449 research outputs found
Molecular mimicry in primary biliary cirrhosis and other hepatic and extra-hepatic diseases.
This Thesis investigates the concept that molecular mimicry may be instrumental to the appearance and/or maintenance of liver autoimmunity, with a main focus on primary biliary cirrhosis (PBC). The first part of the study concentrates on the investigation of immunological cross-reactivity between pyruvate dehydrogenase complex E2 (PDC-E2)212-226, the immunodominant mitochondrial autoepitope in PBC and microbial mimics. Several bacterial and viral sequences were identified that share extensive homology with PDC-E2212-226 and while some from mycobacteria, lactobacillus and E. coli, acted as target of cross-reactivity, similarly good mimicking sequences from other micro-organisms were unreactive. The possible bearing on the mechanism of the disease of this selective cross-reactivity is discussed. Next is the identification of cross-reactive immune responses between hepatitis C virus (HCV) polyprotein and cytochrome P450IID6 (CYP2D6)252-27i, the major autoepitope of anti-liver kidney microsomal type-1 antibody (LKM1), the serological hallmark of autoimmune hepatitis type-2. Viral/self cross-reactivity was documented only in those patients possessing the HLA B51 allele. The evolution of immunological cross-reactivity was investigated over a 10-year period in a girl who developed primary and secondary LKM1 response following HCV infection resulting in a florid autoimmune hepatitis 9 years later. A study in a cohort of subjects vaccinated against hepatitis B provided the opportunity to document the appearance of cross-reactivity between viral sequences and mimics on myelin antigens. The findings of the present Thesis demonstrate that disease-specific microbial/self cross-reactive responses do occur and may be of pathogenic significance
Localizing gravity on thick branes: a solution for massive KK modes of the Schroedinger equation
We generate scalar thick brane configurations in a 5D Riemannian space time
which describes gravity coupled to a self-interacting scalar field. We also
show that 4D gravity can be localized on a thick brane which does not
necessarily respect Z_2-symmetry, generalizing several previous models based on
the Randall-Sundrum system and avoiding the restriction to orbifold geometries
as well as the introduction of the branes in the action by hand. We begin by
obtaining a smooth brane configuration that preserves 4D Poincar'e invariance
and violates reflection symmetry along the fifth dimension. The extra dimension
can have either compact or extended topology, depending on the values of the
parameters of the solution. In the non-compact case, our field configuration
represents a thick brane with positive energy density centered at y=c_2,
whereas in the compact case we get pairs of thick branes. We recast as well the
wave equations of the transverse traceless modes of the linear fluctuations of
the classical solution into a Schroedinger's equation form with a volcano
potential of finite bottom. We solve Schroedinger equation for the massless
zero mode m^2=0 and obtain a single bound wave function which represents a
stable 4D graviton and is free of tachyonic modes with m^2<0. We also get a
continuum spectrum of Kaluza-Klein (KK) states with m^2>0 that are suppressed
at y=c_2 and turn asymptotically into plane waves. We found a particular case
in which the Schroedinger equation can be solved for all m^2>0, giving us the
opportunity of studying analytically the massive modes of the spectrum of KK
excitations, a rare fact when considering thick brane configurations.Comment: 8 pages in latex. We corrected signs in the field equations, the
expressions for the scalar field and the self-interacting potential. Due to
the fact that no changes are introduced in the warp factor, the physics of
the system remains the sam
Brane Cosmology with a Non-Minimally Coupled Bulk-Scalar Field
We consider the cosmological evolution of a brane in the presence of a bulk
scalar field coupled to the Ricci scalar through a term f(\phi)R. We derive the
generalized Friedmann equation on the brane in the presence of arbitrary brane
and bulk-matter, as well as the scalar field equation, allowing for a general
scalar potential V(phi). We focus on a quadratic form of the above non-minimal
coupling and obtain a class of late-time solutions for the scale factor and the
scalar field on the brane that exhibit accelerated expansion for a range of the
non-minimal coupling parameter.Comment: 15 page
Braneworld models with a non-minimally coupled phantom bulk field: a simple way to obtain the -1-crossing at late times
We investigate general braneworld models, with a non-minimally coupled
phantom bulk field and arbitrary brane and bulk matter contents. We show that
the effective dark energy of the brane-universe acquires a dynamical nature, as
a result of the non-minimal coupling which provides a mechanism for an indirect
"bulk-brane interaction" through gravity. For late-time cosmological evolution
and without resorting to special ansatzes or to specific areas of the parameter
space, we show that the -1-crossing of its equation-of-state parameter is
general and can be easily achieved. As an example we provide a simple, but
sufficiently general, approximate analytical solution, that presents the
crossing behavior.Comment: 11 pages, 2 figure
Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis
Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients
The phase portrait of a matter bounce in Horava-Lifshitz cosmology
The occurrence of a bounce in FRW cosmology requires modifications of general
relativity. An example of such a modification is the recently proposed
Horava-Lifshitz theory of gravity, which includes a ``dark radiation'' term
with a negative coefficient in the analog of the Friedmann equation. This paper
describes a phase space analysis of models of this sort with the aim of
determining to what extent bouncing solutions can occur. A simplification,
valid in the relevant region, allows a reduction of the dimension of phase
space so that visualization in three dimensions is possible. It is found that a
bounce is possible, but not generic in models under consideration. Apart from
previously known bouncing solutions some new ones are also described. Other
interesting solutions found include ones which describe a novel sort of
oscillating universes.Comment: 14 pages, 8 figure
Pathological behaviour of the scalar graviton in Ho\v{r}ava-Lifshitz gravity
We confirm the recent claims that, in the infrared limit of
Ho\v{r}ava-Lifshitz gravity, the scalar graviton becomes a ghost if the sound
speed squared is positive on the flat de Sitter and Minkowski background. In
order to avoid the ghost and tame the instability, the sound speed squared
should be negative and very small, which means that the flow parameter
should be very close to its General Relativity (GR) value. We
calculate the cubic interactions for the scalar graviton which are shown to
have a similar structure with those of the curvature perturbation in
k-inflation models. The higher order interactions become increasing important
for a smaller sound speed squared, that is, when the theory approaches GR. This
invalidates any linearized analysis and any predictability is lost in this
limit as quantum corrections are not controllable. This pathological behaviour
of the scalar graviton casts doubt on the validity of the projectable version
of the theory.Comment: 7 pages, references added; v3: Typos corrected, minor changes to text
and precise determination of the strong coupling scale. Replaced to match
published version
The Cosmological Constant and Horava-Lifshitz Gravity
Horava-Lifshitz theory of gravity with detailed balance is plagued by the
presence of a negative bare (or geometrical) cosmological constant which makes
its cosmology clash with observations. We argue that adding the effects of the
large vacuum energy of quantum matter fields, this bare cosmological constant
can be approximately compensated to account for the small observed (total)
cosmological constant. Even though we cannot address the fine-tuning problem in
this way, we are able to establish a relation between the smallness of observed
cosmological constant and the length scale at which dimension 4 corrections to
the Einstein gravity become significant for cosmology. This scale turns out to
be approximately 5 times the Planck length for an (almost) vanishing observed
cosmological constant and we therefore argue that its smallness guarantees that
Lorentz invariance is broken only at very small scales. We are also able to
provide a first rough estimation for the infrared values of the parameters of
the theory and .Comment: 9 pages, Late
Remarks on the Scalar Graviton Decoupling and Consistency of Horava Gravity
Recently Horava proposed a renormalizable gravity theory with higher
derivatives by abandoning the Lorenz invariance in UV. But there have been
confusions regarding the extra scalar graviton mode and the consistency of the
Horava model. I reconsider these problems and show that, in the Minkowski
vacuum background, the scalar graviton mode can be consistency decoupled from
the usual tensor graviton modes by imposing the (local) Hamiltonian as well as
the momentum constraints.Comment: Some clarifications regarding the projectable case added, Typos
corrected, Comments (Footnote No.9, Note Added) added, References updated,
Accepted in CQ
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