A Genome-Wide Over-Expression Screen Identifies Genes Involved in Phagocytosis in the Human Protozoan Parasite, Entamoeba histolytica

Functional genomics and forward genetics seek to assign function to all known genes in a genome. Entamoeba histolytica is a protozoan parasite for which forward genetics approaches have not been extensively applied. It is the causative agent of amoebic dysentery and liver abscess, and infection is prevalent in developing countries that cannot prevent its fecal-oral spread. It is responsible for considerable global morbidity and mortality. Given that the E. histolytica genome has been sequenced, it should be possible to apply genomic approaches to discover gene function. We used a genome-wide over-expression screen to uncover genes regulating an important virulence function of E. histolytica, namely phagocytosis. We developed an episomal E. histolytica cDNA over-expression library, transfected the collection of plasmids into trophozoites, and applied a high-throughput screen to identify phagocytosis mutants in the population of over-expressing cells. The screen was based on the phagocytic uptake of human red blood cells loaded with the metabolic toxin, tubercidin. Expression plasmids were isolated from trophozoites that survived exposure to tubercidin-charged erythrocytes (phagocytosis mutants), and the cDNAs were sequenced. We isolated the gene encoding profilin, a well-characterized cytoskeleton-regulating protein with a known role in phagocytosis. This supports the validity of our approach. Furthermore, we assigned a phagocytic role to several genes not previously known to function in this manner. To our knowledge, this is the first genome-wide forward genetics screen to be applied to this pathogen. The study demonstrates the power of forward genetics in revealing genes regulating virulence in E. histolytica. In addition, the study validates an E. histolytica cDNA over-expression library as a valuable tool for functional genomics

Phenomenology of Hybrid Scenarios of Neutrino Dark Energy

We study the phenomenology of hybrid scenarios of neutrino dark energy, where in addition to a so-called Mass Varying Neutrino (MaVaN) sector a cosmological constant (from a false vacuum) is driving the accelerated expansion of the universe today. For general power law potentials we calculate the effective equation of state parameter w_{eff}(z) in terms of the neutrino mass scale. Due to the interaction of the dark energy field (acceleron) with the neutrino sector, w_{eff}(z) is predicted to become smaller than -1 for z>0, which could be tested in future cosmological observations. For the considered scenarios, the neutrino mass scale additionally determines which fraction of the dark energy is dynamical, and which originates from the cosmological constant like vacuum energy of the false vacuum. On the other hand, the field value of the acceleron field today as well as the masses of the right-handed neutrinos, which appear in the seesaw-type mechanism for small neutrino masses, are not fixed. This, in principle, allows to realise hybrid scenarios of neutrino dark energy with a high-scale seesaw where the right-handed neutrino masses are close to the GUT scale. We also comment on how MaVaN Hybrid Scenarios with high-scale seesaw might help to resolve stability problems of dark energy models with non-relativistic neutrinos.Comment: 22 pages, 5 figures; references and comments added; version to be published in JCA

The Tarantula Massive Binary Monitoring VI: Characterisation of hidden companions in 51 single-lined O-type binaries, a flat mass-ratio distribution, and black-hole binary candidates

We aim to hunt for massive binaries hosting a black hole companion (OB+BH) and establish the natal mass-ratio distribution of massive stars at the subsolar metallicity environment of the Large Magellanic Cloud (LMC). To this end, we use the shift-and-add grid disentangling technique to characterize the hidden companions in 51 SB1 O-type and evolved B-type binaries in the LMC monitored in the framework of the Tarantula Massive Binary Monitoring (TMBM). We find that, out of the 51 SB1 systems, 43 (84%) are found to have non-degenerate stellar companions, of which 28 are confident detections, and 15 are less certain (SB1: or SB2:). Of these 43 targets, one is found to be a triple (VFTS 64), and two are found to be quadruples (VFTS 120, 702). The remaining eight targets (16%) retain an SB1 classification. Aside from the unambiguous case of VFTS 243, analysed in detailed in a separate paper, we identify two additional OB+BH candidates: VFTS 514 and VFTS 779. Additional black holes may be present in the sample but at a lower probability. Our study firmly establishes a virtually flat natal mass-ratio distribution for O-type stars at LMC metallicity, covering the entire mass-ratio range (0.05 < q < 1) and periods in the range 0 < log P < 3 [d]. The nature of the OB+BH candidates should be verified through future monitoring, but the frequency of OB+BH candidates is generally in line with recent predictions at LMC metallicity.Comment: 41 pages (14 main article + 27 appendix), recommended for acceptance in A&A pending minor revisions, comments welcom

Lifshitz spacetimes from AdS null and cosmological solutions

We describe solutions of 10-dimensional supergravity comprising null deformations of $AdS_5\times S^5$ with a scalar field, which have $z=2$ Lifshitz symmetries. The bulk Lifshitz geometry in 3+1-dimensions arises by dimensional reduction of these solutions. The dual field theory in this case is a deformation of the N=4 super Yang-Mills theory. We discuss the holographic 2-point function of operators dual to bulk scalars. We further describe time-dependent (cosmological) solutions which have anisotropic Lifshitz scaling symmetries. We also discuss deformations of $AdS\times X$ in 11-dimensional supergravity, which are somewhat similar to the solutions above. In some cases here, we expect the field theory duals to be deformations of the Chern-Simons theories on M2-branes stacked at singularities.Comment: Latex, 29pgs, v3. references, minor clarifications (subsection on Lifshitz geometry seen by scalar probes) added, to appear in JHE

The particle number in Galilean holography

Recently, gravity duals for certain Galilean-invariant conformal field theories have been constructed. In this paper, we point out that the spectrum of the particle number operator in the examples found so far is not a necessary consequence of the existence of a gravity dual. We record some progress towards more realistic spectra. In particular, we construct bulk systems with asymptotic Schrodinger symmetry and only one extra dimension. In examples, we find solutions which describe these Schrodinger-symmetric systems at finite density. A lift to M-theory is used to resolve a curvature singularity. As a happy byproduct of this analysis, we realize a state which could be called a holographic Mott insulator.Comment: 29 pages, 1 rudimentary figure; v2: typo in eqn (3.4), added comments and ref

Unraveling Twisty Linear Polarization Morphologies in Black Hole Images

We investigate general relativistic magnetohydrodynamic simulations (GRMHD) to determine the physical origin of the twisty patterns of linear polarization seen in spatially resolved black hole images and explain their morphological dependence on black hole spin. By characterising the observed emission with a simple analytic ring model, we find that the twisty morphology is determined by the magnetic field structure in the emitting region. Moreover, the dependence of this twisty pattern on spin can be attributed to changes in the magnetic field geometry that occur due to the frame dragging. By studying an analytic ring model, we find that the roles of Doppler boosting and lensing are subdominant. Faraday rotation may cause a systematic shift in the linear polarization pattern, but we find that its impact is subdominant for models with strong magnetic fields and modest ion-to-electron temperature ratios. Models with weaker magnetic fields are much more strongly affected by Faraday rotation and have more complicated emission geometries than can be captured by a ring model. However, these models are currently disfavoured by the recent EHT observations of M87*. Our results suggest that linear polarization maps can provide a probe of the underlying magnetic field structure around a black hole, which may then be usable to indirectly infer black hole spins. The generality of these results should be tested with alternative codes, initial conditions, and plasma physics prescriptions.Comment: 25 pages, 19 figure

Revisiting the relevance of economic theory to hotel revenue management education and practice in the era of Big Data

Abstract This paper explores the role of economics in hospitality education and industry practice, with a particular focus on revenue management, and puts forward an argument for a return to the inclusion of economic theory in UK hospitality education, not seen since the 1990s. Given the increasing amounts of pricing data available to both managers and customers and the consequent market complexities now seen, developing economic literacy is demonstrated to be a crucial skill required for future hospitality graduates, allowing them to make successful revenue decisions and sense-check with confidence the decisions made by automated revenue systems. Economic literacy is defined as a balanced understanding of economic theory that can be applied in real-life business scenarios, extending beyond simple consideration of supply and demand to a mixture of neoclassical and behavioural approaches to economics

Distributed Parametric and Statistical Model Checking

Statistical Model Checking (SMC) is a trade-off between testing and formal verification. The core idea of the approach is to conduct some simulations of the system and verify if they satisfy some given property. In this paper we show that SMC is easily parallelizable on a master/slaves architecture by introducing a series of algorithms that scale almost linearly with respect to the number of slave computers. Our approach has been implemented in the UPPAAL SMC toolset and applied on non-trivial case studies.Comment: In Proceedings PDMC 2011, arXiv:1111.006

Povezanost između polimorfizama XRCC1 ARG399GLN i P53 ARG72PRO s rizikom od raka želuca i debeloga crijeva u turskoj populaciji

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall fi ve-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence. As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.Rak želuca najčešći je oblik karcinoma probavnoga sustava, a ukupno mu je preživljenje i dalje 15 % do 20 %, budući da se većinom dijagnosticira u poodmakloj fazi razvoja. S druge pak strane, premda rak debeloga crijeva ima prilično dobru prognozu, smrtnost je i dalje 50 %. Vjeruje se da je nastanak karcinoma povezan s reaktivnim radikalima koji uzrokuju stvaranje DNA-adukata, onemogućavaju popravak DNA te slabe supresiju tumora. Stoga bi bilo korisno razumjeti ulogu polimorfi zama gena za enzim XRCC1 koji sudjeluje u popravku isjecanjem nukleotida i tumor-supresorskoga gena p53 u nastanku raka želuca i debeloga crijeva. Naše je ispitivanje obuhvatilo 94 bolesnika s rakom želuca, 96 bolesnika s rakom debeloga crijeva te 108 kontrolnhih ispitanika (koji nisu oboljeli od bilo kojeg oblika raka) s ciljem da se utvrdi povezanost između polimorfi zama XRCC1 Arg399Gln i p53 Arg72Pro i sklonosti nastanku raka. DNA je dobiven iz stanica periferne krvi, a genotip utvrđen s pomoću metode lančane reakcije polimerazom - polimorfi zma restrikcijskih fragmenata na osnovi dužine (PCRRLFP). Polimorfi zam p53 Arg72Pro nije se pokazao povezanim s povećanim rizikom od raka želuca ili debeloga crijeva niti je XRCC1 Arg399Gln bio povezan s povećanim rizikom od raka debeloga crijeva, ali je zato rizik od raka želuca u homozigotnih nositelja ovoga polimorfi zma bio 2,54 puta veći