Experimental modulation of capsule size in Cryptococcus neoformans

Experimental modulation of capsule size is an important technique for the study of the virulence of the encapsulated pathogen Cryptococcus neoformans. In this paper, we summarize the techniques available for experimental modulation of capsule size in this yeast and describe improved methods to induce capsule size changes. The response of the yeast to the various stimuli is highly dependent on the cryptococcal strain. A high CO(2) atmosphere and a low iron concentration have been used classically to increase capsule size. Unfortunately, these stimuli are not reliable for inducing capsular enlargement in all strains. Recently we have identified new and simpler conditions for inducing capsule enlargement that consistently elicited this effect. Specifically, we noted that mammalian serum or diluted Sabouraud broth in MOPS buffer pH 7.3 efficiently induced capsule growth. Media that slowed the growth rate of the yeast correlated with an increase in capsule size. Finally, we summarize the most commonly used media that induce capsule growth in C. neoformans

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

Neurospora from natural populations: Population genomics insights into the Life history of a model microbial Eukaryote

The ascomycete filamentous fungus Neurospora crassa played a historic role in experimental biology and became a model system for genetic research. Stimulated by a systematic effort to collect wild strains initiated by Stanford geneticist David Perkins, the genus Neurospora has also become a basic model for the study of evolutionary processes, speciation, and population biology. In this chapter, we will first trace the history that brought Neurospora into the era of population genomics. We will then cover the major contributions of population genomic investigations using Neurospora to our understanding of microbial biogeography and speciation, and review recent work using population genomics and genome-wide association mapping that illustrates the unique potential of Neurospora as a model for identifying the genetic basis of (potentially adaptive) phenotypes in filamentous fungi. The advent of population genomics has contributed to firmly establish Neurospora as a complete model system and we hope our review will entice biologists to include Neurospora in their research

Generalized Painleve-Gullstrand descriptions of Kerr-Newman black holes

Generalized Painleve-Gullstrand metrics are explicitly constructed for the Kerr-Newman family of charged rotating black holes. These descriptions are free of all coordinate singularities; moreover, unlike the Doran and other proposed metrics, an extra tunable function is introduced to ensure all variables in the metrics remain real for all values of the mass M, charge Q, angular momentum aM, and cosmological constant \Lambda > - 3/(a^2). To describe fermions in Kerr-Newman spacetimes, the stronger requirement of non-singular vierbein one-forms at the horizon(s) is imposed and coordinate singularities are eliminated by local Lorentz boosts. Other known vierbein fields of Kerr-Newman black holes are analysed and discussed; and it is revealed that some of these descriptions are actually not related by physical Lorentz transformations to the original Kerr-Newman expression in Boyer-Lindquist coordinates - which is the reason complex components appear (for certain ranges of the radial coordinate) in these metrics. As an application of our constructions the correct effective Hawking temperature for Kerr black holes is derived with the method of Parikh and Wilczek.Comment: 5 pages; extended to include application to derivation of Hawking radiation for Kerr black holes with Parikh-Wilczek metho

Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study

The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world

Lorentz Violation in Warped Extra Dimensions

Higher dimensional theories which address some of the problematic issues of the Standard Model(SM) naturally involve some form of $D=4+n$-dimensional Lorentz invariance violation (LIV). In such models the fundamental physics which leads to, e.g., field localization, orbifolding, the existence of brane terms and the compactification process all can introduce LIV in the higher dimensional theory while still preserving 4-d Lorentz invariance. In this paper, attempting to capture some of this physics, we extend our previous analysis of LIV in 5-d UED-type models to those with 5-d warped extra dimensions. To be specific, we employ the 5-d analog of the SM Extension of Kostelecky et. al. ~which incorporates a complete set of operators arising from spontaneous LIV. We show that while the response of the bulk scalar, fermion and gauge fields to the addition of LIV operators in warped models is qualitatively similar to what happens in the flat 5-d UED case, the gravity sector of these models reacts very differently than in flat space. Specifically, we show that LIV in this warped case leads to a non-zero bulk mass for the 5-d graviton and so the would-be zero mode, which we identify as the usual 4-d graviton, must necessarily become massive. The origin of this mass term is the simultaneous existence of the constant non-zero $AdS_5$ curvature and the loss of general co-ordinate invariance via LIV in the 5-d theory. Thus warped 5-d models with LIV in the gravity sector are not phenomenologically viable.Comment: 14 pages, 4 figs; discussion added, algebra repaire

Lorentz violation, Gravity, Dissipation and Holography

We reconsider Lorentz Violation (LV) at the fundamental level. We show that Lorentz Violation is intimately connected with gravity and that LV couplings in QFT must always be fields in a gravitational sector. Diffeomorphism invariance must be intact and the LV couplings transform as tensors under coordinate/frame changes. Therefore searching for LV is one of the most sensitive ways of looking for new physics, either new interactions or modifications of known ones. Energy dissipation/Cerenkov radiation is shown to be a generic feature of LV in QFT. A general computation is done in strongly coupled theories with gravity duals. It is shown that in scale invariant regimes, the energy dissipation rate depends non-triviallly on two characteristic exponents, the Lifshitz exponent and the hyperscaling violation exponent.Comment: LateX, 51 pages, 9 figures. (v2) References and comments added. Misprints correcte

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

Advancing Tests of Relativistic Gravity via Laser Ranging to Phobos

Phobos Laser Ranging (PLR) is a concept for a space mission designed to advance tests of relativistic gravity in the solar system. PLR's primary objective is to measure the curvature of space around the Sun, represented by the Eddington parameter $\gamma$, with an accuracy of two parts in $10^7$, thereby improving today's best result by two orders of magnitude. Other mission goals include measurements of the time-rate-of-change of the gravitational constant, $G$ and of the gravitational inverse square law at 1.5 AU distances--with up to two orders-of-magnitude improvement for each. The science parameters will be estimated using laser ranging measurements of the distance between an Earth station and an active laser transponder on Phobos capable of reaching mm-level range resolution. A transponder on Phobos sending 0.25 mJ, 10 ps pulses at 1 kHz, and receiving asynchronous 1 kHz pulses from earth via a 12 cm aperture will permit links that even at maximum range will exceed a photon per second. A total measurement precision of 50 ps demands a few hundred photons to average to 1 mm (3.3 ps) range precision. Existing satellite laser ranging (SLR) facilities--with appropriate augmentation--may be able to participate in PLR. Since Phobos' orbital period is about 8 hours, each observatory is guaranteed visibility of the Phobos instrument every Earth day. Given the current technology readiness level, PLR could be started in 2011 for launch in 2016 for 3 years of science operations. We discuss the PLR's science objectives, instrument, and mission design. We also present the details of science simulations performed to support the mission's primary objectives.Comment: 25 pages, 10 figures, 9 table

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit