Unconventional superstring derived E6_{\bf 6} models and neutrino phenomenology

Conventional superstring derived E$_6$ models can accommodate small neutrino masses if a discrete symmetry is imposed which forbids tree level Dirac neutrino masses but allows for radiative mass generation. Since the only possible symmetries of this kind are known to be generation dependent, we explore the possibility that the three sets of light states in each generation do not have the same assignments with respect to the 27 of $E_6$, leading to non universal gauge interactions under the additional $U(1)'$ factors for the known fermions. We argue that models realising such a scenario are viable, with their structure being constrained mainly by the requirement of the absence of flavor changing neutral currents in the Higgs sector. Moreover, in contrast to the standard case, rank 6 models are not disfavoured with respect to rank 5. By requiring the number of light neutral states to be minimal, these models have an almost unique pattern of neutrino masses and mixings. We construct a model based on the unconventional assignment scenario in which (with a natural choice of the parameters) m_{\nut}\sim O(10)eV is generated at one loop, m_{\num} is generated at two loops and lies in a range interesting for the solar neutrino problem, and \nue remains massless. In addition, since baryon and lepton number are conserved, there is no proton decay in the model. To illustrate the non-standard phenomenology implied by our scheme we also discuss a second scenario in which an attempt for solving the solar neutrino puzzle with matter enhanced oscillations and practically massless neutrinos can be formulated, and in which peculiar effects for the \num --> \nut conversion of the upward-going atmospheric neutrinos could arise as well.Comment: Plain Tex, 33 pages, 3 PostScript figures (uses epsf.tex). Modified file-format. No changes in the tex

Large N and Bosonization in Three Dimensions

Bosonization is normally thought of as a purely two-dimensional phenomenon, and generic field theories with fermions in D>2 are not expected be describable by local bosonic actions, except in some special cases. We point out that 3D SU(N) gauge theories on R^{1,1} x S^{1}_{L} with adjoint fermions can be bosonized in the large N limit. The key feature of such theories is that they enjoy large N volume independence for arbitrary circle size L. A consequence of this is a large N equivalence between these 3D gauge theories and certain 2D gauge theories, which matches a set of correlation functions in the 3D theories to corresponding observables in the 2D theories. As an example, we focus on a 3D SU(N) gauge theory with one flavor of adjoint Majorana fermions and derive the large-N equivalent 2D gauge theory. The extra dimension is encoded in the color degrees of freedom of the 2D theory. We then apply the technique of non-Abelian bosonization to the 2D theory to obtain an equivalent local theory written purely in terms of bosonic variables. Hence the bosonized version of the large N three-dimensional theory turns out to live in two dimensions.Comment: 30 pages, 2 tables. v2 minor revisions, references adde

The 2009 World Average of αs\alpha_s

Measurements of $\alpha_s$, the coupling strength of the Strong Interaction between quarks and gluons, are summarised and an updated value of the world average of $\alpha_s (M_Z)$ is derived. Building up on previous reviews, special emphasis is laid on the most recent determinations of $\alpha_s$. These are obtained from $\tau$-decays, from global fits of electroweak precision data and from measurements of the proton structure function \F_2, which are based on perturbative QCD calculations up to $O(\alpha_s^4)$; from hadronic event shapes and jet production in \epem annihilation, based on $O(\alpha_s^3)$ QCD; from jet production in deep inelastic scattering and from $\Upsilon$ decays, based on $O(\alpha_s^2)$ QCD; and from heavy quarkonia based on unquenched QCD lattice calculations. Applying pragmatic methods to deal with possibly underestimated errors and/or unknown correlations, the world average value of $\alpha_s (M_Z)$ results in $\alpha_s (M_Z) = 0.1184 \pm 0.0007$. The measured values of $\alpha_s (Q)$, covering energy scales from Q \equiv \mtau = 1.78 GeV to 209 GeV, exactly follow the energy dependence predicted by QCD and therefore significantly test the concept af Asymptotic Freedom.Comment: 14 pages, 7 figure

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications.

Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three subsets of metastatic disease: permeable metastases, nonpermeable metastases, and solitary, dormant cancer cells, which likely have very different biology and responses to therapy. The ability to simultaneously monitor the spatial and temporal distribution of dormant cancer cells, metastatic growth, and associated tumor permeability can provide great insight into factors that contribute to malignant proliferation. Our preclinical findings suggest that standard clinical detection strategies may underestimate the true metastatic burden of breast cancer that has metastasized to the brain. A better understanding of true metastatic burden in brains will be important to assist in the development of more effective chemotherapeutics-particularly those targeted to cross the BBB-as well as detection of small nonpermeable metastases

Species Tree Estimation for the Late Blight Pathogen, Phytophthora infestans, and Close Relatives

To better understand the evolutionary history of a group of organisms, an accurate estimate of the species phylogeny must be known. Traditionally, gene trees have served as a proxy for the species tree, although it was acknowledged early on that these trees represented different evolutionary processes. Discordances among gene trees and between the gene trees and the species tree are also expected in closely related species that have rapidly diverged, due to processes such as the incomplete sorting of ancestral polymorphisms. Recently, methods have been developed for the explicit estimation of species trees, using information from multilocus gene trees while accommodating heterogeneity among them. Here we have used three distinct approaches to estimate the species tree for five Phytophthora pathogens, including P. infestans, the causal agent of late blight disease in potato and tomato. Our concatenation-based “supergene” approach was unable to resolve relationships even with data from both the nuclear and mitochondrial genomes, and from multiple isolates per species. Our multispecies coalescent approach using both Bayesian and maximum likelihood methods was able to estimate a moderately supported species tree showing a close relationship among P. infestans, P. andina, and P. ipomoeae. The topology of the species tree was also identical to the dominant phylogenetic history estimated in our third approach, Bayesian concordance analysis. Our results support previous suggestions that P. andina is a hybrid species, with P. infestans representing one parental lineage. The other parental lineage is not known, but represents an independent evolutionary lineage more closely related to P. ipomoeae. While all five species likely originated in the New World, further study is needed to determine when and under what conditions this hybridization event may have occurred

Sonographic assessment of renal length in children: A reappraisal

Ultrasonography (US) has largely replaced the intravenous urogram as the first modality for the evaluation of the kidneys in children suspected of having urinary tract abnormalities. Because many renal disorders are associated with changes in the sizes of the kidneys, normative standards for assessing renal size have been developed. These standards rely upon comparison of the renal lengths or calculated volumes or both, with various assessments of overall body size, including body surface area, weight, height, and chronological age. We discuss some of the limitations of US in assessing renal size in children. Practical recommendations are offered for optimizing the measurement and interpretation of sonographic renal sizes in children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46703/1/247_2005_Article_BF02020164.pd

Phylogeny and evolution of life-history strategies in the Sycophaginae non-pollinating fig wasps (Hymenoptera, Chalcidoidea)

<p>Abstract</p> <p>Background</p> <p>Non-pollinating Sycophaginae (Hymenoptera, Chalcidoidea) form small communities within <it>Urostigma </it>and <it>Sycomorus </it>fig trees. The species show differences in galling habits and exhibit apterous, winged or dimorphic males. The large gall inducers oviposit early in syconium development and lay few eggs; the small gall inducers lay more eggs soon after pollination; the ostiolar gall-inducers enter the syconium to oviposit and the cleptoparasites oviposit in galls induced by other fig wasps. The systematics of the group remains unclear and only one phylogeny based on limited sampling has been published to date. Here we present an expanded phylogeny for sycophagine fig wasps including about 1.5 times the number of described species. We sequenced mitochondrial and nuclear markers (4.2 kb) on 73 species and 145 individuals and conducted maximum likelihood and Bayesian phylogenetic analyses. We then used this phylogeny to reconstruct the evolution of Sycophaginae life-history strategies and test if the presence of winged males and small brood size may be correlated.</p> <p>Results</p> <p>The resulting trees are well resolved and strongly supported. With the exception of <it>Apocrytophagus</it>, which is paraphyletic with respect to <it>Sycophaga</it>, all genera are monophyletic. The Sycophaginae are divided into three clades: (i) <it>Eukoebelea</it>; (ii) <it>Pseudidarnes</it>, <it>Anidarnes </it>and <it>Conidarnes </it>and (iii) <it>Apocryptophagus</it>, <it>Sycophaga </it>and <it>Idarnes</it>. The ancestral states for galling habits and male morphology remain ambiguous and our reconstructions show that the two traits are evolutionary labile.</p> <p>Conclusions</p> <p>The three main clades could be considered as tribes and we list some morphological characters that define them. The same biologies re-evolved several times independently, which make Sycophaginae an interesting model to test predictions on what factors will canalize the evolution of a particular biology. The ostiolar gall-inducers are the only monophyletic group. In 15 Myr, they evolved several morphological adaptations to enter the syconia that make them strongly divergent from their sister taxa. Sycophaginae appears to be another example where sexual selection on male mating opportunities favored winged males in species with small broods and wingless males in species with large broods. However, some species are exceptional in that they lay few eggs but exhibit apterous males, which we hypothesize could be due to other selective pressures selecting against the re-appearance of winged morphs.</p

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