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.     

Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort

Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST^® ELISA and Lumipulse G^® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815⁻²⁷). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.     

DNA-directed immobilization of horseradish peroxidase onto porous SiO2optical transducers

ABSTRACT: Multifunctional porous Si nanostructure is designed to optically monitor enzymatic activity of Horseradish Peroxidase. First, an oxidized PSi optical nanostructure, a Fabry-Perot thin film, is synthesized and is used as the optical transducer element. Immobilization of the enzyme onto the nanostructure is performed through DNA-Directed Immobilization. Preliminary studies demonstrate high enzymatic activity levels of the immobilized Horseradish Peroxidase, while maintaining its specificity. The catalytic activity of the enzymes immobilized within the porous nanostructure is monitored in real time by reflective interferometric Fourier transform spectroscopy. We show that we can easily regenerate the surface for consecutive biosensing analysis by mild de-hybridization conditions.     

Optimization of the silane treatment of cellulosic fibers from eucalyptus wood using response surface methodology

Viscose cellulosic fibers from eucalyptus wood were treated with organosilanes to introduce specific functionalities on the fibers and enhance their wettability and adhesion with phenolic matrices in composites. Modeling procedures were employed to optimize the conditions of the treatments of the fibers with the silanes (3‐aminopropyl) trimethoxysilane (APS) and 3‐(2‐aminoethylamino) propyltrimethoxysilane (AAPS). The analyzed responses were relative intensities of the bands 1565/897 and 1120/897 cm⁻¹, measured by Fourier transform infrared spectroscopy, and the silicon amount incorporated into the cellulosic fibers, which was determined by energy dispersive X‐ray analysis. In addition, surface morphology of the silane treated fibers was observed using scanning electron microscopy. The treatments of the cellulosic fibers with 2.2% APS for 120 min and 1.5% AAPS for 100 min were selected as optimums. According to contact angle measurements, both treatments enhanced the wettability between the fibers and a resol‐type phenolic resin, revealing the possible use of the silane treated fibers as reinforcement in phenolic composites. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42157.     

Dynamics of urban and rural housing stocks in China

The massive migration flows from rural to urban areas in China, combined with an expected decline in the total population over the next decades, leads to two important challenges for China's housing: the growth of its urban housing stock and the shrinkage of rural housing. The rural and urban housing systems in China were analyzed using a dynamic material flow analysis model for the period 1900–2100 for several scenarios assuming different development paths for population, urbanization, housing demand per capita, and building lifetime. The simulation results indicate that new housing construction is likely to decline for several decades due to the fast growth over the past 30 years and the expected increased longevity of dwellings. Such an oscillation of new construction activity would have significant implications for the construction industry, employment, raw material demand, and greenhouse gas emissions to produce the construction materials. Policy and practical options for mitigating the negative impacts are considered.

Les flux migratoires massifs des zones rurales vers les zones urbaines en Chine, conjugués à un déclin prévu de la population totale au cours des prochaines décennies, entraînent deux défis importants pour le logement en Chine : la croissance de son parc de logements urbains et la diminution des logements ruraux. Les systèmes de logements ruraux et urbains en Chine ont été analysés en utilisant un modèle d'analyse dynamique des flux de matériaux sur la période 1900-2100 appliqué à plusieurs scénarios supposant différentes voies de développement concernant la population, l'urbanisation, la demande de logements par habitant et la durée de vie des bâtiments. Les résultats de la simulation indiquent qu'il est probable que la construction de logements neufs diminuera pendant plusieurs décennies en raison de la croissance rapide des 30 dernières années et de l'accroissement prévu de la durée de vie des logements. Une telle oscillation de l'activité de construction de logements neufs aurait d'importantes implications pour l'industrie du bâtiment, l'emploi, la demande en matières premières et les émissions de gaz à effet de serre résultant de la production des matériaux de construction. Les choix politiques et pratiques qui permettraient d'en atténuer les effets négatifs sont envisagés.

Mots clés: parcs de bâtiments, demande de constructions neuves, analyse dynamique des flux de matériaux, parc de logements, durée de vie, tendances, urbanisation, Chine     

Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.     

Influence of the dispersion of Nanoclays on the cellular structure of foams based on polystyrene

In the present work blends of polystyrene (PS) with sepiolites have been produced using a melt extrusion process. The dispersion degree of the sepiolites in the PS has been analyzed by dynamic shear rheology and X-ray micro-computed tomography. Sepiolites treated with quaternary ammonium salts (O-QASEP) are better dispersed in the PS matrix than natural sepiolites (N-SEP) or sepiolites organo-modified with silane groups (O-SGSEP). A percolated network is obtained when using 6.0 wt% of O-QASEP, 8.0 wt% of N-SEP and 10.0 wt% of O-SGSEP. It has been shown that multiple extrusion processes have a negative effect on the polymer architecture. They produce a reduction in the length of the polymeric chains, and they do not lead to a better dispersion of the particles in the polymer matrix. Foams have been produced using a gas dissolution foaming process, where a strong effect of the dispersion degree on the cellular structure of the different foams was found. The effects on the cellular structure obtained by using different types of sepiolites, different contents of sepiolites and different extrusion conditions have been analyzed. The foams produced with the formulations containing O-QASEP present the lowest cell size and the most homogeneous cellular structures.     

In‐Situ Monitoring of the Solid‐State Microstructure Evolution of Polymer:Fullerene Blend Films Using Field‐Effect Transistors

Organic field‐effect transistors (OFETs) are used to investigate the evolution of the solid‐state microstructure of blends of poly(3‐hexylthiophene) (P3HT) and [6,6]‐phenyl C₆₁‐butyric acid methyl ester (PC₆₁BM) upon annealing. Changes in the measured field‐effect mobility of holes and electrons are shown to reveal relevant information about the phase‐segregation in this system, which are in agreement with a eutectic phase behavior. Using dual‐gate OFETs and in‐situ measurements, it is demonstrated that the spatial‐ and time‐dependence of microstructural changes in such polymer:fullerene blend films can also be probed. A percolation‐theory‐based simulation is carried out to illustrate how phase‐segregation in this system is expected to lead to a substantial decrease in the electron conductivity in an OFET channel, in qualitative agreement with experimental results.     

Suppression of dynamic laser speckle signals in multimode fibers of various lengths

The effects of fiber coupling and fiber length on photocurrent fluctuations are studied when the light of a laser diode transmitted to and from a dynamic turbid medium by a step-index multimode fiber is studied. When the laser light is coupled asymmetrically, filling only the higher-order modes, the photocurrent fluctuations are suppressed significantly when fiber lengths of as much as 16 m are added between the laser and the medium. Addition of as much as 16 m of detection fiber, or any fiber in the case of symmetric light coupling, leads to much less or no suppression of the photocurrent fluctuations.