116 research outputs found
3-manifolds which are spacelike slices of flat spacetimes
We continue work initiated in a 1990 preprint of Mess giving a geometric
parameterization of the moduli space of classical solutions to Einstein's
equations in 2+1 dimensions with cosmological constant 0 or -1 (the case +1 has
been worked out in the interim by the present author). In this paper we make a
first step toward the 3+1-dimensional case by determining exactly which closed
3-manifolds M^3 arise as spacelike slices of flat spacetimes, and by finding
all possible holonomy homomorphisms pi_1(M^3) to ISO(3,1).Comment: 10 page
Decoupling Inflation From the String Scale
When Inflation is embedded in a fundamental theory, such as string theory, it
typically begins when the Universe is already substantially larger than the
fundamental scale [such as the one defined by the string length scale]. This is
naturally explained by postulating a pre-inflationary era, during which the
size of the Universe grew from the fundamental scale to the initial
inflationary scale. The problem then arises of maintaining the [presumed]
initial spatial homogeneity throughout this era, so that, when it terminates,
Inflation is able to begin in its potential-dominated state. Linde has proposed
that a spacetime with compact negatively curved spatial sections can achieve
this, by means of chaotic mixing. Such a compactification will however lead to
a Casimir energy, which can lead to effects that defeat the purpose unless the
coupling to gravity is suppressed. We estimate the value of this coupling
required by the proposal, and use it to show that the pre-inflationary
spacetime is stable, despite the violation of the Null Energy Condition
entailed by the Casimir energy.Comment: 24 pages, 5 eps figures, references added, stylistic changes, version
to appear in Classical and Quantum Gravit
Are Small Hyperbolic Universes Observationally Detectable?
Using recent observational constraints on cosmological density parameters,
together with recent mathematical results concerning small volume hyperbolic
manifolds, we argue that, by employing pattern repetitions, the topology of
nearly flat small hyperbolic universes can be observationally undetectable.
This is important in view of the facts that quantum cosmology may favour
hyperbolic universes with small volumes, and from the expectation coming from
inflationary scenarios, that is likely to be very close to one.Comment: 5 pages, 1 figure, LaTeX2e. A reference and two footnotes added. To
appear in Class. Quantum Grav. 18 (2001) in the present for
Computing CMB Anisotropy in Compact Hyperbolic Spaces
The measurements of CMB anisotropy have opened up a window for probing the
global topology of the universe on length scales comparable to and beyond the
Hubble radius. For compact topologies, the two main effects on the CMB are: (1)
the breaking of statistical isotropy in characteristic patterns determined by
the photon geodesic structure of the manifold and (2) an infrared cutoff in the
power spectrum of perturbations imposed by the finite spatial extent. We
present a completely general scheme using the regularized method of images for
calculating CMB anisotropy in models with nontrivial topology, and apply it to
the computationally challenging compact hyperbolic topologies. This new
technique eliminates the need for the difficult task of spatial eigenmode
decomposition on these spaces. We estimate a Bayesian probability for a
selection of models by confronting the theoretical pixel-pixel temperature
correlation function with the COBE-DMR data. Our results demonstrate that
strong constraints on compactness arise: if the universe is small compared to
the `horizon' size, correlations appear in the maps that are irreconcilable
with the observations. If the universe is of comparable size, the likelihood
function is very dependent upon orientation of the manifold wrt the sky. While
most orientations may be strongly ruled out, it sometimes happens that for a
specific orientation the predicted correlation patterns are preferred over the
conventional infinite models.Comment: 15 pages, LaTeX (IOP style included), 3 color figures (GIF) in
separate files. Minor revision to match the version accepted in Class.
Quantum Grav.: Proc. of Topology and Cosmology, Cleveland, 1997. The paper
can be also downloaded from
http://www.cita.utoronto.ca/~pogosyan/cwru_proc.ps.g
Characteristic Energy of the Coulomb Interactions and the Pileup of States
Tunneling data on crystals confirm
Coulomb interaction effects through the dependence of the
density of states. Importantly, the data and analysis at high energy, E, show a
pileup of states: most of the states removed from near the Fermi level are
found between ~40 and 130 meV, from which we infer the possibility of universal
behavior. The agreement of our tunneling data with recent photoemission results
further confirms our analysis.Comment: 4 pages, 4 figures, submitted to PR
EZH2 promotes a bi-lineage identity in basal-like breast cancer cells
The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a ‘bi-lineage’ differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition
Marking gender studies:the (Radical) value of creative-critical assessment
Feminist pedagogies have established the need to query power structures in terms of curriculum content and teaching praxis. However, the topic of student assessment poses difficulties: it is a means through which students’ performance is evaluated and quantified according to set institutionalised criteria that values particular forms of hegemonic knowledge. The following article presents a self-reflexive exploration of assessment within a Gender Studies module taught in the Autumn semesters of the 2017/18 and 2018/19 academic years at a UK university. The module was a core component of the institution’s MA in Gender Studies. This was an exciting opportunity to experiment with assessment styles corresponding to feminist pedagogies to help develop students’ and instructors’ disciplinary scope and explore the radical potential for creative-critical approaches to assessment. This article outlines some the challenges of employing alternative modes of learning and teaching from a feminist perspective and suggests some strategies to address these
Cell death regulation during influenza A virus infection by matrix (M1) protein: a model of viral control over the cellular survival pathway
During early infection, viruses activate cellular stress-response proteins such as heat-shock proteins (Hsps) to counteract apoptosis, but later on, they modulate these proteins to stimulate apoptosis for efficient viral dissemination. Hsp70 has been attributed to modulate viral entry, transcription, nuclear translocation and virion formation. It also exerts its anti-apoptotic function by binding to apoptosis protease-activating factor 1 (Apaf-1) and disrupting apoptosome formation. Here, we show that influenza A virus can regulate the anti-apoptotic function of Hsp70 through viral protein M1 (matrix 1). M1 itself did not induce apoptosis, but enhanced the effects of apoptotic inducers. M1-small-interfering RNA inhibits virus-induced apoptosis in cells after either virus infection or overexpression of the M1 protein. M1 binds to Hsp70, which results in reduced interaction between Hsp70 and Apaf-1. In a cell-free system, the M1 protein mediates procaspase-9 activation induced by cytochrome c/deoxyadenosine triphosphate. A study involving deletion mutants confirmed the role of the C-terminus substrate-binding domain (EEVD) of Hsp70 and amino acids 128–165 of M1 for this association. The M1 mutants, which did not co-immunoprecipitate with Hsp70, failed to induce apoptosis. Overall, the study confirms the proapoptotic function of the M1 protein during influenza virus infection
Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes
Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies
Targeting HSP90 for cancer therapy
Heat-shock proteins (HSPs) are molecular chaperones that regulate protein folding to ensure correct conformation and translocation and to avoid protein aggregation. Heat-shock proteins are increased in many solid tumours and haematological malignancies. Many oncogenic proteins responsible for the transformation of cells to cancerous forms are client proteins of HSP90. Targeting HSP90 with chemical inhibitors would degrade these oncogenic proteins, and thus serve as useful anticancer agents. This review provides an overview of the HSP chaperone machinery and the structure and function of HSP90. We also highlight the key oncogenic proteins that are regulated by HSP90 and describe how inhibition of HSP90 could alter the activity of multiple signalling proteins, receptors and transcriptional factors implicated in carcinogenesis
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