Lung tumorspheres as a drug screening platform against cancer stem cells

Treatment resistance and metastasis are linked to cancer stem cells (CSCs). This population represents a promising target, but remains unexplored in lung cancer. The main objective of this study was to characterize lung CSCs and discover new therapeutic strategies

Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in a phase 3b and subsequent postmarketing observational study.

INTRODUCTION: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise. METHODS: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices. Adverse events (AEs) were tabulated by five time windows after the first ADA injection. Effectiveness measures included achievement of low disease activity (LDA), defined as Simplified Disease Activity Index (SDAI) ≤11, or remission, (REM), defined as SDAI ≤3.3. RESULTS: Of the 6,610 ReAct patients, 3,435 (52%) continued in ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272 patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious AEs occurred most frequently in the first 6 months and deceased thereafter. Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved by 50% and REM by 21% of patients at last observation. CONCLUSIONS: Results of this large observational study of ADA in routine clinical practice were consistent with controlled trials, with no new safety concerns during a follow-up of more than 5 years. Effectiveness of ADA was maintained during long-term observation. TRIAL REGISTRATION: NCT00448383, NCT0023488

Non-coboundary Poisson-Lie structures on the book group

All possible Poisson-Lie (PL) structures on the 3D real Lie group generated by a dilation and two commuting translations are obtained. Its classification is fully performed by relating these PL groups with the corresponding Lie bialgebra structures on the corresponding "book" Lie algebra. By construction, all these Poisson structures are quadratic Poisson-Hopf algebras for which the group multiplication is a Poisson map. In contrast to the case of simple Lie groups, it turns out that most of the PL structures on the book group are non-coboundary ones. Moreover, from the viewpoint of Poisson dynamics, the most interesting PL book structures are just some of these non-coboundaries, which are explicitly analysed. In particular, we show that the two different q-deformed Poisson versions of the sl(2,R) algebra appear as two distinguished cases in this classification, as well as the quadratic Poisson structure that underlies the integrability of a large class of 3D Lotka-Volterra equations. Finally, the quantization problem for these PL groups is sketched.Comment: 15 pages, revised version, some references adde

Self-assembly of thermo and light responsive amphiphilic linear dendritic block copolymers

The synthesis and structural characterization of a new dual responsive linear-dendritic block copolymer (LDBC) is presented. The LDBC is constituted by a thermoresponsive linear block from polymethacrylate of oligo- and diethylene glycol, and a light responsive den- dron block of bis-MPA decorated at the periphery with 4-isobutyloxyazobenzene and alkyl chains in a 50:50 M ratio. Blocks are coupled together by copper(I) catalyzed alkyne–azide cycloaddition (CuAAC). The ability of the LDBC to form vesicle self-assemblies in water is described, as well as the effect of light and temperature on the vesicles morphology, on the basis of transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV–vis spectroscopy studies. The effect of UV light and temperature on the vesicles struc- ture by SAXS and WAXS conducted on real time is also presented. Finally, the potential use of the vesicles to load and stimuli controlled release of small fluorescent molecules is probed

Metabolomics and Lipidomics Profiling of a Combined Mitochondrial Plus Endoplasmic Reticulum Fraction of Human Fibroblasts: A Robust Tool for Clinical Studies

Mitochondria and endoplasmic reticulum (ER) are physically and functionally connected. This close interaction, via mitochondria-associated membranes, is increasingly explored and supports the importance of studying these two organelles as a whole. Metabolomics and lipidomics are powerful approaches for the exploration of metabolic pathways that may be useful to provide deeper information on these organelles\u27 functions, dysfunctions, and interactions. We developed a quick and simple experimental procedure for the purification of a mitochondria-ER fraction from human fibroblasts. We applied combined metabolomics and lipidomics analyses by mass spectrometry with excellent reproducibility. Seventy-two metabolites and 418 complex lipids were detected with a mean coefficient of variation around 12%, among which many were specific to the mitochondrial metabolism. Thus this strategy based on robust mitochondria-ER extraction and "omics" combination will be useful for investigating the pathophysiology of complex diseases

Microwave-induced control of Free Electron Laser radiation

The dynamical response of a relativistic bunch of electrons injected in a planar magnetic undulator and interacting with a counterpropagating electromagnetic wave is studied. We demonstrate a resonance condition for which the free electron laser (FEL) dynamics is strongly influenced by the presence of the external field. It opens up the possibility of control of short wavelength FEL emission characteristics by changing the parameters of the microwave field without requiring change in the undulator's geometry or configuration. Numerical examples, assuming realistic parameter values analogous to those of the TTF-FEL, currently under development at DESY, are given for possible control of the amplitude or the polarization of the emitted radiation.Comment: 14 pages, 5 figures, accepted for publication in Phys. Rev.

Towards Automated Android App Collusion Detection

Android OS supports multiple communication methods between apps. This opens the possibility to carry out threats in a collaborative fashion, c.f. the Soundcomber example from 2011. In this paper we provide a concise definition of collusion and report on a number of automated detection approaches, developed in co-operation with Intel Security

Comment on "X-ray resonant scattering studies of orbital and charge ordering in Pr1-xCaxMnO3"

In a recent published paper [Phys. Rev. B 64, 195133 (2001)], Zimmermann et al. present a systematic x-ray scattering study of charge and orbital ordering phenomena in the Pr1-xCaxMnO3 series with x= 0.25, 0.4 and 0.5. They propose that for Ca concentrations x=0.4 and 0.5, the appearance of (0, k+1/2, 0) reflections are originated by the orbital ordering of the eg electrons in the a-b plane while the (0, 2k+1, 0) reflections are due to the charge ordering among the Mn3+ and Mn4+ ions. Moreover, for small Ca concentrations (x<0.3), the orbital ordering is only considered and it occurs at (0, k, 0) reflections. A rigorous analysis of all these resonance reflections will show the inadequacy of the charge-orbital model proposed to explain the experimental results. In addition, this charge-orbital model is highly inconsistent with the electronic balance. On the contrary, these reflections can be easily understood as arising from the anisotropy of charge distribution induced by the presence of local distortions, i.e. due to a structural phase transition.Comment: 10 pages, 2 figures.To be published Phys. Rev.

Relationship of oxidized low density lipoprotein with lipid profile and oxidative stress markers in healthy young adults: a translational study

BACKGROUND: Despite oxidized low density lipoprotein (ox-LDL) plays important roles in the pro-inflammatory and atherosclerotic processes, the relationships with metabolic and oxidative stress biomarkers have been only scarcely investigated in young adult people. Thus, the aim of this study was to assess plasma ox-LDL concentrations and the potential association with oxidative stress markers as well as with anthropometric and metabolic features in healthy young adults. METHODS: This study enrolled 160 healthy subjects (92 women/68 men; 23±4 y; 22.0±2.9 kg/m2). Anthropometry, body composition, blood pressure, lifestyle features, biochemical data, and oxidative stress markers were assessed with validated tools. Selenium, copper, and zinc nail concentrations were measured by atomic absorption spectrophotometry. RESULTS: Total cholesterol (TC), LDL-c and uric acid concentrations, TC-to-HDL-c ratio, and glutathione peroxidase (GPx) activity were positive predictors of ox-LDL concentrations, while nail selenium level (NSL) was a negative predictor, independently of gender, age, smoking status, physical activity. Those individuals included in the highest tertile of GPx activity (≥611 nmol/[mL/min]) and of NSL (≥430 ng/g of nail) had higher and lower ox-LDL concentrations, respectively, independently of the same covariates plus truncal fat or body mass index, and total cholesterol or LDL-c concentrations. CONCLUSIONS: Ox-LDL concentrations were significantly associated with lipid biomarkers, GPx activity, uric acid concentration, and NSL, independently of different assayed covariates, in young healthy adults. These findings jointly suggest the early and complex relationship between lipid profile and redox status balance

Photoemission study of the metal-insulator transition in VO_2/TiO_2(001) : Evidence for strong electron-electron and electron-phonon interaction

We have made a detailed temperature-dependent photoemission study of VO_2/TiO_2(001) thin films, which show a metal-insulator transition at \sim 300 K. Clean surfaces were obtained by annealing the films in an oxygen atmosphere. Spectral weight transfer between the coherent and incoherent parts accompanying the metal-insulator transition was clearly observed. We also observed a hysteretic behavior of the spectra for heating-cooling cycles. We have derived the ``bulk'' spectrum of the metallic phase and found that it has a strong incoherent part. The width of the coherent part is comparable to that given by band-structure calculation in spite of its reduced spectral weight, indicating that the momentum dependence of the self-energy is significant. This is attributed to by ferromagnetic fluctuation arising from Hund's rule coupling between different d orbitals as originally proposed by Zylbersztejn and Mott. In the insulating phase, the width of the V 3d band shows strong temperature dependence. We attribute this to electron-phonon interaction and have reproduced it using the independent boson model with a very large coupling constant.Comment: 7 pages, 7 figures, submitted to Phys. Rev.