Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink

When an observer detects a target in a rapid stream of visual stimuli, there is a brief period of time during which the detection of subsequent targets is impaired. In this study, event-related potentials (ERPs) were recorded from normal adult observers to determine whether this "attentional blink" reflects a suppression of perceptual processes or an impairment in postperceptual processes. No suppression was observed during the attentional blink interval for ERP components corresponding to sensory processing (the P1 and N1 components) or semantic analysis (the N400 component). However, complete suppression was observed for an ERP component that has been hypothesized to reflect the updating of working memory (the P3 component). Results indicate that the attentional blink reflects an impairment in a postperceptual stage of processing.     

Longitudinal assessment of inpatient use and functioning of seriously mentally ill veterans with and without co-occurring substance use disorders

Within a fungal species, a subset of individuals may have more than the minimal complement of chromosomes. If the extra chromosomes are composed primarily of DNA not found in all representatives of the species, they are most appropriately referred to as supernumerary chromosomes. The patterns of repeated DNA sequences on certain supernumerary chromosomes suggest that they have a different evolutionary history from the essential chromosomes in the same genome. Supernumerary chromosomes can carry functional genes and, in at least two fungal species, genes on such chromosomes play important roles in host-pathogen interactions. Supernumerary chromosomes that confer an adaptive advantage in certain habitats, such as the ability to cause disease on a specific host, may be referred to as "conditionally dispensable" chromosomes in order to reflect their importance in some, but not all, growth conditions. In addition to describing the structural and functional characteristics of known supernumerary chromosomes in fungi, this review discusses the relative merits of the terms that have been used to describe them, and establishes experimental criteria for their identification.     

Fast transmission CT for determining attenuation maps using a collimated line source, rotatable air-copper-lead attenuators and fan-beam collimation

We describe a technique using a line source and a rotatable air-copper-lead assembly to acquire gamma transmission computed tomographic (TCT) data for determining attenuation maps to compensate SPECT emission scans. The technique minimizes problems associated with discriminating 99mTc transmission and 201Tl emission photons and requires only a modest increase in total study time. A 99mTc line source and a stacked foil ("multislat") collimator are placed near the focal line of a fan-beam collimator (114 cm focal length) mounted on one detector of a triple-camera SPECT system. We acquired TCT data of plastic rod and anthropomorphic thorax phantoms to investigate the capability of the line source and rotatable air-copper-lead attenuators to determine attenuation maps. The data were acquired with and without 5.4 MBq (145 microCi) of 201Tl placed in the myocardial chamber of the thorax phantom. Phantoms also were scanned using a curved transmission slab source mounted to a parallel-hole collimator. Fan-beam TCT images have improved resolution compared with parallel-beam TCT images. Two patient scans also were performed to evaluate the clinical usefulness of fan-beam TCT. The rotatable air-copper-lead attenuator method eliminates contamination of emission data by transmission photons and reduces spill-over of emission data into the transmission energy window for some cases. Results show the feasibility of using fast, sequential or interlaced transmission scans of a line source within a rotatable air-copper-lead attenuator assembly to obtain accurate attenuation maps for SPECT attenuation compensation.     

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease

Background: Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform. Immunohistochemical analysis was also performed on human IVD tissue samples obtained from spinal surgery. Immunohistochemical analysis and quantification of neurotrophins and neuropeptides was performed using an in vivo canine model of degenerative disc disease and human degenerative disc tissue sections. Discs injected with NTG-101 showed significantly lower levels of Nerve Growth Factor receptor (NGFr/TrkA, p = 0.0001), BDNF (p = 0.009), TrkB (p = 0.002) and CALCRL (p = 0.008) relative to PBS injections. Human IVD tissue obtained from spinal surgery due to painful DDD show robust expression of NGFr, BDNF, TrkB and CALCRL proteins. A single intradiscal injection of NTG-101 significantly inhibits the expression of NGFr, BDNF, TrkB and CALCRL proteins in degenerative canine IVDs. These results strongly suggest that NTG-101 inhibits the development of neurotrophins that are strongly associated with painful degenerative disc disease and may have profound effects upon the management of patients living with discogenic pain.     

Full Film, Boundary Lubrication and Tribochemistry in Steel Circular Contacts Lubricated with Glycerol

In this article, the lubricating properties of pure glycerol are investigated under both mild and severe EHL regimes. Amazingly low friction coefficients (about 0.01) are reported by experiments in thick film regimes compared to traditional base oils. EHL calculations of film thickness and friction (including thermal effects) predict friction coefficients that are twice those actually found for glycerol. Chemical analysis of glycerol before and after the friction tests were performed by NMR and Karl Fischer methods, and they reveal that water is produced by tribochemical reaction as well as other species like aldehydes. This finding is in agreement with a corrosion pattern observed inside the wear scars of the steel samples. This study provides an explanation to the anomalously low friction observed in the thick film regime. In fact, water produced in the lubricant decreases traction forces due to the drastic decrease of the viscosity of glycerol with water addition.     

Mono‐diffusive Hadley‐Prats flow in a horizontal porous layer subject to variable gravity and internal heat generation

Analysis of internal heated and gravity effect on the onset of Hadley‐Prats flow in a horizontal porous layer with inclined temperature gradients is investigated using the linear and nonlinear instability analysis. The transformed eigenvalue problem is evaluated numerically to find the eigenvalue, which is treated as a vertical thermal Rayleigh number (R_z). It is evaluated by applying shooting and Runge‐Kutta method. Also, the critical R_z is investigated for different parameters governing the flow. A theoretical study is made to understand the influence of gravity field on the mechanism of mono‐diffusive instability of Hadley‐Prats convection in a fluid saturated horizontal porous layer. Nonlinear stability is evaluated by using energy functional. The comparison between linear and nonlinear instability results are presented and it is noted that linear theory of instability may not be useful to capture the complete picture of stability and instabilities may arise before one attains the linear stability threshold. This subcritical instability region is identified between the linear and energy thresholds in the parameter space of the problem considered.     

Prenatal cocaine, alcohol, and undernutrition differentially alter mineral and protein content in fetal rats

Alcohol exposure and undernutrition during pregnancy have been associated with altered fetal body composition. Recent observations suggest that cocaine exposure during pregnancy may impair delivery of nutrients to the fetus and could thereby alter body growth and composition. Such effects are important because they can adversely influence physical and neural development. Consequently, we investigated the dose-dependent effects of cocaine on fetal body composition in an animal (rat) model and compared such effects with those caused by prenatal alcohol exposure and undernutrition. Pregnant Sprague-Dawley rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed (undernutrition) and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups (n = 11 to 14/group). Females were sacrificed on gestation day 20. One male and one female fetus was removed from each dam. The fetuses were minced, dehydrated, defatted, and analyzed for content of protein and the minerals Zn, Ca, Fe, Mg, K, and Na. In terms of concentration per unit of fat-free dry solids, male fetuses in the cocaine groups showed significant decreases in protein compared to untreated controls (15+/-3 to 20+/-2 mg/g vs. 24+/-4 mg/g, p = 0.01). There was a significant treatment effect for Ca (p < 0.05), reflecting a trend for decreased Ca concentrations in the fetuses of the cocaine and undernutrition groups. Male fetuses in the alcohol group had significantly elevated Mg levels compared to male fetuses in the other groups (3.0+/-0.8 vs. 1.0+/-0.2 to 2.3+/-0.7 mg/g, p < 0.05). There were some sex differences, with female fetuses having significantly lower concentrations of Mg, Fe, K, and higher protein concentrations than male fetuses. Although the effects were few and modest, these results suggest that prenatal cocaine, alcohol, and undernutrition can differentially alter fetal body weight and composition and, therefore, adversely influence fetal development.     

Synthesis and differential properties of creatine analogues as inhibitors for human creatine kinase isoenzymes

Fourteen new creatine analogues, all with a guanidine function and either a polar or an apolar group instead of the creatine carboxylic function, were tested as potential inhibitors for human creatine kinase by kinetic analysis of their effects on the reaction rate. Only compounds bearing an apolar aromatic moiety, which was spaced from the guanidine function by at least two bonds, proved to have a significant inhibitory activity and showed a mixed-type inhibition similar to that of creatine. Among these compounds 2,6-dichlorobenzylguanidine (Ki = 5.6 mM and 39.8 mM for muscle-type and brain-type creatine kinases, respectively) and 3-(2,6-dichlorophenyl)propylguanidine (Ki = 15 mM and 4.5 mM) were the more potent inhibitors and showed a significant isoenzyme selectivity between muscle- and brain-type creatine kinases. Our results are in agreement with recent data that suggest the location of a hydrophobic pocket near the guanidine-binding domain of the enzyme. The observed selectivity in isoenzyme inhibition may be useful to study structural differences in catalytic centers.     

Protein thermostability above 100 degreesC: a key role for ionic interactions

The discovery of hyperthermophilic microorganisms and the analysis of hyperthermostable enzymes has established the fact that multisubunit enzymes can survive for prolonged periods at temperatures above 100 degreesC. We have carried out homology-based modeling and direct structure comparison on the hexameric glutamate dehydrogenases from the hyperthermophiles Pyrococcus furiosus and Thermococcus litoralis whose optimal growth temperatures are 100 degreesC and 88 degreesC, respectively, to determine key stabilizing features. These enzymes, which are 87% homologous, differ 16-fold in thermal stability at 104 degreesC. We observed that an intersubunit ion-pair network was substantially reduced in the less stable enzyme from T. litoralis, and two residues were then altered to restore these interactions. The single mutations both had adverse effects on the thermostability of the protein. However, with both mutations in place, we observed a fourfold improvement of stability at 104 degreesC over the wild-type enzyme. The catalytic properties of the enzymes were unaffected by the mutations. These results suggest that extensive ion-pair networks may provide a general strategy for manipulating enzyme thermostability of multisubunit enzymes. However, this study emphasizes the importance of the exact local environment of a residue in determining its effects on stability.