267 research outputs found
Toward High-Precision Measures of Large-Scale Structure
I review some results of estimation of the power spectrum of density
fluctuations from galaxy redshift surveys and discuss advances that may be
possible with the Sloan Digital Sky Survey. I then examine the realities of
power spectrum estimation in the presence of Galactic extinction, photometric
errors, galaxy evolution, clustering evolution, and uncertainty about the
background cosmology.Comment: 24 pages, including 11 postscript figures. Uses crckapb.sty (included
in submission). To appear in ``Ringberg Workshop on Large-Scale Structure,''
ed D. Hamilton (Kluwer, Amsterdam), p. 39
The relativistic Sagnac Effect: two derivations
The phase shift due to the Sagnac Effect, for relativistic matter and
electromagnetic beams, counter-propagating in a rotating interferometer, is
deduced using two different approaches. From one hand, we show that the
relativistic law of velocity addition leads to the well known Sagnac time
difference, which is the same independently of the physical nature of the
interfering beams, evidencing in this way the universality of the effect.
Another derivation is based on a formal analogy with the phase shift induced by
the magnetic potential for charged particles travelling in a region where a
constant vector potential is present: this is the so called Aharonov-Bohm
effect. Both derivations are carried out in a fully relativistic context, using
a suitable 1+3 splitting that allows us to recognize and define the space where
electromagnetic and matter waves propagate: this is an extended 3-space, which
we call "relative space". It is recognized as the only space having an actual
physical meaning from an operational point of view, and it is identified as the
'physical space of the rotating platform': the geometry of this space turns out
to be non Euclidean, according to Einstein's early intuition.Comment: 49 pages, LaTeX, 3 EPS figures. Revised (final) version, minor
corrections; to appear in "Relativity in Rotating Frames", ed. G. Rizzi and
M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht, (2003). See also
http://digilander.libero.it/solciclo
Spin dynamics of molecular nanomagnets fully unraveled by four-dimensional inelastic neutron scattering
Molecular nanomagnets are among the first examples of spin systems of finite
size and have been test-beds for addressing a range of elusive but important
phenomena in quantum dynamics. In fact, for short-enough timescales the spin
wavefunctions evolve coherently according to the an appropriate cluster
spin-Hamiltonian, whose structure can be tailored at the synthetic level to
meet specific requirements. Unfortunately, to this point it has been impossible
to determine the spin dynamics directly. If the molecule is sufficiently
simple, the spin motion can be indirectly assessed by an approximate model
Hamiltonian fitted to experimental measurements of various types. Here we show
that recently-developed instrumentation yields the four-dimensional
inelastic-neutron scattering function S(Q,E) in vast portions of reciprocal
space and enables the spin dynamics to be determined with no need of any model
Hamiltonian. We exploit the Cr8 antiferromagnetic ring as a benchmark to
demonstrate the potential of this new approach. For the first time we extract a
model-free picture of the quantum dynamics of a molecular nanomagnet. This
allows us, for example, to examine how a quantum fluctuation propagates along
the ring and to directly test the degree of validity of the
N\'{e}el-vector-tunneling description of the spin dynamics
Differential neutrino condensation onto cosmic structure
Astrophysical techniques have pioneered the discovery of neutrino mass properties. Current cosmological observations give an upper bound on neutrino masses by attempting to disentangle the small neutrino contribution from the sum of all matter using precise theoretical models. We discover the differential neutrino condensation effect in our TianNu N-body simulation. Neutrino masses can be inferred using this effect by comparing galaxy properties in regions of the universe with different neutrino relative abundance (i.e. the local neutrino to cold dark matter density ratio). In βneutrino-richβ regions, more neutrinos can be captured by massive halos compared to βneutrino-poorβ regions. This effect differentially skews the halo mass function and opens up the path to independent neutrino mass measurements in current or future galaxy surveys
Dobrava-Belgrade Hantavirus from Germany Shows Receptor Usage and Innate Immunity Induction Consistent with the Pathogenicity of the Virus in Humans
BACKGROUND: Dobrava-Belgrade virus (DOBV) is a European hantavirus causing hemorrhagic fever with renal syndrome (HFRS) in humans with fatality rates of up to 12%. DOBV-associated clinical cases typically occur also in the northern part of Germany where the virus is carried by the striped field mouse (Apodemus agrarius). However, the causative agent responsible for human illness has not been previously isolated. METHODOLOGY/PRINCIPAL FINDINGS: Here we report on characterization of a novel cell culture isolate from Germany obtained from a lung tissue of "spillover" infected yellow necked mouse (A. flavicollis) trapped near the city of Greifswald. Phylogenetic analyses demonstrated close clustering of the new strain, designated Greifswald/Aa (GRW/Aa) with the nucleotide sequence obtained from a northern German HFRS patient. The virus was effectively blocked by specific antibodies directed against Ξ²3 integrins and Decay Accelerating Factor (DAF) indicating that the virus uses same receptors as the highly pathogenic Hantaan virus (HTNV). In addition, activation of selected innate immunity markers as interferon Ξ² and Ξ» and antiviral protein MxA after viral infection of A549 cells was investigated and showed that the virus modulates the first-line antiviral response in a similar way as HTNV. CONCLUSIONS/SIGNIFICANCE: In summary, our study reveals novel data on DOBV receptor usage and innate immunity induction in relationship to virus pathogenicity and underlines the potency of German DOBV strains to act as human pathogen
Observational and Physical Classification of Supernovae
This chapter describes the current classification scheme of supernovae (SNe).
This scheme has evolved over many decades and now includes numerous SN Types
and sub-types. Many of these are universally recognized, while there are
controversies regarding the definitions, membership and even the names of some
sub-classes; we will try to review here the commonly-used nomenclature, noting
the main variants when possible. SN Types are defined according to
observational properties; mostly visible-light spectra near maximum light, as
well as according to their photometric properties. However, a long-term goal of
SN classification is to associate observationally-defined classes with specific
physical explosive phenomena. We show here that this aspiration is now finally
coming to fruition, and we establish the SN classification scheme upon direct
observational evidence connecting SN groups with specific progenitor stars.
Observationally, the broad class of Type II SNe contains objects showing strong
spectroscopic signatures of hydrogen, while objects lacking such signatures are
of Type I, which is further divided to numerous subclasses. Recently a class of
super-luminous SNe (SLSNe, typically 10 times more luminous than standard
events) has been identified, and it is discussed. We end this chapter by
briefly describing a proposed alternative classification scheme that is
inspired by the stellar classification system. This system presents our
emerging physical understanding of SN explosions, while clearly separating
robust observational properties from physical inferences that can be debated.
This new system is quantitative, and naturally deals with events distributed
along a continuum, rather than being strictly divided into discrete classes.
Thus, it may be more suitable to the coming era where SN numbers will quickly
expand from a few thousands to millions of events.Comment: Extended final draft of a chapter in the "SN Handbook". Comments most
welcom
An internal ribosome entry site in the 5β² untranslated region of epidermal growth factor receptor allows hypoxic expression
The expression of epidermal growth factor receptor (EGFR/ERBB1/HER1) is implicated in the progress of numerous cancers, a feature that has been exploited in the development of EGFR antibodies and EGFR tyrosine kinase inhibitors as anti-cancer drugs. However, EGFR also has important normal cellular functions, leading to serious side effects when EGFR is inhibited. One damaging characteristic of many oncogenes is the ability to be expressed in the hypoxic conditions associated with the tumour interior. It has previously been demonstrated that expression of EGFR is maintained in hypoxic conditions via an unknown mechanism of translational control, despite global translation rates generally being attenuated under hypoxic conditions. In this report, we demonstrate that the human EGFR 5β² untranslated region (UTR) sequence can initiate the expression of a downstream open reading frame via an internal ribosome entry site (IRES). We show that this effect is not due to either cryptic promoter activity or splicing events. We have investigated the requirement of the EGFR IRES for eukaryotic initiation factor 4A (eIF4A), which is an RNA helicase responsible for processing RNA secondary structure as part of translation initiation. Treatment with hippuristanol (a potent inhibitor of eIF4A) caused a decrease in EGFR 5β² UTR-driven reporter activity and also a reduction in EGFR protein level. Importantly, we show that expression of a reporter gene under the control of the EGFR IRES is maintained under hypoxic conditions despite a fall in global translation rates
High-Throughput Screening of Australian Marine Organism Extracts for Bioactive Molecules Affecting the Cellular Storage of Neutral Lipids
Mammalian cells store excess fatty acids as neutral lipids in specialised organelles called lipid droplets (LDs). Using a simple cell-based assay and open-source software we established a high throughput screen for LD formation in A431 cells in order to identify small bioactive molecules affecting lipid storage. Screening an n-butanol extract library from Australian marine organisms we identified 114 extracts that produced either an increase or a decrease in LD formation in fatty acid-treated A431 cells with varying degrees of cytotoxicity. We selected for further analysis a non-cytotoxic extract derived from the genus Spongia (Heterofibria). Solvent partitioning, HPLC fractionation and spectroscopic analysis (NMR, MS) identified a family of related molecules within this extract with unique structural features, a subset of which reduced LD formation. We selected one of these molecules, heterofibrin A1, for more detailed cellular analysis. Inhibition of LD biogenesis by heterofibrin A1 was observed in both A431 cells and AML12 hepatocytes. The activity of heterofibrin A1 was dose dependent with 20 Β΅M inhibiting LD formation and triglyceride accumulation by βΌ50% in the presence of 50 Β΅M oleic acid. Using a fluorescent fatty acid analogue we found that heterofibrin A1 significantly reduces the intracellular accumulation of fatty acids and results in the formation of distinct fatty acid metabolites in both cultured cells and in embryos of the zebrafish Danio rerio. In summary we have shown using readily accessible software and a relatively simple assay system that we can identify and isolate bioactive molecules from marine extracts, which affect the formation of LDs and the metabolism of fatty acids both in vitro and in vivo
Snake Cytotoxins Bind to Membranes via Interactions with Phosphatidylserine Head Groups of Lipids
The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells
Virus-Receptor Mediated Transduction of Dendritic Cells by Lentiviruses Enveloped with Glycoproteins Derived from Semliki Forest Virus
Lentiviruses have recently attracted considerable interest for their potential as a genetic modification tool for dendritic cells (DCs). In this study, we explore the ability of lentiviruses enveloped with alphaviral envelope glycoproteins derived from Semliki Forest virus (SFV) to mediate transduction of DCs. We found that SFV glycoprotein (SFV-G)-pseudotyped lentiviruses use C-type lectins (DC-SIGN and L-SIGN) as attachment factors for transduction of DCs. Importantly, SFV-G pseudotypes appear to have enhanced transduction towards C-type lectin-expressing cells when produced under conditions limiting glycosylation to simple high-mannose, N-linked glycans. These results, in addition to the natural DC tropism of SFV-G, offer evidence to support the use of SFV-G-bearing lentiviruses to genetically modify DCs for the study of DC biology and DC-based immunotherapy
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