SAGP Program for 1962

Announcement of the meetings of the Society for Ancient Greek Philosophy with the Eastern Division of the American Philosophical Association and with the American Philological Association for 1962

Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons

In many strongly-interacting models of electroweak symmetry breaking the lowest-lying observable particle is a pseudo-Goldstone boson of approximate scale symmetry, the pseudo-dilaton. Its interactions with Standard Model particles can be described using a low-energy effective nonlinear chiral Lagrangian supplemented by terms that restore approximate scale symmetry, yielding couplings of the pseudo-dilaton that differ from those of a Standard Model Higgs boson by fixed factors. We review the experimental constraints on such a pseudo-dilaton in light of new data from the LHC and elsewhere. The effective nonlinear chiral Lagrangian has Skyrmion solutions that may be identified with the `electroweak baryons' of the underlying strongly-interacting theory, whose nature may be revealed by the properties of the Skyrmions. We discuss the finite-temperature electroweak phase transition in the low-energy effective theory, finding that the possibility of a first-order electroweak phase transition is resurrected. We discuss the evolution of the Universe during this transition and derive an order-of-magnitude lower limit on the abundance of electroweak baryons in the absence of a cosmological asymmetry, which suggests that such an asymmetry would be necessary if the electroweak baryons are to provide the cosmological density of dark matter. We revisit estimates of the corresponding spin-independent dark matter scattering cross section, with a view to direct detection experiments.Comment: 34 pages, 4 figures, additional references adde

Geometry of open strings ending on backreacting D3-branes

We investigate open string theory on backreacting D3-branes using a spacetime approach. We study in detail the half-BPS supergravity solutions describing open strings ending on D3-branes, in the near horizon of the D3-branes. We recover quantitatively several non-trivial features of open string physics including the appearance of D3-brane spikes, the polarization of fundamental strings into D5-branes, and the Hanany-Witten effect. Finally we detail the computation of the gravitational potential between two open strings, and contrast it with the holographic computation of Wilson lines. We argue that the D-brane backreaction has a large influence on the low-energy gravity, which may lead to experimental tests for string theory brane-world scenarios.Comment: 64 pages, 20 figure

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI)

Introduction It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g., OLS linear, random effects, mean, robust, spline, quadratic). Results A total of 245 participants completed utility interviews (51.4% female; mean age =45.3y). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g., R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE =0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions The recommended scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach

Composite Higgs Sketch

The coupling of a composite Higgs to the standard model fields can deviate substantially from the standard model values. In this case perturbative unitarity might break down before the scale of compositeness is reached, which would suggest that additional composites should lie well below this scale. In this paper we account for the presence of an additional spin 1 custodial triplet of rhos. We examine the implications of requiring perturbative unitarity up to the compositeness scale and find that one has to be close to saturating certain unitarity sum rules involving the Higgs and the rho couplings. Given these restrictions on the parameter space we investigate the main phenomenological consequences of the spin 1 triplet. We find that they can substantially enhance the Higgs di-photon rate at the LHC even with a reduced Higgs coupling to gauge bosons. The main existing LHC bounds arise from di-boson searches, especially in the experimentally clean channel where the charged rhos decay to a W-boson and a Z, which then decay leptonically. We find that a large range of interesting parameter space with 700 GeV < m(rho) < 2 TeV is currently experimentally viable.Comment: 37 pages, 12 figures; v4: sum rule corrected, conclusions unchange

Doubling up on supersymmetry in the Higgs sector

We explore the possibility that physics at the TeV scale possesses approximate N =2 supersymmetry, which is reduced to the N =1 minimal supersymmetric extension of the Standard Model (MSSM) at the electroweak scale. This doubling of supersymmetry modifies the Higgs sector of the theory, with consequences for the masses, mixings and couplings of the MSSM Higgs bosons, whose phenomenological consequences we explore in this paper. The mass of the lightest neutral Higgs boson h is independent of tan β at the tree level, and the decoupling limit is realized whatever the values of the heavy Higgs boson masses. Radiative corrections to the top quark and stop squarks dominate over those due to particles in N = 2 gauge multiplets. We assume that these radiative corrections fix mh ≃ 125 GeV, whatever the masses of the other neutral Higgs bosons H, A, a scenario that we term the h2MSSM. Since the H, A bosons decouple from the W and Z bosons in the h2MSSM at tree level, only the LHC constraints on H, A and H± couplings to fermions are applicable. These and the indirect constraints from LHC measurements of h couplings are consistent with mA ≳ 200 GeV for tan β ∈ (2, 8) in the h2MSSM

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Thermal Inflation and the Gravitational Wave Background

We consider the impact of thermal inflation -- a short, secondary period of inflation that can arise in supersymmetric scenarios -- on the stochastic gravitational wave background. We show that while the primordial inflationary gravitational wave background is essentially unchanged at CMB scales, it is massively diluted at solar system scales and would be unobservable by a BBO style experiment. Conversely, bubble collisions at the end of thermal inflation can generate a new stochastic background. We calculate the likely properties of the bubbles created during this phase transition, and show that the expected amplitude and frequency of this signal would fall within the BBO range.Comment: 21 pages, 4 figures; accepted for JCAP; a reference added; table reformatte

Exploiting antitumor immunity to overcome relapse and improve remission duration

Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient’s lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient’s own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib’s effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-γ-producing-CD8+, -CD4+, -NK cell, and IFN-γ-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types