Unifying phantom inflation with late-time acceleration: scalar phantom-non-phantom transition model and generalized holographic dark energy

The unifying approach to early-time and late-time universe based on phantom cosmology is proposed. We consider gravity-scalar system which contains usual potential and scalar coupling function in front of kinetic term. As a result, the possibility of phantom-non-phantom transition appears in such a way that universe could have effectively phantom equation of state at early time as well as at late time. In fact, the oscillating universe may have several phantom and non-phantom phases. As a second model we suggest generalized holographic dark energy where infrared cutoff is identified with combination of FRW parameters: Hubble constant, particle and future horizons, cosmological constant and universe life-time (if finite). Depending on the specific choice of the model the number of interesting effects occur: the possibility to solve the coincidence problem, crossing of phantom divide and unification of early-time inflationary and late-time accelerating phantom universe. The bound for holographic entropy which decreases in phantom era is also discussed.Comment: 13 pages, clarifications/refs added, to match with published versio

Could Only Fermions Be Elementary?

In standard Poincare and anti de Sitter SO(2,3) invariant theories, antiparticles are related to negative energy solutions of covariant equations while independent positive energy unitary irreducible representations (UIRs) of the symmetry group are used for describing both a particle and its antiparticle. Such an approach cannot be applied in de Sitter SO(1,4) invariant theory. We argue that it would be more natural to require that (*) one UIR should describe a particle and its antiparticle simultaneously. This would automatically explain the existence of antiparticles and show that a particle and its antiparticle are different states of the same object. If (*) is adopted then among the above groups only the SO(1,4) one can be a candidate for constructing elementary particle theory. It is shown that UIRs of the SO(1,4) group can be interpreted in the framework of (*) and cannot be interpreted in the standard way. By quantizing such UIRs and requiring that the energy should be positive in the Poincare approximation, we conclude that i) elementary particles can be only fermions. It is also shown that ii) C invariance is not exact even in the free massive theory and iii) elementary particles cannot be neutral. This gives a natural explanation of the fact that all observed neutral states are bosons.Comment: The paper is considerably revised and the following results are added: in the SO(1,4) invariant theory i) the C invariance is not exact even for free massive particles; ii) neutral particles cannot be elementar

Interacting entropy-corrected holographic dark energy with apparent horizon as an infrared cutoff

In this work we consider the entropy-corrected version of interacting holographic dark energy (HDE), in the non-flat universe enclosed by apparent horizon. Two corrections of entropy so-called logarithmic 'LEC' and power-law 'PLEC' in HDE model with apparent horizon as an IR-cutoff are studied. The ratio of dark matter to dark energy densities $u$, equation of state parameter $w_D$ and deceleration parameter $q$ are obtained. We show that the cosmic coincidence is satisfied for both interacting models. By studying the effect of interaction in EoS parameter, we see that the phantom divide may be crossed and also find that the interacting models can drive an acceleration expansion at the present and future, while in non-interacting case, this expansion can happen only at the early time. The graphs of deceleration parameter for interacting models, show that the present acceleration expansion is preceded by a sufficiently long period deceleration at past. Moreover, the thermodynamical interpretation of interaction between LECHDE and dark matter is described. We obtain a relation between the interaction term of dark components and thermal fluctuation in a non-flat universe, bounded by the apparent horizon. In limiting case, for ordinary HDE, the relation of interaction term versus thermal fluctuation is also calculated.Comment: 20 pages, 8 figures, figures changed, some Ref. is added, changed some sentences, accepted by General relativity and gravitation (GERG

T cell receptor binding affinity governs the functional profile of cancer-specific CD8+T cells

Antigen-specific T cell receptor (TCR) gene transfer via patient-derived T cells is an attractive approach to cancer therapy, with the potential to circumvent immune regulatory networks. However, high-affinity tumour-specific TCR clonotypes are typically deleted from the available repertoire during thymic selection because the vast majority of targeted epitopes are derived from autologous proteins. This process places intrinsic constraints on the efficacy of T cell-based cancer vaccines and therapeutic strategies that employ naturally generated tumour-specific TCRs. In this study, we used altered peptide ligands and lentivirus-mediated transduction of affinity-enhanced TCRs selected by phage display to study the functional properties of CD8+ T cells specific for three different tumour-associated peptide antigens across a range of binding parameters. The key findings were: (i) TCR affinity controls T cell antigen sensitivity and polyfunctionality; (ii) supraphysiological affinity thresholds exist, above which T cell function cannot be improved; and (iii) T cells transduced with very high-affinity TCRs exhibit cross-reactivity with self-derived peptides presented by the restricting human leucocyte antigen. Optimal system-defined affinity windows above the range established for natural tumour-specific TCRs therefore allow the enhancement of T cell effector function without off-target effects. These findings have major implications for the rational design of novel TCR-based biologics underpinned by rigorous preclinical evaluation

In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo

Hypoxia is an important selective force in the clonal evolution of tumours. Through HIF-1 and other transcription factors combined with tumour-specific genetic alterations, hypoxia is a dominant factor in the angiogenic phenotype. Cellular adaptation to hypoxia is an important requirement of tumour progression independent of angiogenesis. The adaptive changes, insofar as they alter hypoxia-induced apoptosis, are likely to determine responsiveness to antiangiogenic strategies. To investigate this adaptation of tumour cells to hypoxia, we recreated in vitro the in vivo situation of chronic intermittent exposure to low-oxygen levels. The colon carcinoma cell lines HT29 and HCT116 were subjected to 40 episodes of sublethal hypoxia (4 h) three times a week. The resulting two hypoxia-conditioned cell lines have been maintained in culture for more than 2 years. In both cell lines changes in doubling times occurred: in HT29 an increase, and in HCT116 a decrease. Cell survival in response to hypoxia and to DNA damage differed strikingly in the two cell lines. The HT29 hypoxia-conditioned cells were more resistant than the parental line to a 24 h hypoxic challenge, while those from HCT116 surprisingly were more sensitive. Sensitivity to cisplatin in vitro was also significantly different for the hypoxia-conditioned compared with the parental lines, suggesting a change in pathways leading to apoptosis following DNA damage signaling. The growth of both conditioned cell lines in vivo as xenografts in immunodeficient (SCID) mice was more rapid than their parental lines, and was accompanied in each by evidence of enhanced vascular proliferation as a consequence of the hypoxia-conditioning. Thus the changes in apoptotic susceptibility were independent of altered angiogenesis. The derivation of these lines provides a model for events within hypoxic regions of colon cancers, and for the acquisition of resistance and sensitivity characteristics that may have therapeutic implications for the use of antiangiogenesis drugs

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior