Layer In Presence Research Articles

In Vitro and in Vivo Evidence of an Anti-Angiogenic Effect of Lenalidomide in Chronic Lymphocytic Leukemia

AbstractAbstract 1782The exact mechanism of anti-tumor activity of the immunomodulatory drug lenalidomide remains undefined, but it implies the activation of immune effector cells. Little is known concerning the anti-angiogenic properties of lenalidomide in chronic lymphocytic leukemia (CLL) patients.A total of 27 relapsed/refractory CLL patients were treated within a multicenter Phase II trial. Peripheral blood mononuclear cells and plasma samples were collected before and during treatment. Lenalidomide treatment schedule began with 5 mg daily doses and increased by 5 mg daily every two weeks, up to 25 mg daily or maximum tolerated dose. Several angiogenesis-related cytokines were measured by ELISA in plasma. Circulating endothelial cells (CEC), endothelial progenitor cells (EPC), apoptotic CEC (APO-CEC), and activated CEC (aCEC) were evaluated by flow cytometry. In vitro experiments were performed on CLL cells purified from peripheral blood by using CD19Microbeads. Cells were cultured alone (CLL only) or on a EC monolayer (HC condition).First, CLL cells from 9 patients treated in vitro with up to 10 μmol/L of lenalidomide did not show any direct cytotoxic effect. However, an anti-leukemic effect was observed in vivo in our cohort of heavily pre-treated CLL patients. We found a reduction of white blood cell count (WBC, 1×109/L) from 39.9±8.0 before treatment to 15.2±5.2 and 16.0±5.2 after 4 and 12 months of treatment respectively and a decrement of absolute number of lymphocytes from 25.6±6.4 before treatment to 7.9±2.7 and 5.4±2.4 after 4 and 12 months of treatment (p<0.05, Wilcoxon test). To evaluate whether lenalidomide exerts its anti-CLL effect disrupting leukemic cross-talk with endothelial cells, we co-cultured CLL cells (n=9) on EC layer in presence or absence of increasing doses of lenalidomide. All CLL cells cultured on EC layer displayed a significant survival advantage (mean viability, 16% vs. 47% in CLL alone and HC) that was reduced by lenalidomide treatment (28%) (p<0.001).We then evaluated the effect of lenalidomide treatment on circulating endothelial cells in treated CLL patients (n=27). We found that the absolute number of CEC and EPC decreased from 8.2±1.5/μL and 4.7±1.0/μL pre-therapy to 2.1±0.6/μL and 1.0±0.5/μL after 4 months respectively (p=0.002 for CEC and p=0.01 for EPC). Moreover, the percentage of APO-CEC increased from 51% to 84% of the total CEC (p<0.0001). No differences were found in the aCEC subset during treatment. Moreover, we examined the effect of lenalidomide treatment on a panel of angiogenesis-related factors. The plasma levels of vascular endothelial growth factor (VEGF) and thrombospondin-1 (THBS1) showed a significant decrease by month 4 compared to pre-treatment levels (VEGF, 77±13 to 43±8 pg/mL, p=0.014; THBS1, 662±80 to 416±75 ng/mL, p=0.01). Angiogenin plasma levels increased after 4 months of treatment from 441±16 ng/mL to 460±21 ng/mL (p=0.025). No significant differences were detected in plasma levels of basic fibroblast growth factor (bFGF,) and Angiopoietin-1 (Ang1). Angiopoietin-2 (Ang2) showed an increase during the first phase of treatment from 5183 to 8126 pg/mL (p=0.001).Furthermore, patients were grouped under the clinical classification of stable/progressive disease (not responders, NR n=6) and partial response (responders, R n=10). There was an Increased percentage of aCEC detected in NR patients (54% vs. 74% in R and NR at baseline respectively, p=0.039). We also found that VEGF plasma levels significantly decreased during treatment exclusively in the R subset (83±26 pg/mL at baseline to 26±6 pg/mL after 4 months, p=0.007). Moreover, bFGF plasma levels showed a strong decrease in R patients from 168±105 pg/mL at baseline to 41±11 and 19±8 pg/mL after one week and 4 months of treatment (p=0.017 and p=0.005 respectively), whereas increased levels were measured in NR patients from 120±58 pg/mL at baseline to 426±195 and 234±147 pg/mL.Our study provides evidence that the mechanism of action of lenalidomide in CLL patients is mediated not only through the activation of immune effector cells, but also through the modulation of angiogenesis-related factors and disruption of CLL cross-talk with endothelial cells. Of interest, we identified plasmatic factors (VEGF and bFGF) that are correlated with clinical response to lenalidomide. Disclosures:Off Label Use: Lenalidomide, a thalidomide analogue, is an immunomodulatory drug (IMiD) with antitumoural activity reported in various malignant disorders including multiple myeloma and myelodysplastic syndrome (MDS). At preclinical level, lenalidomide has shown to decrease the production of several prosurvival cytokines. This drug is also reported to modulate an effector cell immune response through the activation of T and natural killer (NK) cells, inducing apoptosis directly on tumour cells. Currently available data indicate that Lenalidomide is active also in heavily pre-treated CLL patients with unfavourable prognostic factors. However, in order to optimize the therapeutic index of Lenalidomide treatment in CLL patients, it will be necessary to identify features of tumour cells that differ between responder and non responder patients. Hence, we reported results from a multicenter, phase II study designed in order to identify potential predictive factors correlating with response to Lenalidomide treatment in relapsed/refractory CLL. Marasca:CELGENE CORPORATION: Honoraria, Research Funding.

Corrosion inhibition of iota-carrageenan natural polymer on aluminum in presence of zwitterion mediator in HCl media

ι-Carrageenan a natural polymer has been used as corrosion inhibitor of aluminum in presence of pefloxacin mesylate, acting as zwitterionic mediator, in acidic medium. Considerable improvement in inhibition efficiency occurred in the presence of the mediator. Activation energy of corrosion and other thermodynamic parameters such as standard free energy, standard enthalpy, and standard entropy of the adsorption process revealed better and well-ordered physical adsorption layers in presence of pefloxacin. Adsorption isotherms in absence or presence of pefloxacin mediator appropriately fit in the Langmuir isotherms. The scanning electron microscope (SEM) images demonstrated smooth, glossy, and relatively coherent adsorption layers of the inhibitor on the metal surface in aqueous solution. After the exposure to 2.0M HCl for 2h, a smaller but consistent regular shaped fractured layer is obtained.

Width of the chaotic layer: Maxima due to marginal resonances

Modern theoretical methods for estimating the width of the chaotic layer in the presence of prominent marginal resonances are considered in the perturbed pendulum model of nonlinear resonance. The fields of applicability of these methods are explicitly and precisely formulated. The comparative accuracy is investigated in massive and long-run numerical experiments. It is shown that the methods are naturally subdivided in classes applicable for adiabatic and nonadiabatic cases of perturbation. It is explicitly shown that the pendulum approximation of marginal resonance works well in the nonadiabatic case. In this case, the role of marginal resonances in determining the total layer width is demonstrated to diminish with increasing main parameter λ (equal to the ratio of the perturbation frequency to the frequency of small-amplitude phase oscillations on the resonance). Solely the "bending effect" is important in determining the total amplitude of the energy deviations of the near-separatrix motion at λ≳7. In the adiabatic case, it is demonstrated that the geometrical form of the separatrix cell can be described analytically quite easily by means of using a specific representation of the separatrix map. It is shown that the nonadiabatic (and, to some extent, intermediary) case is most actual, in comparison with the adiabatic one, for the physical or technical applications that concern the energy jumps in the near-separatrix chaotic motion.

Improved Charge Separation Properties of Organic Hetero-Junction Solar Cells by Self-Assembled Monolayers Anchored Ag Nanoparticles

We investigate the effect of self-assembled monolayers and localized surface plasmons of silver nano-particles on an organic solar cell consisting of zinc phthalocyanine as an active layer. The device was fabricated by covalent attachment of silver nanoparticles on n-type silicon substrates using self-assembled monolayer of 4-mercaptophenol. Power conversion efficiency is increased up to 8 times as compared to a reference device with merely 0.13% photo-conversion efficiency containing no self-assembled monolayers and silver nano-particles. We believe that improved conductivity at the interface due to the aromatic self-assembled monolayer and the increased local electric field experienced by the active layer in presence of silver nano-particles act in synergy towards the higher population of excitons and dissipation of charge.

Effects of Sulfate-Reducing Bacteria on the Corrosion of Q235

Various corrosion media were prepared by dual-cells experimental setup, including fresh sterilized culture medium, culture medium with sulfate-reducing bacteria (SRB), and culture medium containing only SRB metabolites. Corrosion exposure tests of Q235 carbon steel were conducted in these media, and effects of SRB on the corrosion behavior of Q235 were studied by electrochemical methods and surface analyses. As the results, Q235 was uniformly corroded in the fresh sterilized culture medium in a mode of active dissolution; in the culture medium of SRB, Q235 was protected by the iron sulfides layer to some extent in the early stage of exposure, but severely localized corrosion subsequently occurred resulting from the localized breakdown of iron sulfides layer in presence of SRB and SRB biofilm; while in the culture medium containing only SRB metabolites, Q235 was well protected over the whole exposure period, suggesting that a uniform and stable layer of iron sulfides was formed in this medium.

Beyond podcasting: creative approaches to designing educational audio

This paper discusses a university-wide pilot designed to encourage academics to creatively explore learner-centred applications for digital audio. Participation in the pilot was diverse in terms of technical competence, confidence and contextual requirements and there was little prior experience of working with digital audio. Many innovative approaches were taken to using audio in a blended context including student-generated vox pops, audio feedback models, audio conversations and task-setting. A podcast was central to the pilot itself, providing a common space for the 25 participants, who were also supported by materials in several other formats. An analysis of podcast interviews involving pilot participants provided the data informing this case study. This paper concludes that audio has the potential to promote academic creativity in engaging students through media intervention. However, institutional scalability is dependent upon the availability of suitable timely support mechanisms that can address the lack of technical confidence evident in many staff. If that is in place, audio can be widely adopted by anyone seeking to add a new layer of presence and connectivity through the use of voice. Keywords: podcasting; digital audio; transformation; creativity; innovation DOI: 10.1080/09687760903033082

Molecular adsorption in graphene with divacancy defects

We have investigated theoretically the adsorption of molecules onto graphene with divacancy defects. Using ab-initio density functional calculations, we have found that O2, CO, N2, B2 and H2O molecules all interact strongly with a divacancy in a graphene layer. Along with a complex geometry of the molecule-graphene bonding, metallic behavior of the graphene layer in presence of CO and N2 molecules have been found with a large density of states in the vicinity of the Fermi level suggesting an increase in the conductivity. The adsorption of N2 is particularly interesting since the N atoms dissociate in the vicinity of the defects, and take the place where the missing C atoms of the divacancy used to sit. In this way, the defected graphene structure is healed geometrically, and at the same time doped with electron states.

Disegno and desire in Pontormo's Alessandro de’ Medici

ABSTRACTPontormo's portrait of Alessandro de’ Medici (c. 1534–35), showing the duke drawing a portrait of his beloved, cleverly engages with the history and fictive nature of art‐making. Pliny's tale about the invention of drawing forms one resonance, Castiglione's praise of the noble art of drawing another, the theorization of disegno by Vasari and others yet a third. Poetic conventions about the picturing of the beloved inform the image of a ruler who is presented as a courtly lover, adept observer, discerning patron, Medicean loyalist, and cultivated prince. Layers of presence and absence, naturalism and idealism are at work in the image, which addresses the perspicacity of sight and the poetics of its very making. The duke adopts a mythic persona but so too does the painter endow his craft with a distinguished pedigree, ranging from Pliny, Petrarch and poets like Lorenzo de’ Medici to the era's notions of perceptual psychology, amorous imprinting and the conceptual basis of disegno.

Normal and friction forces between mucin and mucin–chitosan layers in absence and presence of SDS

Employing the colloidal probe AFM technique we have investigated normal and friction forces between flat mica surfaces and silica particles coated with mucin and combined mucin–chitosan layers in presence and absence of anionic surfactant, SDS, in 30 mM NaCl solution. We have shown that the normal interactions between mucin coated mica and silica surfaces are dominated by long-range steric repulsion on both compression and decompression. Friction forces between such mucin layers are characterized by a low effective friction coefficient, μ eff = 0.03 ± 0.02 , which is lower than the value of 0.13 ± 0.02 observed when chitosan layers were adsorbed. Forces between combined mucin–chitosan layers have also been measured. Adsorption of chitosan on mucin results in considerable compaction of the layer, and development of attractive forces detectable on separation. Friction between mucin–chitosan layers in 30 mM NaCl solution is high, with μ eff ≈ 0.4 . Adsorption of additional mucin to this layer results in no improvement with respect to lubrication as compared to the mucin–chitosan layer, and μ eff ≈ 0.4 is observed. We argue that the layers containing both mucin and chitosan are not strictly layered but rather strongly entangled. As a result attractive interactions between oppositely charged moieties of sialic acid residues from mucin and amine groups from chitosan residing on the opposing surfaces contribute to the increased friction. The effects of SDS on normal and friction forces between combined mucin–chitosan layers were also investigated. The relation between surface interactions and friction properties is discussed.

A comparative study on the effect of VUV radiation in plasma SiO x-coated polyimide and polypropylene films

Wettability of polyimide (PI) and polypropylene (PP) films have been improved using SiO x -like thin layers deposited from a mixture of hexamethyldisiloxane (HMDSO) and oxygen in a microwave distributed electron cyclotron resonance plasma reactor. The films wettability evolution behaviors were evaluated through the results of contact angle measurements, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The plasma depositions of SiO x thin layers in presence of VUV radiation induce a contact angle decrease to about 7° and 35° for PI and PP films, respectively. XPS data showed that such difference in wettability is attributed to the increase of hydrophilic group's proportion at the surface of coated PI films due to VUV irradiation. AFM images showed that the PI surface topography remains relatively smooth when coated in presence of VUV radiation. However, in the case of PP films, AFM images revealed the growth of irregular structure due to a substrate etching effect supported by VUV radiation. For polymers coated without VUV irradiation, the deconvolution of the C1s peaks showed a significant decrease of C O bonds for both PI and PP substrates.

Mechanochemical Additive-Assisted Reconditioning Effects and Mechanism on Worn Ferrous Surfaces

Abstract An additive package of reconditioning functionality for worn ferrous surfaces has been designed in light of the mechanochemical reaction principle. The package is formulated from a fine-powdery multicomponent mixture of Serpentine minerals, surfactants, and catalysts. The main reconditioning component in the package is magnesium silicate hydroxide (Mg6(Si4O10)(OH)8), with the surfactants for dispersing the main component into bulk lubricant and the catalysts for facilitating interfacial mechanochemical reactions, particularly oil pyrolysis and carbonization. With commercial fully-formulated engine oils as benchmark, the reconditioning effects of the reconditioner package have been demonstrated in both laboratory tribotestings and in real-world heavy-duty (locomotive diesel engine) scenarios. Surface examination of sampled worn surfaces on both laboratory test specimens and cylinder bore of locomotive diesel engine has shown that a nano-crystalline layer has been generated which possesses nanometric roughness, higher surface hardness, and proper H/E ratio. Advanced analyses have indicated that the layer is composed of Fe3O4 and FeOOH nanoparticles which are dispersed on the Fe-C matrix. The smoother surface mitigates asperity interlocking which would otherwise induce high friction; the high surface hardness and appropriate H/E ratio result in less elastic deformation within nanocrystalline contact regions, which effectively lessens friction and wear arisen from plastic plowing and adhesion. Further characterization of sampled worn cylinder bore surface and analysis of used oils have suggested that generation of the nanocrystalline layer in presence of Mg6(Si4O10)(OH)8 involves three interwoven processes: oxidative mechanical polishing, lubricant carbonization and graphitization, and mechanical alloying.

Interaction of Bispyridinium Compounds with Phospholipid Layers in Presence and Absence of Electric Field

AbstractThe nonspecific biological activity of compounds with cell membranes is of great importance when considering them for pharmaceutical applications. The interactions of a group of therapeutic bispyridinium compounds with phospholipid monolayers of dioleoyl phosphatidylcholine (DOPC) on a mercury electrode (HMDE) are reported in this paper. Impedance versus frequency plots and capacitance‐potential curves were recorded for the model membrane system. The penetration of the compounds into the monolayer is shown to be dependent on the applied electric field. Both electron withdrawing and electron donating substituents of the bispyridinium compounds promote interaction with the compounds at applied negative potential.

Experimental investigation of 3D acoustic receptivity of an airfoil boundary layer due to surface vibrations

The three-dimensional acoustic receptivity of laminar boundary layers in presence of microscopic surface vibrations (the vibro-acoustic receptivity) is examined. The flow under investigation is the boundary layer on an airfoil at relatively high Reynolds numbers close to realistic ones for gliders. This flow has favourable and adverse pressure gradients and develops on a curved wall. The goal of the present study is to obtain quantitative information about the receptivity characteristics of this flow for excitation of the 3D Tollmien–Schlichting (TS) waves in cases when the frequencies of surface vibrations ( f v ) have the same order of magnitudes as those of the acoustic waves ( f ac ) . The experiments were performed at controlled disturbance conditions. The 2D acoustic field was produced by loudspeakers, while the localised non-stationary surface non-uniformities were simulated by a controlled circular surface vibrator. The TS-wave generation was investigated for several values of the parameter of non-stationarity of the surface non-uniformity K = f v / f ac . The receptivity was investigated in two general cases: in ‘ plus-regimes’ when the TS-waves were excited at combination frequencies f TS + = f ac + f v and in ‘ minus-regimes’ when the excitation occurred at frequencies f TS − = f ac − f v . The complex (amplitude and phase) receptivity coefficients are obtained experimentally as functions of the spanwise wavenumber (and the wave propagation angle) for three different frequency ratios K and also for several TS-wave frequencies at fixed values of K. The obtained vibro-acoustic receptivity coefficients are compared with the acoustic-roughness receptivity coefficients (i.e. for K = 0 ) found in previous experiments and DNS.

High reflectivity Bragg reflectors based on a gold nanoparticle/Teflon-like composite material as a new approach to organic solvent detection

We report on the properties of a new optical sensing element for organic solvents based on polymeric distributed Bragg reflector (DBR), which can be easily interfaced with optical fibers. The DBR is a periodic stack of alternating Teflon-like and gold nanoparticle/Teflon-like composite layers showing high reflectivity in the optical telecommunication spectral range and sensing properties due to the peculiar absorbing properties of the composite layers. The swelling of the composite layers in presence of organic vapors causes a DBR periodicity change and this results in the shift of the high reflectivity window.

Tensioactive Properties of Semidilute Polymer Solutions

We present a scaling description of adsorbed polymer layers in presence of a semi-dilute solution. Within a very simple model where the layer is treated as a thermodynamic ensemble of loops with a large polydispersity in size, we are able to a) describe the influence of the semidilute solution on the structure of the layer of adsorbed chains, and b) estimate the variation of the surface tension $\gamma $ of the solution as a function of the polymerization index of the chains (N) and the monomer volume fraction in the bulk ($\Phi_b$). Concerning point a), this work provides a continuous picture for the variations of the static properties of the interfacial layer from the dilute case ($\Phi_b\rightarrow 0$), to the melt case ($\Phi_b\rightarrow 1$). Concerning point b), we find a law $\gamma (\Phi_b,N)$ of the form (good solvent conditions) $\gamma_{VdW}-A\Phi_b^{5/4}+B\Phi_b^{7/8}/N^{1/2}\ln( N/\Phi_b^{7/12}N*)$, where $\gamma _{VdW}$ accounts for Van der Waals interactions and N* is a characteristic index of polymerization of the polymer under consideration (A and B are calculated within numerical coefficients of order unity). This law is in good quantitative agreement with experimental measurements and generalizes our recent findings on the case of molten polymer liquid. (Aubouy, Manghi, Raphael, to be published in Physical Review Letters).

Density corrections for turbulence models

The present paper deals with the improvement of the predictions of high Mach number boundary layers. Two-equation models have been shown to poorly predict the logarithmic region of the boundary layer in presence of large density gradients. This induces significant errors in the skin friction coefficient prediction. A correction of the diffusion terms in two-equation models is suggested to account for the density variations and to retrieve the logarithmic law. The analysis yields the result that new quantities involved in transport are combinations of the product ρk and the length scale ℓ. Standard forms of transport equations, with extra terms linked to density variations can be derived. Tests cases on flat plate boundary layers, over a wide range of Mach numbers, Reynolds numbers and wall to adiabatic temperature ratios as well as flat plate experiments have confirmed the present analysis.

Synthesis and characterization of laser ablated TiNi films

TiNi thin films with BaTiO3 and PbZr0.52Ti0.48O3 (PZT) as buffer layers were deposited on Si(100) substrates by the pulsed laser deposition (PLD) method. Buffer layers (BaTiO3 and PZT) were deposited at 600 °C in oxygen (O2) environment and TiNi films were deposited on the top of the buffer layer in presence of 15 mTorr nitrogen (N2) at various deposition temperatures (50, 300, and 500 °C). Synthesis and characterization of TiNi films were investigated from the crystallographic point of view by using X-ray diffractometer (XRD) and atomic force microscope (AFM) techniques. It is found that buffer layer of BaTiO3 and PZT have improved the crystallinity of TiNi films deposited at higher temperatures. The TiNi/PZT film was uniform compared to TiNi/BaTiO3 film with the exception of agglomerates that appeared throughout the layer.

Surface Dynamics of Liquids in Nanopores.

${}^{2}$H NMR relaxation of a selectively deuterated polar molecule confined to a set of calibrated nanoporous silica glasses is reported. These experiments, combined with the consideration of different time scales in the theory of surface relaxation, show how confinement effects can provide detailed information on the rotational dynamics of temporarily adsorbed liquid layers in presence of biphasic fast exchange. In particular, the results show the existence of an orientational order parameter within the wetting monolayer.

Surface Rotational Dynamics of Liquids Confined in Nanopores

ABSTRACT2H NMR relaxation times of selectively deuterated polar molecules confined to a set of calibrated nanoporous silica glasses are reported. These experiments, combined with the consideration of different time scales in the theory of surface relaxation, show how confinement effects can provide detailed information on the rotational dynamics of temporarily adsorbed liquid layers in presence of biphasic fast exchange.

Minimum Entropy Production Principle Applied to Decontaminating Regime in a Stochastic Layer in Presence of a Radial Electric Field

AbstractThe Ergodic Divertor of TORE SUPRA induces a stochastic layer at the plasma edge by creating a resonant magnetic perturbation which destroys the magnetic surfaces. A radial electric field directed outwards is then established to confine the electrons along the open magnetic field lines. This electric field tends to deconfine ions. One may then expect that it strongly influences the neoclassical ion transport. We use a variational principle of minimum entropy production to study the transport of impurity ions in the stochastic layer. In low collisionality regime, a decontaminating outwards flux of impurity ions is found, contrasting with the neoclassical inwards flux which produces the deleterious accumulation of impurity ions in the nH profile.