Enthalpy and the Mechanics of AdS Black Holes

We present geometric derivations of the Smarr formula for static AdS black holes and an expanded first law that includes variations in the cosmological constant. These two results are further related by a scaling argument based on Euler's theorem. The key new ingredient in the constructions is a two-form potential for the static Killing field. Surface integrals of the Killing potential determine the coefficient of the variation of the cosmological constant in the first law. This coefficient is proportional to a finite, effective volume for the region outside the AdS black hole horizon, which can also be interpreted as minus the volume excluded from a spatial slice by the black hole horizon. This effective volume also contributes to the Smarr formula. Since the cosmological constant is naturally thought of as a pressure, the new term in the first law has the form of effective volume times change in pressure that arises in the variation of the enthalpy in classical thermodynamics. This and related arguments suggest that the mass of an AdS black hole should be interpreted as the enthalpy of the spacetime.Comment: 21 pages; v2 references adde

Nuclear localization of the mitochondrial factor HIGD1A during metabolic stress.

Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo

Dynamics of proteins: Light scattering study of dilute and dense colloidal suspensions of eye lens homogenates

We report a dynamic light scattering study on protein suspensions of bovine lens homogenates at conditions (pH and ionic strength) similar to the physiological ones. Light scattering data were collected at two temperatures, 20 oC and 37 oC, over a wide range of concentrations from the very dilute limit up to the dense regime approaching to the physiological lens concentration. A comparison with experimental data from intact bovine lenses was advanced revealing differences between dispersions and lenses at similar concentrations. In the dilute regime two scattering entities were detected and identified with the long-time, self-diffusion modes of alpha-crystallins and their aggregates, which naturally exist in lens nucleus. Self-diffusion coefficients are temperature insensitive, whereas the collective diffusion coefficient depends strongly on temperature revealing a reduction of the net repulsive interparticle forces with lowering temperature. While there are no rigorous theoretical approaches on particle diffusion properties for multi-component, non-ideal hard-sphere, polydispersed systems, as the suspensions studied here, a discussion of the volume fraction dependence of the long-time, self-diffusion coefficient in the context of existing theoretical approaches was undertaken. This study is purported to provide some insight into the complex light scattering pattern of intact lenses and the interactions between the constituent proteins that are responsible for lens transparency. This would lead to understand basic mechanisms of specific protein interactions that lead to lens opacification (cataract) under pathological conditions.Comment: To appear in J. Chem. Phy

First inappropriate implantable cardioverter defibrillator therapy is often due to inaccurate device programming: analysis of the French OPERA registry

AIMS:Inappropriate therapy delivered by implantable cardioverter defibrillators (ICDs) remains a challenge. The OPERA registry measured the times to, and studied the determinants of, first appropriate (FAT) and inappropriate (FIT) therapies delivered by single-, dual- and triple-chamber [cardiac resynchronization therapy defibrillator (CRT-D)] ICD. METHODS AND RESULTS: We entered 636 patients (mean age = 62.0 ± 13.5 years; 88% men) in the registry, of whom 251 received single-, 238 dual-, and 147 triple-chamber ICD, for primary (30.5%) or secondary (69.5%) indications. We measured times to FAT and FIT as a function of multiple clinical characteristics, examined the effects of various algorithm components on the likelihood of FAT and FIT delivery, and searched for predictors of FAT and FIT. Over 22.8 ± 8.8 months of observation, 184 patients (28.9%) received FAT and 70 (11.0%) received FIT. Ventricular tachycardia (VT) was the trigger of 88% of FAT, and supraventricular tachycardia was the trigger of 91% of FIT. The median times to FIT (90 days; range 49-258) and FAT (171 days; 50-363) were similar. The rate of FAT was higher (P <0.001) in patients treated for secondary than primary indications, while that of FIT were similar in both groups. Out of 57 analysable FIT, 27 (47.4%) could have been prevented by fine tuning the device programming like the sustained rate duration or the VT discrimination algorithm. CONCLUSIONS: First inappropriate therapy occurred in 11% of 636 ICD recipients followed for ∼2 years. Nearly 50% of FIT could have been prevented by improving device programming

The Study of TeV Variability and Duty Cycle of Mrk 421 from 3 Years of Observations with the Milagro Observatory

TeV flaring activity with time scales as short as tens of minutes and an orphan TeV flare have been observed from the blazar Markarian 421 (Mrk 421). The TeV emission from Mrk 421 is believed to be produced by leptonic synchrotron self-Compton (SSC) emission. In this scenario, correlations between the X-ray and the TeV fluxes are expected, TeV orphan flares are hardly explained and the activity (measured as duty cycle) of the source at TeV energies is expected to be equal or less than that observed in X-rays if only SSC is considered. To estimate the TeV duty cycle of Mrk 421 and to establish limits on its variability at different time scales, we continuously observed Mrk 421 with the Milagro observatory. Mrk 421 was detected by Milagro with a statistical significance of 7.1 standard deviations between 2005 September 21 and 2008 March 15. The observed spectrum is consistent with previous observations by VERITAS. We estimate the duty cycle of Mrk 421 for energies above 1 TeV for different hypothesis of the baseline flux and for different flare selections and we compare our results with the X-ray duty cycle estimated by Resconi et al. 2009. The robustness of the results is discussed.Comment: 27 pages, 6 figures, ApJ accepte

Observation of TeV Gamma Rays from the Crab Nebula with Milagro Using a New Background Rejection Technique

The recent advances in TeV gamma-ray astronomy are largely the result of the ability to differentiate between extensive air showers generated by gamma rays and hadronic cosmic rays. Air Cherenkov telescopes have developed and perfected the "imaging" technique over the past several decades. However until now no background rejection method has been successfully used in an air shower array to detect a source of TeV gamma rays. We report on a method to differentiate hadronic air showers from electromagnetic air showers in the Milagro gamma ray observatory, based on the ability to detect the energetic particles in an extensive air shower. The technique is used to detect TeV emission from the Crab nebula. The flux from the Crab is estimated to be 2.68(+-0.42stat +- 1.4sys) x10^{-7} (E/1TeV)^{-2.59} m^{-2} s^{-1} TeV^{-1}, where the spectral index is assumed to be as given by the HEGRA collaboration.Comment: 22 pages, 11 figures, submitted to Astrophysical Journa

Calibration of the Milagro Cosmic Ray Telescope

The Milagro detector is an air shower array which uses the water Cherenkov technique and is capable of continuously monitoring the sky at energies near 1 TeV. The detector consists of 20000 metric tons of pure water instrumented with 723 photo-multiplier tubes (PMTs). The PMTs are arranged in a two-layer structure on a lattice of 3 m spacing covering 5000 $m^2$ area. The direction of the shower is determined from the relative timing of the PMT signals, necessitating a common time reference and amplitude slewing corrections to improve the time resolution. The calibration system to provide these consists of a pulsed laser driving 30 diffusing light sources deployed in the pond to allow cross-calibration of the PMTs. The system is capable of calibrating times and the pulse-heights from the PMTs using the time-over-threshold technique. The absolute energy scale is provided using single muons passing through the detector. The description of the calibration system of the Milagro detector and its prototype Milagrito will be presented.Comment: 4 pages, submitted to the XXVI International Cosmic Ray Conferenc

On the uniqueness and global dynamics of AdS spacetimes

We study global aspects of complete, non-singular asymptotically locally AdS spacetimes solving the vacuum Einstein equations whose conformal infinity is an arbitrary globally stationary spacetime. It is proved that any such solution which is asymptotically stationary to the past and future is itself globally stationary. This gives certain rigidity or uniqueness results for exact AdS and related spacetimes.Comment: 18pp, significant revision of v

Milagrito Detection of TeV Emission from Mrk 501

The Milagro water Cherenkov detector near Los Alamos, New Mexico, has been operated as a sky monitor at energies of a few TeV between February 1997 and April 1998. Serving as a test run for the full Milagro detector, Milagrito has taken data during the strong and long-lasting 1997 flare of Mrk 501. We present results from the analysis of Mrk 501 and compare the excess and background rates with expectations from the detector simulations.Comment: 4 pages, submitted to XXVI International Cosmic Ray Conference, Salt Lake Cit