Simulated train driving: fatigue, self-awareness and cognitive disengagement

Fatigue is a serious issue for the rail industry, increasing inefficiency and accident risk. The performance of 20 train drivers in a rail simulator was investigated at low, moderate and high fatigue levels. Psychomotor vigilance (PVT), self-rated performance and subjective alertness were also assessed. Alertness, PVT reaction times, extreme speed violations (>25% above the limit) and penalty brake applications increased with increasing fatigue level. In contrast, fuel use, draft (stretch) forces and braking errors were highest at moderate fatigue levels. Thus, at high fatigue levels, errors involving a failure to act (errors of omission) increased, whereas incorrect responses (errors of commission) decreased. The differential effect of fatigue on error types can be explained through a cognitive disengagement with the virtual train at high fatigue levels. Interaction with the train reduced dramatically, and accident risk increased. Awareness of fatigue-related performance changes was moderate at best. These findings are of operational concern.     

Computer tracking of objects moving in space

A method is developed to represent movement of convex blocks in three-dimensional space from a sequence of two-dimensional camera images. The goals are to determine the objects' movement toward or away from the camera as well as left/right and up/down movement in the image plane and to build models of the blocks. The movement information is used as part of a hierarchical matching process that determines the correspondence of blocks between scenes.     

Trying to adopt systems development methodologies — a case-based exploration of business users' interests

Information systems methodologies are an important component of the IS infrastructure and a primary device for organizing systems development work. Evidence suggests that methodology adoption and use are problematic. This research seeks to generate insight into business users' interest in adoption through detailed examination of a case. A framework is developed for organizing relevant research findings. The field research methods are described and details of the case reported. The case highlights the role of business managers in methodology adoption and the influence of business pressures originating in the strategic environment. Analysis shows the organizing framework to require extension to include a more direct role for business decision makers. it is argued that previous research has obscured the legitimate concern of business with systems development methodologies. As business increasingly asserts its interest in and control over IS, it will be necessary to give greater consideration to the needs of business in the selection and adoption of methodologies.     

Drugs,Guts, Brains,but Not Rock and Roll: The Need to Consider the Role of Gut Microbiota in Contemporary Mental Health and Wellness of Emerging Adults

Emerging adulthood (ages 18–25) is a critical period for neurobiological development and the maturation of the hypothalamic–pituitary–adrenal axis. Recent findings also suggest that a natural perturbation of the gut microbiota (GM), combined with other factors, may create a unique vulnerability during this period of life. The GM of emerging adults is thought to be simpler, less diverse, and more unstable than either younger or older people. We postulate that this plasticity in the GM suggests a role in the rising mental health issues seen in westernized societies today via the gut–brain–microbiota axis. Studies have paid particular attention to the diversity of the microbiota, the specific function and abundance of bacteria, and the production of metabolites. In this narrative review, we focus specifically on diet, physical activity/exercise, substance use, and sleep in the context of the emerging adult. We propose that this is a crucial period for establishing a stable and more resilient microbiome for optimal health into adulthood. Recommendations will be made about future research into possible behavioral adjustments that may be beneficial to endorse during this critical period to reduce the probability of a “dysbiotic” GM and the emergence and severity of mental health concerns.     

On the Role of C Addition on α Precipitation in a β Titanium Alloy

The onset of α nucleation in a carbon containing β-titanium alloy has been investigated by coupling atom probe tomography (APT) with transmission electron microscopy. The analysis of the APT results indicates that in addition to ω precipitates that can act as potential α nucleation sites, carbon atoms tend to form clusters within the β-matrix, which in turn give rise to additional nucleation sites for α, resulting in finer scale α precipitates due to increased nucleation density.     

Creating a Village in Modern Suburbia: Parenthood and Social Capital

Local communities with good stocks of social capital nurture and support the families residing within. This qualitative study explored through the perspectives of mothers, how families with children aged 0–5 years build social capital in newer residential areas in Perth, Western Australia. Parenthood generally increased the desire to connect to one's local community, which activated and enhanced social capital. Two themes appear to drive this desire: an increased need for social support and an increased vested interest in the local community. However, newer residential areas commonly have a lag of community infrastructure needed to provide opportunities for families with young children to interact with other families. Urban planning and community sectors need to coordinate to provide infrastructure and opportunities for families with young children to connect and build social capital within their local communities.     

An Atomistic Understanding of Allosteric Inhibition of Glutamate Racemase: a Dampening of Native Activation Dynamics

Glutamate racemases (GR) are members of the family of bacterial enzymes known as cofactor-independent racemases and epimerases and catalyze the stereoinversion of glutamate. D-amino acids are universally important for the proper construction of viable bacterial cell walls, and thus have been repeatedly validated as attractive targets for novel antimicrobial drug design. Significant aspects of the mechanism of this challenging stereoinversion remain unknown. The current study employs a combination of MD and QM/MM computational approaches to show that the GR from H. pylori must proceed via a pre-activation step, which is dependent on the enzyme's flexibility. This mechanism is starkly different from previously proposed mechanisms. These findings have immediate pharmaceutical relevance, as the H. pylori GR enzyme is a very attractive allosteric drug target. The results presented in this study offer a distinctly novel understanding of how AstraZeneca's lead series of inhibitors cripple the H. pylori GR's native motions, via prevention of this critical chemical pre-activation step. Our experimental studies, using SPR, fluorescence and NMR WaterLOGSY, show that H. pylori GR is not inhibited by the uncompetitive mechanism originally put forward by Lundqvist et al.. The current study supports a deep connection between native enzyme motions and chemical reactivity, which has strong relevance to the field of allosteric drug discovery.     

Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current,If, in Adult Mouse Heart Primary Pacemaker Myocytes

A number of distinct electrophysiological mechanisms that modulate the myogenic spontaneous pacemaker activity in the sinoatrial node (SAN) of the mammalian heart have been investigated extensively. There is agreement that several (3 or 4) different transmembrane ionic current changes (referred to as the voltage clock) are involved; and that the resulting net current interacts with direct and indirect effects of changes in intracellular Ca²⁺ (the calcium clock). However, significant uncertainties, and important knowledge gaps, remain concerning the functional roles in SAN spontaneous pacing of many of the individual ion channel- or exchanger-mediated transmembrane current changes. We report results from patch clamp studies and mathematical modeling of the hyperpolarization-activated current, I_f, in the generation/modulation of the diastolic depolarization, or pacemaker potential, produced by individual myocytes that were enzymatically isolated from the adult mouse sinoatrial node (SAN). Amphotericin-mediated patch microelectrode recordings at 35 °C were made under control conditions and in the presence of 5 or 10 nM isoproterenol (ISO). These sets of results were complemented and integrated with mathematical modeling of the current changes that take place in the range of membrane potentials (−70 to −50 mV), which corresponds to the ‘pacemaker depolarization’ in the adult mouse SAN. Our results reveal a very small, but functionally important, approximately steady-state or time-independent current generated by residual activation of I_f channels that are expressed in these pacemaker myocytes. Recordings of the pacemaker depolarization and action potential, combined with measurements of changes in I_f, and the well-known increases in the L-type Ca²⁺ current, I_CaL, demonstrated that I_CaL activation, is essential for myogenic pacing. Moreover, after being enhanced (approximately 3-fold) by 5 or 10 nM ISO, I_CaL contributes significantly to the positive chronotropic effect. Our mathematical model has been developed in an attempt to better understand the underlying mechanisms for the pacemaker depolarization and action potential in adult mouse SAN myocytes. After being updated with our new experimental data describing I_f, our simulations reveal a novel functional component of I_f in adult mouse SAN. Computational work carried out with this model also confirms that in the presence of ISO the residual activation of I_f and opening of I_CaL channels combine to generate a net current change during the slow diastolic depolarization phase that is essential for the observed accelerated pacemaking rate of these SAN myocytes.     

Synthesis and isolation of <Emphasis Type="Italic">trans</Emphasis>-7, <Emphasis Type="Italic">cis</Emphasis>-9 octadecadienoic acid and other CLA isomers by base conjugation of partially hydrogenated γ-linolenic acid

CLA is of considerable interest because of reported potentially beneficial effects in animal studies. CLA, while not yet unambiguously defined, is a mixture of octadecadienoic acids with conjugated double bonds. The major isomer in natural products is generally considered to be cis-9,trans-11-octadecadienoic acid (c9, t11), which represents >75% of the total CLA in most cases. Other isomers are drawing increased attention. The t7,c9 isomer, which is often the second-most prevalent CLA in natural products, has been reported to represent as much as 40% of total CLA in milk from cows fed a high-fat diet. The need for a reference material became apparent in a recent study directed specifically at measuring t7,c9-CLA in milk, plasma, and rumen. A suitable standard mixture was produced by stirring 0.5 g of γ-linolenic acid (all cis-6,9, 12-C_18∶3) with 100 mL of 10% hydrazine hydrate in methanol for 2.5 h at 45°C. The solution was diluted with H₂O and acidified with HCl. The resulting partially hydrogenated FA were extracted with ether/petroleum ether, dried with Na₂SO₄, and conjugated by adding of 6.6% KOH in ethlylene glycol and heating for 1.5 h at 150–160°C. Approximately 20 mg each of cis-6, trans-8; trans-7, cis-9; cis-9, trans-11; and rans-10, cis-12 were obtained along with other FA. Methyl esters (FAME) of these four cis/trans isomers were resolved by Ag⁺HPLC (UV 233) and partially resolved by GC/(MS or FID) (CP-Sil 88). Treatment of these FAME with I₂ yielded all possible cis/trans (geometric) isomers for the four positions 6,8; 7,9; 9,11; and 10,12.