Fos co-operation with PTEN loss elicits keratoacanthoma not carcinoma due to p53/p21^WAF-induced differentiation triggered by GSK3b inactivation and reduced AKT activity

To investigate gene synergism in multistage skin carcinogenesis, the RU486-inducible cre/lox system was employed to ablate PTEN function [K14.cre/D5PTENflx] in mouse epidermis expressing activated v-fos [HK1.fos]. RU486-treated HK1.fos/D5PTENflx mice exhibited hyperplasia, hyperkeratosis and tumours that progressed to highly differentiated keratoacanthomas rather than carcinomas, due to re-expression of high p53 and p21WAF levels. Despite elevated MAP kinase activity, cyclin D1/E2 over expression and increased AKT activity forming areas of highly proliferative, papillomatous keratinocytes, increasing levels of GSK3b inactivation exceeded a threshold that induced p53/p21WAF expression to halt proliferation and accelerate differentiation, giving the hallmark keratosis of keratoacanthomas. A pivotal facet to this GSK3b-triggered mechanism centred on increasing p53 expression in basal layer keratinocytes. This reduced activated AKT expression and released inhibition of p21WAF, which accelerated keratinocyte differentiation, as indicated by unique basal layer expression of differentiation-specific keratin K1, alongside premature filaggrin and loricrin expression. Thus, fos synergism with PTEN loss elicited a benign tumour context where GSK3b-induced, p53/p21WAF expression continually switched AKT-associated proliferation into one of differentiation, preventing further progression. This putative compensatory mechanism required the critical availability of normal p53 and/or p21WAF otherwise deregulated fos, Akt and GSK3b associate with malignant progression

Conceptual Ecological Modelling of Shallow Sublittoral Sand Habitats to Inform Indicator Selection

The purpose of this study is to produce a series of conceptual ecological models (CEMs) which represent shallow sublittoral sand habitats in the UK. CEMs are diagrammatic representations of the influences and processes which occur within an ecosystem. They can be used to identify critical aspects of an ecosystem which may be taken forward for further study, or serve as the basis for the selection of indicators for environmental monitoring purposes. The models produced by this project are control diagrams, representing the unimpacted state of the environment free from anthropogenic pressures. The project scope included the Marine Strategy Framework Directive (MSFD) predominant habitat type ‘shallow sublittoral sand’. This definition includes those habitats which fall into the EUNIS Level 4 classifications A5.23 Infralittoral Fine Sand, A5.24 Infralittoral Muddy Sand, A5.25 Circalittoral Fine Sand and A5.26 Circalittoral Muddy Sand, along with their constituent Level 5 biotopes which are relevant to UK waters. A species list of characterising fauna to be included within the scope of the models was identified using an iterative process to refine the full list of species found within the relevant Level 5 biotopes. A literature review was conducted to gather evidence regarding species traits and information to inform the models. All information gathered during the literature review was entered into a data logging pro forma spreadsheet which accompanies this report. Wherever possible, attempts were made to collect information from UK-specific peer-reviewed studies, although other sources were used where necessary. All data gathered was subject to a detailed confidence assessment. Expert judgement by the project team was utilised to provide information for aspects of the models for which references could not be sourced within the project timeframe. A model hierarchy was developed based on groups of fauna with similar species traits which aligned with previous sensitivity studies of ecological groups. A general model was produced to indicate the high level drivers, inputs, biological assemblages, ecosystem processes and outputs which occur in shallow sublittoral sand habitats. In addition to this, four detailed sub-models were produced. Each focussed on a particular functional group of fauna within the habitat: “suspension and deposit feeding infauna”, “small mobile fauna and tube dwelling species”, “mobile epifauna, scavengers and predators”, and “attached epifauna and macroalgae”. Each sub-model is accompanied by an associated confidence model which presents confidence in the links between each model component. The models are split into seven levels and take spatial and temporal scale into account through their design, as well as magnitude and direction of influence. The seven levels include regional to global drivers, water column processes, local inputs/processes at the seabed, habitat and biological assemblage, output processes, local ecosystem functions, and regional to global ecosystem functions. The models indicate that whilst the high level drivers which affect each functional group are largely similar, the output processes performed by the biota and the resulting ecosystem functions vary both in number and importance between groups. Confidence within the models as a whole is generally high, reflecting the level of information gathered during the literature review. Important drivers which influence the ecosystem include factors such as wave exposure, depth, water currents, climate and propagule supply. These factors, in combination with seabed and water column processes such as primary production, seabed mobility, suspended sediments, water chemistry and temperature and recruitment define and influence the biological assemblages. In addition, the habitat sediment type plays an important factor in shaping the biology of the habitat. Conceptual Ecological Modelling of Shallow Sublittoral Sand Habitats Output processes are variable between functional faunal groups depending on the fauna present. Important processes include secondary production, biodeposition, bioturbation, bioengineering and the supply of propagules. These influence ecosystem functions at the local scale such as nutrient and biogeochemical cycling, supply of food resources, sediment stability, habitat provision and in some cases microbial activity. The export of biodiversity and organic matter, biodiversity enhancement and biotope stability are the resulting ecosystem functions which occur at the regional to global scale. Features within the models which are most useful for monitoring habitat status and change due to natural variation have been identified using the information gathered during the literature review, through interpretation of the models and through the application of expert judgement. Features within the models which may be useful for monitoring to identify anthropogenic causes of change within the ecosystem have also been identified. Physical and biological features of the ecosystem have mostly been identified as potential indicators to monitor natural variation, whilst physical features and output processes have predominantly been identified as most likely to indicate change due to anthropogenic pressures

Conceptual Ecological Modelling of Shallow Sublittoral Mixed Sediment Habitats to Inform Indicator Selection.

The purpose of this study is to produce a series of conceptual ecological models (CEMs) which represent shallow sublittoral mixed sediment habitats in the UK. CEMs are diagrammatic representations of the influences and processes which occur within an ecosystem. They can be used to identify critical aspects of an ecosystem which may be taken forward for further study, or serve as the basis for the selection of indicators for environmental monitoring purposes. The models produced by this project are control diagrams, representing the unimpacted state of the environment free from anthropogenic pressures. The project scope included the Marine Strategy Framework Directive (MSFD) predominant habitat type ‘shallow sublittoral mixed sediment’. This definition includes those habitats which fall into the EUNIS Level 4 classifications A5.43 Infralittoral Mixed Sediments and A5.44 Circalittoral Mixed Sediments, along with their constituent Level 5 biotopes which are relevant to UK waters. A species list of characterising fauna to be included within the scope of the models was identified using an iterative process to refine the full list of species found within the relevant Level 5 biotopes. A literature review was conducted to gather evidence regarding species traits and information to inform the models. All information gathered during the literature review was entered into a data logging pro forma spreadsheet which accompanies this report. Wherever possible, attempts were made to collect information from UK-specific peer-reviewed studies, although other sources were used where necessary. All data gathered was subject to a detailed confidence assessment. Expert judgement by the project team was utilised to provide information for aspects of the models for which references could not be sourced within the project timeframe. A model hierarchy was developed based on groups of fauna with similar species traits which aligned with previous sensitivity studies of ecological groups. A general model was produced to indicate the high level drivers, inputs, biological assemblages, ecosystem processes and outputs which occur in shallow sublittoral mixed sediment habitats. In addition to this, five detailed sub-models were produced. Each focussed on a particular functional group of fauna within the habitat: ‘temporary or permanently attached epifauna’, ‘mobile epifauna, scavengers and predators’, ‘suspension and deposit feeding fauna’, ‘temporary or permanently attached surface dwelling or shallowly buried larger bivalves’ and ‘small mobile epifauna and tube dwelling crustaceans’. Each sub-model is accompanied by an associated confidence model which presents confidence in the links between each model component. The models are split into seven levels and take spatial and temporal scale into account through their design, as well as magnitude and direction of influence. The seven levels include regional to global drivers, water column processes, local inputs/processes at the seabed, habitat and biological assemblage, output processes, local ecosystem functions, and regional to global ecosystem functions. The models indicate that whilst the high level drivers which affect each functional group are largely similar, the output processes performed by the biota and the resulting ecosystem functions vary both in number and importance between groups. Confidence within the models as a whole is generally high, reflecting the level of information gathered during the literature review. Important drivers which influence the ecosystem include factors such as wave exposure, depth, water currents, climate and propagule supply. These factors, in combination with seabed and water column processes such as primary production, seabed mobility, suspended sediments, water chemistry and temperature and recruitment define and Conceptual Ecological Modelling of Shallow Sublittoral Mixed Sediment Habitats influence the biological assemblages. In addition, the habitat sediment type plays an important factor in shaping the biology of the habitat. Output processes are variable between functional faunal groups depending on the fauna present. Important processes include secondary production, biodeposition, bioturbation, bioengineering and the supply of propagules. These influence ecosystem functions at the local scale such as nutrient and biogeochemical cycling, supply of food resources, sediment stability, habitat provision and in some cases microbial activity. The export of biodiversity and organic matter, biodiversity enhancement and biotope stability are the resulting ecosystem functions which occur at the regional to global scale. Features within the models which are most useful for monitoring habitat status and change due to natural variation have been identified using the information gathered during the literature review, through interpretation of the models and through the application of expert judgement. Features within the models which may be useful for monitoring to identify anthropogenic causes of change within the ecosystem have also been identified. Physical and biological features of the ecosystem have mostly been identified as potential indicators to monitor natural variation, whilst physical features and output processes have predominantly been identified as most likely to indicate change due to anthropogenic pressures

Linear Perturbations in Brane Gas Cosmology

We consider the effect of string inhomogeneities on the time dependent background of Brane Gas Cosmology. We derive the equations governing the linear perturbations of the dilaton-gravity background in the presence of string matter sources. We focus on long wavelength fluctuations and find that there are no instabilities. Thus, the predictions of Brane Gas Cosmology are robust against the introduction of linear perturbations. In particular, we find that the stabilization of the extra dimensions (moduli) remains valid in the presence of dilaton and string perturbations.Comment: 17 pages, 1 figur

The use of egg attenuated bluetongue virus in the production of a polyvalent vaccine for sheep. A. Propagation of the virus in sheep

(1) A brief description of Theiler's classical method of bluetongue vaccine production is given and various modifications introduced from time to time are recorded. (2) In an attempt to adapt the recognized technique to the routine mass production of a polyvalent vaccine using fully attenuated egg adapted (A) strains of virus three difficulties were encountered : (a) As a result of even a single passage through susceptible sheep the adapted (A) strains were transformed at least partially into apparently original or sheep strains (O) so that quantitative control could not be carried out in eggs. (b) During the course of change from the A to the pseudo-O phase at least some strains show a marked change in antigenic structure. (c) Since the majority of sheep infected with egg attenuated virus show no clinical reaction it is impossible to eliminate animals included by accident amongst the virus donors. In the final mixture specific antibodies in the serum of such immune sheep neutralize the virus propagated in the susceptible donors, thus making the vaccine inert. This has proved an insurmountable difficulty. (3) Though passage through sheep causes a change from the A to the pseudo-O type of virus there is no reversion to original virulence.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

T and S dualities and The cosmological evolution of the dilaton and the scale factors

Cosmologically stabilizing radion along with the dilaton is one of the major concerns of low energy string theory. One can hope that T and S dualities can provide a plausible answer. In this work we study the impact of S and T duality invariances on dilaton gravity. We have shown various instances where physically interesting models arise as a result of imposing the mentioned invariances. In particular S duality has a very privileged effect in that the dilaton equations partially decouple from the evolution of the scale factors. This makes it easy to understand the general rules for the stabilization of the dilaton. We also show that certain T duality invariant actions become S duality invariance compatible. That is they mimic S duality when extra dimensions stabilize.Comment: Corrected a misleading interpretation of the S duality transformation and a wrong comment on d=10. I thank A.Kaya for pointing this out to me in time. So the new version is dealing with d=10 only. Added references and corrected some typos. Minor re-editing. Omitted a section for elaboration in a further study. Corrected further typo

Brane Gas Cosmology, M-theory and Little String Theory

We generalize the Brane Gas Cosmological Scenario to M-theory degrees of freedom, namely $M5$ and $M2$ branes. Without brane intersections, the Brandenberger Vafa(BV) arguments applied to M-theory degrees of freedom generically predict a large 6 dimensional spacetime. We show that intersections of $M5$ and $M2$ branes can instead lead to a large 4 dimensional spacetime. One dimensional intersections in 11D is related to (2,0) little strings (LST) on NS5 branes in type IIA. The gas regime of membranes in M-theory corresponds to the thermodynamics of LST obtained from holography. We propose a mechanism whereby LST living on the worldvolume of NS5 (M5)-branes wrapping a five dimensional torus, annihilate most efficiently in 3+1 dimensions leading to a large 3+1 dimensional spacetime. We also show that this picture is consistent with the gas approximation in M-theory.Comment: 8 page

Vortex ordering in fully-frustrated superconducting systems with dice lattice

The structure and the degenracy of the ground state of a fully-frustrated XY-model are investigated for the case of a dice lattice geometry. The results are applicable for the description of Josephson junction arrays and thin superconducting wire networks in the external magnetic field providing half-integer number of flux quanta per plaquette. The mechanisms of disordering of vortex pattern in such systems are briefly discussed.Comment: 10 pages, 3 figure

Detailed analysis of paternal knockout <i>Grb10 </i>mice suggests effects on stability of social behavior, rather than social dominance

Imprinted genes are highly expressed in monoaminergic regions of the midbrain and their functions in this area are thought to have an impact on mammalian social behaviors. One such imprinted gene is Grb10, of which the paternal allele is generally recognized as mediating social dominance behavior. However, there has been no detailed study of social dominance in Grb10 +/p mice. Moreover, the original study examined tube‐test behavior in isolated mice 10 months of age. Isolation testing favors more territorial and aggressive behaviors, and does not address social dominance strategies employed in group housing contexts. Furthermore, isolation stress impacts midbrain function and dominance related behavior, often through alterations in monoaminergic signaling. Thus, we undertook a systematic study of Grb10 +/p social rank and dominance behavior within the cage group, using a number of convergent behavioral tests. We examined both male and female mice to account for sex differences and tested cohorts aged 2, 6 and 10 months to examine any developments related to age. We found group‐housed Grb10 +/p mice do not show evidence of enhanced social dominance, but cages containing Grb10 +/p and wild‐type mice lacked the normal correlation between three different measures of social rank. Moreover, a separate study indicated isolation stress induced inconsistent changes in tube test behavior. Taken together, these data suggest future research on Grb10 +/p mice should focus on the stability of social behaviors, rather than dominance per se

Synchrotron studies of top-down grown silicon nanowires

Morphology of the top-down grown silicon nanowires obtained by metal-assisted wet-chemical approach on silicon substrates with different resistance were studied by scanning electron microscopy. Obtained arrays of compact grown Si nanowires were a subject for the high resolution electronic structures studies by X-ray absorption near edge structure technique performed with the usage of high intensity synchrotron radiation of the SRC storage ring of the University of Wisconsin-Madison. The different oxidation rates were found by investigation of silicon atoms local surrounding specificity of the highly developed surface and near surface layer that is not exceeded 70 nm. Flexibility of the wires arrays surface morphology and its composition is demonstrated allowing smoothly form necessary surface oxidation rate and using Si nanowires as a useful matrixes for a wide range of further functionalization