2,350 research outputs found
Real-time crowd control of existing interfaces
Crowdsourcing has been shown to be an effective approach for solving difficult problems, but current crowdsourcing systems suffer two main limitations: (i) tasks must be repackaged for proper display to crowd workers, which generally requires substantial one-off programming effort and support infrastructure, and (ii) crowd workers generally lack a tight feedback loop with their task. In this paper, we introduce Legion, a system that allows end users to easily capture existing GUIs and outsource them for collaborative, real-time control by the crowd. We present mediation strategies for integrating the input of multiple crowd workers in real-time, evaluate these mediation strategies across several applications, and further validate Legion by exploring the space of novel applications that it enables
The Application of Reversible Intramolecular Sulfonamide Ligation to Modulate Reactivity in Organometallic Ruthenium(II) Diamine Complexes
Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5?-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner
Composition Operators and Endomorphisms
If is an inner function, then composition with induces an
endomorphism, , of that leaves
invariant. We investigate the structure of the
endomorphisms of and that implement
through the representations of and
in terms of multiplication operators on
and . Our analysis, which is based on work
of R. Rochberg and J. McDonald, will wind its way through the theory of
composition operators on spaces of analytic functions to recent work on Cuntz
families of isometries and Hilbert -modules
Disseminated Effects in Agent Based Models: A Potential Outcomes Framework and Application to Inform Pre-Exposure Prophylaxis Coverage Levels for HIV Prevention
Pre-exposure prophylaxis (PrEP) for HIV prevention may not only benefit the individual who uses it, but also their uninfected sexual risk contacts. We developed an agent-based model using a novel trial emulation approach to quantify disseminated effects of PrEP use among men who have sex with men in Atlanta, USA from 2015 to 2017. Components (subsets of agents connected through partnerships in a sexual network, but not sharing partnerships with any other agents) were first randomized to an intervention coverage level or control, then within intervention components, eligible agents were randomized to PrEP. We estimated direct and disseminated (indirect) effects using randomization-based estimators and reported corresponding 95% simulation intervals across scenarios ranging from 10% to 90% coverage in the intervention components. A population of 11,245 agents was simulated with an average of 1,551 components identified. Comparing agents randomized to PrEP in 70% coverage components to control agents, there was a 15% disseminated risk reduction in HIV incidence (95% simulation intervals = 0.65, 1.05). Individuals not on PrEP may receive a protective benefit by being in a sexual network with higher PrEP coverage. Agent-based models are useful to evaluate possible direct and disseminated effects of HIV prevention modalities in sexual networks
Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009.
BACKGROUND: In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing.
OBJECTIVE: To explain recent CHD trends in Tunisia between 1997 and 2009.
METHODS: DATA SOURCES: Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys.
ANALYSIS: Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity).
RESULTS: CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (-0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75).
CONCLUSIONS: Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and cholesterol, BMI and diabetes. Current prevention strategies are mainly focused on treatments but should become more comprehensive
Mapping similarities in mTOR pathway perturbations in mouse lupus nephritis models and human lupus nephritis
Correction: Mapping similarities in mTOR pathway perturbations in mouse lupus nephritis models and human lupus nephritis
Cognitive Information Processing
Contains research objectives.National Institutes of Health (Grant 5 POI GM14940-06)National Institutes of Health (Grant 1 P01 GM19428-01)National Science Foundation (Grant GK-33736X)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300Grant from the Associated PressPeter Bent Brigham Hospital Purchase Orders F64088Peter Bent Brigham Hospital Purchase Orders F6580
Secreted Phosphoprotein 24 kD (Spp24) and Spp14 Affect TGF-β Induced Bone Formation Differently
Transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-β1 and TGF-β2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-β with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-β2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-β2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-β administration in vivo is associated with greater bone formation than high-dose TGF-β administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-β activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-β compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders. © 2013 Tian et al
Evaluation of next generation sequencing platforms for population targeted sequencing studies
Human sequence generated from three next-generation sequencing platforms reveals systematic variability in sequence coverage due to local sequence characteristics
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