Pilot interaction with automated airborne decision making systems

The current research is focused on detection of human error and protection from its consequences. A program for monitoring pilot error by comparing pilot actions to a script was described. It dealt primarily with routine errors (slips) that occurred during checklist activity. The model to which operator actions were compared was a script. Current research is an extension along these two dimensions. The ORS fault detection aid uses a sophisticated device model rather than a script. The newer initiative, the model-based and constraint-based warning system, uses an even more sophisticated device model and is to prevent all types of error, not just slips or bad decision

DEVELOPMENT OF A NON-INVASIVE RESPIRATORY ENERGY HARVESTER USING TRIBOELECTRIC EFFECT

The need to recharge and eventually replace batteries is increasingly significant for operating a variety of wearable electronic devices. Rapid advances in the functions of electronic devices have stimulated the requirements for portable and sustainable power sources, thus opening the possibility of using human biomechanical energy as a promising alternative power source. Respiration is a unique form of spontaneous and stable source of human biomechanical energy that is currently untapped, and has the potential to be converted to a sustainable power source for low power wearable electronic devices and integrated body sensor networks. However, effectively harvesting respiration energy characterized by low frequency and low force, is currently a technological challenge, and cannot be well-achieved by classical energy harvesting methods. In this work, a triboelectric nanogenerator (TENG) is demonstrated as a small and light-weight wearable respiratory energy harvester (wREH), capable of tracking rate and depth of respiration, and can be utilized as a self-powered respiratory motion sensor. Although TENGs have been demonstrated as a promising technology for mechanical energy harvesting, they have a high inherent impedance which poses a major challenge to their effective integration with electronic systems for practical applications. The high inherent impedance creates a huge mismatch when TENGs are directly integrated with energy storage devices that usually have low impedance, resulting in low energy conversion efficiency. This problem is generally treated by power management circuits which have a limited effect. In this work, a synchronous switching approach is developed, which has been shown to enhance the TENG output energy by over a factor of two and lower the optimum load resistance, from megaohms to ohms. Contact electrification in a TENG occurs only when two dissimilar triboelectric surfaces are contacted. However, there exists no theoretical relationship between contact force and triboelectric charge transfer in TENGs. Accordingly, a charge-force relationship is presented by combining the theories of contact electrification and contact mechanics, which successfully explains the tendency of charge transfer. Furthermore, a method to design simulation experiments to predict the TENG output within an order of magnitude using its structural parameters, is presented as an effective design tool

Adenovirus-mediated hPNPase(old-35) gene transfer as a therapeutic strategy for neuroblastoma

Current treatment options for neuroblastoma fail to eradicate the disease in the majority of high-risk patients, clearly mandating development of innovative therapeutic strategies. Gene therapy represents a promising approach for reversing the neoplastic phenotype or driving tumor cells to self-destruction. We presently studied the effects of adenovirus-mediated gene transfer of human polynucleotide phosphorylase (hPNPase(old-35)), a 3',5'-exoribonuclease with growth-inhibitory properties, in neuroblastoma cells. Transgene expression was driven by either the cytomegalovirus (CMV) promoter or by a tumor-selective promoter derived from progression elevated gene-3 (PEG-3). Our data demonstrate that efficient adenoviral transduction of neuroblastoma cells and robust transgene expression are feasible objectives, that the PEG-3 promoter is capable of selectively targeting gene expression in the majority of neuroblastoma cells, and that hPNPase(old-35) induces profound growth suppression and apoptosis of malignant neuroblastoma cells, while exerting limited effects on normal neural crest-derived melanocytes. These findings support future applications of hPNPase(old-35) for targeted gene-based therapy of neuroblastoma and suggest that combination with the PEG-3 promoter holds promise for creating a potent and selective neuroblastoma therapeutic

Knowledge and attitudes about antibiotics and antibiotic resistance of 2404 UK healthcare workers

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs’) knowledge, attitudes and behaviours towards antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented here. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1315 respondents. Results: In total, 2404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic-resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic-resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the previous week to responding to the survey due to a fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals

Synthesis and Interactions of 7-Deoxy-, 10-Deacetoxy, and 10-Deacetoxy-7-Deoxypaclitaxel with NCI/ADR-RES Cancer Cells and Bovine Brain Microvessel Endothelial Cells

Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.7-Deoxypaclitaxel, 10-deacetoxypaclitaxel and 10-deacetoxy-7-deoxypaclitaxel were prepared and evaluated for their ability to promote assembly of tubulin into microtubules, their cytotoxicity against NCI/ADR-RES cells and for their interactions with Pglycoprotein in bovine brain microvessel endothelial cells. The three compounds were essentially equivalent to paclitaxel in cytotoxicity against NCI/ADR-RES cells. They also appeared to interact with P-glycoprotein in the endothelial cells with the two 10-deacetoxy compounds having less interaction than paclitaxel and 7-deoxypaclitaxel. ©2000 Elsevier Science Ltd. All rights reserved

Paclitaxel Succinate Analogs: Anionic Introduction as a Strategy to Impart Blood Brain Barrier Permeability

A focused library of TX-67 (C10 hemi-succinate) analogs have been prepared including regioisomeric, functional group, and one-carbon homologs. These were prepared to investigate TX-67’s lack of interaction with P-glycoprotein (Pgp). Tubulin stabilization ability, cytotoxicity, and Pgp interactions were evaluated. All carboxylic acid analogs had no apparent interactions with Pgp whereas the ester variants of the same compounds displayed characteristics of Pgp substrates. Furthermore, it is demonstrated that hydrogen-bonding properties were significant with respect to Pgp interactions. This anionic introduction strategy may allow for delivery of paclitaxel into the CNS as well as establishing a new method for delivery of other, non-CNS permeable drugs

A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation

<p>Abstract</p> <p>Background</p> <p>Ribonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase.</p> <p>Methods</p> <p>Cytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.</p> <p>Results</p> <p>We show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G₂/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21^WAF1/CIP1together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP</p> <p>Conclusions</p> <p>We conclude that PE5 kills the cells through apoptosis associated with the p21^WAF1/CIP1induction and the inactivation of JNK. This mechanism is significantly different from that found for onconase.</p