The M3 muscarinic receptor Is required for optimal adaptive immunity to Helminth and bacterial infection

Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection

Spontaneous Creation of Inflationary Universes and the Cosmic Landscape

We study some gravitational instanton solutions that offer a natural realization of the spontaneous creation of inflationary universes in the brane world context in string theory. Decoherence due to couplings of higher (perturbative) modes of the metric as well as matter fields modifies the Hartle-Hawking wavefunction for de Sitter space. Generalizing this new wavefunction to be used in string theory, we propose a principle in string theory that hopefully will lead us to the particular vacuum we live in, thus avoiding the anthropic principle. As an illustration of this idea, we give a phenomenological analysis of the probability of quantum tunneling to various stringy vacua. We find that the preferred tunneling is to an inflationary universe (like our early universe), not to a universe with a very small cosmological constant (i.e., like today's universe) and not to a 10-dimensional uncompactified de Sitter universe. Such preferred solutions are interesting as they offer a cosmological mechanism for the stabilization of extra dimensions during the inflationary epoch.Comment: 52 pages, 7 figures, 1 table. Added discussion on supercritical string vacua, added reference

The institutional shaping of management: in the tracks of English individualism

Globalisation raises important questions about the shaping of economic action by cultural factors. This article explores the formation of what is seen by some as a prime influence on the formation of British management: individualism. Drawing on a range of historical sources, it argues for a comparative approach. In this case, the primary comparison drawn is between England and Scotland. The contention is that there is a systemic approach to authority in Scotland that can be contrasted to a personal approach in England. An examination of the careers of a number of Scottish pioneers of management suggests the roots of this systemic approach in practices of church governance. Ultimately this systemic approach was to take a secondary role to the personal approach engendered by institutions like the universities of Oxford and Cambridge, but it found more success in the different institutional context of the USA. The complexities of dealing with historical evidence are stressed, as is the value of taking a comparative approach. In this case this indicates a need to take religious practice as seriously as religious belief as a source of transferable practice. The article suggests that management should not be seen as a simple response to economic imperatives, but as shaped by the social and cultural context from which it emerges

The training and professional expectations of medical students in Angola, Guinea-Bissau and Mozambique

<p>Abstract</p> <p>Background</p> <p>The purpose of this paper is to describe and analyze the professional expectations of medical students during the 2007-2008 academic year at the public medical schools of Angola, Guinea-Bissau and Mozambique, and to identify their social and geographical origins, their professional expectations and difficulties relating to their education and professional future.</p> <p>Methods</p> <p>Data were collected through a standardised questionnaire applied to all medical students registered during the 2007-2008 academic year.</p> <p>Results</p> <p>Students decide to study medicine at an early age. Relatives and friends seem to have an especially important influence in encouraging, reinforcing and promoting the desire to be a doctor.</p> <p>The degree of feminization of the student population differs among the different countries.</p> <p>Although most medical students are from outside the capital cities, expectations of getting into medical school are already associated with migration from the periphery to the capital city, even before entering medical education.</p> <p>Academic performance is poor. This seems to be related to difficulties in accessing materials, finances and insufficient high school preparation.</p> <p>Medical students recognize the public sector demand but their expectations are to combine public sector practice with private work, in order to improve their earnings. Salary expectations of students vary between the three countries.</p> <p>Approximately 75% want to train as hospital specialists and to follow a hospital-based career. A significant proportion is unsure about their future area of specialization, which for many students is equated with migration to study abroad.</p> <p>Conclusions</p> <p>Medical education is an important national investment, but the returns obtained are not as efficient as expected. Investments in high-school preparation, tutoring, and infrastructure are likely to have a significant impact on the success rate of medical schools. Special attention should be given to the socialization of students and the role model status of their teachers.</p> <p>In countries with scarce medical resources, the hospital orientation of students' expectations is understandable, although it should be associated with the development of skills to coordinate hospital work with the network of peripheral facilities. Developing a local postgraduate training capacity for doctors might be an important strategy to help retain medical doctors in the home country.</p

An Inflaton Mass Problem in String Inflation from Threshold Corrections to Volume Stabilization

Inflationary models whose vacuum energy arises from a D-term are believed not to suffer from the supergravity eta problem of F-term inflation. That is, D-term models have the desirable property that the inflaton mass can naturally remain much smaller than the Hubble scale. We observe that this advantage is lost in models based on string compactifications whose volume is stabilized by a nonperturbative superpotential: the F-term energy associated with volume stabilization causes the eta problem to reappear. Moreover, any shift symmetries introduced to protect the inflaton mass will typically be lifted by threshold corrections to the volume-stabilizing superpotential. Using threshold corrections computed by Berg, Haack, and Kors, we illustrate this point in the example of the D3-D7 inflationary model, and conclude that inflation is possible, but only for fine-tuned values of the stabilized moduli. More generally, we conclude that inflationary models in stable string compactifications, even D-term models with shift symmetries, will require a certain amount of fine-tuning to avoid this new contribution to the eta problem.Comment: 25 page

Inflation in Realistic D-Brane Models

We find successful models of D-brane/anti-brane inflation within a string context. We work within the GKP-KKLT class of type IIB string vacua for which many moduli are stabilized through fluxes, as recently modified to include `realistic' orbifold sectors containing standard-model type particles. We allow all moduli to roll when searching for inflationary solutions and find that inflation is not generic inasmuch as special choices must be made for the parameters describing the vacuum. But given these choices inflation can occur for a reasonably wide range of initial conditions for the brane and antibrane. We find that D-terms associated with the orbifold blowing-up modes play an important role in the inflationary dynamics. Since the models contain a standard-model-like sector after inflation, they open up the possibility of addressing reheating issues. We calculate predictions for the CMB temperature fluctuations and find that these can be consistent with observations, but are generically not deep within the scale-invariant regime and so can allow appreciable values for $dn_s/d\ln k$ as well as predicting a potentially observable gravity-wave signal. It is also possible to generate some admixture of isocurvature fluctuations.Comment: 39 pages, 21 figures; added references; identified parameters combining successful inflation with strong warping, as needed for consistency of the approximation

Big Data -- A 21st Century Science Maginot Line? No-Boundary Thinking: Shifting from the Big Data Paradigm

Whether your interests lie in scientific arenas, the corporate world, or in government, you have certainly heard the praises of big data: Big data will give you new insights, allow you to become more efficient, and/or will solve your problems. While big data has had some outstanding successes, many are now beginning to see that it is not the Silver Bullet that it has been touted to be. Here our main concern is the overall impact of big data; the current manifestation of big data is constructing a Maginot Line in science in the 21st century. Big data is not lots of data as a phenomena anymore; the big data paradigm is putting the spirit of the Maginot Line into lots of data. Big data overall is disconnecting researchers and science challenges. We propose No-Boundary Thinking (NBT), applying no-boundary thinking in problem defining to address science challenges