that visual competencies and media literacy skills may, indeed, be mutually dependent. [ABSTRACT FROM AUTHOR]

Abstract: Dihydrodipicolinate synthase (DHDPS) is an essential enzyme in (S)-lysine biosynthesis and an important antibiotic target. All X-ray crystal structures solved to date reveal a homotetrameric enzyme. In order to explore the role of this quaternary structure, dimeric variants of Escherichia coli DHDPS were engineered and their properties were compared to those of the wild-type tetrameric form. X-ray crystallography reveals that the active site is not disturbed when the quaternary structure is disrupted. However, the activity of the dimeric enzymes in solution is substantially reduced, and a tetrahedral adduct of a substrate analogue is observed to be trapped at the active site in the crystal form. Remarkably, heating the dimeric enzymes increases activity. We propose that the homotetrameric structure of DHDPS reduces dynamic fluctuations present in the dimeric forms and increases specificity for the first substrate, pyruvate. By restricting motion in a key catalytic motif, a competing, non-productive reaction with a substrate analogue is avoided. Small-angle X-ray scattering and mutagenesis data, together with a B-factor analysis of the crystal structures, support this hypothesis and lead to the suggestion that in at least some cases, the evolution of quaternary enzyme structures might serve to optimise the dynamic properties of the protein subunits. [Copyright &y& Elsevier]

Abstract: Oscillatory motions of handles, seats, and floors produce complex patterns of sensations in the body with the detection of these motions dependent on the sensitivity of the body to the applied vibration. This study examined the effect of input location (the hand, the seat, and the foot) and vibration frequency (8–315Hz at the hand and foot; 2–315Hz at the seat) on absolute thresholds for the perception of vibration in each of three axes (fore-and-aft, lateral, and vertical). Perception thresholds were determined with 96 males aged 20–29 years divided into eight groups of 12 subjects; each group received vibration at either the hand, the seat, or the foot in one of the three axes (one group experienced both lateral and vertical vibration at the hand). A frequency dependence in the thresholds was apparent for each of the three directions at each of the three locations; U-shaped acceleration threshold contours at frequencies greater than 80Hz suggest the same psychophysical channel-mediated high-frequency thresholds at the hand, the seat, and the foot. Among the nine axes, sensitivity was greatest for vertical vibration at the seat at frequencies between 8 and 80Hz, whereas sensitivity was greatest for vertical vibration at the hand at frequencies greater than 100Hz. Absolute thresholds for the perception of vibration at the hand, the seat, and the foot are not consistent with the relevant frequency weightings in current standards. [Copyright &y& Elsevier]

Abstract: Nonlinear biodynamic responses are evident in many studies of the apparent masses of sitting and standing subjects in static postures that require muscle activity for postural control. In the present study, 12 male subjects adopted a relaxed semi-supine posture assumed to involve less muscle activity than during static sitting and standing. The supine subjects were exposed to two types of vertical vibration (in the x-axis of the semi-supine body): (i) continuous random vibration (0.25–20Hz) at five magnitudes (0.125, 0.25, 0.5, 0.75, and 1.0ms−2 rms); (ii) intermittent random vibration (0.25–20Hz) alternately at 0.25 and 1.0ms−2 rms. With continuous random vibration, the dominant primary resonance frequency in the median normalised apparent mass decreased from 10.35 to 7.32Hz as the vibration magnitude increased from 0.125 to 1.0ms−2 rms. This nonlinear response was apparent in both the vertical (x-axis) apparent mass and in the horizontal (z-axis) cross-axis apparent mass. As the vibration magnitude increased from 0.25 to 1.0ms−2 rms, the median resonance frequency of the apparent mass with intermittent random vibration decreased from 9.28 to 8.06Hz whereas, over the same range of magnitudes with continuous random vibration, the resonance frequency decreased from 9.62 to 7.81Hz. The median change in the resonance frequency (between 0.25 and 1.0ms−2 rms) was 1.37Hz with the intermittent random vibration and 1.71 with the continuous random vibration. With the intermittent vibration, the resonance frequency was higher at the high magnitude and lower at the low magnitude than with continuous vibration of the same magnitudes. The response was typical of thixotropy that may be a primary cause of the nonlinear biodynamic responses to whole-body vibration. [Copyright &y& Elsevier]

Abstract: The resonance frequencies in frequency response functions of the human body (e.g. apparent mass and transmissibility) decrease with increasing vibration magnitude. This nonlinear biodynamic response is found with various sitting and standing postures requiring postural control. The present study measured the apparent mass of the body in a relaxed semi-supine posture with two types of longitudinal horizontal vibration (in the z-axis of the semi-supine body): (i) continuous random excitation (0.25–20Hz) at five magnitudes (0.125, 0.25, 0.5, 0.75 and 1.0ms−2 rms); (ii) intermittent random excitation (0.25–20Hz) alternately at 0.25 and 1.0ms−2 rms. With continuous random vibration, the dominant primary resonance frequency in the median normalised apparent mass decreased from 3.7 to 2.4Hz as the vibration magnitude increased from 0.125 to 1.0ms−2 rms. A nonlinear response was apparent in both the horizontal (z-axis) apparent mass and the vertical (x-axis) cross-axis apparent mass. With intermittent random vibration, as the vibration magnitude increased from 0.25 to 1.0ms−2 rms, the median resonance frequency of the apparent mass decreased from 3.2 to 2.5Hz whereas, with continuous random vibration over the same range of magnitudes, the resonance frequency decreased from 3.4 to 2.4Hz. The median change in the resonance frequency (between 0.25 and 1.0ms−2 rms) was 0.6Hz with the intermittent random vibration and 0.9Hz with the continuous random vibration. With intermittent vibration, the resonance frequency was higher at the high magnitude and lower at the low magnitude than with continuous vibration at the same magnitudes. The responses were consistent with passive thixotropy being a primary cause of nonlinear biodynamic responses to whole-body vibration, although reflex activity of the muscles may also have an influence. [Copyright &y& Elsevier]

Abstract: The discomfort of seated subjects exposed to a wide range of vertical mechanical shocks has been studied experimentally. Shocks were produced from responses of single degree-of-freedom models with 16 fundamental frequencies (0.5–16Hz) and four damping ratios (0.05, 0.1, 0.2 and 0.4) to half-sine force inputs. Shocks with a damping ratio of 0.4 were presented with both polarities. Each type of shock was presented at five unweighted vibration dose values (0.35–2.89ms−1.75). The magnitude estimates of 15 subjects to all 400 shocks showed that the rate of growth in discomfort (the exponent in Stevens’ power law) decreased with increasing shock frequency from 0.5 to 4Hz. Equivalent comfort contours showed greatest sensitivity from 4 to 12.5Hz. At lower magnitudes, variations in discomfort with frequency were similar to weighting Wb in British Standard 6841. At higher magnitudes, low frequencies were judged relatively more uncomfortable than predicted by this weighting. There were small but statistically significant differences in discomfort associated with variations in damping ratios and shock direction. It is concluded that the frequency dependence of discomfort produced by vertical shocks depends on shock magnitude, but for shocks of low and moderate discomfort, the current evaluation methods are reasonable. [Copyright &y& Elsevier]

If the negligence of an employer results in the disability in an employee, the employer is responsible, in whole or in part, for the disability. The employer is wholly responsible when the worker would not have developed the disability if the employer had taken all reasonable preventative measures. The employer is only partly responsible if the worker would probably have developed some disability even if the employer had taken all reasonable precautions. The employer’s responsibility may be estimated from the difference between the actual disability of the worker and the disability that the worker would have suffered if the employer had taken all reasonable preventative measures. This paper considers alternative ways of apportioning negligent and non-negligent exposures to hand-transmitted vibration. The equivalent daily vibration exposure, A(8), used in current EU Directives is shown to be unsuitable for distinguishing between the consequences of negligent and non-negligent exposures because the risks of developing a disorder from hand-transmitted vibration also depend on the years of exposure. Furthermore, daily exposures take no account of individual susceptibility or the practicality of reducing exposure. The consequences of employer negligence may be estimated from the delay in the onset and progression of disorder that would have been achieved if the employer had acted reasonably, such as by reducing vibration magnitude and exposure duration to the minimum that was reasonably achievable in the circumstances. This seems to be fair and reasonable for both employers and employees and indicates the consequences of negligence—the period of the worker’s life with disease as a result of negligence and the period for which their employment opportunities may be restricted as a result of the onset of the disorder due to negligence. The effects of negligence may be estimated from the delay in the onset of disease or disability that would have occurred if the employer had behaved reasonably. This definition of negligence encourages employers to reduce risks to the lowest reasonably practical level, consistent with EU Directives. [ABSTRACT FROM AUTHOR]

Regular exposure to hand-transmitted vibration can result in symptoms and signs of peripheral vascular, neurological and other disorders collectively known as the hand-arm vibration syndrome. The measurement of the effects of hand-transmitted vibration involves converting the evidence of disorder (symptoms and signs) into information that can be stored. Evaluation requires the use of scales on which to indicate the severity of the various symptoms and signs. Assessment involves a judgement of severity relative to a criterion, usually for a specific purpose (e.g. to decide on removal from work or compensation). The measurement and evaluation of symptoms and signs is necessary when monitoring patient health and when performing epidemiological studies for research. The assessment of the severity of the hand-arm vibration syndrome is currently performed with staging systems, but the criteria are not clear and not related to defined methods for measuring or evaluating the symptoms and signs. Recognizing that similar symptoms can occur without injury from occupational exposures to hand-transmitted vibration, this paper attempts to define significant peripheral neurological symptoms caused by hand-transmitted vibration (i.e. ‘unusual symptoms’) and how these symptoms and related signs may be measured. Scales for evaluating the symptoms (e.g. their extent) and the related signs (e.g. their probability relative to the probability of the sign being present in persons not exposed to vibration) are defined. A method of relating unusual symptoms to both the signs of disorder and the pattern of vibration exposure is illustrated. Assessments of severity will vary according to the reasons for assessing the health effects of vibration, and will depend on local practice and convenience, but a way of combining evaluations of symptoms and signs is demonstrated in a staging system. Although inherently complex, the methods may assist the collection of data required to improve understanding of the effects of hand-transmitted vibration and also support a more complete reporting of the condition in those adversely affected by hand-transmitted vibration. [ABSTRACT FROM AUTHOR]

This study was undertaken to compare normal values of thermotactile and vibrotactile thresholds in males and females and in younger and older age groups. In addition, for thermal thresholds, the effects of the contact area (small and large) and stimulus location (glabrous and non-glabrous skin) were investigated. Eighty healthy subjects participated in the study: 20 males and 20 females aged 20–30 years, and 20 males and 20 females aged 55–65 years. Subjects attended one 45 min experimental session consisting of acclimatisation for 10 min followed by 35 min of testing. Using the method of limits, hot thresholds and cold thresholds were measured on the non-dominant upper limb at three locations (the distal phalanx of the middle finger, the thenar eminence, and the dorsal surface of the forearm) using two circular contactors 1.0 and 2.8 cm in diameter. Using the von Békésy method, vibrotactile thresholds at 31.5 and 125 Hz were measured on the distal phalanx of the middle finger of the non-dominant hand. Among the younger subjects there were significant gender differences in thermotactile thresholds but not vibrotactile thresholds. Age did not have any significant effect on thermotactile or vibrotactile thresholds. Hot thresholds were significantly higher and cold thresholds significantly lower when the larger stimulus area was used. The thresholds exceeded by 18% of the population (the mean plus one standard deviation) and by 2.5% (the mean plus two standard deviations) are provided and may be used to consider whether measured thresholds are within a “normal” range. For males and females the same ranges of normal values may be used for vibrotactile thresholds but different ranges of normal values may be required for thermotactile thresholds. An age correction may not be needed for thermotactile or vibrotactile thresholds in persons aged 20–65 years. Contact area has an influence on thermotactile thresholds and should be controlled. [ABSTRACT FROM AUTHOR]

To compare finger systolic blood pressures in males and females and in younger and older persons and provide normal values for all four fingers in younger and older males and females. Eighty healthy subjects participated in the study: 20 males and 20 females aged 20–30 years, and 20 males and 20 females aged 55–65 years. Finger systolic blood pressures (FSBPs) were measured using strain-gauge plethysmography following local cooling at 30 and 10°C in accord with International Standard 14835-2. The FSBPs were measured simultaneously in the thumb and the four fingers of the dominant hand and the percentage changes in finger systolic blood pressures (%FSBPs) due to the cold provocation were calculated. The median finger systolic blood pressures increased with increasing age in both females and males, with the increase highly significant at 30°C but not at 10°C. The %FSBPs were not significantly affected by the age of males, but were significantly lower in older females than younger females. The FSBPs were lower in females than in males at 30°C but there was no significant difference between genders at 10°C. The %FSBPs were higher in younger females than younger males, but only significantly higher in the middle finger and there were no significant differences between the genders in the older age group. There were only minor differences between the four fingers in the FSBPs at 30 and 10°C. The %FSBPs across the four fingers were similar in the younger subjects and in the older females, but varied with finger in the older males. Although there are some differences in the %FSBPs associated with age, gender, and finger, the differences may be sufficiently small to use a single value criterion when deciding on abnormalities in FSBP associated with cold provocation for persons aged 20–65 years. [ABSTRACT FROM AUTHOR]

This study used a prospective design to investigate startle reactivity following trauma exposure. Startle response was evaluated using loud tones during which measures of eyeblink electromyogram (EMG) and heart rate (HR) were collected. Participants were 40 female sexual or physical assault survivors assessed at 1 month and 6 months postassault. There were no significant differences in startle reactivity between posttraumatic stress disorder (PTSD) and non-PTSD groups at the initial assessment. However, at 6 months postassault there was a significantly greater EMG and HR response in the PTSD group as well as a significant increase in startle reactivity from 1 month to 6 months postassault. The findings lend support to a sensitization model of trauma reactivity in which startle response develops over time along with PTSD symptoms. [ABSTRACT FROM AUTHOR]

Abstract: A common feature of many of the most important and prominent amyloid-forming proteins is their ability to bind lipids and lipid complexes. Lipids are ubiquitous components of disease-associated amyloid plaques and deposits in humans, yet the specific roles of lipid in the process of amyloid fibril formation are poorly understood. This study investigated the effect of phospholipids on amyloid fibril formation by human apolipoprotein (apo) C-II using phosphatidylcholine derivatives comprising acyl chains of up to 14 carbon atoms. Submicellar concentrations of short-chain phospholipids increase the rate of apoC-II fibril formation in an acyl-chain-length- and concentration-dependent fashion, while high micellar concentrations of phospholipids completely inhibited amyloid formation. At lower concentrations of soluble phospholipid complexes, fibril formation by apoC-II was only partially inhibited, and under these conditions, aggregation followed a two-phase process. Electron microscopy showed that the fibrils resulting from the second phase of aggregation were straight, cablelike, and about 13 nm wide, in contrast to the homogeneous twisted-ribbon morphology of apoC-II fibrils formed under lipid-free conditions. Seeding experiments showed that this alternative fibril structure could be templated both in the presence and in the absence of lipid complex, suggesting that the two morphologies result from distinct assembly pathways. Circular dichroism spectroscopy studies indicated that the secondary structural conformation within the straight-type and ribbon-type fibrils were distinct, further suggesting divergent assembly pathways. These studies show that phospholipid complexes can change the structural architecture of mature fibrils and generate new fibril morphologies with the potential to alter the in vivo behaviour of amyloid. Such lipid interactions may play a role in defining the structural features of fibrils formed by diverse amyloidogenic proteins. [Copyright &y& Elsevier]

The author attempts to discern themes underlying his clinical practice. Although his approach is somewhat behaviourist in orientation, it is hoped that the 12 themes (or organising principles) can be compared and contrasted with those arising from other approaches to child, adolescent, and family work. The author invites readers to analyse the way they have pieced together a composite approach from a range of sources. [ABSTRACT FROM AUTHOR]

The article presents quotes from Michael Griffin, an administrator at the U.S. National Aeronautics and Space Administration, regarding the issue of global warming, U.S. Congressman Vernon J. Ehlers commenting on the weather satellite program, and climatologist Bill Patzert regarding the drought-like conditions in Southern California.

The author reflects on the notions of culture and Celticism and argues that such essentialist notions were by-products of a utopian process best illustrated in author Matthew Arnold's connection of the two. According to the author, Arnold's utopian thought sought to find its model in a Hellenic antecedent that in turn provided a template for fixing contemporary society. He states that the mingling of Celtic and Saxon essences improves the Saxon and consolidates the colonial standing of the Irish Celt.

To understand the molecular mechanisms underlying transcriptional activation of fatty-acid synthase (FAS), we examined the relationship between upstream stimulatory factor (USF) and SREBP-1c, two transcription factors that we have shown previously to be critical for FAS induction by feeding/insulin. Here, by using a combination of tandem affinity purification and coimmunoprecipitation, we demonstrate, for the first time, that USF and SREBP-1 interact in vitro and in vivo. Glutathione S-transferase pulldown experiments with various USF and sterol regulatory element-binding protein (SREBP) deletion constructs indicate that the basic helix-loop-helix domain of USF interacts directly with the basic helix-loop-helix and an N-terminal region of SREBP-1c. Furthermore, cotransfection of USF and SREBP-1c with an FAS promoter-luciferase reporter construct in Drosophila SL2 cells results in highly synergistic activation of the FAS promoter. We also show similar cooperative activation of the mitochondrial glycerol-3-phosphate acyltransferase promoter by USF and SREBP-1c. Chromatin immunoprecipitation analysis of mouse liver demonstrates that USF binds constitutively to the mitochondrial glycerol 3-phosphate acyltransferase promoter during fasting/refeeding in vivo, whereas binding of SREBP-1 is observed only during refeeding, in a manner identical to that of the FAS promoter. In addition, we show that the synergy we have observed depends on the activation domains of both proteins and that mutated USF or SREBP lacking the N-terminal activation domain could inhibit the transactivation of the other. Closely positioned E-boxes and sterol regulatory elements found in the promoters of several lipogenic genes suggest a common mechanism of induction by feeding/insulin. [ABSTRACT FROM AUTHOR]

Abstract: The transmissibility of a seat depends on the dynamic response of the human body (which varies between individuals, body locations, and vibration magnitudes) and the dynamic response of the seat (which varies according to seat design). In the fore-and-aft direction, the transmissibility of a seat backrest was therefore expected to vary with vertical position on the backrest. This experimental study with 12 subjects investigated how backrest transmissibility varied with both the vertical measurement position and the magnitude of vibration. The transmissibilities of the backrest of a car seat and a block of solid foam were measured at five heights above the seat surface with random fore-and-aft vibration at five magnitudes (0.1, 0.2, 0.4, 0.8 and 1.6ms−2 rms) over the range 0.25–20Hz. The median transmissibilities exhibited resonances in the range 4–5Hz for the car seat and in the range 3–6Hz for the foam. The backrests showed clear changes in transmissibility with vertical position, but there were minimal changes in the resonance frequencies. For both backrests, the transmissibilities were greatest at the middle of the backrest. The least transmissibility was measured at the top of the car seat but at the bottom of the foam backrest. At each measurement position on both backrests, the transmissibility was non-linear with vibration magnitude: the resonance frequencies and transmissibilities at resonance decreased with increasing vibration magnitude. The variations in backrest transmissibility with vertical position and with vibration magnitude were sufficiently great to affect assessments of backrest dynamic performance. The results suggest that the fore-and-aft transmissibilities of backrests should be evaluated from more than one measurement location. [Copyright &y& Elsevier]

Abstract: Car seats have inclined backrests and inclined seat-pans, but there has been little study of how the inclinations of the surfaces of a seat influence the transmission of fore-and-aft vibration through the backrest. The effects of backrest inclination and seat-pan inclination on the fore-and-aft transmissibilities of two seats (a car seat and a rigid seat with solid foam backrest) have been investigated in the laboratory. With 12 subjects, each seat was exposed to random fore-and-aft vibration in the frequency range 0.25–20Hz with a vibration magnitude of 0.4ms−2 rms. At six vertical locations on each backrest, the fore-and-aft transmissibilities of the backrests were measured with four backrest inclinations (90° (i.e. vertical), 105°, 100°, and 105°) and up to four seat-pan inclinations (0° (i.e. horizontal), 5°, 10°, and 15°). At all six measurement locations, there was a resonance of both backrests at about 4Hz, which increased in frequency with increasing backrest inclination for the car seat but showed little change with inclination for the foam backrest. The inclination of the backrest had more influence at the bottom that at the top of the backrest of the car seat, but showed little variation with position on the foam backrest. Variations in seat-pan inclination had little influence on the resonance frequencies of either backrest at any location. Inclining the backrest and the seat-pan increased the transmissibility at resonance with the car seat, but produced little change with the foam backrest. It is concluded that both the backrest inclination and the seat inclination can affect the fore-and-aft transmissibility of backrests but, with moderate changes of inclination, the effects are not large. [Copyright &y& Elsevier]

Abstract: The principal resonance frequency in the driving-point impedance of the human body decreases with increasing vibration magnitude—a nonlinear response. An understanding of the nonlinearities may advance understanding of the mechanisms controlling body movement and improve anthropodynamic modelling of responses to vibration at various magnitudes. This study investigated the effects of vibration magnitude and voluntary periodic muscle activity on the apparent mass resonance frequency using vertical random vibration in the frequency range 0.5–20Hz. Each of 14 subjects was exposed to 14 combinations of two vibration magnitudes (0.25 and 2.0ms−2 root-mean square (rms)) in seven sitting conditions: two without voluntary periodic movement (A: upright; B: upper-body tensed), and five with voluntary periodic movement (C: back-abdomen bending; D: folding-stretching arms from back to front; E: stretching arms from rest to front; F: folding arms from elbow; G: deep breathing). Three conditions with voluntary periodic movement significantly reduced the difference in resonance frequency at the two vibration magnitudes compared with the difference in a static sitting condition. Without voluntary periodic movement (condition A: upright), the median apparent mass resonance frequency was 5.47Hz at the low vibration magnitude and 4.39Hz at the high vibration magnitude. With voluntary periodic movement (C: back-abdomen bending), the resonance frequency was 4.69Hz at the low vibration magnitude and 4.59Hz at the high vibration magnitude. It is concluded that back muscles, or other muscles or tissues in the upper body, influence biodynamic responses of the human body to vibration and that voluntary muscular activity or involuntary movement of these parts can alter their equivalent stiffness. [Copyright &y& Elsevier]

Abstract: Oscillatory motions can cause injury in transport when standing passengers or crew lose balance and fall. To predict the loss of balance of standing people, a model is required of the relationship between the input motion and the stability of the human body. This experimental study investigated the effect of frequency, magnitude and direction of oscillation on the postural stability of standing subjects and whether response to rotational oscillation can be predicted from knowledge of response to translational oscillation. Twelve male subjects stood on a floor that oscillated in either horizontal (fore-and-aft or lateral) or rotational (pitch or roll) directions. The oscillations were one-third octave bands of random motion centred on five preferred octave centre frequencies (0.125, 0.25, 0.5, 1.0, and 2.0Hz). The horizontal motions were presented at each of four velocities (0.04, 0.062, 0.099, and 0.16ms−1 rms) and the rotational motions were presented at each of four rotational angles (0.73, 1.46, 2.92, and 5.85°rms) corresponding to four accelerations (0.125, 0.25, 0.5, and 1.0ms−2 rms), where the acceleration is that caused by rotation through the gravitational vector. Postural stability was determined by subjective methods and by measuring the displacement of the centre of pressure at the feet during horizontal oscillation. During horizontal oscillation, increases in motion magnitude increased instability and, with the same velocity at all frequencies from 0.125 to 2.0Hz, most instability occurred in the region of 0.5Hz. Fore-and-aft oscillation produced more instability than lateral oscillation, although displacements of the centre of pressure were similar in both directions. With the same angular displacement at all frequencies from 0.125 to 2.0Hz, pitch oscillation caused more instability than roll oscillation, but in both directions instability increased with increased frequency of oscillation. Frequency weightings for acceleration in the plane of the floor during translational and rotational excitation show the significance of low-frequency translational oscillation and high-frequency rotational motion, and show that it is necessary to know whether the measured acceleration is caused by translation or rotation through gravity. [Copyright &y& Elsevier]

Abstract: It is currently assumed that the same frequency weightings, derived from studies of vibration discomfort, can be used to evaluate the severity of vibration at all vibration magnitudes from the threshold of vibration perception to the vibration magnitudes associated with risks to health. This experimental study determined equivalent comfort contours for the whole-body vibration of seated subjects over the frequency range 2–315Hz in each of the three orthogonal axes (fore-and-aft, lateral and vertical). The contours were determined at vibration magnitudes from the threshold of perception to levels associated with severe discomfort and risks to health. At frequencies greater than 10Hz, thresholds for the perception of vertical vibration were lower than thresholds for fore-and-aft and lateral vibration. At frequencies less than 4Hz, thresholds for vertical vibration were higher than thresholds for fore-and-aft and lateral vibration. The rate of growth of sensation with increasing vibration magnitude was highly dependent on the frequency and axis of vibration. Consequently, the shapes of the equivalent comfort contours depended on vibration magnitude. At medium and high vibration magnitudes, the equivalent comfort contours were reasonably consistent with the frequency weightings for vibration discomfort in current standards (i.e. W b and W d). At low vibration magnitudes, the contours indicate that relative to lower frequencies the standards underestimate sensitivity at frequencies greater than about 30Hz. The results imply that no single linear frequency weighting can provide accurate predictions of discomfort caused by a wide range of magnitudes of whole-body vibration. [Copyright &y& Elsevier]

Abstract: This review investigates whether there is evidence of an association between car driving and low back pain, and evidence that whole-body vibration contributes to low back pain in car drivers. The evidence of an association between various physical, psychosocial and individual factors and low back pain in car drivers was also investigated. From 23 epidemiological studies of low back problems in groups that reported car driving, nine studies fulfilled simple criteria for detailed review: four cross-sectional studies, three case-control studies and two longitudinal studies. The definition of low back pain was often unclear and, mostly, the physiological mechanisms causing low back pain were not considered. Eight of the nine studies concluded that there was an increase in low back pain among car drivers but there was little consideration of the influence of the many physical factors, individual factors and psychosocial factors that might be associated with an increase in low back pain. Consequently, there is insufficient evidence to form a conclusion on whether whole-body vibration, postural stressors or other factors, specific or not specific to driving, are common causes of low back problems in car drivers. [Copyright &y& Elsevier]

Abstract: The strength of sensation produced by vibration applied to the glabrous skin of the hand varies with the magnitude, frequency, and direction of the vibration and the contact conditions. With groups of 12 subjects gripping a cylindrical handle, this experimental study investigated perception thresholds (in the frequency range 8–315Hz) and the strength of sensation caused by each of the three axes of hand-transmitted vibration (in the frequency range 8–400Hz) at vibration magnitudes from threshold up to levels associated with discomfort and injury. In all three axes, acceleration thresholds for the perception of vibration showed a U-shaped frequency-dependence with greatest sensitivity around 80–160Hz. At supra-threshold levels, the frequency-dependence of the equivalent comfort contours in each of the three axes was highly dependent on vibration magnitude. With increasing vibration magnitude, equivalent sensation approximated towards constant velocity, whereas with decreasing magnitudes the sensation became similar to the absolute perception threshold. This magnitude-dependence of equivalent comfort contours suggests differential mediation of psychophysical channels responsible for perception at different vibration magnitudes. The results imply that no single linear frequency weighting can provide accurate predictions of subjective judgments of discomfort caused by hand-transmitted vibration. [Copyright &y& Elsevier]

The article examines the disparity between community view, public policy and treatment effectiveness for sex offenders in the United States. Community and media understanding of recidivism rates, the efficacy of sex offender treatment and the factors leading to sex crimes need to be changed. It is important to change practices that lead to the dismissal of sex offenders' constitutionally guaranteed right to privacy which makes it difficult for them to complete treatment.

In an effort to improve the zinc-chelating portion of matrix metalloproteinase (MMP) inhibitors, we have developed a family of heterocyclic zinc-binding groups (ZBGs) as alternatives to the widely used hydroxamic acid moiety. Elaborating on findings from an earlier report, we performed in vitro inhibition assays with recombinant MMP-1, MMP-2, and in a cell culture assay using neonatal rat cardiac fibroblast cells. In both recombinant and cell culture assays, the new ZBGs were found to be effective inhibitors, typically 10–100-fold more potent than acetohydroxamic acid. The toxicity of these chelators was examined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium salt cytotoxicity assays, which demonstrate that most of these compounds are nontoxic at concentrations of almost 100 μM. To address the possible interaction of sulfur-containing ZBGs with biological reductants, the reactivity of these chelators with 5,5′-dithiobis(2-nitrobenzoic acid) was examined. Finally, thione ZBGs were shown to be effective inhibitors of cell invasion through an extracellular matrix membrane. The data presented herein suggest these heterocyclic ZBGs are potent, nontoxic, and biocompatible compounds that show promise for incorporation into a new family of MMP inhibitors. [ABSTRACT FROM AUTHOR]

The detection of vibration applied to the glabrous skin of the hand varies with contact conditions. Three experiments have been conducted to relate variations in the perception of hand-transmitted vibration to previously reported properties of tactile channels. The effects of a surround around the area of contact, the size of the area of contact, the location of the area of contact, the contact force, and the hand posture on perception of thresholds were determined for 8–500?Hz vibration. Removal of a surround around a contact area on the fingertip elevated thresholds of the NP II channel (FA I fibres) at frequencies less than 31.5?Hz and reduced thresholds of the Pacinian channel (FA II fibres) at frequencies greater than about 63?Hz. When no surround was present, thresholds reduced systematically as the contact area increased from the fingertip to the whole hand at frequencies from 16 to 125?Hz, although the decrease was not inversely proportional to the increase in contact area. The results are partly explained by spatial summation in the Pacinian channel (FA II fibres) and the involvement of the NP II channel (SA II) with some influence of biodynamic responses and contact pressures. There were regional differences in sensitivity over the hand within the NP I channel but not within the Pacinian channel: the NP I thresholds (less than 31.5?Hz) decreased from proximal to distal regions of the hand, whereas the Pacinian thresholds (125?Hz) were independent of contact location over the hand. [ABSTRACT FROM AUTHOR]

Abstract: The effect of the magnitude of continuous and transient whole-body vibration in the vertical direction on both subjective and biodynamic responses of human subjects has been investigated experimentally. Additionally, the relation between the subjective responses and the dynamic responses has also been studied. Twelve subjects were exposed to sinusoidal continuous vibrations at five frequencies (3.15–8.0Hz) and at three magnitudes (0.5–2.0ms−2 rms). They were also exposed to transient vibrations that were modulated one-and-half cycle sinusoidal waveforms at the same frequencies as the continuous vibrations and at three magnitudes corresponding to the magnitudes used for the continuous vibrations. Discomfort was measured by the method of magnitude estimation with reference stimuli having frequency components in the middle of the frequency range used in this study. The driving-point dynamic responses (the ratio between the force and the motion, i.e., acceleration and velocity, at the driving point) were also measured and divided by the responses to the reference stimuli used in the measurement of discomfort so as to allow the comparison of the dynamic responses with the discomfort responses. Both the discomfort estimates and the normalised driving-point dynamic responses were influenced by the stimuli magnitudes, especially with the continuous vibration. At 3.15 and 4.0Hz, the discomfort estimates and the normalised mechanical impedance and apparent mass increased significantly with increases in vibration magnitude from 0.5–2.0ms−2 rms. Magnitude estimates for discomfort were correlated with the normalised mechanical impedance and apparent mass in the frequency range investigated. For the transient vibrations, the discomfort estimates and the driving-point dynamic responses were interpreted as responses in frequency bands around the fundamental frequency of the input motion. The results indicate similar nonlinearities in discomfort and driving-point dynamic responses associated with the principal body response within the range 3.15–8Hz. The nonlinearity in discomfort at these frequencies may be partially caused by the nonlinear dynamic response of the body and is sufficient to require consideration in methods of predicting discomfort caused by vertical whole-body vibration. [Copyright &y& Elsevier]

Dihydrodipicolinate synthase (DHDPS) mediates the key first reaction common to the biosynthesis of (S)-lysine and meso-diaminopimelate. The activity of DHDPS is allosterically regulated by the feedback inhibitor (S)-lysine. The crystal structure of DHDPS from Escherichia coli has previously been published, but to only a resolution of 2.5 Å , and the structure of the lysine-bound adduct was known to only 2.94 Å resolution. Here, the crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from E. coli are presented to 1.9 and 2.0 Å , respectively, resolutions that allow, in particular, more accurate definition of the protein structure. The general architecture of the active site is found to be consistent with previously determined structures, but with some important differences. Arg138, which is situated at the entrance of the active site and is thought to be involved in substrate binding, has an altered conformation and is connected via a water molecule to Tyr133 of the active-site catalytic triad. This suggests a hitherto unknown function for Arg138 in the DHDPS mechanism. Additionally, a reevaluation of the dimer-dimer interface reveals a more extensive network of interactions than first thought. Of particular interest is the higher resolution structure of DHDPS with (S)-lysine bound at the allosteric site, which is remote to the active site, although connected to it by a chain of conserved water molecules. (S)-Lysine has a slightly altered conformation from that originally determined and does not appear to alter the DHDPS structure as others have reported. [ABSTRACT FROM AUTHOR]

Self-association of protein monomers to higher-order oligomers plays an important role in a plethora of biological phenomena. The classical biophysical technique of analytical ultracentrifugation is a key method used to measure protein oligomerisation. Recent advances in sedimentation data analysis have enabled the effects of diffusion to be deconvoluted from sample heterogeneity, permitting the direct identification of oligomeric species in self-associating systems. Two such systems are described and reviewed in this study. First, we examine the enzyme dihydrodipicolinate synthase (DHDPS), which crystallises as a tetramer. Wild-type DHDPS plays a critical role in lysine biosynthesis in microbes and is therefore an important antibiotic target. To confirm the state of association of DHDPS in solution, we employed sedimentation velocity and sedimentation equilibrium studies in an analytical ultracentrifuge to show that DHDPS exists in a slow dimer–tetramer equilibrium with a dissociation constant of 76 nM. Second, we review works describing the hexamerisation of GDP-mannose pyrophosphorylase (GDP-MP), an enzyme that plays a critical role in mannose metabolism in Leishmania species. Although the structure of the GDP-MP hexamer has not yet been determined, we describe a three-dimensional model of the hexamer based largely on homology with the uridyltransferase enzyme, Glmu. GDP-MP is a novel drug target for the treatment of leishmaniasis, a devastating parasitic disease that infects more than 12 million people worldwide. Given that both GDP-MP and DHDPS are only active in their oligomeric states, we propose that inhibition of the self-association of critical enzymes in disease is an emerging paradigm for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Abstract: Twelve male subjects have been exposed to whole-body vertical random vibration so as to investigate the effect of seat surface angle, vibration magnitude and contact with a backrest on the ‘vertical apparent mass’ (calculated from forces normal to the seat surface and vertical acceleration) and ‘fore-and-aft cross-axis apparent mass’ (calculated from forces parallel to the seat surface and vertical acceleration). At each of four seat surface angles (0°, 5°, 10°, and 15°), the subjects were exposed to four vibration magnitudes (0.125, 0.25, 0.625, and 1.25ms−2 rms) in the frequency range 0.25–15Hz. The ‘vertical apparent mass’ and ‘fore-and-aft cross-axis apparent mass’ on the seat surface suggested resonances in the vicinity of 5 and 4Hz, respectively. At all seat angles, both with and without a backrest, the resonance frequency in the ‘vertical apparent mass’ was greater than the resonance frequency in the ‘fore-and-aft cross-axis apparent mass’. Within subjects, the two resonance frequencies were not correlated in any condition. Seat angles up to 15° had a negligible effect on the ‘vertical apparent mass’ but a considerable effect on the ‘fore-and-aft cross-axis apparent mass’ on the seat surface, where ‘cross-axis apparent mass’ increased with increasing seat angle. At all seat angles, increasing the vibration magnitude decreased the resonance frequency in both directions. The least significant decrease in resonance frequency with increasing vibration magnitude occurred in the ‘fore-and-aft cross-axis apparent mass’ at the maximum seat angle of 15°. At low frequencies, the backrest reduced the forces in both directions, with the reduction greatest in the ‘fore-and-aft’ direction. The ‘fore-and-aft cross-axis apparent mass’ at resonance was correlated with subject mass and subject stature. [Copyright &y& Elsevier]

Objective: The authors compared responses of female domestic violence survivors and a matched group of nontraumatized participants to a low-dose (0.5 mg) dexamethasone suppression test (DST).Method: Seventy female domestic violence survivors and 14 nontraumatized women matched for age and race were recruited. Participants were assessed for trauma severity, severity of PTSD and depressive symptoms, and DST cortisol response. Of the domestic violence survivors who were DST-compliant, comparisons were made among those with PTSD (N=15), those with PTSD plus depression (N=27), and those with no PTSD or depression diagnosis (N=8) along with the nontraumatized comparison subjects (N=14).Results: Domestic violence survivors with PTSD, regardless of whether or not they had comorbid depression, had significantly lower baseline cortisol levels at 9:00 a.m. than the healthy subjects and trauma survivors with no diagnosis. Survivors with a sole diagnosis of PTSD showed significantly greater cortisol suppression to dexamethasone than did healthy subjects or the group diagnosed with PTSD plus depression.Conclusions: These findings agree with previous studies showing hypothalamic-pituitary-adrenal (HPA) axis abnormalities in PTSD. The findings suggest that the chronic nature of domestic violence leads to a severe dysregulation of the HPA axis. [ABSTRACT FROM AUTHOR]

The article aims to describe the implications of music and noise for utopian design, with reference to issues of discipline and luxury. Luxury can be describe in various contexts. The relationships between music, luxury and utopia are described in several stages. According to Immanuel Kant's book "Critique of Judgment," the vector of musical effect went from sensations to indeterminate ideas.

Abstract: The fore-and-aft, lateral and vertical forces on a seat and a backrest have been investigated with 12 male subjects exposed to random fore-and-aft whole-body vibration (0.25–10Hz) at four vibration magnitudes (0.125, 0.25, 0.625, and 1.25ms-2rms). Subjects sat in each of four sitting postures having varying foot heights, so as to produce differing thigh contact with the seat. The fore-and-aft forces on the seat depended on whether the feet were supported on a footrest: peaks were found at two frequencies when the feet were not supported, compared to only one peak when the feet were supported. The fore-and-aft forces at the backrest were high, with their peak magnitudes correlated with subject mass. Vertical forces were high on the seat but not on the backrest. Lateral forces were relatively low on both the seat and the backrest. In all directions, forces on the seat and the backrest showed a nonlinear behaviour. In comparison with a previous study undertaken with no backrest, it was found that the backrest reduced forces on the seat at low frequencies (in the fore-and-aft and vertical directions) but increased these forces at high frequencies. [Copyright &y& Elsevier]

This study was designed to identify psychophysical channels responsible for the detection of hand-transmitted vibration. Perception thresholds for vibration (16, 31.5, 63 and 125?Hz sinusoidal for 600?ms) at the distal phalanx of the middle finger and the whole hand were determined with and without simultaneous masking stimuli (1/3 octave bandwidth Gaussian random vibration centered on either 16?Hz or 125?Hz for 3000?ms, varying in magnitude 0 to 30?dB above threshold). At all frequencies from 16 to 125?Hz, absolute thresholds for the hand were significantly lower than those for the finger. Changes in threshold as a function of masker level were used to estimate the thresholds of three psychophysical channels (i.e. P, NP I, and NP II channels). Increased vibrotactile sensitivity of the hand compared to the finger seems to be not entirely due to increased spatial summation via the Pacinian system (P channel); non-Pacinian system (NP I and NP II channels) also contributed to perception. Differing transmission of vibration between the hand and the finger may have also influenced the thresholds. [ABSTRACT FROM AUTHOR]

The posttraumatic diagnostic scale (PDS) is a self-report instrument for PTSD that is simple to administer and has demonstrated good psychometric properties. We compared the PDS with the gold standard clinician administered PTSD scale (CAPS) diagnostic interview for PTSD. We assessed 138 women who were victims of domestic violence using both the PDS and the CAPS. Findings confirmed that PTSD develops at a high base rate in this sample. The PDS generally performed well in relation to the CAPS although with a tendency to overdiagnose PTSD. The findings lend further support to the use of the PDS as a diagnostic tool for PTSD but indicate that it is better at identifying survivors with PTSD than those without the disorder. [ABSTRACT FROM AUTHOR]

Examines the history and evolution of Greek literature relevant to English folk ornithology citing Apollo's Hawk in the play by Aristophanes "Birds." Portrayal of the image of the hawl which represents swiftness, cruel rapacity for prey and greed, cruelty and self-interest in general; Incorporation of the same imagery in archaic and classical literature; Justification for Apollo's association with the rapacious hawk at "Birds."

The transcriptional regulation of lipogenesis is a highly coordinated process occurring in concert with transcriptional as well as post-transcriptional regulation of enzymes involved in glycolysis and gluconeogenesis. Fatty acid synthase (FAS) plays a central role in de novo lipogenesis by converting acetyl-CoA and malonyl-CoA into the final end product, palmitate, which can subsequently be esterified into triacylglycerols and then stored in adipose tissue. Ultimately, this helps to prevent buildup of excess glucose in other types of cells and tissues, the effects of which can be readily observed in the pathophysiology of disease states such as Type-II diabetes and obesity. Thus, elucidating the transcriptional mechanisms of lipogenic enzyme genes is important for understanding the normal regulation of lipogenesis and ultimately the dysregulation that may occur in certain metabolic disease. In this review, we discuss advances in our understanding of the regulation of lipogenesis at the genetic level, with a special emphasis on the common cis - and trans -acting factors involved in regulation of FAS. Two transcription factors, Upstream Stimulatory Factor (USF) and Sterol Regulatory Element Binding Protein-1c (SREBP-1c), seem to play a dominant and possibly cooperative role in regulating FAS transcription. IUBMB Life, 56: 595-600, 2004 [ABSTRACT FROM AUTHOR]

Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) mediates the first unique reaction of (S)-lysine biosynthesis in plants and microbes—the condensation of (S)-aspartate-β-semialdehyde ((S)-ASA) and pyruvate. It has been shown that DHDPS is partially feedback inhibited by (S)-lysine; it is suggested that this mechanism regulates flux through the DAP biosynthetic pathway. Others have characterised DHDPS from Escherichia coli with respect to (S)-lysine inhibition. They have concluded that, with respect to pyruvate, the first substrate of the reaction, DHDPS shows uncompetitive inhibition: as such, they further suggest that (S)-lysine inhibits DHDPS via interaction with the binding site for the second substrate, (S)-ASA. Yet, this finding is based on the assumption that (S)-lysine is a fully uncompetitive inhibitor. In light of crystallographic studies, which lead to the proposal that (S)-lysine affects the putative proton-relay of DHDPS, we re-evaluated the inhibition mechanism of DHDPS with respect to (S)-lysine by incorporating the observed hyperbolic inhibition. Our data showed that lysine is not an uncompetitive inhibitor, but a mixed inhibitor when pyruvate and (S)-lysine concentrations were varied. Thus, consistent with the crystallographic data, (S)-lysine must have an effect on the initial steps of the DHDPS reaction, including the binding of pyruvate and Schiff base formation. [Copyright &y& Elsevier]

Objectives. To compare vibrotactile thresholds between five international test centres, to determine causes of variability, and to provide normative data for use by health professionals. Methods. Vibrotactile thresholds were measured on various fingers in 1,008 subjects at 31.5 Hz (2,531 measurements) and at 125 Hz (2,807 measurements). Three centres used the up-and-down method of limits, rate of change of stimulus 3dB/s, to obtain vibrotactile thresholds. The push force on the surround was 2 N, the probe contact force was 1 N and the probe diameter was 6 mm concentric to a 10-mm diameter hole in the surround. One centre used an up-and-down method of limits with a 5-dB step and a 1.26-mm diameter probe with no surround. Another centre used a stepping algorithm, no surround, and the force on the 6-mm-diameter probe was unspecified. Results. The 31.5-Hz thresholds and 125-Hz thresholds, expressed in dB, were similar between centres using similar methods. There were small (<5 dB) differences in vibrotactile thresholds between male and female subjects, between white-collar and blue-collar workers and between fingers. Both 31.5-Hz and 125-Hz thresholds increased with age; the mean effect of age on 31.5-Hz thresholds was approximately 2 dB over 25 years, while the effect of age on 125 Hz-thresholds was as high as 10 dB over 25 years. Conclusions. Vibrotactile thresholds are influenced by measurement method but can be similar at different centres if similar methods are used. Effects of measurement location and gender are often negligible. Thresholds depend on age, but over the range of ages considered, only the effect on 125-Hz thresholds is sufficient for correction; methods of correcting for age are given. These normative data may be used to assist the diagnosis of peripheral neuropathy involving vibrotactile sensation. [ABSTRACT FROM AUTHOR]

Upstream regulatory factor (USF) and sterol regulatory element binding protein (SREBP) play key roles in the transcriptional regulation of the fatty acid synthase (FAS) gene by feeding and insulin. Due to the dual binding specificity of SREBP, as well as the presence of multiple consensus sites for these transcription factors in the FAS promoter, their physiologically relevant functional binding sites have been controversial. Here, in order to determine the occupancy of the putative USF and SREBP binding sites, we examined their proteinDNA interactions in living animals by using formaldehyde cross-linking and immunoprecipitation of chromatin and tested the function of these elements by employing mice transgenic for a reporter gene driven by various 5' deletions as well as site-specific mutations of the FAS promoter. We show that the -332 and -65 E-boxes are bound by USF in both fasted and refed mice, while the -150 SRE is bound by SREBP-1 only in refed mice. We also found that mutation of either the -150 SRE or the -65 E-box abolishes the feeding-induced activation of the FAS promoter in transgenic mice. Furthermore, in vivo occupancy of the FAS promoter by SREBP in the fed state can be prevented by mutation not only of the -150 SRE but, unexpectedly, of the -65 E-box as well. We conclude that the FAS promoter is activated during refeeding via the induced binding of SREBP to the -150 SRE and that USF binding to the -65 E-box is also required for SREBP binding and activation of the FAS promoter. [ABSTRACT FROM AUTHOR]

Few studies have examined the impact of trauma research participation upon trauma survivors. Empirical data regarding reactions to research participation would be very useful to address the question of whether it is harmful for trauma survivors to participate in trauma studies. We examined participant reactions to different trauma assessment procedures in domestic violence (N = 260), rape (N = 108), and physical assault (N = 62) samples. Results indicated that participation was very well tolerated by the vast majority of the trauma survivors. Participants generally found that the assessment experience was not distressing and was, in fact, viewed as an interesting and valuable experience. The findings suggest that trauma survivors are not too fragile to participate in trauma research even in the acute aftermath of a traumatic experience. [ABSTRACT FROM AUTHOR]

We compared the binding properties of selective muscarinic antagonists with their potencies for antagonizing muscarinic responses in Chinese hamster ovary (CHO) cells expressing M2 and M3 muscarinic receptors in combination and in isolation. When measured by the competitive displacement of [3H]N-methylscopolamine binding to CHO cells expressing both M2 and M3 muscarinic receptors (CHO M2+M3 cells), the competition curves of the subtype-selective muscarinic antagonists were consistent with a two-site model. One site exhibited binding properties identical to those of CHO M2 cells, whereas the other site exhibited properties like those of CHO M3 cells. Oxotremorine-M, a muscarinic agonist, elicited a robust, pertussis toxin-insensitive stimulation of phosphoinositide hydrolysis in both CHO M3 and CHO M2+M3 cells, but not in CHO M2 cells. The pharmacological antagonism of the phosphoinositide response exhibited similar properties in both CHO M3 and CHO M2+M3 cells. Oxotremorine-M elicited a pertussis toxin-sensitive, robust inhibition of forskolin-stimulated cyclic AMP (cAMP) accumulation in both CHO M2 and CHO M2+M3 cells and a less robust inhibition in CHO M3 cells. At higher concentrations, oxotremorine-M elicited an increase in cAMP accumulation over the maximal inhibition noted at lower concentrations in both CHO M3 and CHO M2+M3 cells. Following pertussis toxin treatment, only the stimulatory phase of the cAMP response to oxotremorine-M was observed in CHO M2, CHO M3, and CHO M2+M3 cells. The pharmacological antagonism of the cAMP response in CHO M2+M3 cells resembled that expected for a response mediated independently by both M2 and M3 receptors. [Copyright &y& Elsevier]