A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in sorsby's fundus dystrophy

Sorsby’s fundus dystrophy (SFD) is a dominantly inherited degenerative disease of the retina that leads to loss of vision in middle age. It has been shown to be caused by mutations in the gene for tissue inhibitor of metalloproteinases-3 (TIMP-3). Five different mutations have previously been identified, all introducing an extra cysteine residue into exon 5 (which forms part of the C-terminal domain) of the TIMP-3 molecule; however, the significance of these mutations to the disease phenotype was unknown. In this report, we describe the expression of several of these mutated genes, together with a previously unreported novel TIMP-3 mutation from a family with SFD that results in truncation of most of the C-terminal domain of the molecule. Despite these differences, all of these molecules are expressed and exhibit characteristics of the normal protein, including inhibition of metalloproteinases and binding to the extracellular matrix. However, unlike wild-type TIMP-3, they all form dimers. These observations, together with the recent finding that expression of TIMP-3 is increased, rather than decreased, in eyes from patients with SFD, provides compelling evidence that dimerized TIMP-3 plays an active role in the disease process by accumulating in the eye. Increased expression of TIMP-3 is also observed in other degenerative retinal diseases, including the more severe forms of agerelated macular degeneration, the most common cause of blindness in the elderly in developed countries. We hypothesize that overexpression of TIMP-3 may prove to be a critical step in the progression of a variety of degenerative retinopathies

An accelerated closed universe

We study a model in which a closed universe with dust and quintessence matter components may look like an accelerated flat Friedmann-Robertson-Walker (FRW) universe at low redshifts. Several quantities relevant to the model are expressed in terms of observed density parameters, $\Omega_M$ and $\Omega_{\Lambda}$, and of the associated density parameter $\Omega_Q$ related to the quintessence scalar field $Q$.Comment: 11 pages. For a festschrift honoring Alberto Garcia. To appear in Gen. Rel. Gra

CBR Anisotropy from Primordial Gravitational Waves in Two-Component Inflationary Cosmology

We examine stochastic temperature fluctuations of the cosmic background radiation (CBR) arising via the Sachs-Wolfe effect from gravitational wave perturbations produced in the early universe. We consider spatially flat, perturbed FRW models that begin with an inflationary phase, followed by a mixed phase containing both radiation and dust. The scale factor during the mixed phase takes the form $a(\eta)=c_1\eta^2+c_2\eta+c_3$, where $c_i$ are constants. During the mixed phase the universe smoothly transforms from being radiation to dust dominated. We find analytic expressions for the graviton mode function during the mixed phase in terms of spheroidal wave functions. This mode function is used to find an analytic expression for the multipole moments $\langle a_l^2\rangle$ of the two-point angular correlation function $C(\gamma)$ for the CBR anisotropy. The analytic expression for the multipole moments is written in terms of two integrals, which are evaluated numerically. The results are compared to multipoles calculated for models that are {\it completely} dust dominated at last-scattering. We find that the multipoles $\langle a_l^2\rangle$ of the CBR temperature perturbations for $l>10$ are significantly larger for a universe that contains both radiation and dust at last-scattering. We compare our results with recent, similar numerical work and find good agreement. The spheroidal wave functions may have applications to other problems of cosmological interest.Comment: 28 pgs + 6 postscript figures, RevTe

Modified gravity without dark matter

On an empirical level, the most successful alternative to dark matter in bound gravitational systems is the modified Newtonian dynamics, or MOND, proposed by Milgrom. Here I discuss the attempts to formulate MOND as a modification of General Relativity. I begin with a summary of the phenomenological successes of MOND and then discuss the various covariant theories that have been proposed as a basis for the idea. I show why these proposals have led inevitably to a multi-field theory. I describe in some detail TeVeS, the tensor-vector-scalar theory proposed by Bekenstein, and discuss its successes and shortcomings. This lecture is primarily pedagogical and directed to those with some, but not a deep, background in General RelativityComment: 28 pages, 10 figures, lecture given at Third Aegean Summer School, The Invisible Universe: Dark Matter and Dark Energy, minor errors corrected, references update

Study of variable stars in the MOA data base: long-period red variables in the Large Magellanic Cloud

One hundred and forty six long-period red variable stars in the Large Magellanic Cloud (LMC) from the three year MOA project database were analysed. A careful periodic analysis was performed on these stars and a catalogue of their magnitudes, colours, periods and amplitudes is presented. We convert our blue and red magnitudes to $K$ band values using 19 oxygen-rich stars. A group of red short-period stars separated from the Mira sequence has been found on a (log P, K) diagram. They are located at the short period side of the Mira sequence consistent with the work of Wood and Sebo (1996). There are two interpretations for such stars; a difference in pulsation mode or a difference in chemical composition. We investigated the properties of these stars together with their colour, amplitude and periodicity. We conclude that they have small amplitudes and less regular variability. They are likely to be higher mode pulsators. A large scatter has been also found on the long period side of the (log P, K) diagram. This is possibly a systematic spread given that the blue band of our photometric system covers both standard B and V bands and affects carbon-rich stars.Comment: 19 pages, 19 figures, accepted for publication in MNRA

Current constraints on Cosmological Parameters from Microwave Background Anisotropies

We compare the latest observations of Cosmic Microwave Background (CMB) Anisotropies with the theoretical predictions of the standard scenario of structure formation. Assuming a primordial power spectrum of adiabatic perturbations we found that the total energy density is constrained to be $\Omega_{tot}=1.03\pm0.06$ while the energy density in baryon and Cold Dark Matter (CDM) are $\Omega_bh^2=0.021\pm0.003$ and $\Omega_{cdm}h^2=0.12\pm0.02$, (all at 68% C.L.) respectively. The primordial spectrum is consistent with scale invariance, ($n_s=0.97\pm0.04$) and the age of the universe is $t_0=14.6\pm0.9$ Gyrs. Adding informations from Large Scale Structure and Supernovae, we found a strong evidence for a cosmological constant $\Omega_{\Lambda}=0.70_{-0.05}^{+0.07}$ and a value of the Hubble parameter $h=0.69\pm0.07$. Restricting this combined analysis to flat universes, we put constraints on possible 'extensions' of the standard scenario. A gravity waves contribution to the quadrupole anisotropy is limited to be $r \le 0.42$ (95% c.l.). A constant equation of state for the dark energy component is bound to be $w_Q \le -0.74$ (95% c.l.). We constrain the effective relativistic degrees of freedom $N_\nu \leq 6.2$ and the neutrino chemical potential $-0.01 \leq \xi_e \leq 0.18$ and $|\xi_{\mu,\tau}|\leq 2.3$ (massless neutrinos).Comment: The status of cosmological parameters before WMAP. In press on Phys. Rev. D., Rapid Communication, 6 pages, 5 figure

BotSwindler: Tamper Resistant Injection of Believable Decoys in VM-Based Hosts for Crimeware Detection

We introduce BotSwindler, a bait injection system designed to delude and detect crimeware by forcing it to reveal during the exploitation of monitored information. The implementation of BotSwindler relies upon an out-of-host software agent that drives user-like interactions in a virtual machine, seeking to convince malware residing within the guest OS that it has captured legitimate credentials. To aid in the accuracy and realism of the simulations, we propose a low overhead approach, called virtual machine verification, for verifying whether the guest OS is in one of a predefined set of states. We present results from experiments with real credential-collecting malware that demonstrate the injection of monitored financial bait for detecting compromises. Additionally, using a computational analysis and a user study, we illustrate the believability of the simulations and we demonstrate that they are sufficiently human-like. Finally, we provide results from performance measurements to show our approach does not impose a performance burden

First attempt at measuring the CMB cross-polarization

We compute upper limits on CMB cross-polarization by cross-correlating the PIQUE and Saskatoon experiments. We also discuss theoretical and practical issues relevant to measuring cross-polarization and illustrate them with simulations of the upcoming BOOMERanG 2002 experiment. We present a method that separates all six polarization power spectra (TT, EE, BB, TE, TB, EB) without any other "leakage" than the familiar EE-BB mixing caused by incomplete sky coverage. Since E and B get mixed, one might expect leakage between TE and TB, between EE and EB and between BB and EB - our method eliminates this by preserving the parity symmetry under which TB and EB are odd and the other four power spectra are even.Comment: Polarization movies can be found at http://www.hep.upenn.edu/~angelica/polarization.htm

Last Glacial Period Cryptotephra Deposits in an Eastern North Atlantic Marine Sequence: Exploring Linkages to the Greenland Ice-Cores

The establishment of a tephra framework for the Greenland ice-cores spanning the last glacial period, particularly between 25 and 45 ka b2k, provides strong potential for precisely correlating other palaeoclimatic records to these key archives. Tephra-based synchronisation allows the relative timing of past climatic changes recorded within different depositional environments and potential causal mechanisms to be assessed. Recent studies of North Atlantic marine records have demonstrated the potential of tracing cryptotephra horizons in these sequences and the development of protocols now allows a careful assessment of the isochronous nature of such horizons. Here we report on tephrochronological investigations of a marine sequence retrieved from the Goban Spur, Eastern North Atlantic, covering ?25–60 ka b2k. Density and magnetic separation techniques and an assessment of potential transport and depositional mechanisms have identified three previously unknown isochronous tephra horizons along with deposits of the widespread North Atlantic Ash Zone II and Faroe Marine Ash Zone III. Correlations between the new horizons and the Greenland ice-core tephra framework are explored and despite no tie-lines being identified the key roles that high-resolution climatostratigraphy and shard-specific trace element analysis can play within the assessment of correlations is demonstrated. The previously unknown horizons are new additions to the overall North Atlantic tephra framework for the last glacial period and could be key horizons for future correlations

The State of the Dark Energy Equation of State

By combining data from seven cosmic microwave background experiments (including the latest WMAP results) with large scale structure data, the Hubble parameter measurement from the Hubble Space Telescope and luminosity measurements of Type Ia supernovae we demonstrate the bounds on the dark energy equation of state $w_Q$ to be $-1.38< w_Q <-0.82$ at the 95% confidence level. Although our limit on $w_Q$ is improved with respect to previous analyses, cosmological data does not rule out the possibility that the equation of state parameter $w_Q$ of the dark energy $Q$ is less than -1. We present a tracking model that ensures $w_Q \le -1$ at recent times and discuss the observational consequences.Comment: 7 pages, 4 figures, added a referenc