Model-Based Systems Engineering Approach to Distributed and Hybrid Simulation Systems

INCOSE defines Model-Based Systems Engineering (MBSE) as the formalized application of modeling to support system requirements, design, analysis, verification, and validation activities beginning in the conceptual design phase and continuing throughout development and later life cycle phases. One very important development is the utilization of MBSE to develop distributed and hybrid (discrete-continuous) simulation modeling systems. MBSE can help to describe the systems to be modeled and help make the right decisions and partitions to tame complexity. The ability to embrace conceptual modeling and interoperability techniques during systems specification and design presents a great advantage in distributed and hybrid simulation systems development efforts. Our research is aimed at the definition of a methodological framework that uses MBSE languages, methods and tools for the development of these simulation systems. A model-based composition approach is defined at the initial steps to identify distributed systems interoperability requirements and hybrid simulation systems characteristics. Guidelines are developed to adopt simulation interoperability standards and conceptual modeling techniques using MBSE methods and tools. Domain specific system complexity and behavior can be captured with model-based approaches during the system architecture and functional design requirements definition. MBSE can allow simulation engineers to formally model different aspects of a problem ranging from architectures to corresponding behavioral analysis, to functional decompositions and user requirements (Jobe, 2008)

Effect of Preexisting Neutralizing Antibodies on the Anti-tumor Immune Response Induced by Chimeric Human Papillomavirus Virus-like Particle Vaccines

AbstractChimeric human papillomavirus virus-like particles (HPV cVLPs) carrying HPV16 E7 protein are potent vaccines for inducing cell-mediated immunity (CMI) against HPV-induced tumors in animal models. We tested the hypothesis that virion-neutralizing antibodies generated during an initial vaccination might prevent effective boosting of CMI to the cVLPs. Mice with circulating HPV16-neutralizing antibodies, generated by direct immunization with wild-type VLPs or by passive transfer of hyperimmune anti-HPV16 VLP mouse sera, were subsequently vaccinated with HPV16 E7-containing cVLPs. Mice with preexisting neutralizing antibodies were not protected from HPV16 E7-positive TC-1 tumor challenge, compared to the protection seen in mice lacking these antibodies. Antibody-coated VLPs bound very inefficiently to receptor-positive cell lines, suggesting that one of the mechanisms of antibody interference is blocking of VLP binding to its receptor and thereby uptake of VLPs by antigen-presenting cells. Our results suggest that repetitive vaccination with a cVLP for induction of cellular immune responses to an incorporated antigen may be of limited effectiveness due to the presence of neutralizing antibodies against the capsid proteins induced after the first application. This limitation could potentially be overcome by boosting with cVLPs containing the same target antigen incorporated into other papillomavirus-type VLPs

Generation of three-dimensional multiple spheroid model of olfactory ensheathing cells using floating liquid marbles

We describe a novel protocol for three-dimensional culturing of olfactory ensheathing cells (OECs), which can be used to understand how OECs interact with other cells in three dimensions. Transplantation of OECs is being trialled for repair of the paralysed spinal cord, with promising but variable results and thus the therapy needs improving. To date, studies of OEC behaviour in a multicellular environment have been hampered by the lack of suitable three-dimensional cell culture models. Here, we exploit the floating liquid marble, a liquid droplet coated with hydrophobic powder and placed on a liquid bath. The presence of the liquid bath increases the humidity and minimises the effect of evaporation. Floating liquid marbles allow the OECs to freely associate and interact to produce OEC spheroids with uniform shapes and sizes. In contrast, a sessile liquid marble on a solid surface suffers from evaporation and the cells aggregate with irregular shapes. We used floating liquid marbles to co-culture OECs with Schwann cells and astrocytes which formed natural structures without the confines of gels or bounding layers. This protocol can be used to determine how OECs and other cell types associate and interact while forming complex cell structuresJSJ was funded by a grant from the Perry Cross Spinal Research Foundation; NTN was funded from Griffith University through a start-up grant and a grant from the Griffith University Research Infrastructure Program; JAK was funded by an Australian Research Council Discovery Grant DP150104495; JT was funded by an Eskitis Institute scholarship; CO was funded by a Griffith Sciences scholarship; RV was funded by a Griffith University International Postgraduate Research Scholarshi

PÍLDORAS INFORMATIVAS COMO HERRAMIENTAS DE FORMACIÓN DOCENTE EN LA LICENCIATURA INFORMÁTICA Y MEDIOS AUDIOVISUALES

The purpose of this article is to establish the importance of training pills as teaching support tools in the bachelor’s degree program in Computer Science and Audiovisual Media at the University of Cordoba from the first semester. The type of research is descriptive since it is intended to establish how the resources of the formative pills are a good formative resource, which have a great educational trend and can be used in virtual learning environments, becoming an excellent support for students and will serve as reference material, bearing in mind that the current globalization of education allows them to develop pedagogical and technological skills as instructional designers. During this period, activities will be developed through educational pills and a series of follow-up reports will be made by the proponents of this project. The purpose of the report is to evaluate compliance by the proponents of this initiative to follow up on the activities established in the work plan as an element of vital importance for professional and educational competence. El presente artículo tiene como objetivo establecer la importancia de las píldoras informativas como herramientas de apoyo docente en el programa de Licenciatura en Informática y Medios Audiovisuales en la Universidad de Córdoba desde el primer semestre. El tipo investigación es descriptiva dado que se pretende establecer cómo los recursos de las píldoras informativas son un buen recurso formativo, las cuales contienen elementos de educación contemporánea presentados a través de entornos virtuales de aprendizaje. Así, se evidencia en los resultados el acompañamiento a estudiantes con material educativo actualizado que atiende la actual globalización de la educación. Del mismo modo, las píldoras permiten a los participantes desarrollar habilidades pedagógicas y tecnológicas como diseños instruccionales. Como conclusiones, es posible derivar en que esta propuesta de formación desarrolla actividades físicas y digitales mediante píldoras informativas que dan seguimiento a cada una de las categorías conceptuales del proyecto investigativo. Asociadas con, el plan de trabajo como elemento de vital importancia para la competencia profesional y educativa

Cross-neutralization of cutaneous and mucosal Papillomavirus types with anti-sera to the amino terminus of L2

AbstractVaccination with papillomavirus L2 has been shown to induce neutralizing antibodies that protect against homologous type infection and cross-neutralize a limited number of genital HPVs. Surprisingly, we found that antibodies to bovine papillomavirus (BPV1) L2 amino acids 1–88 induced similar titers of neutralizing antibodies against Human papillomavirus (HPV)16 and 18 and BPV1 pseudoviruses and also neutralized HPV11 native virions. These antibodies also neutralized each of the other pseudovirus types tested, HPV31, HPV6 and Cottontail rabbit papillomavirus (CRPV) pseudoviruses, albeit with lower titers. HPV16, HPV18, HPV31, HPV6 and CRPV L2 anti-sera also displayed some cross-neutralization, but the titers were lower and did not encompass all pseudoviruses tested. This study demonstrates the presence of broadly cross-neutralizing epitopes at the N-terminus of L2 that are shared by cutaneous and mucosal types and by types that infect divergent species. BPV1 L2 was exceptionally effective at inducing cross-neutralizing antibodies to these shared epitopes

Modelo prolab: Total Diabetes, una propuesta para mejorar la salud de diabéticos

La diabetes es una enfermedad que afecta la calidad de vida de las personas que la padecen, ya que una vez detectada no tiene cura, lamentablemente en el Perú muchas personas empeoran y fallecen por un inadecuado control de la enfermedad. Luego de realizar un análisis de mercado, se pudo distinguir las necesidades de los pacientes diabéticos, y validar que a nivel nacional no existen negocios de aplicaciones móviles en el cuidado de la salud, con ello se identificó la oportunidad de negocio, Total Diabetes, el cual es un modelo de negocio de aplicación virtual y página web que ofrece el desarrollo de una comunidad que da soporte a las personas que padecen la enfermedad, ya que no sólo ayuda a controlar el nivel de azúcar en la sangre, sino a fomentar hábitos y costumbres que ayuden a mejorar su estilo de vida. Con ello se pretende lograr mejorar los aspectos más relevantes tales como nutrición, concientización, accesibilidad a la atención, entre otros. En la etapa de evaluación de la deseabilidad se hicieron encuestas, las cuales validaron las hipótesis de calidad percibida, precio, frecuencia de compra y usabilidad. Asimismo, para evaluar la factibilidad se realizó un plan de mercadeo y simulaciones que permitieron validar el análisis financiero en diferentes escenarios, de los cuales lo más relevante es que el VAN Financiero es S/ 2’214,021.46, una TIR Financiera de 76.67% y el IR de 4.7. Finalmente, en relación a la rentabilidad social del proyecto, luego de realizar una proyección social financiera, se obtuvo un VAN social de S/ 8,601506.99, con lo cual se demuestra que Total Diabetes es una propuesta que genera valor a la sociedad. Lo cual está alineado de manera positiva con el ODS 3: Salud y bienestar, que espera impactar de manera positiva en la calidad de vida de los pacientes.Diabetes is a disease that affects the quality of life of people who suffer from it, since once detected there is no cure, unfortunately in Peru many people worsen and die due to inadequate control of the disease. After carrying out a market analysis, it was possible to distinguish the needs of diabetic patients, and validate that at the national level there are no mobile application businesses in health care, thereby identifying the business opportunity, Total Diabetes, which It is a virtual application and web page business model that offers the development of a community that supports people who suffer from the disease, since it not only helps to control the level of sugar in the blood, but also to promote habits and customs that help improve your lifestyle. This is intended to improve the most relevant aspects such as nutrition, awareness, accessibility to care, among others. In the desirability evaluation stage, surveys were carried out, which validated the hypotheses of perceived quality, price, purchase frequency, and usability. Likewise, to evaluate the feasibility, a marketing plan and simulations were carried out that allowed validating the financial analysis in different scenarios, of which the most relevant is that the Financial NPV is S/ 2'214,021.46, a Financial IRR of 76.67% and the IR of 4.7. Finally, in relation to the social profitability of the project, after carrying out a financial social projection, a social NPV of S/ 8,601506.99 was obtained, which demonstrates that Total Diabetes is a proposal that generates value for society. This is positively aligned with SDG 3: Health and well-being, which is expected to have a positive impact on the quality of life of patients

Noninvasive optical and nuclear imaging of Staphylococcus-specific infection with a human monoclonal antibody-based probe

Staphylococcus aureus infections are a major threat in healthcare, requiring adequate early-stage diagnosis and treatment. This calls for novel diagnostic tools that allow noninvasive in vivo detection of staphylococci. Here we performed a preclinical study to investigate a novel fully-human monoclonal antibody 1D9 that specifically targets the immunodominant staphylococcal antigen A (IsaA). We show that 1D9 binds invariantly to S. aureus cells and may further target other staphylococcal species. Importantly, using a human post-mortem implant model and an in vivo murine skin infection model, preclinical feasibility was demonstrated for 1D9 labeled with the near-infrared fluorophore IRDye800CW to be applied for direct optical imaging of in vivo S. aureus infections. Additionally, (89)Zirconium-labeled 1D9 could be used for positron emission tomography imaging of an in vivo S. aureus thigh infection model. Our findings pave the way towards clinical implementation of targeted imaging of staphylococcal infections using the human monoclonal antibod

Discovery of several thousand highly diverse circular DNA viruses.

Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere