A Lorentz-Violating Alternative to Higgs Mechanism?

We consider a four-dimensional field-theory model with two massless fermions, coupled to an Abelian vector field without flavour mixing, and to another Abelian vector field with flavour mixing. Both Abelian vectors have a Lorentz-violating kinetic term, introducing a Lorentz-violation mass scale $M$, from which fermions and the flavour-mixing vector get their dynamical masses, whereas the vector coupled without flavour mixing remains massless. When the two coupling constants have similar values in order of magnitude, a mass hierarchy pattern emerges, in which one fermion is very light compared to the other, whilst the vector mass is larger than the mass of the heavy fermion. The work presented here may be considered as a Lorentz-symmetry-Violating alternative to the Higgs mechanism, in the sense that no scalar particle (fundamental or composite) is necessary for the generation of the vector-meson mass. However, the model is not realistic given that, as a result of Lorentz Violation, the maximal (light-cone) speed seen by the fermions is smaller than that of the massless gauge boson (which equals the speed of light in vacuo) by an amount which is unacceptably large to be compatible with the current tests of Lorentz Invariance, unless the gauge couplings assume unnaturally small values. Possible ways out of this phenomenological drawback are briefly discussed, postponing a detailed construction of more realistic models for future work.Comment: 16 pages revtex, three eps figures incorporate

The spread, treatment, and prevention of HIV-1: evolution of a global pandemic

The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference — male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise

The complete genome sequence of a Neandertal from the Altai Mountains

We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A forensic STR profiling system for the Eurasian badger: a framework for developing profiling systems for wildlife species

Developing short tandem repeat (STR) profiling systems for forensic identification is complicated in animal species. Obtaining a representative number of individuals from populations, limited access to family groups and a lack of developed STR markers can make adhering to human forensic guidelines difficult. Furthermore, a lack of animal specific guidelines may explain why many wildlife forensic STR profiling systems developed to date have not appropriately addressed areas such as marker validation or the publication and analysis of population data necessary for the application of these tools to forensic science. Here we present a methodology used to develop an STR profiling system for a legally protected wildlife species, the Eurasian badger Meles meles. Ten previously isolated STR loci were selected based on their level of polymorphism, adherence to Hardy-Weinberg expectations and their fragment size. Each locus was individually validated with respect to its reproducibility, inheritance, species specificity, DNA template concentration and thermocycling parameters. The effects of chemical, substrate and environmental exposure were also investigated. All ten STR loci provided reliable and reproducible results, and optimal amplification conditions were defined. Allele frequencies from 20 representative populations in England and Wales are presented and used to calculate the level of population substructure (theta) and inbreeding (f). Accounting for these estimates, the average probability of identity (PIave) was 2.18 x 10(-7). This case study can act as a framework for others attempting to develop wildlife forensic profiling systems. (C) 2007 Elsevier Ireland Ltd. All rights reserved

The complete genome sequence of a Neanderthal from the Altai Mountains.

We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans