142 research outputs found

    Trustworthy Wireless Personal Area Networks

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    In the Internet of Things (IoT), everyday objects are equipped with the ability to compute and communicate. These smart things have invaded the lives of everyday people, being constantly carried or worn on our bodies, and entering into our homes, our healthcare, and beyond. This has given rise to wireless networks of smart, connected, always-on, personal things that are constantly around us, and have unfettered access to our most personal data as well as all of the other devices that we own and encounter throughout our day. It should, therefore, come as no surprise that our personal devices and data are frequent targets of ever-present threats. Securing these devices and networks, however, is challenging. In this dissertation, we outline three critical problems in the context of Wireless Personal Area Networks (WPANs) and present our solutions to these problems. First, I present our Trusted I/O solution (BASTION-SGX) for protecting sensitive user data transferred between wirelessly connected (Bluetooth) devices. This work shows how in-transit data can be protected from privileged threats, such as a compromised OS, on commodity systems. I present insights into the Bluetooth architecture, Intel’s Software Guard Extensions (SGX), and how a Trusted I/O solution can be engineered on commodity devices equipped with SGX. Second, I present our work on AMULET and how we successfully built a wearable health hub that can run multiple health applications, provide strong security properties, and operate on a single charge for weeks or even months at a time. I present the design and evaluation of our highly efficient event-driven programming model, the design of our low-power operating system, and developer tools for profiling ultra-low-power applications at compile time. Third, I present a new approach (VIA) that helps devices at the center of WPANs (e.g., smartphones) to verify the authenticity of interactions with other devices. This work builds on past work in anomaly detection techniques and shows how these techniques can be applied to Bluetooth network traffic. Specifically, we show how to create normality models based on fine- and course-grained insights from network traffic, which can be used to verify the authenticity of future interactions

    A possible new syndrome with growth-hormone secreting pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familial testicular germ cell malignancy: A case report

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    BACKGROUND: Germ-cell testicular cancer has not been definitively linked to any known hereditary cancer susceptibility disorder. Familial testicular cancer in the presence of other findings in affected and unaffected family members might indicate a previously-unidentified hereditary cancer syndrome. CASE PRESENTATION: The patient was diagnosed with a left testicular seminoma at age 28, and treated with left orchiectomy followed by adjuvant cobalt radiation. His family history is significant for testicular seminoma in his son, bladder cancer in his sister, and lipomatosis in his father. His evaluation as part of an etiologic study of familial testicular cancer revealed multiple colon polyps (adenomatous, hyperplastic, and hamartomatous) first found in his 50 s, multiple lipomas, multiple hyperpigmented skin lesions, left kidney cancer diagnosed at age 64, and a growth-hormone producing pituitary adenoma with associated acromegaly diagnosed at age 64. The patient underwent genetic testing for Cowden syndrome (PTEN gene), Carney complex (PRKAR1A gene), and multiple endocrine neoplasia syndrome type 1 (MEN1 gene); no deleterious mutations were identified. DISCUSSION: The constellation of benign and malignant neoplasms in the context of this patient's familial testicular cancer raised the possibility that these might be manifestations of a known hereditary susceptibility cancer syndrome; however, genetic testing for the three syndromes that were most likely to explain these findings did not show any mutation. Alternatively, this family's phenotype might represent a novel neoplasm susceptibility disorder. This possibility cannot be evaluated definitively on the basis of a single case report; additional observations and studies are necessary to investigate this hypothesis further

    Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy

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    BACKGROUND: Malaria remains a serious health problem because resistance develops to all currently used drugs when their parasite targets mutate. Novel antimalarial drug targets are urgently needed to reduce global morbidity and mortality. Our prior results suggested that inhibiting erythrocyte G(s) signaling blocked invasion by the human malaria parasite Plasmodium falciparum. METHODS AND FINDINGS: We investigated the erythrocyte guanine nucleotide regulatory protein G(s) as a novel antimalarial target. Erythrocyte “ghosts” loaded with a G(s) peptide designed to block G(s) interaction with its receptors, were blocked in β-adrenergic agonist-induced signaling. This finding directly demonstrates that erythrocyte G(s) is functional and that propranolol, an antagonist of G protein–coupled β-adrenergic receptors, dampens G(s) activity in erythrocytes. We subsequently used the ghost system to directly link inhibition of host G(s) to parasite entry. In addition, we discovered that ghosts loaded with the peptide were inhibited in intracellular parasite maturation. Propranolol also inhibited blood-stage parasite growth, as did other β(2)-antagonists. β-blocker growth inhibition appeared to be due to delay in the terminal schizont stage. When used in combination with existing antimalarials in cell culture, propranolol reduced the 50% and 90% inhibitory concentrations for existing drugs against P. falciparum by 5- to 10-fold and was also effective in reducing drug dose in animal models of infection. CONCLUSIONS: Together these data establish that, in addition to invasion, erythrocyte G protein signaling is needed for intracellular parasite proliferation and thus may present a novel antimalarial target. The results provide proof of the concept that erythrocyte G(s) antagonism offers a novel strategy to fight infection and that it has potential to be used to develop combination therapies with existing antimalarials

    Ecosystem resilience despite large-scale altered hydroclimatic conditions

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    Climate change is predicted to increase both drought frequency and duration, and when coupled with substantial warming, will establish a new hydroclimatological model for many regions. Large-scale, warm droughts have recently occurred in North America, Africa, Europe, Amazonia and Australia, resulting in major effects on terrestrial ecosystems, carbon balance and food security. Here we compare the functional response of above-ground net primary production to contrasting hydroclimatic periods in the late twentieth century (1975-1998), and drier, warmer conditions in the early twenty-first century (2000-2009) in the Northern and Southern Hemispheres. We find a common ecosystem water-use efficiency (WUE e: Above-ground net primary production/ evapotranspiration) across biomes ranging from grassland to forest that indicates an intrinsic system sensitivity to water availability across rainfall regimes, regardless of hydroclimatic conditions. We found higher WUE e in drier years that increased significantly with drought to a maximum WUE e across all biomes; and a minimum native state in wetter years that was common across hydroclimatic periods. This indicates biome-scale resilience to the interannual variability associated with the early twenty-first century drought - that is, the capacity to tolerate low, annual precipitation and to respond to subsequent periods of favourable water balance. These findings provide a conceptual model of ecosystem properties at the decadal scale applicable to the widespread altered hydroclimatic conditions that are predicted for later this century. Understanding the hydroclimatic threshold that will break down ecosystem resilience and alter maximum WUE e may allow us to predict land-surface consequences as large regions become more arid, starting with water-limited, low-productivity grasslands. © 2013 Macmillan Publishers Limited. All rights reserved

    Ovarian cancer risk factors by tumor aggressiveness: an analysis from the Ovarian Cancer Cohort Consortium

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    Ovarian cancer risk factors differ by histotype; however, within subtype there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n=864), very aggressive (death in 1-<3 years, n=1,390), moderately aggressive (death in 3-<5 years, n=639), and less aggressive (lived 5+ years, n=1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet =0.01), family history of ovarian cancer (phet =0.02), body mass index (BMI; phet ≤0.04) and smoking (phet <0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20-<25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted

    Research-policy partnerships - experiences of the Mental Health and Poverty Project in Ghana, South Africa, Uganda and Zambia

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    Background: Partnerships are increasingly common in conducting research. However, there is little published evidence about processes in research-policy partnerships in different contexts. This paper contributes to filling this gap by analysing experiences of research-policy partnerships between Ministries of Health and research organisations for the implementation of the Mental Health and Poverty Project in Ghana, South Africa, Uganda and Zambia. Methods: A conceptual framework for understanding and assessing research-policy partnerships was developed and guided this study. The data collection methods for this qualitative study included semi-structured interviews with Ministry of Health Partners (MOHPs) and Research Partners (RPs) in each country. Results: The term partnership was perceived by the partners as a collaboration involving mutually-agreed goals and objectives. The principles of trust, openness, equality and mutual respect were identified as constituting the core of partnerships. The MOHPs and RPs had clearly defined roles, with the MOHPs largely providing political support and RPs leading the research agenda. Different influences affected partnerships. At the individual level, personal relationships and ability to compromise within partnerships were seen as important. At the organisational level, the main influences included the degree of formalisation of roles and responsibilities and the internal structures and procedures affecting decision-making. At the contextual level, political environment and the degree of health system decentralisation affected partnerships. Conclusions: Several lessons can be learned from these experiences. Taking account of influences on the partnership at individual, organisation and contextual/system levels can increase its effectiveness. A common understanding of mutually-agreed goals and objectives of the partnership is essential. It is important to give attention to the processes of initiating and maintaining partnerships, based on clear roles, responsibilities and commitment of parties at different levels. Although partnerships are often established for a specific purpose, such as carrying out a particular project, the effects of partnership go beyond a particular initiative

    TGF-β in tolerance, development and regulation of immunity

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    AbstractThe TGF-β superfamily is an ancient metazoan protein class which cuts across cell and tissue differentiation, developmental biology and immunology. Its many members are regulated at multiple levels from intricate control of gene transcription, post-translational processing and activation, and signaling through overlapping receptor structures and downstream intracellular messengers. We have been interested in TGF-β homologues firstly as key players in the induction of immunological tolerance, the topic so closely associated with Ray Owen. Secondly, our interests in how parasites may manipulate the immune system of their host has also brought us to study the TGF-β pathway in infections with longlived, essentially tolerogenic, helminth parasites. Finally, within the spectrum of mammalian TGF-β proteins is an exquisitely tightly-regulated gene, anti-Müllerian hormone (AMH), whose role in sex determination underpins the phenotype of freemartin calves that formed the focus of Ray’s seminal work on immunological tolerance

    Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

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    Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences

    Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review

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    The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG
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