14 research outputs found

    The Binational English & Spanish Telecommunications Network

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    BESTNET was established in the early 1980\u27s, as an effort to link universities on both sides of the U.S.- Mexico border through microwave, satellite and cable television technologies. In the late 1980\u27s BESTNET focused primarily on the development of asynchronous computer mediated learning and teaching in an internationally networked virtual environment. For the past six years (1990\u27s) BESTNET has strengthened its binational ties and continued its high tech focus through the development of active or vibrant model technology which is assisting in the creation of an on-line binational university setting that is borderless (albeit, seamless to the user). Today, this type of design and linkage for curriculum, learning, teaching, research and performing collaborative scholarly work is called a global virtual university . The design center for BESTNET is the vibrant global model based on METIS software. While the binational (U.S.-Mexico) design of BESTNET continues to flourish, new technologies are being continually assimilated into this highly adaptive project. Specifically, as we are able to combine the interests of a multitude of globally located campuses. We are also working towards a virtual project for higher education. Our operating, developmental premise has always been to redefine faculty, staff and student roles towards this purpose. BESTNET was created with the assistance of the founder of ARPANET a direct precursor to the Internet (even before the Internet was popularized) as a scholar\u27s collaborative network, with the explicit charge of exploring alternative approaches to the structures, substance, and processes which have traditionally defined the scholarly work of institutions of higher education. We have continually demonstrated courage in tackling difficult, but essential, issues of technological renewal. We are committed to developing educational programs which are especially responsive to both regional and global needs, student-centered, interdisciplinary in scope, and technologically innovative in nature. The tremendous success of the BESTNET paradigm is that we are not only renewing, we are also brandnewing an ambitious global and virtual educational model that will yield improved educational outcomes (in both low- and high-tech) settings, within the financial resources of most academic institutions. We have especially developed positive outcomes in Africa, Latin America, the United States and Europe. Because we barter and share collectively our on line resources, we avoid the exchange of funds, academic credits and the multitude of bureaucracies that are associated with traditional institutional exchanges. In short, we create a virtual learning environment for the world evolving student to experience like never before. While other projects are undergoing transformation from the Industrial Age to the Information Age, BESTNET is successfully aligning to the global needs of the Cyber-Age, by design

    Creating A New University Through Object Oriented Enterprise Modeling: A Study of Communications Knowledge Management & Distributed Cognition

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    Enterprise based object oriented (OO) and Unified Modeling Language (UML) modeling makes it possible to build the needed visual environments to organize people, technologies and activities (Arias, 1999d). In our modeling approach, the focus is on things and relationships between things described in commonly used terms. The modeling software bridges the so-called semantic gap between the people and the computer language (Booch, Rumbaugh & Jacobson, 1999). An object can be a product, a process, a person, a team, a company, an application or the inter-relationship between other objects. Objects can be pictured on the screen as maps formed by personalized “icons” with their relationships. Once a “map” of objects has been produced, users can navigate and visualize very complex relationships. Objects can hold data, such as cost, schedule data, weight and other relevant information (Zack & Serino, 1996). Another important property of an Object is its ability to perform work scripted in “methods.” Thus an Object can be given the capability to perform functions, such as performing computations, gathering data from other computers, showing video of servicing a part or accessing a 3D-CAD drawing for viewing. This “active model” is much more than a map for navigation in an abstract process model (Arias, 1999a). It becomes the actual work environment for individuals and teams. It creates an occasioned environment for learning, assessing issues and impacts, communication, configuration management and control and more. In short, it is the user interface or “ control center” from where to manage the organization (whether it be an institution of higher education or a corporation). UML technology allows us to model a complex enterprise, while OO technology builds on the former and generates complex applications. The point at which these two technologies meet becomes the intersection that enables planners and stakeholders to develop a new paradigm for looking not only at their organization, but also at precisely what their contributions are to the overall enterprise (Arias, 1998). In this paper we will present the use and design of object oriented enterprise computer models (OO) for the purposes of creating and/or transforming organizations. We will also provide proof of concept on how OO contributes to the reshaping of relationships among people and their organizations and, also, how OO can transform the processes of discovery, learning, research and communication through emerging forms of distributed cognition (Arias & Bellman, 1995)

    Deletion Mutants of VPg Reveal New Cytopathology Determinants in a Picornavirus

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    BACKGROUND: Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes 3 copies of VPg. Why FMDV encodes three VPgs is unknown. METHODOLOGY AND PRINCIPAL FINDINGS: we have constructed four mutant FMDVS that encode only one VPG: either VPg(1), VPg(3), or two chimeric versions containing part of VPg(1) and VPg(3). All mutants, except that encoding only VPg(1), were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The effect of R55W in 2C was to mediate an increase in the extracellular viral RNA release without a detectable increase of total viral RNA that correlated with an enhanced capacity to alter and detach BHK-21 cells from the monolayer, the first stage of cell killing. CONCLUSIONS: The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. Implications for picornaviruses pathogenesis are discussed

    A Multi-Step Process of Viral Adaptation to a Mutagenic Nucleoside Analogue by Modulation of Transition Types Leads to Extinction-Escape

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    Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-ÎČ-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV) in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S) in the viral polymerase (3D). The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin —by avoiding the biased repertoire of transition mutations produced by this purine analogue—and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP), as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure

    Rab11 and Actin Cytoskeleton Participate in Giardia lamblia Encystation, Guiding the Specific Vesicles to the Cyst Wall

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    The encystation process is crucial for survival and transmission of Giardia lamblia to new hosts. During this process, vesicular trafficking and the cytoskeleton play important roles. In eukaryotic cells, intracellular transport is regulated by proteins, including Rab-GTPases and SNAREs, which regulate vesicle formation along with recognition of and binding to the target membrane. Cytoskeletal structures are also involved in these processes. In this study, we demonstrate the participation of Rab11 in the transport of encystation-specific vesicles (ESVs). Additionally, we demonstrate that disruption of actin microfilaments affects ESVs transport. The modification of actin dynamics was also correlated with a reduction in rab11 and cwp1 expression. Furthermore, down-regulation of rab11 mRNA by a specific hammerhead ribozyme caused nonspecific localization of CWP1. We thus provide new information about the molecular machinery that regulates Giardia lamblia encystation. Given our findings, Rab11 and actin may be useful targets to block Giardia encystation

    Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

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    Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

    Virus genomes reveal factors that spread and sustained the Ebola epidemic.

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    The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics

    COVID-19-related mortality in kidney transplant and dialysis patients: Results of the ERACODA collaboration

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    Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 6 13 and 67 6 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3\u201330.2%] in kidney transplant and 25.0% (95% CI 20.2\u201330.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59\u20131.10, P \ubc 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n \ubc 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation &lt;1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07\u20130.56, P &lt; 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients
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