Modelling Pancreatic Neuroendocrine Cancer: From Bench Side to Clinic

Pancreatic neuroendocrine tumours (pNETs) are a heterogeneous group of epithelial tumours with neuroendocrine differentiation. Although rare (incidence of <1 in 100,000), they are the second most common group of pancreatic neoplasms after pancreatic ductal adenocarcinoma (PDAC). pNET incidence is however on the rise and patient outcomes, although variable, have been linked with 5-year survival rates as low as 40%. Improvement of diagnostic and treatment modalities strongly relies on disease models that reconstruct the disease ex vivo. A key constraint in pNET research, however, is the absence of human pNET models that accurately capture the original tumour phenotype. In attempts to more closely mimic the disease in its native environment, three-dimensional culture models as well as in vivo models, such as genetically engineered mouse models (GEMMs), have been developed. Despite adding significant contributions to our understanding of more complex biological processes associated with the development and progression of pNETs, factors such as ethical considerations and low rates of clinical translatability limit their use. Furthermore, a role for the site-specific extracellular matrix (ECM) in disease development and progression has become clear. Advances in tissue engineering have enabled the use of tissue constructs that are designed to establish disease ex vivo within a close to native ECM that can recapitulate tumour-associated tissue remodelling. Yet, such advanced models for studying pNETs remain underdeveloped. This review summarises the most clinically relevant disease models of pNETs currently used, as well as future directions for improved modelling of the disease

Anti-symmetric rank-2 Matter Field on Superspace for N_{T}=2

In this work, we discuss the interaction between anti-symmetric rank-two tensor matter and topological Yang-Mills fields. The matter field considered here is the rank-2 Avdeev-Chizhov tensor matter field in a suitably extended $N_{T}=2$ SUSY. We start off from the $N_{T}=2$, D=4 superspace formulation and we go over to Riemannian manifolds. The matter field is coupled to the topological Yang-Mills field. We show that both actions are obtained as $Q-$exact forms, which allows us to write the energy-momentum tensor as $Q-$exact observables.Comment: 10 pages, no figure, LaTe

Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches

The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies

Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or metastatic stage when surgical resection is not possible and treatment options are limited. Thus, novel and more effective therapeutic strategies are urgently needed. Molecular profiling together with targeted therapies against key hallmarks of pancreatic cancer appear as a promising approach that could overcome the limitations of conventional chemo- and radio-therapy. In this review, we focus on the latest personalised and multimodal targeted therapies currently undergoing phase II or III clinical trials. We discuss the most promising findings of agents targeting surface receptors, angiogenesis, DNA damage and cell cycle arrest, key signalling pathways, immunotherapies, and the tumour microenvironment

Global-String and Vortex Superfluids in a Supersymmetric Scenario

The main goal of this work is to investigate the possibility of finding the supersymmetric version of the U(1)-global string model which behaves as a vortex-superfluid. To describe the superfluid phase, we introduce a Lorentz-symmetry breaking background that, in an approach based on supersymmetry, leads to a discussion on the relation between the violation of Lorentz symmetry and explicit soft supersymmetry breakings. We also study the relation between the string configuration and the vortex-superfluid phase. In the framework we settle down in terms of superspace and superfields, we actually establish a duality between the vortex degrees of freedom and the component fields of the Kalb-Ramond superfield. We make also considerations about the fermionic excitations that may appear in connection with the vortex formation.Comment: 9 pages. This version presented the relation between Lorentz symmetry violation by the background and the appearance of terms that explicitly break SUS

Chaos and Universality in a Four-Dimensional Spin Glass

We present a finite size scaling analysis of Monte Carlo simulation results on a four dimensional Ising spin glass. We study chaos with both coupling and temperature perturbations, and find the same chaos exponent in each case. Chaos is investigated both at the critical temperature and below where it seems to be more efficient (larger exponent). Dimension four seems to be above the critical dimension where chaos with temperature is no more present in the critical region. Our results are consistent with the Gaussian and bimodal coupling distributions being in the same universality class.Comment: 11 pages, including 6 postscript figures. Latex with revtex macro

Lorentz Violating Supersymmetric Quantum Electrodynamics

Theory of Supersymmetric Quantum Electrodynamics is extended by interactions with external vector and tensor backgrounds, that are assumed to be generated by some Lorentz-violating (LV) dynamics at an ultraviolet scale perhaps related to the Planck scale. Exact supersymmetry requires that such interactions correspond to LV operators of dimension five or higher, providing a solution to the naturalness problem in the LV sector. We classify all dimension five and six LV operators, analyze their properties at the quantum level and describe observational consequences of LV in this theory. We show that LV operators do not induce destabilizing D-terms, gauge anomaly and the Chern-Simons term for photons. We calculate the renormalization group evolution of dimension five LV operators and their mixing with dimension three LV operators, controlled by the scale of the soft-breaking masses. Dimension five LV operators are constrained by the low-energy precision measurements at 10^{-10}-10^{-5} level in units of the inverse Planck scale, while the Planck-scale suppressed dimension six LV operators are allowed by observational data.Comment: 37 pages LaTeX, minor revisions, and typos correcte

Spin glasses and algorithm benchmarks: A one-dimensional view

Spin glasses are paradigmatic models that deliver concepts relevant for a variety of systems. However, rigorous analytical results are difficult to obtain for spin-glass models, in particular for realistic short-range models. Therefore large-scale numerical simulations are the tool of choice. Concepts and algorithms derived from the study of spin glasses have been applied to diverse fields in computer science and physics. In this work a one-dimensional long-range spin-glass model with power-law interactions is discussed. The model has the advantage over conventional systems in that by tuning the power-law exponent of the interactions the effective space dimension can be changed thus effectively allowing the study of large high-dimensional spin-glass systems to address questions as diverse as the existence of an Almeida-Thouless line, ultrametricity and chaos in short range spin glasses. Furthermore, because the range of interactions can be changed, the model is a formidable test-bed for optimization algorithms.Comment: 10 pages, 8 figures (two in crappy quality due to archive restrictions). Proceedings of the International Workshop on Statistical-Mechanical Informatics 2007, Kyoto (Japan) September 16-19, 200