3,711 research outputs found

    White paper: A plan for cooperation between NASA and DARPA to establish a center for advanced architectures

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    Large, complex computer systems require many years of development. It is recognized that large scale systems are unlikely to be delivered in useful condition unless users are intimately involved throughout the design process. A mechanism is described that will involve users in the design of advanced computing systems and will accelerate the insertion of new systems into scientific research. This mechanism is embodied in a facility called the Center for Advanced Architectures (CAA). CAA would be a division of RIACS (Research Institute for Advanced Computer Science) and would receive its technical direction from a Scientific Advisory Board established by RIACS. The CAA described here is a possible implementation of a center envisaged in a proposed cooperation between NASA and DARPA

    Serious fungal infections in the Philippines

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    The Philippines is a low middle-income, tropical country in Southeast Asia. Infectious diseases remain the main causes of morbidity, including tuberculosis. AIDS/HIV prevalence is still low at <1%, but is rapidly increasing. Fungal disease surveillance has not been done, and its burden has never been estimated. This becomes more important as the population of immunocompromised patients increases, drawn from patients with AIDS, TB, malignancies, autoimmune diseases requiring chronic steroid use.MethodsUsing the methodology of the LIFE program (www.LIFE-worldwide.org), estimates were derived from data gathered from WHO, UNAIDS, Philippine Health Statistics 2011, Philippine Dermatological Society Health Information System database, HIV/AIDS and ART registry of the Philippines, epidemiological studies like The TREAT Asia HIV Observational Database 2005, and personal communication.ResultsAspergillosis and candidiasis were the top causes of fungal infections in the Philippines. Chronic pulmonary aspergillosis (CPA), drawn from the number of tuberculosis patients, affects 77,172 people. Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) frequencies, which were derived from the number of asthmatic patients, affect 121,113 and 159,869 respectively. Recurrent candidal vaginitis, (>/= 4 acute episodes annually) affects 1,481,899 women. Other estimates were cryptococcal meningitis 84, Pneumocystis pneumonia 391, oral candidiasis 3,467, esophageal candidiasis 1,522 (all in HIV-infected people), invasive aspergillosis 3,085, candidemia 1,968, candida peritonitis 246, mucormycosis 20, fungal keratitis 358, tinea capitis 846 and mycetoma 97 annually. ConclusionA total of 1,852,137 (1.9% of population) are afflicted with a serious fungal infection. Epidemiological studies are needed to validate these estimates, facilitating appropriate medical care of patients and proper prioritization of limited resources

    The PER model of abstract non-interference

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    Abstract. In this paper, we study the relationship between two models of secure information flow: the PER model (which uses equivalence relations) and the abstract non-interference model (which uses upper closure operators). We embed the lattice of equivalence relations into the lattice of closures, re-interpreting abstract non-interference over the lattice of equivalence relations. For narrow abstract non-interference, we show non-interference it is strictly less general. The relational presentation of abstract non-interference leads to a simplified construction of the most concrete harmless attacker. Moreover, the PER model of abstract noninterference allows us to derive unconstrained attacker models, which do not necessarily either observe all public information or ignore all private information. Finally, we show how abstract domain completeness can be used for enforcing the PER model of abstract non-interference

    Automated electrophysiological and pharmacological evaluation of human pluripotent stem cell-derived cardiomyocytes

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    Automated planar patch clamp systems are widely used in drug evaluation studies because of their ability to provide accurate, reliable, and reproducible data in a high-throughput manner. Typically, CHO and HEK tumorigenic cell lines overexpressing single ion channels are used since they can be harvested as high-density, homogenous, single-cell suspensions. While human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are physiologically more relevant, these cells are fragile, have complex culture requirements, are inherently heterogeneous, and are expensive to produce, which has restricted their use on automated patch clamp (APC) devices. Here, we used high efficiency differentiation protocols to produce cardiomyocytes from six different hPSC lines for analysis on the Patchliner (Nanion Technologies GmbH) APC platform. We developed a two-step cell preparation protocol that yielded cell catch rates and whole-cell breakthroughs of ∼80%, with ∼40% of these cells allowing electrical activity to be recorded. The protocol permitted formation of long-lasting (>15 min), high quality seals (>2 GΩ) in both voltage- and current-clamp modes. This enabled density of sodium, calcium, and potassium currents to be evaluated, along with dose–response curves to their respective channel inhibitors, tetrodotoxin, nifedipine, and E-4031. Thus, we show the feasibility of using the Patchliner platform for automated evaluation of the electrophysiology and pharmacology of hPSC-CMs, which will enable considerable increase in throughput for reliable and efficient drug evaluation

    Prochlo: Strong Privacy for Analytics in the Crowd

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    The large-scale monitoring of computer users' software activities has become commonplace, e.g., for application telemetry, error reporting, or demographic profiling. This paper describes a principled systems architecture---Encode, Shuffle, Analyze (ESA)---for performing such monitoring with high utility while also protecting user privacy. The ESA design, and its Prochlo implementation, are informed by our practical experiences with an existing, large deployment of privacy-preserving software monitoring. (cont.; see the paper

    Development and validation of broad-spectrum magnetic particle labelling processes for cell therapy manufacturing

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    Background Stem cells are increasingly seen as a solution for many health challenges for an ageing population. However, their potential benefits in the clinic are currently curtailed by technical challenges such as high cell dose requirements and point of care delivery, which pose sourcing and logistics challenges. Cell manufacturing solutions are currently in development to address the supply issue, and ancillary technologies such as nanoparticle-based labelling are being developed to improve stem cell delivery and enable post-treatment follow-up. Methods The application of magnetic particle (MP) labelling to potentially scalable cell manufacturing processes was investigated in a range of therapeutically relevant cells, including mesenchymal stromal cells (MSC), cardiomyocytes (CMC) and neural progenitor cells (ReN). The efficiency and the biological effect of particle labelling were analysed using fluorescent imaging and cellular assays. Results Flow cytometry and fluorescent microscopy confirmed efficient labelling of monolayer cultures. Viability was shown to be retained post labelling for all three cell types. MSC and CMC demonstrated higher tolerance to MP doses up to 100× the standard concentration. This approach was also successful for MP labelling of suspension cultures, demonstrating efficient MP uptake within 3 h, while cell viability was unaffected by this suspension labelling process. Furthermore, a procedure to enable the storing of MP-labelled cell populations to facilitate cold chain transport to the site of clinical use was investigated. When MP-labelled cells were stored in hypothermic conditions using HypoThermosol solution for 24 h, cell viability and differentiation potential were retained post storage for ReN, MSC and beating CMC. Conclusions Our results show that a generic MP labelling strategy was successfully developed for a range of clinically relevant cell populations, in both monolayer and suspension cultures. MP-labelled cell populations were able to undergo transient low-temperature storage whilst maintaining functional capacity in vitro. These results suggest that this MP labelling approach can be integrated into cell manufacturing and cold chain transport processes required for future cell therapy approaches

    Serious fungal infections in Portugal

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    There is a lack of knowledge on the epidemiology of fungal infections worldwide because there are no reporting obligations. The aim of this study was to estimate the burden of fungal disease in Portugal as part of a global fungal burden project. Most published epidemiology papers reporting fungal infection rates from Portugal were identified. Where no data existed, specific populations at risk and fungal infection frequencies in those populations were used in order to estimate national incidence or prevalence, depending on the condition. An estimated 1,510,391 persons develop a skin or nail fungal infection each year. The second most common fungal infection in Portugal is recurrent vulvovaginal candidiasis, with an estimated 150,700 women (15-50 years of age) suffering from it every year. In human immunodeficiency virus (HIV)-infected people, oral or oesophageal candidiasis rates were estimated to be 19.5 and 16.8/100,000, respectively. Candidaemia affects 2.19/100,000 patients, in a total of 231 cases nationally. Invasive aspergillosis is less common than in other countries as chronic obstructive pulmonary disease (COPD) is uncommon in Portugal, a total of 240 cases annually. The estimated prevalence of chronic pulmonary aspergillosis after tuberculosis (TB) is 194 cases, whereas its prevalence for all underlying pulmonary conditions was 776 patients. Asthma is common (10% in adults) and we estimate 16,614 and 12,600 people with severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis, respectively. Sixty-five patients develop Pneumocystis pneumonia in acquired immune deficiency syndrome (AIDS) and 13 develop cryptococcosis. Overall, we estimate a total number of 1,695,514 fungal infections starting each year in Portugal.info:eu-repo/semantics/publishedVersio

    Security analysis of standard authentication and key agreement protocols utilising timestamps

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    We propose a generic modelling technique that can be used to extend existing frameworks for theoretical security analysis in order to capture the use of timestamps. We apply this technique to two of the most popular models adopted in literature (Bellare-Rogaway and Canetti-Krawczyk). We analyse previous results obtained using these models in light of the proposed extensions, and demonstrate their application to a new class of protocols. In the timed CK model we concentrate on modular design and analysis of protocols, and propose a more efficient timed authenticator relying on timestamps. The structure of this new authenticator implies that an authentication mechanism standardised in ISO-9798 is secure. Finally, we use our timed extension to the BR model to establish the security of an efficient ISO protocol for key transport and unilateral entity authentication

    Ensuring Secure Non-interference of Programs by Game Semantics

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    Non-interference is a security property which states that improper information leakages due to direct and indirect flows have not occurred through executing programs. In this paper we investigate a game semantics based formulation ofnon-interference that allows to perform a security analysis of closed and open procedural programs. We show that such formulation is amenable to automated verification techniques. The practicality of this method is illustrated by several examples, which also emphasize its advantage compared to known operational methods for reasoning about open programs.<br/
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