2,997 research outputs found
Analysis of Dialogical Argumentation via Finite State Machines
Dialogical argumentation is an important cognitive activity by which agents
exchange arguments and counterarguments as part of some process such as
discussion, debate, persuasion and negotiation. Whilst numerous formal systems
have been proposed, there is a lack of frameworks for implementing and
evaluating these proposals. First-order executable logic has been proposed as a
general framework for specifying and analysing dialogical argumentation. In
this paper, we investigate how we can implement systems for dialogical
argumentation using propositional executable logic. Our approach is to present
and evaluate an algorithm that generates a finite state machine that reflects a
propositional executable logic specification for a dialogical argumentation
together with an initial state. We also consider how the finite state machines
can be analysed, with the minimax strategy being used as an illustration of the
kinds of empirical analysis that can be undertaken.Comment: 10 page
Gravitational wave astronomy
The first decade of the new millenium should see the first direct detections
of gravitational waves. This will be a milestone for fundamental physics and it
will open the new observational science of gravitational wave astronomy. But
gravitational waves already play an important role in the modeling of
astrophysical systems. I review here the present state of gravitational
radiation theory in relativity and astrophysics, and I then look at the
development of detector sensitivity over the next decade, both on the ground
(such as LIGO) and in space (LISA). I review the sources of gravitational waves
that are likely to play an important role in observations by first- and
second-generation interferometers, including the astrophysical information that
will come from these observations. The review covers some 10 decades of
gravitational wave frequency, from the high-frequency normal modes of neutron
stars down to the lowest frequencies observable from space. The discussion of
sources includes recent developments regarding binary black holes, spinning
neutron stars, and the stochastic background.Comment: 29 pages, 2 figures, as submitted for special millenium issue of
Classical and Quantum Gravit
An oxanthroquinone derivative that disrupts RAS plasma membrane localization inhibits cancer cell growth
Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examine the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalizes HRAS and KRAS from the PM with similar potency and disrupts the spatial organization of RAS proteins remaining on the PM. G01 also inhibited recycling of epidermal growth factor receptor and transferrin receptor, but did not impair internalization of cholera toxin, indicating suppression of recycling endosome function. In searching for the mechanism of impaired endosomal recycling we observed that G01 also enhanced cellular sphingomyelin (SM) and ceramide levels and disrupted the localization of several lipid and cholesterol reporters, suggesting that the G01 molecular target may involve SM metabolism. Indeed, G01 exhibited potent synergy with other compounds that target SM metabolism in KRAS localization assays. Furthermore, G01 significantly abrogated RAS-RAF-MAPK signaling in MDCK cells expressing constitutively activated, oncogenic mutant RASG12V. G01 also inhibited the proliferation of RAS-less mouse embryo fibroblasts (MEFs) expressing oncogenic mutant KRASG12V or KRASG12D but not RAS-less MEFs expressing oncogenic mutant BRAFV600E. Consistent with these effects, G01 selectively inhibited the proliferation of KRAS-transformed pancreatic, colon, and endometrial cancer cells. Taken together, these results suggest that G01 should undergo further evaluation as a potential anti-RAS therapeutic
Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus
Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response
Precision Measurement of KS Meson Lifetime with the KLOE detector
Using a large sample of pure, slow, short lived K0 mesons collected with KLOE
detector at DaFne, we have measured the KS lifetime. From a fit to the proper
time distribution we find tau = (89.562 +- 0.029_stat +- 0.043_syst) ps. This
is the most precise measurement today in good agreement with the world average
derived from previous measurements. We observe no dependence of the lifetime on
the direction of the Ks.Comment: 5 pages, 7 figure
The history, geography, and sociology of slums and the health problems of people who live in slums
Massive slums have become major features of cities in many low-income and middle-income countries. Here, in the first in a Series of two papers, we discuss why slums are unhealthy places with especially high risks of infection and injury. We show that children are especially vulnerable, and that the combination of malnutrition and recurrent diarrhoea leads to stunted growth and longer-term effects on cognitive development. We find that the scientific literature on slum health is underdeveloped in comparison to urban health, and poverty and health. This shortcoming is important because health is affected by factors arising from the shared physical and social environment, which have effects beyond those of poverty alone. In the second paper we will consider what can be done to improve health and make recommendations for the development of slum health as a field of study
A Study of the Radiative Ke3 Decay and Search for Direct Photon Emission with the KLOE Detector
We present a measurement of the ratio R =
\Gamma(\keg;\Estar>30\mev,\qstar>20^\circ)\Gamma(\kegf) of data corresponding to about 3.5
million Ke3(g) events and about 9000 radiative events. Our result is R=(924 +/-
23(stat) +/-16(syst)10^{-5} for the branching ratio and X=-2.3 +/- 1.3(stat)
+/- 1.4(syst) for the parameter describing direct emission.Comment: 8 pages, 7 figure
Improving the health and welfare of people who live in slums
Summary
In the first paper in this Series we assessed theoretical and empirical evidence and concluded that the health of people living in slums is a function not only of poverty but of intimately shared physical and social environments. In this paper we extend the theory of so-called neighbourhood effects. Slums offer high returns on investment because beneficial effects are shared across many people in densely populated neighbourhoods. Neighbourhood effects also help explain how and why the benefits of interventions vary between slum and non-slum spaces and between slums. We build on this spatial concept of slums to argue that, in all low-income and-middle-income countries, census tracts should henceforth be designated slum or non-slum both to inform local policy and as the basis for research surveys that build on censuses. We argue that slum health should be promoted as a topic of enquiry alongside poverty and health
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