Reduced-order models for microelectromechanical rectangular and circular plates incorporating the Casimir force

AbstractWe consider the von Kármán nonlinearity and the Casimir force to develop reduced-order models for prestressed clamped rectangular and circular electrostatically actuated microplates. Reduced-order models are derived by taking flexural vibration mode shapes as basis functions for the transverse displacement. The in-plane displacement vector is decomposed as the sum of displacements for irrotational and isochoric waves in a two-dimensional medium. Each of these two displacement vector fields satisfies an eigenvalue problem analogous to that of transverse vibrations of a linear elastic membrane. Basis functions for the transverse and the in-plane displacements are related by using the nonlinear equation governing the plate in-plane motion. The reduced-order model is derived from the equation yielding the transverse deflection of a point. For static deformations of a plate, the pull-in parameters are found by using the displacement iteration pull-in extraction method. Reduced-order models are also used to study linear vibrations about a predeformed configuration. It is found that 9 basis functions for a rectangular plate give a converged solution, while 3 basis functions give pull-in parameters with an error of at most 4%. For a circular plate, 3 basis functions give a converged solution while the pull-in parameters computed with 2 basis functions have an error of at most 3%. The value of the Casimir force at the onset of pull-in instability is used to compute device size that can be safely fabricated

Medial Features for Superpixel Segmentation

Image segmentation plays an important role in computer vision and human scene perception. Image oversegmentation is a common technique to overcome the problem of managing the high number of pixels and the reasoning among them. Specifically, a local and coherent cluster that contains a statistically homogeneous region is denoted as a superpixel. In this paper we propose a novel algorithm that segments an image into superpixels employing a new kind of shape centered feature which serve as a seed points for image segmentation, based on Gradient Vector Flow fields (GVF) [14]. The features are located at image locations with salient symmetry. We compare our algorithm to state-of-the-art superpixel algorithms and demonstrate a performance increase on the standard Berkeley Segmentation Dataset

A synthetic derivative of antimicrobial peptide holothuroidin 2 from mediterranean sea cucumber (Holothuria tubulosa) in the control of Listeria monocytogenes

Due to the limited number of available antibiotics, antimicrobial peptides (AMPs) are considered antimicrobial candidates to fight difficult-to-treat infections such as those associated with biofilms. Marine environments are precious sources of AMPs, as shown by the recent discovery of antibiofilm properties of Holothuroidin 2 (H2), an AMP produced by the Mediterranean sea cucumber Holothuria tubulosa. In this study, we considered the properties of a new H2 derivative, named H2d, and we tested it against seven strains of the dangerous foodborne pathogen Listeria monocytogenes. This peptide was more active than H2 in inhibiting the growth of planktonic L. monocytogenes and was able to interfere with biofilm formation at sub-minimum inhibitory concentrations (MICs). Atomic-level molecular dynamics (MD) simulations revealed insights related to the enhanced inhibitory activity of H2d, showing that the peptide is characterized by a more defined tertiary structure with respect to its ancestor. This allows the peptide to better exhibit an amphipathic character, which is an essential requirement for the interaction with cell membranes, similarly to other AMPs. Altogether, these results support the potential use of our synthetic peptide, H2d, as a template for the development of novel AMP-based drugs able to fight foodborne that are resistant to conventional antibiotics

A qualitative study of stakeholders' perspectives on the social network service environment

Over two billion people are using the Internet at present, assisted by the mediating activities of software agents which deal with the diversity and complexity of information. There are, however, ethical issues due to the monitoring-and-surveillance, data mining and autonomous nature of software agents. Considering the context, this study aims to comprehend stakeholders' perspectives on the social network service environment in order to identify the main considerations for the design of software agents in social network services in the near future. Twenty-one stakeholders, belonging to three key stakeholder groups, were recruited using a purposive sampling strategy for unstandardised semi-structured e-mail interviews. The interview data were analysed using a qualitative content analysis method. It was possible to identify three main considerations for the design of software agents in social network services, which were classified into the following categories: comprehensive understanding of users' perception of privacy, user type recognition algorithms for software agent development and existing software agents enhancement

Imperative ethical behaviours in making systems development and deployment compliant with health & safety and well-being

Literature on systems development has been progressively identifying the importance of social aspects in systems development, to the extent that this process has been considered a socio-technical system. More often than not there is a failure of participants in the recognition, and fulfilment, of ethical duties concerning the concepts of health and safety and wellbeing. The purpose of normative ethics is to scrutinise moral standards for the rightness and wrongness of actions, the ultimate goal being the identification of the true human good. A rational appeal can be made to normative defensible ethical rules in order to arrive at a judicious, morally justifiable judgement. In this paper our first step is to report on the findings of a literature review, which presents the current health and safety issues concerning usage of computers in organisations and the workplace. Secondly, we identify and list some basic generic Deontological and Teleological moral principles and theories that can serve as normative guidelines for addressing the issues pinpointed in the initial step. Thirdly, we prescribe a set of moral rights and duties that must be exercised and fulfilled by protagonists in systems development and software engineering in order for them to exhibit moral behaviour. Each of these suggested actions are substantiated via an appeal to one, or a number of the normative guidelines, identified in the second step. By identifying, and recommending a set of defensible moral obligations that must be fulfilled in the development and deployment of systems, protagonists such as: project managers, software engineering teams, systems analysts, clients, etc. can fulfil their ethical duties, thus increasing the likelihood a deployed system that is compliant with principles of health and safety and wellbeing of its users. Ultimately systems development and deployment must be underpinned with ethical consideration

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies

Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study

Background: Erythropoiesis-stimulating agents (ESAs) are biological molecules approved for the treatment of anemia associated with chronic renal failure. Biosimilars were licensed for use in Europe in 2007. Aim: This study aimed to compare the safety profile of biosimilars with respect to the reference product in a nephrology setting. Methods: A prospective study was conducted in four Italian regions between 1 October 2013 and 30 June 2015. The study population included patients aged 65 18 years undergoing hemodialysis and treated with epoetins as per the clinical practice of the participating centers. The two comparison cohorts included patients treated with either an originator or a biosimilar epoetin alfa. Each patient was followed up until occurrence of any safety outcome of interest (grouped into three major categories), switch to a different ESA product, transplant or peritoneal dialysis, death, or end of the study period, whichever came first. Results: Overall, 867 subjects were included in the study (originator: N = 423; biosimilar: N = 444). Biosimilar users were older than originator users (median age of 76 vs 64 years, respectively), more frequently affected by arrhythmia (29.3 vs 22.5%), and less frequently candidates for transplantation (3.8 vs 18.2%). Cox-regression analysis showed no increase in risk of safety outcomes in biosimilar users, even after adjusting for confounding factors: 1.0 (95% confidence interval [CI] 0.7\u20131.3) for any outcomes; 1.1 (95% CI 0.7\u20131.8) for problems related to dialysis device; 0.9 (95% CI 0.6\u20131.5) for cardio- and cerebro-vascular conditions; 0.9 (95% CI 0.6\u20131.5) for infections. Conclusion: This study confirms the comparable safety profiles of originator and biosimilar epoetin alfa drugs when used in patients receiving dialysis