Folate Receptor Beta as a Direct and Indirect Target for Antibody-Based Cancer Immunotherapy

Folate receptor beta (FRβ) is a folate binding receptor expressed on myeloid lineage hematopoietic cells. FRβ is commonly expressed at high levels on malignant blasts in patients with acute myeloid leukemia (AML), as well as on M2 polarized tumor-associated macrophages (TAMs) in the tumor microenvironment of many solid tumors. Therefore, FRβ is a potential target for both direct and indirect cancer therapy. We demonstrate that FRβ is expressed in both AML cell lines and patient-derived AML samples and that a high-affinity monoclonal antibody against FRβ (m909) has the ability to cause dose- and expression-dependent ADCC against these cells in vitro. Importantly, we find that administration of m909 has a significant impact on tumor growth in a humanized mouse model of AML. Surprisingly, m909 functions in vivo with and without the infusion of human NK cells as mediators of ADCC, suggesting potential involvement of mouse macrophages as effector cells. We also found that TAMs from primary ovarian ascites samples expressed appreciable levels of FRβ and that m909 has the ability to cause ADCC in these samples. These results indicate that the targeting of FRβ using m909 has the potential to limit the outgrowth of AML in vitro and in vivo. Additionally, m909 causes cytotoxicity to TAMs in the tumor microenvironment of ovarian cancer warranting further investigation of m909 and its derivatives as therapeutic agents in patients with FRβ-expressing cancers.     

Bioactive TiOB‐Coating on Titanium Alloy Implants Enhances Osseointegration in a Rat Model

The surface properties of titanium alloy implants for improved osseointegration in orthopaedic and dental surgery have been modified by many technologies. Hydroxyapatite coatings with a facultative integration of growth factors deposited by plasma spraying showed improved osseointegration. Our approach in order to enhance osseointegration was carried out by a surface modification method of titanium alloy implants called plasma chemical oxidation (PCO). PCO is an electrochemical procedure that converts the nm‐thin natural occurring titanium‐oxide layer on an implant to a 5 µm thick ceramic coating (TiOB‐surface). Bioactive TiOB‐surfaces have a porous microstructure and were loaded with calcium and phosphorous, while bioinert TiOB‐surfaces with less calcium and phosphorous loadings are smooth. A rat tibial model with bilateral placement of titanium alloy implants was employed to analyze the bone response to TiOB‐surfaces in vivo. 64 rats were randomly assigned to four groups of implants: (i) pure titanium alloy (control), ii) titanium alloy, type III anodization, (iii) bioinert TiOB‐surface, and (iv) bioactive TiOB‐surface. Mechanical fixation was evaluated by pull out tests at 3 and 8 weeks. The bioactive TiOB‐surface showed significantly increased shear strength at 8 weeks compared to all other groups.     

Correlations between the catalytic layer composition,the relative humidity and the performance for PEMFC carbon aerogel based membrane electrode assemblies

The parameters influencing the water management or the gas diffusion have a large impact on the performances of the PEMFC. In this work, we focused on the influence of the composition of the cathode catalytic layer on the performance of the MEA in relation to the relative humidity. A carbon aerogel was synthesized as catalyst support with a texture minimizing diffusive losses. We studied the influence of the Nafion content by preparing various cathode catalytic layers whose hydric properties were modified by adding PTFE as a hydrophobic agent. We evaluated the impact of the cathodic relative humidity by testing MEAs on a single cell test bench. We showed that modifying the composition of the catalytic layers playing on the content of both Nafion and PTFE, enables to improve the performance due to a better water management. The best performance was obtained with a Nafion/Carbon mass ratio (N/C) of 0.5 and a PTFE/Carbon (PTFE/C) mass ratio of 0.35 allowing 40% more power at 0.4 V and 75%RH. A first positive evaluation of the impact of PTFE is also done with TEC10E40E.     

Determination of key parameters responsible for polymeric liner collapse in hyperbaric type IV hydrogen storage vessels

Depressurization tests at a laboratory scale, coupled with numerical modelling, are used to determine the key parameters responsible for the polymeric liner collapse in hyperbaric type IV hydrogen storage vessels. X-ray tomography allows to determine the damages suffered by the sample during the depressurization step. Results show that the differential pressure induced during the depressurization step between the liner/composite interface and the free surface of the liner is the main factor responsible for the collapse of the liner. For a given temperature, this pressure gradient can be modified by changing the maximum H₂ pressure, the emptying rate or by adding a residual pressure plateau. Temperature is also of prime importance by influencing the yield point of the liner, the interface resistance and the amount of gas dissolved into the vessel. Thus, increasing temperature also increases the risk of liner collapse for the same gas exposure conditions.     

All-optical regeneration techniques

Basic principles of all-optical signal regeneration are presented, and main state-of-art techniques are reviewed. Optical fiber and semiconductor based devices are addressed, and some recently reported 2R and 3R signal regeneration experiments are discussed.     

Elaboration of PEG/PA66 blends in a twin-screw batch-type mini-extruder: Process study and modelling

This paper deals with the development of the morphology in polyethylene glycol (PEG) and polyamide 66 (PA66) immiscible blends exhibiting an extremely low viscosity ratio (η_PEG/η_PA66=3-4×10^-5). These materials were obtained by melt mixing, under different operating conditions, using a twin-screw batch-type DSM mini-extruder.Scanning electron microscopy, followed by quantitative image analysis was used to determine PEG particles size distribution (PSD) as a function of blends composition and screw rotation speed. Experiments carried out with two mixing time (5 and 10 min) showed no significant difference of PSD. So, to avoid thermal degradation of the products, the mixing time was set up at 5 min for all experiments. The influence of PEG concentration and screw rotation speed on PSD appeared to be similar to that obtained in a previous study for the same blends elaborated in a Haake internal mixer. The results clearly showed that the average particle diameters decreased as screw rotation speed increased and as PEG concentration decreased. However, this decrease is less important using the twin-screw batch-type mini-extruder with which the particle sizes are smaller. The particles sizes were then correlated to blend composition, shear rate and viscosity ratio owing to an extension of Serpe's model. The unknown parameters of the corresponding model were estimated on the basis of experimental data. This enabled then to predict with a good precision the influence of the process operating conditions on the morphology of the dispersed phase.     

Effect of TiO2 and 11 minor elements on the reactivity of ground-granulated blast-furnace slag in blended cements

Ground-granulated blast-furnace slags (GGBS) are glasses (>99%) of the CaO-Al₂O₃-SiO₂ compositional system and are widely used as supplementary cementitious materials. Differences in reactivity of GGBS were screened by modifying the content of 12 minor elements (namely Ba, Ce, Cs, Cr, K, Mn, P, Sn, Sr, Ti, V, and Zr). Scanning electron microscopy observations showed that most elements entered the silicate glass matrix, only Sn was reduced to its metallic form and P accumulated in minor minerals. Mortar strength tests showed that 2 day compressive strength was reduced by >50% for a TiO₂ content of 2.5 wt% in the slag. At 28 days the loss in compressive strength was still >40%. Calorimetric tests on other element additions showed that the content of network modifiers (Ba, Cs, K and Sr) and GGBS reactivity are positively correlated, whereas Ce, Cr, V, and Zr significantly decreased reactivity. Finally, it is shown that these effects can be estimated by the concentration and the weighted field strength of the added element.     

Pharmacophore‐Based Design of Novel Oxadiazoles as Selective Sphingosine‐1‐phosphate (S1P) Receptor Agonists with in vivo Efficacy

Sphingosine‐1‐phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure–activity relationship exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five‐membered heterocycles, and the use of diverse 2,2′‐disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochemical properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds. From these optimization studies, a selective S1P₁ agonist, N‐methyl‐N‐(4‐{5‐[2‐methyl‐2′‐(trifluoromethyl)biphenyl‐4‐yl]‐1,2,4‐oxadiazol‐3‐yl}benzyl)glycine ( 45 ), and a dual S1P_1,5 agonist, N‐methyl‐N‐(3‐{5‐[2′‐methyl‐2‐(trifluoromethyl)biphenyl‐4‐yl]‐1,2,4‐oxadiazol‐3‐yl}benzyl)glycine ( 49 ), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head‐to‐head in an experimental autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan‐S1P receptor agonist, S1P_1,5 agonist 49 demonstrated comparable efficacy while S1P₁‐selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS.     

Transparent anodes for polymer photovoltaics: Oxygen permeability of PEDOT

The oxygen permeability of the transparent organic anode poly(3,4,-ethylene dioxythiophene) with paratoluenesulphonate as the anion (PEDOT:pTS) was determined to be (STP) , and is thus comparable in magnitude to the oxygen permeability of polyethyleneterephthalate (PET). The oxygen diffusion through bilayers of polyethylene (PE) and PEDOT:pTS and bilayers of PET and PEDOT:pTS was established. The bilayer structures were applied as the carrier substrate and the transparent anode in polymer-based photovoltaic devices employing a mixture of poly(1-methoxy-4-(2-ethylhexyloxy)-p-phenylenevinylene) (MEH-PPV) and [6,6]-phenyl-C₆₁-butanoicacidmethylester (PCBM) as the active layer and aluminium as the cathode. The oxygen permeability of the layers and the aluminium cathode was correlated with the lifetime of the solar cell devices. It was found that the performance of the devices with PET as the carrier substrate degraded more slowly due to the lower oxygen and water permeability, whereas devices using PE as the carrier substrate gave devices with a very short lifetime. It was found that PEDOT:pTS on its own is a not a significant barrier for oxygen in the context of photovoltaic devices where long lifetimes are anticipated. It is concluded that the large oxygen permeability of the barrier layers contribute to the short device lifetimes while other permeates such as water also contribute to device degradation.     

Analysis of permeability of food plastic monolayers to methylethylketone (2-butanone) with the aromatran®

It is very important that measurements of the diffusion of aromas and volatile substances in trace amounts (p.p.m.) through synthetic materials, such as PVC, PE and PP monolayers, be accurate and repeatable. The primary goal of this work was to familiarize ourselves with the Aromatran®, a new, fully automated analytical instrument, for the measurement of a ketone (2-butanone or MEK) at 23°C. A discussion of results is provided, along with comments on the system's userfriendliness and the cost of the tests.