Targeted therapies in the management of locally advanced and metastatic pancreatic cancer: a systematic review

Pancreatic cancer has a dismal prognosis particularly in patients presenting with unresectable tumors. We performed a bibliometric analysis of clinical trials for pancreatic cancer conducted between 2014-2016 focusing on patients that presented with unresectable (locally advanced or metastatic) tumors. We discuss a range of studies that employed FOLFIRINOX, the gemcitabine + nab-paclitaxel combination and studies that used molecularly-targeted therapy. Major areas of focus have been dual targeting of EGFR and VEGFR, immunotherapy or a multimodal approach – combining chemotherapy with radiotherapy. We also point out the need for molecular selection for low prevalence subtypes. Key insights sourced from these pivotal trials should improve clinical outcomes for this devastating cancer

Biologically-Active Gold(III) Complexes

A review is given of the background to and results of the succesful pharmacological testing of [AuX2(damp)] (X = Cl, OAc; damp = 2−Me2 NCH2C6 H4) against a range of microbes, fungi and tumouts, culminating in in vivo xenografts of ZR-1-75. These are the first fully evaluated gold(III) complexes. The activity and reactions of the diacetato-complex bear a resemblance to cisplatin, and some of the relevant chemistry is discussed. Preliminary screening data for C,P-chelated tertiary phosphine derivatives of gold(III) are presented

Bound states in a quasi-two-dimensional Fermi gas

We consider the problem of N identical fermions of mass M and one distinguishable particle of mass m interacting via short-range interactions in a confined quasi-two-dimensional (quasi-2D) geometry. For N=2 and mass ratios M/m<13.6, we find non-Efimov trimers that smoothly evolve from 2D to 3D. In the limit of strong 2D confinement, we show that the energy of the N+1 system can be approximated by an effective two-channel model. We use this approximation to solve the 3+1 problem and we find that a bound tetramer can exist for mass ratios M/m as low as 5 for strong confinement, thus providing the first example of a universal, non-Efimov tetramer involving three identical fermions.Comment: 5 pages, 4 figure

Supersolidity in electron-hole bilayers with a large density imbalance

We consider an electron-hole bilayer in the limit of extreme density imbalance, where we have a single particle in one layer interacting attractively with a Fermi liquid in the other parallel layer. Using an appropriate variational wave function for the dressed exciton, we provide strong evidence for the existence of the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) phase in electron-hole bilayers with a large density imbalance. Furthermore, within this unusual limit of FFLO, we find that a dilute gas of minority particles forms excitons that condense into a two-dimensional "supersolid".Comment: 6 pages, 2 figure

Performance Comparison of Marine Renewable Energy Converter Mooring Lines Subjected to Real Sea and Accelerated Loads

Accepted© EWTEC 2015One immediate challenge for the commercial development of floating Marine Renewable Energy Converters is reducing the weight and associated costs of mooring lines in deep water (>75m). Synthetic fibre ropes offer already a solution to the weight problems of using steel lines in deep-water offshore oil and gas installations as they have a very low weight in water. The present study focuses on the performance of fibre ropes in shallow waters, subjected to laboratory tests based on loads measured at sea in addition to (time) accelerated tests. Determining fatigue life is one of the most important aspects of long-term mooring analysis. At present, the fatigue analyses are usually based on S-N or T-N curves that are obtained with regular loads even when these loads are completely different to the ones measured at sea by a wave energy converter. The differences between the standard fatigue test and the real life of a mooring system are mainly the rate in which the loads are applied and the profile of the loads. Here, these two elements are analysed to get the fatigue damage, obtaining important differences in this measure

Quantum Phases of Dipolar Bosons in Bilayer Geometry

We investigate the quantum phases of hard-core dipolar bosons confined to a square lattice in a bilayer geometry. Using exact theoretical techniques, we discuss the many-body effects resulting from pairing of particles across layers at finite density, including a novel pair supersolid phase, superfluid and solid phases. These results are of direct relevance to experiments with polar molecules and atoms with large magnetic dipole moments trapped in optical lattices.Comment: 7 pages, 5 figure

Role of P-selectin in platelet sequestration in pulmonary capillaries during endotoxemia

Background: There is growing evidence that platelets accumulate in the lung and contribute to the pathogenesis of acute lung injury during endotoxemia. The aims of the present study were to localize platelet sequestration in the pulmonary microcirculation and to investigate the role of P-selectin as a molecular mechanism of platelet endothelial cell interaction. Methods: We used in vivo fluorescence microscopy to quantify the kinetics of fluorescently labeled erythrocytes and platelets in alveolar capillary networks in rabbit lungs. Results: Six hours after onset of endotoxin infusion we observed a massive rolling along and firm adherence of platelets to lung capillary endothelial cells whereas under control conditions no platelet sequestration was detected. P-selectin was expressed on the surface of separated platelets which were incubated with endotoxin and in lung tissue. Pretreatment of platelets with fucoidin, a P-selectin antagonist, significantly attenuated the endotoxin-induced platelet rolling and adherence. In contrast, intravenous infusion of fucoidin in endotoxin-treated rabbits did not inhibit platelet sequestration in pulmonary capillaries. Conclusion: We conclude that platelets accumulate in alveolar capillaries following endotoxemia. P-selectin expressed on the surface of platelets seems to play an important role in mediating this platelet-endothelial cell interaction. Copyright (c) 2006 S. Karger AG, Basel

Ultra-cold Polarized Fermi Gases

Recent experiments with ultra-cold atoms have demonstrated the possibility of realizing experimentally fermionic superfluids with imbalanced spin populations. We discuss how these developments have shed a new light on a half- century old open problem in condensed matter physics, and raised new interrogations of their own.Comment: 27 pages; 8 figures; Published in Report in Rep. Prog. Phys. 73 112401 (2010

Theory of ultracold Fermi gases

The physics of quantum degenerate Fermi gases in uniform as well as in harmonically trapped configurations is reviewed from a theoretical perspective. Emphasis is given to the effect of interactions which play a crucial role, bringing the gas into a superfluid phase at low temperature. In these dilute systems interactions are characterized by a single parameter, the s-wave scattering length, whose value can be tuned using an external magnetic field near a Feshbach resonance. The BCS limit of ordinary Fermi superfluidity, the Bose-Einstein condensation (BEC) of dimers and the unitary limit of large scattering length are important regimes exhibited by interacting Fermi gases. In particular the BEC and the unitary regimes are characterized by a high value of the superfluid critical temperature, of the order of the Fermi temperature. Different physical properties are discussed, including the density profiles and the energy of the ground-state configurations, the momentum distribution, the fraction of condensed pairs, collective oscillations and pair breaking effects, the expansion of the gas, the main thermodynamic properties, the behavior in the presence of optical lattices and the signatures of superfluidity, such as the existence of quantized vortices, the quenching of the moment of inertia and the consequences of spin polarization. Various theoretical approaches are considered, ranging from the mean-field description of the BCS-BEC crossover to non-perturbative methods based on quantum Monte Carlo techniques. A major goal of the review is to compare the theoretical predictions with the available experimental results.Comment: Revised and abridged version accepted for publication in Rev. Mod. Phys.: 63 pages, 36 figure

Sustained CD28 Expression Delays Multiple Features of Replicative Senescence in Human CD8 T Lymphocytes

CD28 costimulatory signal transduction in T lymphocytes is essential for optimal telomerase activity, stabilization of cytokine mRNAs, and glucose metabolism. During aging and chronic infection with HIV-1, there are increased proportions of CD8 T lymphocytes that lack CD28 expression and show additional features of replicative senescence. Moreover, the abundance of these cells correlates with decreased vaccine responsiveness, early mortality in the very old, and accelerated HIV disease progression. Here, we show that sustained expression of CD28, via gene transduction, retards the process of replicative senescence, as evidenced by enhanced telomerase activity, increased overall proliferative potential, and reduced secretion of pro-inflammatory cytokines. Nevertheless, the transduced cultures eventually do reach senescence, which is associated with increased CTLA-4 gene expression and a loss of CD28 cell surface expression. These findings further elucidate the central role of CD28 in the replicative senescence program, and may ultimately lead to novel therapies for diseases associated with replicative senescence