Modulated linear dynamics of nanobeams accounting for higher gradient effects

We present some numerical results for the linear dynamics of nanobeams modulated by an axial force, basing on a recent proposal of literature that encompasses both the standard nonlocal elasticity, according to Eringen, and second-order strain elasticity. Three different possibilities for the elastic potential energy provide different responses that highlight the contributions of nonlocality and strain gradient, plus their combination. An axial force affects the linear stationary dynamics of such nanobeams, inducing suitable variation of the natural angular frequencies for benchmark cases, until static buckling occurs when the natural angular frequency vanishes. Effects of the various elastic potentials on this modulation are investigated and thoroughly commented

Flavor Dependence of the S-parameter

We extend the results of [arXiv:1006.0207 [hep-lat]] by computing the S-parameter at two loops in the perturbative region of the conformal window. Consistently using the expression for the location of the infra-red fixed point at the two-loop order we express the S-parameter in terms of the number of flavors, colors and matter representation. We show that S, normalized to the number of flavors, increases as we decrease the number of flavors. Our findings support the conjecture presented in [arXiv:1006.0207 [hep-lat]] according to which the normalized value of the S-parameter at the upper end of the conformal window constitutes the lower bound across the entire phase diagram for the given underlying asymptotically free gauge theory. We also show that the non-trivial dependence on the number of flavors merges naturally with the non-perturbative estimate of the S-parameter close to the lower end of the conformal window obtained using gauge duality [arXiv:1007.0254 [hep-ph]]. Our results are natural benchmarks for lattice computations of the S-parameter for vector-like gauge theories.Comment: Version to match the one published in Phys. Lett. B. The file is prepared in the 2-columns RevTeX format has 9 pages, 4 figures and one tabl

High expression of HOXA13 correlates with poorly differentiated hepatocellular carcinomas and modulates sorafenib response in in vitro models

Hepatocellular carcinoma (HCC) represents the fifth and ninth cause of mortality among male and female cancer patients, respectively and typically arises on a background of a cirrhotic liver. HCC develops in a multi-step process, often encompassing chronic liver injury, steatosis and cirrhosis eventually leading to the malignant transformation of hepatocytes. Aberrant expression of the class I homeobox gene family (HOX), a group of genes crucial in embryogenesis, has been reported in a variety of malignancies including solid tumors. Among HOX genes, HOXA13 is most overexpressed in HCC and is known to be directly regulated by the long non-coding RNA HOTTIP. In this study, taking advantage of a tissue microarray containing 305 tissue specimens, we found that HOXA13 protein expression increased monotonically from normal liver to cirrhotic liver to HCC and that HOXA13-positive HCCs were preferentially poorly differentiated and had fewer E-cadherin-positive cells. In two independent cohorts, patients with HOXA13-positive HCC had worse overall survival than those with HOXA13-negative HCC. Using HOXA13 immunohistochemistry and HOTTIP RNA in situ hybridization on consecutive sections of 16 resected HCCs, we demonstrated that HOXA13 and HOTTIP were expressed in the same neoplastic hepatocyte populations. Stable overexpression of HOXA13 in liver cancer cell lines resulted in increased colony formation on soft agar and migration potential as well as reduced sensitivity to sorafenib in vitro. Our results provide compelling evidence of a role for HOXA13 in HCC development and highlight for the first time its ability to modulate response to sorafenib

Linear dynamic response of nanobeams accounting for higher gradient effects

Linear dynamic response of simply supported nanobeams subjected to a variable axial force is assessed by Galerkin numerical approach. Constitutive behavior is described by three functional forms of elastic energy densities enclosing nonlocal and strain gradient effects and their combination. Linear stationary dynamics of nanobeams is modulated by an axial force which controls the global stiffness of nanostrucure and hence its angular frequencies. Influence of the considered elastic energy densities on dynamical response is investigated and thoroughly commented

KRAS Mutant Allele Specific Imbalance (MASI) assessment in routine samples of metastatic colorectal cancer patients

AIMS: Patients with colorectal cancer harbouring KRAS mutations do not respond to antiepidermal growth factor receptor (anti-EGFR) therapy. Community screening for KRAS mutation selects patients for treatment. When a KRAS mutation is identified by direct sequencing, mutant and wild type alleles are seen on the sequencing electropherograms. KRAS mutant allele-specific imbalance (MASI) occurs when the mutant allele peak is higher than the wild type one. The aims of this study were to verify the rate and tissue distribution of KRAS MASI as well as its clinical relevance. METHODS: A total of 437 sequencing electropherograms showing KRAS exon 2 mutation was reviewed and in 30 cases next generation sequencing (NGS) was also carried out. Five primary tumours were extensively laser capture microdissected to investigated KRAS MASI tissue spatial distribution. KRAS MASI influence on the overall survival was evaluated in 58 patients. In vitro response to anti-EGFR therapy in relation to different G13D KRAS MASI status was also evaluated. RESULTS: On the overall, KRAS MASI occurred in 58/436 cases (12.8%), being more frequently associated with G13D mutation (p=0.05) and having a heterogeneous tissue distribution. KRAS MASI detection by Sanger Sequencing and NGS showed 94% (28/30) concordance. The longer overall survival of KRAS MASI negative patients did not reach statistical significance (p=0.08). In cell line model G13D KRAS MASI conferred resistance to cetuximab treatment. CONCLUSIONS: KRAS MASI is a significant event in colorectal cancer, specifically associated with G13D mutation, and featuring a heterogeneous spatial distribution, that may have a role to predict the response to EGFR inhibitors. The foreseen implementation of NGS in community KRAS testing may help to define KRAS MASI prognostic and predictive significance

UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients

Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. Despite the progresses made in diagnosis and treatment, the identification of tumor markers is still a strong clinical need, because current treatments are efficacious only in a subgroup of patients. UbcH10 represents a potential candidate biomarker, whose expression levels could be employed to predict response or resistance to chemotherapy or targeted agents. UbcH10 mRNA and protein expression levels have been evaluated in a large group of CRC patients and correlated with clinico-pathological characteristics, including KRAS mutations. Moreover, the endogenous levels of UbcH10 and its role on cell growth have been evaluated in CRC cells. Finally, to investigate the impact of UbcH10 protein expression on the response to irinotecan, its active metabolite SN-38 and cetuximab treatment, UbcH10 silencing experiments were carried-out on two colon carcinoma cell lines, Caco-2, and DLD1. Overexpression of UbcH10 mRNA and protein was observed in the vast majority of patients analyzed. UbcH10 suppression decreased CRC cell growth rate (at least in part through deregulation of Cyclin B and ERK1) and sensitized them to pharmacological treatments with irinotecan, SN-38 and cetuximab (at least in part through a down-regulation of AKT). Taken together, these findings indicate that UbcH10 expression regulates CRC growth and could play an important role in the personalization of the therapy of CRC patients. © 2015 Wiley Periodicals, Inc