Metabolic Dependencies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity. However, alternative metabolic targets beyond DNA may prove to be much more effective. PDA cells are forced to live within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. Thus, PDA cells must possess biochemical flexibility in order to adapt to austere conditions. A better understanding of the metabolic dependencies required by PDA to survive and thrive within a harsh metabolic milieu could reveal specific metabolic vulnerabilities. These molecular requirements can then be targeted therapeutically, and would likely be associated with a clinically significant therapeutic window since the normal tissue is so well-perfused with an abundant nutrient supply. Recent work has uncovered a number of promising therapeutic targets in the metabolic domain, and clinicians are already translating some of these discoveries to the clinic. In this review, we highlight mitochondria metabolism, non-canonical nutrient acquisition pathways (macropinocytosis and use of pancreatic stellate cell-derived alanine), and redox homeostasis as compelling therapeutic opportunities in the metabolic domain

A Cretaceous foraminiferal assemblage from West of Kerman area (Iran)

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Triggered qutrits for Quantum Communication protocols

A general protocol in Quantum Information and Communication relies in the ability of producing, transmitting and reconstructing, in general, qunits. In this letter we show for the first time the experimental implementation of these three basic steps on a pure state in a three dimensional space, by means of the orbital angular momentum of the photons. The reconstruction of the qutrit is performed with tomographic techniques and a Maximum-Likelihood estimation method. In this way we also demonstrate that we can perform any transformation in the three dimensional space

Compressive damage modeling of fiber-reinforced composite laminates using 2D higher-order layer-wise models

A refined progressive damage analysis of fiber-reinforced laminated composites subjected to compressive loads is presented here. The numerical analysis exploits higher-order theories developed using the Carrera Unified Formulation, specifically 2D plate theories with Lagrange polynomials to enhance the kinematic approximation through each ply’s thickness resulting in a layer-wise structural model. The CODAM2 material model, based on continuum damage mechanics, governs the intralaminar composite damage. The Hashin criteria and the crack-band approach provide failure initiation and propagation, respectively. Fiber micro-buckling and kinking are taken into account via the use of nonlinear post-peak softening models. It is shown that linear-brittle stress-strain softening is effective for accurate compressive strength predictions. A series of numerical assessments on coupon level composite laminates is carried out to verify the proposed numerical framework while its validation is demonstrated by successfully applying the numerical tool to test cases for which experimental data is available from the literature. Various through-the-thickness structural models are evaluated to provide insights for proper modeling. Numerical assessments considered quasi-isotropic laminates, the compressive strength, and size-effects under brittle fracture of notched laminates, and progressive damage characteristics due to stable crack growth in compact compression tests. The results show the possibility of using coarser meshes than those used in standard FEM approaches as the accuracy of predictions is preserved through the use of higher-order structural theories

Optical vernier technique for in-situ measurement of the length of long Fabry-Perot cavities

We propose a method for in-situ measurement of the length of kilometer size Fabry-Perot cavities in laser gravitational wave detectors. The method is based on the vernier, which occurs naturally when the laser incident on the cavity has a sideband. By changing the length of the cavity over several wavelengths we obtain a set of carrier resonances alternating with sideband resonances. From the measurement of the separation between the carrier and a sideband resonance we determine the length of the cavity. We apply the technique to the measurement of the length of a Fabry-Perot cavity in the Caltech 40m Interferometer and discuss the accuracy of the technique.Comment: LaTeX 2e, 12 pages, 4 figure

Experimental Quantum Coin Tossing

In this letter we present the first implementation of a quantum coin tossing protocol. This protocol belongs to a class of ``two-party'' cryptographic problems, where the communication partners distrust each other. As with a number of such two-party protocols, the best implementation of the quantum coin tossing requires qutrits. In this way, we have also performed the first complete quantum communication protocol with qutrits. In our experiment the two partners succeeded to remotely toss a row of coins using photons entangled in the orbital angular momentum. We also show the experimental bounds of a possible cheater and the ways of detecting him

HIGH-FIDELITY DAMAGE ANALYSIS OF COMPOSITES USING A PLY-BASED CONTINUUM MODEL

The current work is based on the implementation of the CODAM2 intralaminar damage model in CUF-Explicit, an explicit nonlinear dynamics solver based on the Carrera Unified Formulation (CUF). The CODAM2 model is based on the concept of continuum damage mechanics, and stress-based failure criteria are used to determine the onset of damage. The damage progression makes use of the crack-band theory to scale the fracture energies, thus ensuring mesh objectivity. The structural modelling is performed using high-order 2D theories based on CUF. 2D elements are used to model the structural geometry, and 1D expansions based on Lagrange polynomials are used to define the thickness, resulting in a layer-wise modelling approach. Numerical assessments are performed considering single elements and tensile coupons. The results are in good agreement with reference numerical solutions and experimental data, thus verifying the current implementation

Curvature condensation and bifurcation in an elastic shell

We study the formation and evolution of localized geometrical defects in an indented cylindrical elastic shell using a combination of experiment and numerical simulation. We find that as a symmetric localized indentation on a semi-cylindrical shell increases, there is a transition from a global mode of deformation to a localized one which leads to the condensation of curvature along a symmetric parabolic crease. This process introduces a soft mode in the system, converting a load-bearing structure into a hinged, kinematic mechanism. Further indentation leads to twinning wherein the parabolic crease bifurcates into two creases that move apart on either side of the line of symmetry. A qualitative theory captures the main features of the phenomena and leads to sharper questions about the nucleation of these defects.Comment: 4 pages, 5 figures, submitted to Physical Review Letter

Entanglement by linear SU(2) transformations: generation and evolution of quantum vortex states

We consider the evolution of a two-mode system of bosons under the action of a Hamiltonian that generates linear SU(2) transformations. The Hamiltonian is generic in that it represents a host of entanglement mechanisms, which can thus be treated in a unified way. We start by solving the quantum dynamics analytically when the system is initially in a Fock state. We show how the two modes get entangled by evolution to produce a coherent superposition of vortex states in general, and a single vortex state under certain conditions. The degree of entanglement between the modes is measured by finding the explicit analytical dependence of the Von Neumann entropy on the system parameters. The reduced state of each mode is analyzed by means of its correlation function and spatial coherence function. Remarkably, our analysis is shown to be equally as valid for a variety of initial states that can be prepared from a two-mode Fock state via a unitary transformation and for which the results can be obtained by mere inspection of the corresponding results for an initial Fock state. As an example, we consider a quantum vortex as the initial state and also find conditions for its revival and charge conjugation. While studying the evolution of the initial vortex state, we have encountered and explained an interesting situation in which the entropy of the system does not evolve whereas its wave function does. Although the modal concept has been used throughout the paper, it is important to note that the theory is equally applicable for a two-particle system in which each particle is represented by its bosonic creation and annihilation operators.Comment: 6 figure