Reply: Did animal offer relevant model for bevacizumab testing?

growth factor (VEGF)-blocking antibodies completely inhibit the growt

Combined effects of bevacizumab with erlotinib and irradiation: a preclinical study on a head and neck cancer orthotopic model

Clinical benefit has been demonstrated in patients with head and neck tumours receiving an anti-epidermal growth factor receptor (EGFR) agent in combination with radiotherapy (RT). Recent preclinical and clinical studies suggest beneficial effects from combining anti-angiogenic drugs with RT. To investigate the effect of combining these approaches, we evaluated in vivo the anti-tumour efficacy of the anti-angiogenic compound bevacizumab, a highly specific monoclonal antibody directed against the vascular endothelial growth factor (VEGF), erlotinib, an EGFR tyrosine kinase inhibitor, and irradiation given alone and in combination. Investigations were performed using a VEGF-secreting human head and neck tumour cell line, CAL33, with a high EGFR content, injected as orthotopic xenografts into the mouth floor of nude mice. Three days after tumour cell injection, bevacizumab (5 mg kg−1, 5 days a week, i.p.), erlotinib (100 mg kg−1, 5 days a week, orally) and irradiation (6 Gy, 3 days a week) were administered alone and in combination for 10 days. As compared with the control, concomitant administration of drugs produced a marked and significant supra-additive decrease in tumour mass; the addition of irradiation almost completely abolished tumour growth. The drug association markedly reduced the number of metastatic nodes and the triple combination significantly reduced the total number of pathologically positive lymph nodes as compared with controls. The RT-induced proliferation, reflected by Ki67 labelling, was reduced to control level with the triple combination. Radiotherapy induced a strong and very significant increase in tumour angiogenesis, which was no longer observed when combined with erlotinib and bevacizumab. The efficacy of the combination of bevacizumab+erlotinib and RT may be of clinical importance in the management of head and neck cancer patients

Controlled environment neutron radiography of moisture sorption/desorption in nanocellulose-treated cotton painting canvases

Nanocellulose-based materials have recently been used to consolidate degraded cotton painting canvases. Canvas-supported paintings consist of materials that are sensitive to moisture and especially susceptible to environmental fluctuations in temperature and relative humidity (RH). These environmental fluctuations occur in uncontrolled environments found in historic houses and palaces and can lead to hydrolytic degradation and mechanical damage to canvases. To simulate this situation in an experimental setting, canvas samples were mounted in a custom-made closed-cell and subjected to programmed cycles of RH at a controlled temperature while exposed to the neutron beam. Results are presented for both untreated samples and those treated with a polar consolidant, cellulose nanofibrils (CNF(aq)) in water, and an apolar consolidant, a composite of persilylated methyl cellulose with surface silylated cellulose nanocrystals (MC+CNC(h)) in heptane. They were then compared with changes in ionic conductivities as measured by dielectric analysis (DEA) with the same cyclic RH program and temperature. Although the samples were exposed to the same experimental conditions, they presented treatment-specific responses. CNF-treated canvas showed higher hygroscopicity than the untreated sample and facilitated moisture diffusion across the sample to areas not exposed to the environment. A sample treated with MC+CNC(h) retarded moisture diffusion during the increase in RH and could, therefore, afford protection to moisture absorption in uncontrolled environments. Thus, the experimental setup and resulting data provide a pilot study demonstrating the potential of neutron radiography in following and comparing real-time moisture diffusion dynamics in untreated and nanocellulose-consolidated cotton canvases and assisting in validating the overall benefit of the treatmen

The GRA Beam-Splitter Experiments and Particle-Wave Duality of Light

Grangier, Roger and Aspect (GRA) performed a beam-splitter experiment to demonstrate the particle behaviour of light and a Mach-Zehnder interferometer experiment to demonstrate the wave behaviour of light. The distinguishing feature of these experiments is the use of a gating system to produce near ideal single photon states. With the demonstration of both wave and particle behaviour (in two mutually exclusive experiments) they claim to have demonstrated the dual particle-wave behaviour of light and hence to have confirmed Bohr's principle of complementarity. The demonstration of the wave behaviour of light is not in dispute. But we want to demonstrate, contrary to the claims of GRA, that their beam-splitter experiment does not conclusively confirm the particle behaviour of light, and hence does not confirm particle-wave duality, nor, more generally, does it confirm complementarity. Our demonstration consists of providing a detailed model based on the Causal Interpretation of Quantum Fields (CIEM), which does not involve the particle concept, of GRA's which-path experiment. We will also give a brief outline of a CIEM model for the second, interference, GRA experiment.Comment: 24 pages, 4 figure

Evolution of Linear Absorption and Nonlinear Optical Properties in V-Shaped Ruthenium(II)-Based Chromophores

In this article, we describe a series of complexes with electron-rich cis-{Ru^(II)(NH_3)_4}^(2+) centers coordinated to two pyridyl ligands bearing N-methyl/arylpyridinium electron-acceptor groups. These V-shaped dipolar species are new, extended members of a class of chromophores first reported by us (Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845−4859). They have been isolated as their PF_6− salts and characterized by using various techniques including ^1H NMR and electronic absorption spectroscopies and cyclic voltammetry. Reversible Ru^(III/II) waves show that the new complexes are potentially redox-switchable chromophores. Single crystal X-ray structures have been obtained for four complex salts; three of these crystallize noncentrosymmetrically, but with the individual molecular dipoles aligned largely antiparallel. Very large molecular first hyperpolarizabilities β have been determined by using hyper-Rayleigh scattering (HRS) with an 800 nm laser and also via Stark (electroabsorption) spectroscopic studies on the intense, visible d → π^* metal-to-ligand charge-transfer (MLCT) and π → π^* intraligand charge-transfer (ILCT) bands. The latter measurements afford total nonresonant β_0 responses as high as ca. 600 × 10^(−30) esu. These pseudo-C_(2v) chromophores show two substantial components of the β tensor, β_(zzz) and β_(zyy), although the relative significance of these varies with the physical method applied. According to HRS, β_(zzz) dominates in all cases, whereas the Stark analyses indicate that β_(zyy) is dominant in the shorter chromophores, but β_(zzz) and β_(zyy) are similar for the extended species. In contrast, finite field calculations predict that β_(zyy) is always the major component. Time-dependent density functional theory calculations predict increasing ILCT character for the nominally MLCT transitions and accompanying blue-shifts of the visible absorptions, as the ligand π-systems are extended. Such unusual behavior has also been observed with related 1D complexes (Coe, B. J. et al. J. Am. Chem. Soc. 2004, 126, 3880−3891)

Electroactive biofilms: new means for electrochemistry

This work demonstrates that electrochemical reactions can be catalysed by the natural biofilms that form on electrode surfaces dipping into drinking water or compost. In drinking water, oxygen reduction was monitored with stainless steel ultra-microelectrodes under constant potential electrolysis at )0.30 V/SCE for 13 days. 16 independent experiments were conducted in drinking water, either pure or with the addition of acetate or dextrose. In most cases, the current increased and reached 1.5–9.5 times the initial current. The current increase was attributed to biofilm forming on the electrode in a similar way to that has been observed in seawater. Epifluorescence microscopy showed that the bacteria size and the biofilm morphology depended on the nutrients added, but no quantitative correlation between biofilm morphology and current was established. In compost, the oxidation process was investigated using a titanium based electrode under constant polarisation in the range 0.10–0.70 V/SCE. It was demonstrated that the indigenous micro-organisms were responsible for the current increase observed after a few days, up to 60 mA m)2. Adding 10 mM acetate to the compost amplified the current density to 145 mA m)2 at 0.50 V/SCE. The study suggests that many natural environments, other than marine sediments, waste waters and seawaters that have been predominantly investigated until now, may be able to produce electrochemically active biofilm

Impact of horizontal resolution on global ocean–sea ice model simulations based on the experimental protocols of the Ocean Model Intercomparison Project phase 2 (OMIP-2)

This paper presents global comparisons of fundamental global climate variables from a suite of four pairs of matched low- and high-resolution ocean and sea ice simulations that are obtained following the OMIP-2 protocol (Griffies et al., 2016) and integrated for one cycle (1958–2018) of the JRA55-do atmospheric state and runoff dataset (Tsujino et al., 2018). Our goal is to assess the robustness of climate-relevant improvements in ocean simulations (mean and variability) associated with moving from coarse (∼ 1∘) to eddy-resolving (∼ 0.1∘) horizontal resolutions. The models are diverse in their numerics and parameterizations, but each low-resolution and high-resolution pair of models is matched so as to isolate, to the extent possible, the effects of horizontal resolution. A variety of observational datasets are used to assess the fidelity of simulated temperature and salinity, sea surface height, kinetic energy, heat and volume transports, and sea ice distribution. This paper provides a crucial benchmark for future studies comparing and improving different schemes in any of the models used in this study or similar ones. The biases in the low-resolution simulations are familiar, and their gross features – position, strength, and variability of western boundary currents, equatorial currents, and the Antarctic Circumpolar Current – are significantly improved in the high-resolution models. However, despite the fact that the high-resolution models “resolve” most of these features, the improvements in temperature and salinity are inconsistent among the different model families, and some regions show increased bias over their low-resolution counterparts. Greatly enhanced horizontal resolution does not deliver unambiguous bias improvement in all regions for all models

Nanomaterials for the cleaning and pH adjustment of vegetable tanned leather

Leather artifacts in historical collections and archives are often contaminated by physical changes such as soiling, which alter their appearance and readability, and by chemical changes which occur on ageing and give rise to excessive proportion of acids that promote hydrolysis of collagen, eventually leading to gelatinization and loss of mechanical properties. However, both cleaning and pH adjustment of vegetable tanned leather pose a great challenge for conservators, owing to the sensitivity of these materials to the action of solvents, especially water-based formulations and alkaline chemicals. In this study the cleaning of historical leather samples was optimized by confining an oil-in-water (o/w) nanostructured fluid in a highly retentive chemical hydrogel, which allows the controlled release of the cleaning fluid on sensitive surfaces. The chemical gel exhibits optimal viscoelasticity, which facilitates its removal after the application without leaving residues on the object. Nanoparticles of calcium hydroxide and lactate, dispersed in 2-propanol, were used to adjust the pH up to the natural value of leather, preventing too high alkalinity which causes swelling of fibers and denaturation of the collagen. The treated samples were characterized using Scanning Electron Microscopy (FE SEM), controlled environment dynamic mechanical analysis (DMA-RH), and infrared spectroscopy (ATR-FTIR). The analytical assessment validated the use of tools derived from colloid and materials science for the preservation of collagen-based artifacts