A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility

Steven–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line treatment of human immunodeficiency virus infection. In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis. We hypothesized that this gene, involved in immune response and in NF-κB activation, could also be implicated in the SJS/TEN susceptibility. We performed a full resequencing of TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We identified eight exonic and three intronic already described variants. The case/control association analysis highlighted an association between the rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the variant allele (C) resulted significantly associated with a higher risk to develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33–10.01)). A multivariate analysis by logistic regression confirmed its significant contribution (p = 0.027, OR = 4.39 (95% CI 1.19–16.23)). In conclusion, our study suggests that a variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN.     

Different bacterial models for in vitro induction of non‐cavitated enamel caries‐like lesions: Microhardness and polarized light miscroscopy analyses

The aim of this study was to compare different bacterial models for in vitro induction of non‐cavitated enamel caries‐like lesions by microhardness and polarized light microscopy analyses. One hundred blocks of bovine enamel were randomly divided into four groups (n = 25) according to the bacterial model for caries induction: (A) Streptococcus mutans, (B) S. mutans and Lactobacillus acidophilus, (C) S. mutans and L. casei, and (D) S. mutans, L. acidophilus, and L. casei. Within each group, the blocks were randomly divided into five subgroups according to the duration of the period of caries induction (4–20 days). The enamel blocks were immersed in cariogenic solution containing the microorganisms, which was changed every 48 h. Groups C and D presented lower surface hardness values (SMH) and higher area of hardness loss (ΔS) after the cariogenic challenge than groups A and B (P < 0.05). As regards lesion depth, under polarized light microscopy, group A presented significantly lower values, and groups C and D the highest values. Group B showed a higher value than group A (P < 0.05). Groups A and B exhibited subsurface caries lesions after all treatment durations, while groups C and D presented erosion‐type lesions with surface softening. The model using S. mutans, whether or not it was associated with L. acidophilus, was less aggressive and may be used for the induction of non‐cavitated enamel caries‐like lesions. The optimal period for inducing caries‐like lesions was 8 days. Microsc. Res. Tech. 78:444–451, 2015. © 2015 Wiley Periodicals, Inc.     

Industry–research co‐operation within and across regional boundaries. What does innovation policy add?

The paper aims to show how regional policy‐makers can stimulate firms' co‐operation with research organizations by granting an R&D subsidy. Using an original dataset for the Italian region of Emilia‐Romagna, propensity score matching is first applied to identify the impact of the subsidy received. A generalized propensity score technique is then employed to investigate the effect of an increasing amount of support. The firm's co‐operation is policy sensitive. The award of a subsidy to regional firms affects their intra‐regional more than their extra‐regional co‐operation. The propensity toward the latter appears subject to a monetary effect and is influenced by the amount of public funding received providing the subsidy overcomes a minimum threshold.     

Capacitance DNA bio-chips improved by new probe immobilization strategies

Label-free DNA detection plays a crucial role in developing point-of-care biochips. Capacitance detection is a promising technology for label-free detection. However, data published in literature often show evident time drift, large standard deviation, scattered data points, and poor reproducibility. To address these problems, mercapto-hexanol or similar alkanethiols are usually considered as blocking agents. The aim of the present paper is to investigate new blocking agents to further improve DNA probe surfaces. Data from AFM, SPR, florescence microscopy, and capacitance measurements are used to investigate new lipoate and ethylene-glycol molecules. The new surfaces offer further improvements in terms of diminished detection errors. Film structures are investigated at the nano-scale to justify the detection improvements in terms of probe surface quality. This study demonstrates the superiority of lipoate and ethylene-glycol molecules as blocking candidates when immobilizing molecular probes onto spot surfaces in label-free DNA biochip.     

Modulation on C‐ and N‐Terminal Moieties of a Series of Potent and Selective Linear Tachykinin NK2 Receptor Antagonists

Herein we describe the synthesis of a series of new potent tachykinin NK₂ receptor antagonists by the modulation of the C‐ and N‐terminal moieties of ibodutant (MEN 15596, 1 ). The N‐terminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C‐terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK₂ receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK₂ receptor. Selected compounds were tested in vivo confirming their activity as NK₂ antagonists. In particular, after both iv and id administration to guinea pig, compound 61 b was able to antagonize NK₂‐induced colonic contractions with a potency and duration‐of‐action fully comparable to the reference compound 1 (MEN 15596, ibodutant).     

Investigation of Enhancement Band Using Double Screen Frequency Selective Surfaces with Koch Fractal Geometry at Millimeter Wave Range

Numerical and theoretical investigations are presented for a double screen frequency selective surface (DSFSS) with perfectly conducting Koch fractal patch elements. The work was developed in two steps, in the first step two Koch fractal FSS screens were designed using the commercial software Ansoft Designer^TM. In the second these FSS were cascaded and separated by an air gap layer, forming the so-called DSFSS, to improve the bandwidth behavior. Thereafter, a numerical cascading technique is used to analyze the effect of the air gap on the DSFSS. The results were compared and a good agreement was observed.     

Application of a three-component competitive adsorption model to evaluate and optimize granular activated carbon systems

A recently developed kinetic model for granular activated carbon (GAC) adsorbers (COMPSORB-GAC) that quantitatively describes the adsorption of trace organic contaminant in the presence of competing natural organic matter (NOM) was applied to evaluate the performance of different GAC system configurations: conventional fixed-bed adsorbers, layered upflow carbon adsorbers (LUCA), and moving-bed adsorbers (with few or many bed sections). COMPSORB-GAC separately tracks the adsorption of three components: a trace compound, a strongly competing NOM fraction that reduces trace compound equilibrium capacity, and a pore-blocking NOM fraction that reduces kinetics. Performance was simulated for various design criteria and with model parameters derived for two natural waters with significantly different NOM concentrations. For the range of simulated conditions and with baseline performance defined by a fixed-bed adsorber, LUCA generally reduced carbon usage rates (CURs) by 15-35%. A 2-section and a 16-section moving-bed reactor reduced baseline CURs by 20-30% and 45-55%, respectively. Projected CURs for the water source with a relatively high NOM concentration were 2-3 times higher for all reactor configurations and indicated that NOM preloading would cause performance deterioration in deep GAC beds, which highlights the importance of source water quality. These results show how COMPSORB-GAC can be used in a comprehensive, site-specific optimization of GAC systems to ensure robust system performance and to balance capital and operating costs.     

A new sawing machine by diamond wire

Diamond wire is widely used for stone cutting; it is typically employed to extract a block in quarry and to square the block in a machining company. In particular, the frames to square or to cut the blocks present many technological limits, such as the high costs of the diamond wire, the frequent break of the diamond wire during cutting, the poor quality of cut surfaces, and the dangerous process and productivity lower than that of the same tool used in a quarry. The present work shows an innovative prototype machine to cut by a diamond wire which overcomes the aforementioned technological limits. The developed machine has a bridge frame among which two pulleys move the diamond wire as regards the stone block according with the feed speed. The diamond wire moves on the two pulleys with a cutting speed. A tensile force is applied to the wire that twists it during the contact with the stone, instead of keeping it along a straight direction parallel to the foundation of the machine. The twisting of the diamond wire makes the use of the wire itself more productive and safer, since the wear of each single bead during cutting is more uniform. Moreover, the resulting specific pressure acts on each bead along the arc of contact with the cut block and increases along the cutting direction from the entrance to the exit of the contact with the stone. The increasing of the specific pressure causes a bending of the diamond wire during the contact with the stone. The developed prototype was provided with a sensory system to measure both the cutting power and the tensile force of the diamond wire during experimental tests. In this way it was possible to verify the functionality of the prototype plant and, in the same time, to evaluate the productivity of the implemented cutting process.     

Enzymatic changes in pectic polysaccharides related to the beneficial effect of soaking on bean cooking time

BACKGROUND: Cooking time decreases when beans are soaked first. However, the molecular basis of this decrease remains unclear. To determine the mechanisms involved, changes in both pectic polysaccharides and cell wall enzymes were monitored during soaking. Two cultivars and one breeding line were studied. RESULTS: Soaking increased the activity of the cell wall enzymes rhamnogalacturonase, galactanase and polygalacturonase. Their activity in the cell wall was detected as changes in chemical composition of pectic polysaccharides. Rhamnose content decreased but galactose and uronic acid contents increased in the polysaccharides of soaked beans. A decrease in the average molecular weight of the pectin fraction was induced during soaking. The decrease in rhamnose and the polygalacturonase activity were associated (r = 0.933, P = 0.01, and r = 0.725, P = 0.01, respectively) with shorter cooking time after soaking. CONCLUSION: Pectic cell wall enzymes are responsible for the changes in rhamnogalacturonan I and polygalacturonan induced during soaking and constitute the biochemical factors that give bean cell walls new polysaccharide arrangements. Rhamnogalacturonan I is dispersed throughout the entire cell wall and interacts with cellulose and hemicellulose fibres, resulting in a higher rate of pectic polysaccharide thermosolubility and, therefore, a shorter cooking time. Copyright © 2011 Society of Chemical Industry