EFFECTS OF TIME PRESSURE ON THE USE OF AN AUTOMATED DECISION SUPPORT SYSTEM FOR STRIKE PLANNING

This paper describes the results of an experiment designed to examine the effects of time pressure on behavioral patterns. The main research hypothesis is that people under time pressure tend to increasingly rely on automation in order to cope with the added workload. The context is that of a missile strike planner having to create a set of matches between resources (missiles) and requirements (missions). We introduce time pressure by changing the temporal requirements towards the end of the mission. Overall performance, calls to automation and qualitative strategies are recorded and analyzed using ANOVA and other nonparametric tests. The main finding of this study is that while the number of calls to the automation did significantly increase under time pressure, there did not seem to be a statistically significant shift in problem solving strategies under time pressure. The experimental results show the importance of good automation-human interface design so as to gain maximum benefit from the use of an automated decision support systems.Boeing Corporatio

A Model-Based Measure to Assess Operator Adherence to Procedures

Procedures play an important role in domains where humans interact with critical, complex systems. In such environments, the operator’s ability to correctly follow a given set of procedures can directly impact system safety. A quantitative measure of procedural adherence during training for complex system operation would be useful to assess trainee performance and evaluate a training program. This paper presents a novel model-based objective metric for quantifying procedural adherence in training. This metric is sensitive to both the number and nature of procedural deviations, and can be used with cluster analysis to classify trainee performance based on adherence. The metric was tested on an experimental data set gathered from volunteers using aircraft maintenance computer-based training (CBT). The properties of the metric are discussed, along with future possibilities

Melanoma tumour vasculature heterogeneity: from mice models to human

Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3.106 SK-Mel-28 melanoma cells in C57BL/6 and nude mice, respectively. Tumour growth was evaluated weekly, while vasculature was analysed through fluorescent labelling via CD31 and desmin. Significant differences in tumour growth and mice survival were evidenced between the two melanoma models. A fast evolution of tumours was observed for B16F10 melanoma, reaching a tumour size of 100 mm3 in 7 days compared to SK-Mel-28 which needed 21 days to reach the same volumes. Important differences in vascularization were exposed between the melanoma models, characterized by a significant enhancement of vascular density and a significant lumen size for mice melanoma models compared to human. Immunostaining revealed irregularities in endothelium structure for both melanoma models, but structural differences of vasculature were observed, characterized by a stronger expression of desmin in SK-Mel-28 tumours. While human melanoma mainly develops capillaries, structural irregularities are also observed on the samples of this tumour model. Our study revealed an impact of cell type and tumour progression on the structural vasculature of melanoma, which could impact the distribution of drugs in the tumour environment

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

The malignant phenotype in breast cancer is driven by eIF4A1-mediated changes in the translational landscape

Human mRNA DeXD/H-box helicases are ubiquitous molecular motors that are required for the majority of cellular processes that involve RNA metabolism. One of the most abundant is eIF4A, which is required during the initiation phase of protein synthesis to unwind regions of highly structured mRNA that would otherwise impede the scanning ribosome. Dysregulation of protein synthesis is associated with tumorigenesis, but little is known about the detailed relationships between RNA helicase function and the malignant phenotype in solid malignancies. Therefore, immunohistochemical analysis was performed on over 3000 breast tumors to investigate the relationship among expression of eIF4A1, the helicase-modulating proteins eIF4B, eIF4E and PDCD4, and clinical outcome. We found eIF4A1, eIF4B and eIF4E to be independent predictors of poor outcome in ER-negative disease, while in contrast, the eIF4A1 inhibitor PDCD4 was related to improved outcome in ER-positive breast cancer. Consistent with these data, modulation of eIF4A1, eIF4B and PCDC4 expression in cultured MCF7 cells all restricted breast cancer cell growth and cycling. The eIF4A1-dependent translatome of MCF7 cells was defined by polysome profiling, and was shown to be highly enriched for several classes of oncogenic genes, including G-protein constituents, cyclins and protein kinases, and for mRNAs with G/C-rich 5′UTRs with potential to form G-quadruplexes and with 3′UTRs containing microRNA target sites. Overall, our data show that dysregulation of mRNA unwinding contributes to the malignant phenotype in breast cancer via preferential translation of a class of genes involved in pro-oncogenic signaling at numerous levels. Furthermore, immunohistochemical tests are promising biomarkers for tumors sensitive to anti-helicase therapies

Electrochemical methods for speciation of trace elements in marine waters. Dynamic aspects

The contribution of electrochemical methods to the knowledge of dynamic speciation of toxic trace elements in marine waters is critically reviewed. Due to the importance of dynamic considerations in the interpretation of the electrochemical signal, the principles and recent developments of kinetic features in the interconversion of metal complex species will be presented. As dynamic electrochemical methods, only stripping techniques (anodic stripping voltammetry and stripping chronopotentiometry) will be used because they are the most important for the determination of trace elements. Competitive ligand ex- change-adsorptive cathodic stripping voltammetry, which should be considered an equilibrium technique rather than a dynamic method, will be also discussed because the complexing parameters may be affected by some kinetic limitations if equilibrium before analysis is not attained and/or the flux of the adsorbed complex is in fluenced by the lability of the natural complexes in the water sample. For a correct data interpretation and system characterization the comparison of results obtained from different techniques seems essential in the articulation of a serious discussion of their meaning

Total Factor Productivity and the Role of Entrepreneurship

Total factor productivity of twenty OECD countries for a recent period (1971-2002) is explained using six different models based on the established literature. Traditionally, entrepreneurship is not dealt with in these models. In the present paper it is shown that – when this variable is added - in all models there is a significant influence of entrepreneurship while the remaining effects mainly stay the same. Entrepreneurship is measured as the business ownership rate (number of business owners per workforce) corrected for the level of economic development (GDP per capita)