Imitation, mirror neurons and autism

Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism. Crown Copyright (C) 2001 Published by Elsevier Science Ltd. All rights reserved.

Generalization by symbolic abstraction in cascaded recurrent networks

Generalization performance in recurrent neural networks is enhanced by cascading several networks. By discretizing abstractions induced in one network, other networks can operate on a coarse symbolic level with increased performance on sparse and structural prediction tasks. The level of systematicity exhibited by the cascade of recurrent networks is assessed on the basis of three language domains. (C) 2004 Elsevier B.V. All rights reserved.

Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88)

The phosphosulfomannan 1 (PI-88) is a mixture of highly sulfated oligosaccharides that is currently undergoing clinical evaluation in cancer patients. As well as it's anticancer properties, 1 displays a number of other interesting biological activities. A series of analogues of 1 were synthesized with a single carbon (pentasaccharide) backbone to facilitate structural characterization and interpretation of biological results. In a fashion similar to 1, all compounds were able to inhibit heparanase and to bind tightly to the proangiogenic growth factors FGF-1, FGF-2, and VEGF. The compounds also inhibited the infection of cells and cell-to-cell spread of herpes simplex virus (HSV-1). Preliminary pharmacokinetic data indicated that the compounds displayed different pharmacokinetic behavior compared with 1. Of particular note was the n-octyl derivative, which was cleared 3 times less rapidly than 1 and may provide increased systemic exposure.

Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas

TSLC1 (tumor suppressor in lung cancer-1, IGSF4) encodes a member of the immunoglobulin superfamily molecules, which is involved in cell-cell adhesion. TSLC1 is connected to the actin cytoskeleton by DAL-1 (differentially expressed in adenocarcinoma of the lung-1, EPB41L3) and it directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large. Recent data suggest that aberrant promoter methylation is important for TSLC1 inactivation in lung carcinomas. However, little is known about the other two genes in this cascade, DAL-1 and MPP3. Thus, we investigated the expression and methylation patterns of these genes in lung cancer cell lines, primary lung carcinomas and nonmalignant lung tissue samples. By reverse transcription-polymerase chain reaction, loss of TSLC1 expression was observed in seven of 16 (44%) non-small-cell lung cancer (NSCLC) cell lines and in one of 11 (9%) small-cell lung cancer (SCLC) cell lines, while loss of DAL- 1 expression was seen in 14 of 16 (87%) NSCLC cell lines and in four of 11 (36%) SCLC cell lines. By contrast, MPP3 expression was found in all tumor cell lines analysed. Similar results were obtained by microarray analysis. TSLC1 methylation was seen in 13 of 39 (33%) NSC LC cell lines, in one of 11 (9%) SCLC cell lines and in 100 of 268 (37%) primary NSCLCs. DAL-1 methylation was observed in 17 of 39 (44%) NSCLC cell lines, in three of 11 (27%) SCLC cell lines and in 147 of 268 (55%) primary NSCLCs. In tumors of NSCLC patients with stage II-III disease, DAL-1 methylation was seen at a statistically significant higher frequency compared to tumors of patients with stage I disease. A significant correlation between loss of expression and methylation of the genes in lung cancer cell lines was found. Overall, 65% of primary NSCLCs had either TSLC1 or DAL-1 methylated. Methylation of one of these genes was detected in 59% of NSCLC cell lines; however, in SCLC cell lines, methylation was much less frequently observed. The majority of nonmalignant lung tissue samples was not TSLC1 and DAL-1 methylated. Re-expression of TSLC1 and DAL-1 was seen after treatment of lung cancer cell lines with 5-aza-2$-deoxy-cytidine. Our results suggest that methylation of TSLC1 and/or DAL-1, leading to loss of their expression, is an important event in the pathogenesis of NSCLC.

Double-heater-wire circuits and heat-and-moisture exchangers and the risk of ventilator-associated pneumonia

Objective: To compare the incidence of ventilator-associated pneumonia (VAP) in patients ventilated in intensive care by means of circuits humidified with a hygroscopic heat-and-moisture exchanger with a bacterial viral filter (HME) or hot-water humidification with a heater wire in both inspiratory and expiratory circuit limbs (DHW) or the inspiratory limb only (SHW). Design: A prospective, randomized trial. Setting: A metropolitan teaching hospital's general intensive care unit. Patients: Three hundred eighty-one patients requiring a minimum period of mechanical ventilation of 48 hrs. Interventions: Patients were randomized to humidification with use of an HME (n = 190), SHW (n = 94), or DHW (n = 97). Measurements and Main Results. Study end points were VAP diagnosed on the basis of Clinical Pulmonary Infection Score (CPIS) (1), HME resistance after 24 hrs of use, endotracheal tube resistance, and HME use per patient. VAP occurred with similar frequency in all groups (13%, HME; 14%, DHW; 10%, SHW; p = 0.61) and was predicted only by current smoking (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1-3.9; p =.03) and ventilation days (AOR, 1.05; 95% Cl, 1.0-1.2; p =.001); VAP was less likely for patients with an admission diagnosis of pneumonia (AOR, 0.40; 95% Cl, 0.4-0.2; p =.04). HME resistance after 24 hrs of use measured at a gas flow of 50 L/min was 0.9 cm H2O (0.4-2.9). Endotracheal tube resistance was similar for all three groups (16-19 cm H2O min/L; p =.2), as were suction frequency, secretion thickness, and blood on suctioning (p =.32, p =.06, and p =.34, respectively). The HME use per patient per day was 1.13. Conclusions: Humidification technique does not influence either VAP incidence or secretion characteristics, but HMEs may have air-flow resistance higher than manufacturer specifications after 24 hrs of use.

Applications of the Jameson cell at the head of base metal flotation circuits

The Jameson Cell is a high intensity flotation device, which utilises induced air from the atmosphere. It was developed jointly by Mount Isa Mines and Professor Graeme Jameson of the University of Newcastle in the 1980s. It is proven to generate fine bubbles, in the order of 300 to 500 µm, in a high intensity, high shear and compact zone contained in the downcomer. This aerated mixture exits the downcomer into the pulp zone, which is the quiescent mineral and gangue separation zone. A number of Australian base metal flotation circuits feature a reverse flotation stage at the head of the circuit. Testwork and plant operating data has shown that the use of a Jameson Cell in the prefloat cleaner application has further improved prefloat gangue recovery and selectivity. Operation of a Jameson Cell in a carbonaceous/pyrite prefloat cleaner duty at the Mt Isa copper concentrator increased copper recovery and reduced pyrite in the copper concentrate. Testwork at Zinifex Century Zinc Mine showed a decrease in zinc losses by the utilisation of Jameson Cell prefloat cleaner. Appraisal of a Jameson Cell in a scalping role within the Mt Isa Copper Concentrator indicated significant benefits could be achieved.

Parallel implementation of stochastic simulation for large scale cellular processes

Experimental and theoretical studies have shown the importance of stochastic processes in genetic regulatory networks and cellular processes. Cellular networks and genetic circuits often involve small numbers of key proteins such as transcriptional factors and signaling proteins. In recent years stochastic models have been used successfully for studying noise in biological pathways, and stochastic modelling of biological systems has become a very important research field in computational biology. One of the challenge problems in this field is the reduction of the huge computing time in stochastic simulations. Based on the system of the mitogen-activated protein kinase cascade that is activated by epidermal growth factor, this work give a parallel implementation by using OpenMP and parallelism across the simulation. Special attention is paid to the independence of the generated random numbers in parallel computing, that is a key criterion for the success of stochastic simulations. Numerical results indicate that parallel computers can be used as an efficient tool for simulating the dynamics of large-scale genetic regulatory networks and cellular processes