BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Thermal evaluation of the use of porous ceramic plates on ventilated façades—part II: Thermal behavior

The effects of porous ceramic plates on the thermal behavior of ventilated façades were evaluated, and the results are presented herein. Thermal behavior in a ventilated façade of specimens containing 40 wt% of lime mud and a firing temperature of 1100°C was evaluated and compared with a commercial porcelain ceramic tile, which was the reference material. An experimental apparatus was designed to evaluate the thermal performance of the studied ventilated façades. The results revealed that the ventilated façade composed of the studied porous ceramic tiles produced a greater reduction in temperature between the external environmental and the interior of a box representing a building (ΔT5) of 65.7°C, compared with the façade composed of the commercial porcelain ceramic tiles (ΔT5 = 56.0°C) and even the traditional façade (ΔT5 = 49.1°C). Thus, porous ceramic tiles based on byproducts are promising candidates for ventilated façade systems.     

Reaction of Hydrogen Bromide with Long Chain 1,2-Diols

The reactions of 1,2-hexadecanediol and 1,2-octadecanediol with hydrogen bromide in the presence of acetic anhydride have been investigated. The treatment of hydrogen bromide (48%) in acetic anhydride with 1,2-hexadecanediol gives mainly 1-bromo-2-acetoxy hexadecane (66%), 2-acetoxy hexadecanol (26%), and 1,3-hexadecanediol (8%). Similar products result from 1,2-octadecanediol. The structures of the products are based on combustion data, spectroscopic, and chemical evidences. The mechanism of the reaction has been discussed.     

Consequences of different cutting regimes on regrowth and nutrient stoichiometry of Sparganium erectum L. and Potamogeton natans L.

Aquatic vegetation forms an essential component in freshwater ecosystems but due to changed environmental and anthropogenic conditions often needs management to reduce nuisance for human land‐use. In this paper, the authors looked at the regrowth of two macrophyte species (Potamogeton natans and Sparganium erectum) in two lowland rivers under different cutting treatments. After an initial cross‐sectional transect was manually removed from bank to bank at the beginning of the growth season, a monthly repetitive removal of biomass in plots on that transect was done during the rest of the growth season (testing frequency of mowing). Additional new transects were also cut in subsequent months (testing timing of mowing). Finally, biomass was repetitively removed in plots in those additional transects too (testing frequency of mowing × timing of mowing). The biomass at the end of the growth season was analysed for C, N, P, and Si. It was demonstrated that timing and frequency of vegetation cutting has an important effect on the capacity and rate of species' recovery and therefore on the efficiency of the applied management. Nutrient stoichiometry of the regrown biomass was directly affected by cutting. Caused by differences in the applied timing and frequency of the cutting, C/N and N/P ratios and BSi concentrations were highly variable. Yet, overall, there was a clear tendency towards a higher C/N ratio and BSi concentration and lower N/P ratio in biomass that recovered after cutting. This human impact on the quantity and quality of autochthonous organic matter may have knock‐on effects on the decomposers food web and mineralization process.     

Bathymetry and siltation rate for Dokan Reservoir,Iraq

The Dokan Reservoir dam is a concrete cylindrical arch with gravity abutments, located on the Lesser Zab River about 60 km from the city of Sulaimani in north‐eastern Iraq. A bathymetric survey was conducted in November 2014 for a period of 10 days, using an echo sounder of 200‐kHz single beam. The survey results indicated an annual average sediment deposition of 3.8 million m³. Thirty‐two sediment samples were collected from the reservoir bed. The ratio of gravel, sand, silt and clay was 15:14:48:23, respectively. The reservoir bed is covered mainly with silt. The sediments are composed of silty clay (77.6%), silty sandy clay (10%), sandy gravely silty clay (1.2%) and gravely sandy silty clay (1%).     

The fatty acids of wax esters and sterol esters from vernix caseosa and from human skin surface lipid

Separation of sterol esters from wax esters in the lipids of vernix caseosa and adult human skin surface was accomplished by column chromatography on MgO. The fatty acids of the sterol esters and wax esters of both samples were separated into saturates and monoenes, and examined in detail by gas liquid chromatography (GLC). The saturated fatty acids of the wax esters of vernix caseosa and of adult human skin surface were remarkably similar. They ranged in chain length from at least C₁₁ to C₃₀, six skeletal types being present: straight even, straight odd, iso, anteiso, other monomethyl branched and dimethyl branched. A large number of patterns of monoenes were observed, each pattern consisting of desaturation of a specific chain at Δ6 or Δ9 plus its extension or degradation products. The mole per cent of the total Δ6 and Δ9 patterns of wax ester fatty acid monoenes of vernix caseosa were 87% and 12%, respectively, and 98% and 1%, respectively, for adult human skin surface lipid. The sterol ester fatty acids of vernix caseosa were much different from those of adult human skin surface: vernix caseosa saturates were largely branched and of lengths greater than C₁₈, whereas the saturates of adult human surface lipid resembled the wax ester fatty acids. Of the vernix caseosa monoene patterns, the mole per cent was 30% Δ6 and 70% Δ9, whereas of the adult human skin surface sterol ester fatty acids 89% were Δ6 and 11% Δ9. Chain extension was particularly pronounced in the sterol ester fatty acid monoenes of vernix caseosa amounting to 7–8 C₂ units in some cases. The fatty acids of the sterol esters of both vernix caseosa and adult human skin surface appear to be derived from the sebaceous gland and from the keratinizing epidermis, but those of the wax esters are from the sebaceous glands only.     

Shape optimization of a micromixer with staggered herringbone groove

Shape optimization of a staggered herringbone groove micromixer using three-dimensional Navier-Stokes analysis has been carried out. The analysis of the degree of mixing is performed by the calculation of spatial data statistics. The calculation of the variance of the mass fraction at various nodes on a plane in the channel is used to quantify mixing. A numerical optimization technique is applied to optimize the shape of the grooves on a single wall of the channel. Two design variables, namely, the ratio of the groove depth to channel height ratio and the angle of the groove, are selected for optimization. A mixing index is used as the objective function. The results of the optimization show that the mixing is very sensitive to the shape of the groove which can be used in controlling the mixing in microdevices. The mixing is affected by the depth of the groove much more than the angle of the groove.     

Electrochemistry at capped platinum nanoparticle Langmuir Blodgett films: A study of the influence of platinum amount and of number of LB layers

Platinum nanoparticles (n-Pt), over-grafted with 2-thiophenecarbonyl chloride are assembled on gold electrodes, by the Langmuir Blodgett (LB) technique using behenic acid (BHA) as promoting agent. These layers are electrochemically active without any preliminary activation. The [Fe(CN)₆]^3−/4− redox couple was used as electrochemical probe. This paper reports on the influence of the number of deposited LB layers, and the n-Pt density on the electrochemical response. n-Pt density was modified by the change of the “BHA/n-Pt” ratio. Cyclic voltammograms of “[Fe(CN)₆]^3−/4−” were observed whatever the coating conditions. As soon as the first layer was deposited the electrochemical response was associated to the n-Pt coverage, its response slightly increased up to a steady state for five or seven layers. As expected, the increase of the Pt density favored the increase of the current density. XPS analysis performed before and after electrochemical cycling showed that 4-mercaptoaniline capped platinum nanoparticles, and their over grafting were chemically and electrochemically stable. Analysis of influence of the number or the n-Pt density of the layers showed that the electrochemically active part of LB electrodes was provided by the last layer plus a part of the underlying one.     

15 years of processing and dissemination of SPOT-VEGETATION products

Throughout the VEGETATION programme, the Flemish Institute for Technological Research (VITO) uninterruptedly hosted the prime user segment of both VEGETATION 1 and VEGETATION 2 multispectral instruments on board the Satellite Pour l’Observation de la Terre 4 (SPOT 4) and SPOT 5 satellites. Operational since the launch of SPOT 4 in March 1998, and foreseen to continue at least until the end of the SPOT 5 mission (anticipated in spring 2014), this user segment comprises a processing facility (PF), actively receiving, processing, correcting, archiving, and distributing the VEGETATION data and derived added-value products. First and foremost, the VEGETATION programme has been serving the needs of operational users – both institutional and commercial – requesting data in near-real time. However, scientific and educational users too benefited significantly, in particular from VEGETATION’s unique time series of the Earth’s land cover, and more specifically the vegetation cover. Over the years, the centralized archive houses processed data covering the equivalent of 11,000 times the Earth’s surface, and delivered more than 50 terapixels to around 10.000 users. As such, VEGETATION’s mission is a prime example of what Europe wants to achieve through the Global Monitoring for Environment and Security (GMES) initiative: truly operational services providing reliable and up-to-date information.

This article describes the processing facility, the way the data and products are archived, the different dissemination channels as well as the data policy adopted and the users served. One of the recent evolutions, the development of an entirely new product distribution facility (PDF), implemented as part of the Project for On-Board Autonomy – Vegetation (PROBA-V) user segment is discussed.