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For positive rank r elliptic curves E (Q) , we employ ideal class pairings E (Q) × E − D (Q) → CL (− D) , for quadratic twists E − D (Q) with a suitable "small y -height" rational point, to obtain explicit class number lower bounds that improve on earlier work by the authors. For the curves E (a) : y 2 = x 3 − a , with rank r (a) , this gives h (− D) ≥ 1 10 ⋅ | E tor (Q) | R Q (E) ⋅ π r (a) 2 2 r (a) Γ (r (a) 2 + 1) ⋅ log ⁡ (D) r (a) 2 log ⁡ log ⁡ D , representing a general improvement to the classical lower bound of Goldfeld, Gross and Zagier when r (a) ≥ 3. We prove that the number of twists E − D (a) (Q) with such a suitable point (resp. with such a point and rank ≥2 under the Parity Conjecture) is ≫ a , ε X 1 2 − ε. We give infinitely many cases where r (a) ≥ 6. These results can be viewed as an analogue of the classical estimate of Gouvêa and Mazur for the number of rank ≥2 quadratic twists, where in addition we obtain "log-power" improvements to the Goldfeld-Gross-Zagier class number lower bound. [ABSTRACT FROM AUTHOR]

Ideal class pairings map the rational points of rank r ≥ 1 elliptic curves E / Q to the ideal class groups CL (− D) of certain imaginary quadratic fields. These pairings imply that h (− D) ≥ 1 2 (c (E) − ε) (log ⁡ D) r 2 for sufficiently large discriminants − D in certain families, where c (E) is a natural constant. These bounds are effective, and they offer improvements to known lower bounds for many discriminants. [ABSTRACT FROM AUTHOR]

• Phosphonic acids were deposited onto four different platinum catalyst supports. • Deposited modifiers provide Brønsted acid sites, creating an acid-metal catalyst. • The strength of Brønsted acid sites is dependent on the modifier tail functionality. • On supports with weak or no Brønsted acidity, modifiers enhance deoxygenation. • On strongly acidic supports, modification leads to a loss of deoxygenation activity. Bifunctional catalysts comprised of both noble metal and Brønsted acid sites are of growing interest for many reactions, such as the hydrodeoxygenation (HDO) of oxygenates produced by the deconstruction of lignocellulosic biomass. One method of preparing a bifunctional metal-acid catalyst is to modify the supporting material of a metal catalyst with acid-containing ligands, such as phosphonic acids (PAs), which provide tunable Brønsted acid sites at the metal-support interface. Here, we explore the potential for PA modification to improve HDO rates on Al 2 O 3 , TiO 2 , CeO 2 , and SiO 2 -Al 2 O 3 supports. PAs containing either alkyl or carboxylic acid (CA) tails were used to modify Pt catalysts on each support. PA modification improved HDO rates for the model compound benzyl alcohol when applied to Pt supported by Al 2 O 3 , TiO 2 , and CeO 2 , but had a negative effect on the HDO rate of Pt/SiO 2 -Al 2 O 3. Measurements of the relative strength of Brønsted acid sites present on the modified and unmodified catalysts suggested that PAs improved HDO when they provided new or stronger Brønsted acid sites. Additionally, the strength of the Brønsted acid sites provided by PA modifiers were tunable by altering the tail functionality, which affected the rates of HDO. These results suggest that PAs can be used to modify a variety of supports to prepare bifunctional acid-metal catalysts. [ABSTRACT FROM AUTHOR]

We investigate ξ (s) = 1 2 s (s − 1) π − s 2 Γ (s 2) ζ (s) , where ζ (s) is the Riemann zeta function. The Riemann hypothesis (RH) asserts that if ξ (s) = 0 , then Re (s) = 1 2. Pólya proved that RH is equivalent to the hyperbolicity of the Jensen polynomials J d , n (X) constructed from certain Taylor coefficients of ξ (s). For each d ≥ 1 , recent work proves that J d , n (X) is hyperbolic for sufficiently large n. In this paper, we make this result effective. Moreover, we show how the low-lying zeros of the derivatives ξ (n) (s) influence the hyperbolicity of J d , n (X). [ABSTRACT FROM AUTHOR]

Highlights: [•] Ethylene glycol and 1,2-propanediol were oxidized on Pd, Au, and Au–Pd catalysts. [•] Enhanced oxidation rates were observed on the bimetallic catalysts. [•] Rate enhancements result from decreased poisoning and lower activation barriers. [•] C–H bond scission is the rate-limiting step. [Copyright &y& Elsevier]

Abstract: Amyloid fibrils and their soluble oligomeric intermediates are implicated in several age-related diseases including Alzheimer''s and Parkinson''s diseases. The distribution of oligomers and fibrils is related to toxicity and is dependent on the pathways for fibril assembly, generally considered to occur via a slow nucleation step that precedes fibril elongation. Human apolipoprotein (apo) C-II forms amyloid fibrils via a reversible self-assembly process accompanied by closed-loop formation and fibril breaking and joining. Our fluorescence quenching and sedimentation velocity experiments with Alexa488-labeled apoC-II indicated a time-dependent subunit interchange for both linear and closed-loop fibrils, while dilution experiments using mature fibrils indicated a shift to smaller size distributions consistent with a reversible assembly pathway. To account for this behavior, we developed an equilibrium self-association model that describes the final size distributions of apoC-II fibrils formed at different starting concentrations. The model proposes a reversible isomerization of apoC-II monomer to form an active conformer that self-assembles into fibrils via an isodesmic self-association pathway coupled to fibril length-dependent closed-loop formation. The model adequately described fibril size distributions and the proportion of closed loops as a function of total apoC-II concentration over the concentration range 0.1–0.5 mg/ml. Extension of the model to include the rates of isomerization, self-association and fibril breaking and joining provided satisfactory global fits to kinetic data on fibril formation and changes in average fibril size at different apoC-II starting concentrations. The model provides a simple thermodynamic description of the processes governing the size distribution of apoC-II fibrils at equilibrium and the formation of discrete oligomeric intermediates. [Copyright &y& Elsevier]

Abstract: The misfolding and aggregation of proteins to form amyloid fibrils is a characteristic feature of several common age-related diseases. Agents that directly inhibit formation of amyloid fibrils represent one approach to combating these diseases. We have investigated the potential of a cyclic peptide to inhibit fibril formation by fibrillogenic peptides from human apolipoprotein C-II (apoC-II). Cyc[60–70] was formed by disulfide cross-linking of cysteine residues added to the termini of the fibrillogenic peptide comprising apoC-II residues 60–70. This cyclic peptide did not self-associate into fibrils. However, substoichiometric concentrations of cyc[60–70] significantly delayed fibril formation by the fibrillogenic, linear peptides apoC-II[60–70] and apoC-II[56–76]. Reduction of the disulfide bond or scrambling the amino acid sequence within cyc[60–70] significantly impaired its inhibitory activity. The solution structure of cyc[60–70] was solved using NMR spectroscopy, revealing a well-defined structure comprising a hydrophilic face and a more hydrophobic face containing the Met60, Tyr63, Ile66 and Phe67 side chains. Molecular dynamics (MD) studies identified a flexible central region within cyc[60–70], while MD simulations of “scrambled” cyc[60–70] indicated an increased formation of intramolecular hydrogen bonds and a reduction in the overall flexibility of the peptide. Our structural studies suggest that the inhibitory activity of cyc[60–70] is mediated by an elongated structure with inherent flexibility and distinct hydrophobic and hydrophilic faces, enabling cyc[60–70] to interact transiently with fibrillogenic peptides and inhibit fibril assembly. These results suggest that cyclic peptides based on amyloidogenic core peptides could be useful as specific inhibitors of amyloid fibril formation. [Copyright &y& Elsevier]

Abstract: Although the discomfort or injury associated with whole-body vibration cannot be predicted directly from the power absorbed during exposure to vibration, the absorbed power may contribute to understanding of the biodynamics involved in such responses. From measurements of force and acceleration at the seat, the feet, and the backrest, the power absorbed at these three locations was calculated for subjects sitting in four postures (feet hanging, maximum thigh contact, average thigh contact, and minimum thigh contact) both with and without a rigid vertical backrest while exposed to four magnitudes (0.125, 0.25, 0.625, and 1.25ms−2 rms) of random fore-and-aft vibration. The power absorbed by the body at the supporting seat surface when there was no backrest showed a peak around 1Hz and another peak between 3 and 4Hz. Supporting the back with the backrest decreased the power absorbed at the seat at low frequencies but increased the power absorbed at high frequencies. Foot support influenced both the magnitude and the frequency of the peaks in the absorbed power spectra as well as the total absorbed power. The measurements of absorbed power are consistent with backrests being beneficial during exposure to low frequency fore-and-aft vibration but detrimental with high frequency fore-and-aft vibration. [Copyright &y& Elsevier]

Abstract: The transmission of vibration through a seat depends on the impedance of the seat and the apparent mass of the seat occupant. This study was designed to determine how factors affecting the apparent mass of the body (age, gender, physical characteristics, backrest contact, and magnitude of vibration) affect seat transmissibility. The transmission of vertical vibration through a car seat was measured with 80 adults (41 males and 39 females aged 18–65) at frequencies between 0.6 and 20Hz with two backrest conditions (no backrest and backrest), and with three magnitudes of random vibration (0.5, 1.0, and 1.5ms-2 rms). Linear regression models were used to study the effects of subject physical characteristics (age, gender, and anthropometry) and features of their apparent mass (resonance frequency, apparent mass at resonance and at 12Hz) on the measured seat transmissibility. The strongest predictor of both the frequency of the principal resonance in seat transmissibility and the seat transmissibility at resonance was subject age, with other factors having only marginal effects. The transmissibility of the seat at 12Hz depended on subject age, body mass index, and gender. Although subject weight was strongly associated with apparent mass, weight was not strongly associated with seat transmissibility. The resonance frequency of the seat decreased with increases in the magnitude of the vibration excitation and increased when subjects made contact with the backrest. Inter-subject variability in the resonance frequency and transmissibility at resonance was less with greater vibration excitation, but was largely unaffected by backrest contact. A lumped parameter seat–person model showed that changes in seat transmissibility with age can be predicted from changes in apparent mass with age, and that the dynamic stiffness of the seat appeared to increase with increased loading so as to compensate for increases in subject apparent mass associated with increased sitting weight. [Copyright &y& Elsevier]

Abstract: The vibration of backrests contributes to the discomfort of drivers and passengers. A frequency weighting exists for evaluating the vibration of vertical backrests but not for reclined backrests often used during travel. This experimental study was designed to determine how backrest inclination and the frequency of vibration influence perception thresholds and vibration discomfort when the vibration is applied normal to the back (i.e. fore-and-aft vibration when seated upright and vertical vibration when fully reclined). Twelve subjects experienced the vibration of a backrest (at each of the 11 preferred one-third octave centre frequencies in the range 2.5–25Hz) at vibration magnitudes from the threshold of perception to 24dB above threshold. Initially, absolute thresholds for the perception of vibration were determined with four backrest inclinations: 0° (upright), 30°, 60° and 90° (recumbent). The method of magnitude estimation was then used to obtain judgements of vibration discomfort with each of the four backrest angles. Finally, the relative discomfort between the four backrest angles, and the principal locations for feeling vibration discomfort in the body, were determined. With all backrest inclinations, absolute thresholds for the perception of vibration acceleration were dependent on the frequency of vibration. As the backrest inclination became more horizontal, the thresholds increased at frequencies between 4 and 8Hz. For all backrest inclinations, the rate of growth of discomfort with increasing magnitude of vibration was independent of the frequency of vibration, so the frequency-dependence of discomfort was similar over the range of magnitudes investigated (0.04–0.6ms−2 rms). With an upright backrest, the discomfort caused by vibration acceleration tended to be greatest at frequencies less than about 8Hz. With inclined backrests (at 30°, 60°, and 90°), the equivalent comfort contours were broadly similar to each other, with greatest discomfort caused by acceleration around 10 or 12.5Hz. At frequencies from 4 to 8Hz, 30–40 percent greater magnitudes of vibration were required with the three inclined backrests to cause discomfort equivalent to that caused by the upright backrest. It is concluded that with an upright backrest the frequency weighting W c used in current standards is appropriate for predicting the discomfort caused by fore-and-aft backrest vibration. With inclined and horizontal backrests, a weighting similar to frequency weighting W b (used to predict discomfort caused by vertical seat vibration) appears more appropriate. [Copyright &y& Elsevier]

Abstract: The misfolding and aggregation of proteins to form amyloid fibrils are associated with a number of debilitating, age-related diseases. Many of the proteins that form amyloid in vivo are lipid-binding proteins, accounting for the significant impact of lipids on the rate of formation and morphology of amyloid fibrils. To systematically investigate the effect of lipid-like compounds, we screened a range of amphipathic lipids and detergents for their effect on amyloid fibril formation by human apolipoprotein (apo) C-II. The initial screen, conducted using a set of amphiphiles at half critical micelle concentration, identified several activators and inhibitors that were selected for further analysis. Sedimentation analysis and circular dichroism studies of apoC-II at low, non-fibril-forming concentrations (0.05 mg/ml) revealed that all of the inhibitors induced the formation of apoC-II dimers enriched in α-helical content while the activators promoted the formation of stable apoC-II tetramers with increased β-structure. Kinetic analysis identified modulators of apoC-II fibril formation that were effective at concentrations as low as 10 μM, corresponding to a modulator-to-apoC-II ratio of approximately 1:10. Delayed addition of the test compounds after fibril formation had commenced allowed the effects of selected amphiphiles on fibril elongation to be determined separately from their effects on fibril nucleation. The results indicated that specific amphiphiles induce structural changes in apoC-II that cause separate and independent effects on fibril nucleation and elongation. Low-molecular-weight amphipathic lipids and detergents may serve as useful, stage-specific modulators of protein self-assembly and fibril formation in disease-prevention strategies. [Copyright &y& Elsevier]

Abstract: The biodynamic responses of the seated human body to whole-body vibration vary considerably between people, but the reasons for the variability are not well understood. This study was designed to determine how the physical characteristics of people affect their apparent mass and whether inter-subject variability is influenced by the magnitude of vibration and the support of a seat backrest. The vertical apparent masses of 80 seated adults (41 males and 39 females aged 18–65) were measured at frequencies between 0.6 and 20Hz with four backrest conditions (no backrest, upright rigid backrest, reclined rigid backrest, reclined foam backrest) and with three magnitudes of random vibration (0.5, 1.0 and 1.5ms-2 rms). Relationships between subject physical characteristics (age, gender, weight, and anthropometry) and subject apparent mass were investigated with multiple regression models. The strongest predictor of the modulus of the vertical apparent mass at 0.6Hz, at resonance, and at 12Hz was body weight, with other factors having only a marginal effect. After correction for other variables, the principal resonance frequency was most consistently associated with age and body mass index. As age increased from 18 to 65 years, the resonance frequency increased by up to 1.7Hz, and when the body mass index was increased from 18 to 34kgm−2 the resonance frequency decreased by up to 1.7Hz. These changes were greater than the 0.9-Hz increase in resonance frequency between sitting without a backrest and sitting with a reclined rigid backrest, and greater than the 1.0-Hz reduction in resonance frequency when the magnitude of vibration increased from 0.5 to 1.5ms−2 rms. It is concluded that the effects of age, body mass index, posture, vibration magnitude, and weight should be taken into account when defining the vertical apparent mass of the seated human body. [Copyright &y& Elsevier]

Abstract: To minimise the discomfort of standing people caused by vibration of a floor, it is necessary to know how their sensitivity to vibration depends on the frequency of the vibration. This study was designed to determine how the discomfort of standing people exposed to horizontal and vertical vibration depends on vibration frequency over the range 0.5–16Hz. Using the method of magnitude estimation, sixteen subjects judged the discomfort caused by fore-and-aft, lateral, and vertical sinusoidal vibration at each of the sixteen preferred one-third octave centre frequencies from 0.5 to 16Hz at each of nine magnitudes. Subjects also reported the main cause of their discomfort. Equivalent comfort contours were constructed, reflecting the effect of frequency on subject sensitivity to vibration acceleration. With horizontal vibration, at frequencies between 0.5 and 3.15Hz the discomfort was similar when the vibration velocity was similar, whereas at frequencies between 3.15 and 16Hz the discomfort was similar when the vibration acceleration was similar. At frequencies less than 3.15Hz, the subjects experienced problems with their stability, whereas at higher frequencies vibration discomfort was mostly experienced from sensations in the legs and feet. With vertical vibration, discomfort was felt in the lower-body and upper-body at all frequencies. The frequency weightings in current standards for predicting the vibration discomfort of standing persons have been greatly influenced by the findings of studies with seated subjects: the weightings are consistent with the experimentally determined frequency-dependence of discomfort caused by vertical vibration but inconsistent with the experimentally determined frequency-dependence of discomfort caused by horizontal vibration. The results suggest that the responses of seated and standing people are similar for vertical vibration, but differ for horizontal vibration, partly due to greater instability in standing persons. [Copyright &y& Elsevier]

Abstract: The smallest change in vibration intensity for the change to be perceptible (i.e. intensity difference threshold) has not previously been reported for vibration of the foot. This study investigated the influence of vibration magnitude and vibration frequency on intensity difference thresholds for the perception of vertical sinusoidal vibration of the foot. It was hypothesised that relative intensity difference thresholds (i.e. Weber fractions) for 16-Hz vibration mediated by the non-Pacinian I (NPI) channel would differ from relative intensity difference thresholds for 125-Hz vibration mediated by the Pacinian (P) channel. Absolute thresholds, difference thresholds, and the locations of vibration sensation caused by vertical vibration of the right foot were determined for 12 subjects using the up-down-transformed-response method together with the three-down-one-up rule. The difference thresholds and locations of sensation were obtained at six reference magnitudes (at 6, 9, 12, 18, 24, 30dB above absolute threshold—i.e. sensation levels, SL). For 16-Hz vibration, the median relative difference thresholds were not significantly dependent on vibration magnitude and were in the range 0.19 (at 30dB SL) to 0.27 (at 9dB SL). For 125-Hz vibration, the median relative difference thresholds varied between 0.17 (at 9dB SL) and 0.34 (at 30dB SL), with difference thresholds from 6 to 12dB SL significantly less than those from 18 to 30dB SL. At vibration magnitudes slightly in excess of absolute thresholds (i.e. 6–12dB SL) there were no significant differences between Weber fractions obtained from the P channel (at 125Hz) and the NPI channel (at 16Hz). At 24 and 30dB SL, the 125-Hz Weber fractions were significantly greater than the 16-Hz Weber fractions. Differences in the 125-Hz Weber fractions may have been caused by a reduction in the discriminability of the P channel at high levels of excitation, resulting in one or more NP channel mediating the difference thresholds at magnitudes greater than 18dB SL. At high magnitudes, a change of channel mediating the Weber fractions may have been responsible for different Weber fractions with 16- and 125-Hz vibration. [Copyright &y& Elsevier]

Abstract: Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad-spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline''s multiple mechanisms of action as a means to understand their beneficial effects. [Copyright &y& Elsevier]

Abstract: Previous studies have quantified the power absorbed in the seated human body during exposure to vibration but have not investigated the effects of body posture or the power absorbed at the back and the feet. This study investigated the effects of support for the feet and back and the magnitude of vibration on the power absorbed during whole-body vertical vibration. Twelve subjects were exposed to four magnitudes (0.125, 0.25, 0.625, and 1.25ms−2 rms) of random vertical vibration (0.25–20Hz) while sitting on a rigid seat in four postures (feet hanging, maximum thigh contact, average thigh contact, and minimum thigh contact) both with and without a rigid vertical backrest. Force and acceleration were measured at the seat, the feet, and the backrest to calculate the power absorbed at these three locations. At all three interfaces (seat, feet, and back) the absorbed power increased in proportion to the square of the magnitude of vibration, with most power absorbed from vibration at the seat. Supporting the back with the backrest decreased the power absorbed at the seat at low frequencies but increased the power absorbed at high frequencies. Supporting the feet with the footrest reduced the total absorbed power at the seat, with greater reductions with higher footrests. It is concluded that contact between the thighs and the seat increases the power absorbed at the seat whereas a backrest can either increase or decrease the power absorbed at the seat. [Copyright &y& Elsevier]

Abstract: Vibration at the feet can contribute to discomfort in many forms of transport and in some buildings. Knowledge of the frequency-dependence of discomfort caused by foot vibration, and how this varies with vibration magnitude, will assist the prediction of discomfort caused by vibration. With groups of 12 seated subjects, this experimental study determined absolute thresholds for the perception of foot vibration and quantified the discomfort caused by vibration at the foot. The study investigated a wide range of magnitudes (from the threshold of perception to levels associated with severe discomfort) over a wide range of frequencies (from 8 to 315Hz in one-third octave steps) in each of the three orthogonal translational axes (fore-and-aft, lateral, and vertical). The effects of gender and shoes on absolute thresholds for the perception of vertical vibration at the foot were also investigated. Within each of the three axes, the vibration acceleration corresponding to the absolute thresholds for the perception of vibration, and also all contours showing conditions producing equivalent discomfort, were highly frequency-dependent at frequencies greater than about 40Hz. The acceleration threshold contours were U-shaped at frequencies greater than 80Hz in all three axes of excitation, suggesting the involvement of the Pacinian channel in vibration perception. 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, the conditions causing similar discomfort across the frequency range approximated towards constant velocity. Thresholds were not greatly affected by wearing shoes or subject gender. The derived frequency weightings imply that no single linear frequency weighting can provide accurate predictions of discomfort caused by a wide range of magnitudes of foot vibration. [Copyright &y& Elsevier]

Abstract: Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) is a tetrameric enzyme that catalyses the first committed step of the lysine biosynthetic pathway. Dimeric variants of DHDPS have impaired catalytic activity due to aberrant protein motions within the dimer unit. Thus, it is thought that the tetrameric structure functions to restrict these motions and optimise enzyme dynamics for catalysis. Despite the importance of dimer–dimer association, the interface between subunits of each dimer is small, accounting for only 4.3% of the total monomer surface area, and the structure of the interface is not conserved across species. We have probed the tolerance of dimer–dimer association to mutation by introducing amino acid substitutions within the interface. All point mutations resulted in destabilisation of the ‘dimer of dimers’ tetrameric structure. Both the position of the mutation in the interface and the physico-chemical nature of the substitution appeared to effect tetramerisation. Despite only weak destabilisation of the tetramer by some mutations, catalytic activity was reduced to ∼10–15% of the wild-type in all cases, suggesting that the dimer–dimer interface is finely tuned to optimise function. [Copyright &y& Elsevier]

Abstract: The transmission of vibration through a seat depends on various characteristics of the seat and the dynamic response of the human body. The dynamic response of the body can be represented by its apparent mass, but the effect of the seat on the apparent mass of the body is not well understood. This study was designed to quantify the effect of foam and rigid backrests on the vertical apparent mass of the human measured at the seat surface supporting the body. The apparent masses of 12 subjects were measured during exposure to random vertical vibration (1.0ms−2 rms from 0.125 to 40Hz) in a seat with a rigid backrest, in the same rigid seat with three thicknesses of foam backrest (50, 100 and 150mm), and in the same seat with no backrest. The backrests were inclined at various angles: 0°, 5°, 10°, 15°, 20°, 25° and 30° for the rigid and 100mm foam backrests, and 0°, 10°, 20° and 30° for the 50 and 150mm foam backrests. With all vertical backrests (i.e., 0° inclination), there were resonances in the apparent mass of the body around 5 and 10Hz. With no backrest, the apparent mass was increased at frequencies less than the resonance frequency but decreased at frequencies between 8 and 20Hz, relative to the apparent mass with the vertical rigid and foam backrests. With the rigid backrest, the primary resonance frequencies in the apparent mass increased with increasing backrest inclination. With the foam backrests, the resonance frequencies decreased with increasing backrest inclination. At frequencies less than the primary resonance, the apparent mass decreased with increasing backrest inclination, particularly with the rigid backrest. Between 8 and 15Hz, the apparent mass decreased with increasing inclination, most notably with the foam backrests. At inclinations less than 30°, there was little effect of foam thickness on the apparent mass, but at 30° an increase in the thickness of the foam decreased the frequency of the first resonances. Since contact with backrests and the characteristics of backrests influence the vertical apparent mass of the seated body, backrests should be expected to influence the transmission of vertical vibration through a supporting seat cushion. [Copyright &y& Elsevier]

Abstract: Although hand-transmitted vibration causes injury and disease, most often evident in the fingers, the biodynamic responses of the fingers, hand, and arm are not yet well understood. A method of investigating the motion of the entire finger–hand–arm system, based on the simultaneous measurement of the biodynamic response at the driving point and the transmissibility to many points on the finger–hand–arm system, is illustrated. Fourteen male subjects participated in an experiment in which they pushed down on a vertically vibrating metal plate with their right forearm pronated and their elbow bent at 90°. The apparent mass and mechanical impedance of the finger–hand–arm system were measured for each of seven different contact conditions between the plate and the fingers and hand. Simultaneously, the vibration of the fingers, hand, and arm was measured at 41 locations using a scanning laser Doppler vibrometer. Transmissibilities showed how the vibration was transmitted along the arm and allowed the construction of spectral operating deflection shapes showing the vibration pattern of the fingers, hand, and arm for each of the seven contact conditions. The vibration patterns at critical frequencies for each contact condition have been used to explain features in the driving point biodynamic responses and the vibration behaviour of the hand–arm system. Spectral operating deflection shapes for the upper limb assist the interpretation of driving point biodynamic responses and help to advance understanding required to predict, explain, and control the various effects of hand-transmitted vibration. [Copyright &y& Elsevier]

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: 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]

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]

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]

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]

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]

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]

Abstract: The vertical apparent mass of the human body exhibits nonlinearity, with the principal resonance frequency reducing as the vibration magnitude increases. Measures of the transmission of vibration to the spine and the pelvis have suggested complex modes are responsible for the dominant resonance during vertical excitation, but the modes present with dual-axis excitation have not been investigated. This study was designed to examine how the apparent mass and transmissibility of the human body depend on the magnitude of vertical excitation and the addition of fore-and-aft excitation, and the relation between the apparent mass and the transmissibility of the body. The movement of the body (over the first, fifth and twelfth thoracic vertebrae, the third lumbar vertebra, and the pelvis) in the fore-and-aft and vertical directions (and in pitch at the pelvis) was measured in 12 male subjects sitting with their hands on their laps during random vertical vibration excitation (over the range 0.25–20Hz) at three vibration magnitudes (0.25, 0.5 and 1.0ms−2 rms). At the highest magnitude of vertical excitation (1.0ms−2 rms) the effect of adding fore-aft vibration (at 0.25, 0.5, and 1.0ms−2 rms) was investigated. The forces in the vertical and fore-and-aft directions on the seat surface were also measured so as to calculate apparent masses. Resonances in the apparent mass and transmissibility to the spine and pelvis in the fore-and-aft and vertical directions, and pitch transmissibility to the pelvis, shifted to lower frequencies as the magnitude of vertical excitation increased and as the magnitude of the additional fore-and-aft excitation increased. The nonlinear resonant behaviour of the apparent mass and transmissibility during dual-axis vibration excitation suggests coupling between the principal mode associated with vertical excitation and the cross-axis influence of fore-and-aft excitation. The transmissibility measures are consistent with complex modes contributing to motion of the body at the principal resonance: pitch motions of the upper thoracic and lumbar spine, and vertical and fore-aft motion of the pelvis and spine. The mode varies with the magnitude of vertical and fore-and-aft excitation. [Copyright &y& Elsevier]

Abstract: During vertical excitation of the seated human body there are vertical and fore-and-aft forces at the seat that are influenced by contact with a backrest, so it is desirable to take into account the effect of a backrest when developing models of the seated human body. Initially, a seven degree-of-freedom multi-body dynamic model was developed for the human body sitting with an upright posture unsupported by a backrest and exposed to vertical vibration. The model was optimized to fit the vertical apparent mass and the fore-and-aft cross-axis apparent mass measured on a seat. The model was then extended by the addition of vertical and fore-and-aft reaction forces to the upper lumbar spine to model the interaction between the human body and a backrest. By minimizing the least square error between experimental data and the analytical solution of the apparent masses on the seat and at the back, the human body model was able to represent both the vertical apparent mass and the fore-and-aft cross-axis apparent mass on the seat and at the back. Parameter sensitivity studies showed that the vertical apparent mass and the fore-and-aft cross-axis apparent mass on the seat and the backrest were all highly sensitive to the axial stiffness of the tissue beneath the pelvis. Pitch motion of the upper-body contributed to the vertical apparent mass and the fore-and-aft cross-axis apparent mass on the seat. The apparent mass at the back was more sensitive to the stiffness and damping of the lower back than the properties of the upper back. [Copyright &y& Elsevier]

Abstract: Dihydrodipicolinate synthase (DHDPS) is a validated antibiotic target for which a new approach to inhibitor design has been proposed: disrupting native tetramer formation by targeting the dimer–dimer interface. In this study, rational design afforded a variant of Mycobacterium tuberculosis, Mtb-DHDPS-A204R, with disrupted quaternary structure. X-ray crystallography (at a resolution of 2.1Å) revealed a dimeric protein with an identical fold and active-site structure to the tetrameric wild-type enzyme. Analytical ultracentrifugation confirmed the dimeric structure in solution, yet the dimeric mutant has similar activity to the wild-type enzyme. Although the affinity for both substrates was somewhat decreased, the high catalytic competency of the enzyme was surprising in the light of previous results showing that dimeric variants of the Escherichia coli and Bacillus anthracis DHDPS enzymes have dramatically reduced activity compared to their wild-type tetrameric counterparts. These results suggest that Mtb-DHDPS-A204R is similar to the natively dimeric enzyme from Staphylococcus aureus, and highlight our incomplete understanding of the role played by oligomerisation in relating protein structure and function. [Copyright &y& Elsevier]

Abstract: Amyloid fibrils and their oligomeric intermediates accumulate in several age-related diseases where their presence is considered to play an active role in disease progression. A common characteristic of amyloid fibril formation is an initial lag phase indicative of a nucleation–elongation mechanism for fibril assembly. We have investigated fibril formation by human apolipoprotein (apo) C-II. ApoC-II readily forms amyloid fibrils in a lipid-dependent manner via an initial nucleation step followed by fibril elongation, breaking, and joining. We used fluorescence techniques and stopped-flow analysis to identify the individual kinetic steps involved in the activation of apoC-II fibril formation by the short-chain phospholipid dihexanoyl phosphatidylcholine (DHPC). Submicellar DHPC activates fibril formation by promoting the rapid formation of a tetrameric species followed by a slow isomerisation that precedes monomer addition and fibril growth. Global fitting of the concentration dependence of apoC-II fibril formation showed that DHPC increased the overall tetramerisation constant from 7.5×10−13 to 1.2×10−6 μM−3 without significantly affecting the rate of fibril elongation, breaking, or joining. Studies on the effect of DHPC on the free pool of apoC-II monomer and on fibril formation by cross-linked apoC-II dimers further demonstrate that DHPC affects nucleation but not elongation. These studies demonstrate the capacity of small lipid compounds to selectively target individual steps in the amyloid fibril forming pathway. [Copyright &y& Elsevier]

J. R. Torrealba, E. Lozano, M. Griffin, S. Stoker, K. Mcdonald, M. Greaser and M. R. Wolff. Maximal ATPase Activity and Calcium Sensitivity of Reconstituted Myofilaments are unaltered by the Fetal Troponin T Re-expressed During Human Heart Failure. Journal of Molecular and Cellular Cardiology (2002) 34, 797–805. Re-expression of a fetal isoform of troponin T (TnT4) has been demonstrated in failing human ventricular myocardium and associated with a decrease in myofibrillar ATPase activity. In order to elucidate the regulatory role of the re-expressed TnT4 in the failing human heart, we measured ATPase activity in reconstituted cardiac myofilaments prepared with recombinant human TnT4 or the adult human isoform of troponin T (TnT3). Neither the maximal calcium-activated ATPase activity nor the calcium sensitivity of this biochemical assay was significantly different between reconstituted myofilaments containing adult TnT3 or fetal TnT4. Our results suggest that the re-expressed fetal TnT4 is not responsible for the depressed ATPase activity of failing ventricular myofibrils. The increased expression of the fetal isoform of this thin filament regulatory protein in the failing ventricle may be a consequence of a programmed change in gene expression occurring in response to hemodynamic stress, but probably does not contribute to depressed ventricular function characteristic of dilated cardiomyopathies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Small heat-shock proteins populate a monomer–dimer-oligomer equilibrium. • The alpha-crystallin domain binds at fibril ends to inhibit elongation. • Chaperone-activity is inhibited by disulfide crosslinking at the dimer interface. • Monomers of the alpha-crystallin domain are proposed to interact with fibril ends. Small heat-shock proteins (sHSPs) are ubiquitously expressed molecular chaperones present in all kingdoms of life that inhibit protein misfolding and aggregation. Despite their importance in proteostasis, the structure–function relationships of sHSPs remain elusive. Human sHSPs are characterised by a central, highly conserved α-crystallin domain (ACD) and variable-length N- and C-terminal regions. The ACD forms antiparallel homodimers via an extended β-strand, creating a shared β-sheet at the dimer interface. The N- and C-terminal regions mediate formation of higher order oligomers that are thought to act as storage forms for chaperone-active dimers. We investigated the interactions of the ACD of two human sHSPs, αB-crystallin (αB-C) and Hsp27, with apolipoprotein C-II amyloid fibrils using analytical ultracentrifugation and nuclear magnetic resonance spectroscopy. The ACD was found to interact transiently with amyloid fibrils to inhibit fibril elongation and naturally occurring fibril end-to-end joining. This interaction was sensitive to the concentration of fibril ends indicating a 'fibril-capping' interaction. Furthermore, resonances arising from the ACD monomer were attenuated to a greater extent than those of the ACD dimer in the presence of fibrils, suggesting that the monomer may bind fibrils. This hypothesis was supported by mutagenesis studies in which disulfide cross-linked ACD dimers formed by both αB-C and Hsp27 were less effective at inhibiting amyloid fibril elongation and fibril end-to-end joining than ACD constructs lacking disulfide cross-linking. Our results indicate that sHSP monomers inhibit amyloid fibril elongation, highlighting the importance of the dynamic oligomeric nature of sHSPs for client binding. [ABSTRACT FROM AUTHOR]

A majority of well pads for unconventional gas wells that are drilled into the Marcellus shale (northeastern USA) consist of multiple wells (in some cases as many as 12 wells per pad), yet the influence of the evolution of well pad development on the extent of environmental violations and wastewater production is unknown. Although the development of multi-well pads (MWP) at the expense of single well pads (SWP) has been mostly driven by economic factors, the concentrated nature of drilling activities from hydraulic fracturing and horizontal drilling operations on MWP suggests that MWP may create less surface disturbance, produce more volumes of wastewater, and generate more environmental violations than SWP. To explore these hypotheses, we use geospatial techniques and statistical analyses (i.e., regression and Mann–Whitney tests) to assess development of unconventional shale gas wells, and quantify environmental violations and wastewater volumes on SWP and MWP in Pennsylvania. The analyses include assessments of the influence of different types of well pads on potential, minor and major environmental events. Results reveal that (a) in recent years, a majority of pads on which new wells for unconventional gas were drilled are MWP, (b) on average, MWP have about five wells located on each pad and thus, had the transition to MWP not occurred, between two and four times as much land surface disturbance would have occurred per year if drilling was relegated to SWP, (c) there were more environmental violations on MWP than SWP, but when the number of wells were taken into account, fewer environmental violations per well were observed on MWP than on SWP, (d) there were more wastewater and recycled wastewater volumes per pad and per well produced on MWP than on SWP, and (e) the proportion of wastewater that was recycled was higher on MWP than SWP. This study sheds light on how the evolution from SWP to MWP has influenced environmental violations and wastewater production in a field that has undergone rapid development in recent years. [Copyright &y& Elsevier]