Strong-coupling expansions for chiral models of electroweak symmetry breaking

We consider chiral $U(N)\times U(N)$ models with fermions in the limit of infinitely large local bare Yukawa coupling. When the scalar field is subject to non-linear constraint, phase transitions in these models are seen to be identical to those in the corresponding purely bosonic ones. Relaxing the non-linear constraint, we compute the seventh-order strong-coupling series for the susceptibility in these models and analyze them numerically for the $U(2)\times U(2)$ case. We find that in four dimensions the approach to the phase transition follows to a good accuracy the mean-field critical behavior, indicating the absence of non-trivial fixed points at strong coupling and being consistent with the first-order nature of the transition. In three dimensions, the strongly-coupled bosonic $U(2)\times U(2)$ model (without gauge fields) has a first-order transition strong enough to accommodate electroweak baryogenesis only for a narrow region of the bare parameter space.Comment: 11 pages, latex, no figure

Angiogenesis : from tumor initiation to therapeutic resistance

Cancer is a leading cause of morbidity and mortality worldwide. In 2012 approximately 14 million new cases were diagnosed and 8.2 million cancer-related deaths were recorded. A better understanding of the strategies employed by cancer cells to grow and disseminate through the body is still required. Precise characterization of the signaling pathways involved in these processes will allow us to propose new diagnostic and prognostic markers but also to improve therapeutic strategies. Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, has been proposed as a suitable target in order to curtail cancer. In particular, it has been proposed that preventing the supply of nutrients and oxygen supply to the tumor would starve it to death. However, the clinical outcome of anti-angiogenic therapy has been sobering; despite initial therapeutic effects, patients relapse with cancers that have developed resistance to the therapy. Tumors treated with bevacizumab, a monoclonal antibody targeting the master regulator of angiogenesis, Vascular Endothelial Growth Factor-A (VEGF-A), have been found to activate alternative pro-angiogenic signaling pathways in order to revascularize and resume growth. Therefore, it becomes critical to decipher the molecular mechanisms implicated in tumor angiogenesis in general but also the mechanisms underlying the development of resistance to anti-angiogenic therapies. In my Ph.D. thesis, I first aimed to decipher the mechanisms of resistance to anti-angiogenic therapy. In order to overcome revascularization through activation of alternative pro-angiogenic signaling pathways, several pan-tyrosine kinase inhibitors have been developed. They demonstrated increased efficacy compared with bevacizumab. Here, we assessed the efficacy of nintedanib, a multikinase inhibitor targeting VEGFRs, FGFRs and PDGFRs in a mouse model of breast cancer. While tumors primarily responded to nintedanib treatment and demonstrated decreased tumor mass after short-term treatment, prolonged nintedanib treatment was associated with tumor regrowth. However, angiogenesis was still repressed in tumors escaping therapy and no revascularization was observed. Microarray analysis of FAC-sorted tumor cells revealed a metabolic shift towards anaerobic glycolysis. Moreover, tumors established metabolic symbiosis as suggested by the alternation between highly hypoxic, glycolytic and normoxic areas. Indeed, the inhibition of glycolysis or the disruption of metabolic symbiosis by genetically ablating MCT4 expression, a protein involved in metabolic symbiosis, efficiently overcame resistance to anti-angiogenic therapy. In order to reach blood vessels and to metastasize, epithelial cancer cells have to gain motile properties. The first step of the metastatic cascade consists of an epithelial-mesenchymal transtition (EMT). Epithelial cells undergoing this program lose apico-basal polarity and their epithelial markers and cell-cell and cell-matrix contacts, yet express mesenchymal markers and gain migratory capacity. Moreover, cells undergoing an EMT acquire cancer stem cell (CSC) traits. Mesenchymal cells are, for example, able to initiate tumor formation in a more efficient way compared to epithelial cells. While this feature is expected to rely on increased self-renewal capacity in mesenchymal cells, our laboratory identified VEGF-A as a causal agent in tumor initiation. By secreting VEGF-A, mesenchymal cells induce a precocious angiogenic switch, therefore sustaining tumor growth. In a second project, I aimed to identify the upstream regulator of VEGF-A in cells undergoing an EMT. Here, by performing a low throughput siRNA screen for transcription factors possessing a binding site on the VEGF-A gene promoter, I could identify JunB as the main regulator of VEGF-A expression in mesenchymal cells. JunB inhibition in diverse mesenchymal cell lines led to decreased VEGF-A expression, suggesting a key role for JunB in EMT-induced angiogenesis and thus tumor growth. In summary, my Ph.D. work provided new insights into tumor angiogenesis as: - I identified a new mechanism of resistance to anti-angiogenic therapy, in which tumor cells resumed growth despite lack of blood vessels by switching their metabolism towards glycolysis. This work highlighted the use of glycolysis inhibitors to overcome anti-angiogenic resistance; - I highlighted a new role for JunB as a regulator of EMT-induced angiogenesis and tumor growth

An immature B cell population from peripheral blood serves as surrogate marker for monitoring tumor angiogenesis and anti-angiogenic therapy in mouse models

Tumor growth depends on the formation of new blood vessels (tumor angiogenesis) either from preexisting vessels or by the recruitment of bone marrow-derived cells. Despite encouraging results obtained with preclinical cancer models, the therapeutic targeting of tumor angiogenesis has thus far failed to deliver an enduring clinical response in cancer patients. One major obstacle for improving anti-angiogenic therapy is the lack of validated biomarkers, which allow patient stratification for suitable treatment and a rapid assessment of therapy response. Toward these goals, we have employed several mouse models of tumor angiogenesis to identify cell populations circulating in their blood that correlated with the extent of tumor angiogenesis and therapy response. Flow cytometry analyses of different combinations of cell surface markers that define subsets of bone marrow-derived cells were performed on peripheral blood mononuclear cells from tumor-bearing and healthy mice. We identified one cell population, CD45dimVEGFR1⁻CD31low, that was increased in levels during active tumor angiogenesis in a variety of transgenic and syngeneic transplantation mouse models of cancer. Treatment with various anti-angiogenic drugs did not affect CD45dimVEGFR1⁻CD31low cells in healthy mice, whereas in tumor-bearing mice, a consistent reduction in their levels was observed. Gene expression profiling of CD45dimVEGFR1⁻CD31low cells characterized these cells as an immature B cell population. These immature B cells were then directly validated as surrogate marker for tumor angiogenesis and of pharmacologic responses to anti-angiogenic therapies in various mouse models of cancer

A Comparison of Methods to Estimate Forest Canopy Structure in Cedarville, Ohio

Plant canopy architecture results from the relationships of species composition, historical land use, succession, and species competition. Each forest’s canopy architecture influences the plant and animal community that live below. Key variables used to quantify the canopy architecture are leaf area index (LAI, m2 leaf m-2 ground) and canopy openness. The objective of our study was to analyze the accuracy of several mobile phone applications in interpreting the varying light environments of a second-growth forest in Ohio as compared to the standard technique using hemispherical photography. For this pilot project we measured 30 randomly selected points throughout a 15 acre forest stand in Greene County, Ohio. Mean canopy openness (minimum - maximum) for the site was 14.7 (5.7 - 23.8) and 46.1 (20.0 - 77.4) for GLAMA and Canopeo, respectively. Additionally, we processed digital hemispherical photographs using Gap Light Analyzer (GLA v 2.0) and calculated a mean % openness of 20.6 (12.2 - 45.5) and LAI of 2.1. When compared to the standard method of hemispherical photographs Canopeo and GLAMA described 41 and 19% of the total variability in forest canopy openness as measured by GLA. Our data show that GLAMA consistently over estimated while Canopeo underestimated openness. The data from this study reveals how each application used image processing methods to calculate canopy openness. The various applications showed inadequacies regarding the typical methods used to calculate canopy openness; none of the applications proved to be more accurate at calculating canopy openness than the others

Special Features of the Forming of Thermal Waters of the Eastern Part of the Khangay Neotectonic Uplift

Khangay neotectonic uplift is a large block of the earth’s crust confined to the area between two sublatitudinal deep faults (Bulnay and Goby-Altay). They are active faults accommodating main compression stresses in contract to the extension existed in the other area of the Khangay uplift. In contrast to continental rift zones of Khangay it is the region of compression. It is area with the increased values of the heat flux.DOI: http://dx.doi.org/10.5564/pmas.v0i4.48 Proceedings of the Mongolian Academy of Sciences 2009 No 4 pp.64-7

Small Mammal Survey Finds Strong Inverse Spatial Relationship with Forest Canopy Cover

The distribution of small mammals within a habitat is not uniform, but rather varies depending on favorable conditions of a species throughout the region. Within the selected 15-acre forest plot, an experiment was developed to detect where small mammals most reside and which conditions they favor. The objective of our study was to evaluate if forest canopy cover estimates (LAI, leaf area index) were a good predictor of small mammal presence. Using baited Sherman traps we completed 167 trap nights with 8 total captures. At the same time we estimated tree canopy cover using hemispherical photography. We processed photos from 30 co-located sites throughout the 15 acre forest plot. Mean LAI (m2 leaf per m2 ground) was found to be 2.1 with a range of 0.96 - 3.08. Each sample was geolocated to allow us to analyze spatial patterns. We used interpolation methods to visualize the LAI estimates and intensity of capture rates. This revealed an inverse pattern between LAI and small mammal captures at this site. In other words, small mammals were found most abundant where vegetative canopy cover was least dense

On the nature and order of the deconfining transition in QCD

The determination of the parameters of the deconfining transition in N_f=2 QCD is discussed, and its relevance to the understanding of the mechanism of color confinement.Comment: 10 pages. In honour of Yu. A. Simonov on his seventyth birthday; to be published in Yadernaya Fizik

Equation of state and Goldstone-mode effects of the three-dimensional O(2) model

We investigate numerically the three-dimensional O(2) model on 8^3-160^3 lattices as a function of the magnetic field H. In the low-temperature phase we verify the H-dependence of the magnetization M induced by Goldstone modes and determine M in the thermodynamic limit both by extrapolation and by chiral perturbation theory. This enables us to calculate the corresponding critical amplitude. At T_c the critical scaling behaviour of the magnetization as a function of H is used to determine another critical amplitude. In both cases we find negative corrections-to-scaling. Our low-temperature results are well described by the perturbative form of the model's magnetic equation of state, with coefficients determined nonperturbatively from our data. The O(2) scaling function for the magnetization is found to have a smaller slope than the one for the O(4) model.Comment: 15 pages, Latex2e, Fig.6b replaced, several comments and two references added, final version for Phys. Lett.

QED in a Strong External Magnetic Field: Beyond the Constant Mass Approximation

We solve the Schwinger-Dyson equations for QED in 2+1 or 3+1 dimensions in the presence of a strong homogeneous external magnetic field. The magnetic field is assumed strong enough, so that the lowest Landau level approximation holds, but the usual assumption of a momentum-independent self-energy is not made. In 2+1 dimensions, the scaling with logarithm changes to a square root dependence on the magnetic field, but the most spectacular result takes place in 3+1 dimensions, where the constant mass approximation turns out to be unreliable and the (momentum-dependent) dynamical mass is larger by several orders of magnitude compared to what has been found till now using the constant mass approximation.Comment: 21 pages, 8 figures, plain latex, references adde

Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO) efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients