Identification of differentially expressed proteins in papillary thyroid carcinomas with V600E mutation of BRAF

BRAF, a serine/threonine kinase of the RAF family, is a downstream transducer of the RAS-regulated MAPK pathway. V600E mutation of BRAF protein is the most common genetic alteration occurring in papillary thyroid carcinomas and is prognostic of poor clinicopathological outcomes. Protein expression in the subclass of PTC bearing the BRAF(V600E) mutation was investigated by using 2-DE and MS/MS techniques and compared to that of matched normal thyroid tissues from seven patients. 2-D gel image analysis revealed that the expression of eight polypeptide spots, corresponding to five proteins, were significantly underexpressed in PTC bearing BRAF(V600E) mutation whereas 25 polypeptides, representing 19 distinct proteins, were significantly upregulated in tumour tissue, as compared to normal thyroid. Among the differentially expressed polypeptides, mitochondrial proteins, ROS-scavenger enzymes, apoptosis-related proteins as well as proteins involved in tumour cell proliferation were identified. Although dissimilarities between the present results and those previously reported can be ascribed to the use of different 2-DE techniques, the possibility that BRAF(V600E) mutation is responsible for changes in protein expression distinct from those induced by other oncogenes cannot be ruled out.     

A 3 × 3 digitally programmable CNN chip

In this paper a VLSI implementation of a 3 × 3 cell digitally programmable cellular neural networks (CNN) with discrete templates is presented. This chip is the first successfully tested, multichip-oriented CNN chip. In fact, this chip has been designed to be easily interconnected to others to carry out very large CNN arrays. This feature has been verified in a two-chip prototype board. The fully programmable capability covers most of the available one-neighbourhood fixed templates.     

Molecular Profiling and Novel Therapeutic Strategies for Mucosal Melanoma: A Comprehensive Review

Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to immunotherapy. Over the last years, whole-genome and exome sequencing techniques have led to increased knowledge on the molecular landscape of mucosal melanoma. Molecular studies have underlined noteworthy findings with potential therapeutic implications, including the presence of KIT mutations, which are potential targets of tyrosine kinase inhibitors currently in use in the clinic (imatinib), but also SF3B1 mutation, CDK4 amplifications, and CDKN2A gene deletions, which are presently under investigation in clinical trials. Recent results from a pooled analysis of patients with mucosal melanoma treated with immunotherapy have suggested that the combination of immune checkpoint inhibitors might improve survival outcomes in this subset of patients, as compared with single-agent immunotherapy. However, these results are not confirmed across different studies, and combo-immunotherapy correlates with a higher rate of adverse events. In this review, we describe the clinical, biological, and genetic features of mucosal melanoma. We also provide an update on the results of approved systemic treatment in this setting and overview the therapeutic strategies currently under investigation in clinical trials.     

Compressive evaluation of mansory bricks produced with industrial byproduct aggregates

This study evaluates the effect upon the compressive strength of ceramic masonry bricks when industrial byproducts known as soot are added. The research includes an analysis of the granulometric properties of the constituent components, performed manually with ASTM C136-01 screens to determine particle size using apertures sized from large to small; an analysis by XRD of the mineralogical phases present; a compressive strength analysis performed using standard compression testing machinery; and a water absorption measurement calculated according to Colombian Technical Standard: 4017:2015—Methods for the Sampling and Testing of Masonry Elements and other Clay Products. Five trials were performed using different mixtures of clay and soot, at substitution rates of 20%, 30%, 40%, 50%, and 60%. These mixtures were prepared under identical conditions in order to ensure validity of the resulting comparisons. The results showed that bricks with 20%, 30%, 40%, and 50% added soot demonstrated superior structural strength compared to conventional units. Bricks incorporating 60% soot, however, were found to have lower strength and high porosity.     

Fuel with advanced burnable absorbers design for the IRIS reactor core: Combined Erbia and IFBA

IRIS is an advanced medium-size (1000 MW) PWR with integral primary system targeting deployment already around 2015–2017. Consistent with its aggressive development and deployment schedule, the “first IRIS” core design assumes current, licensed fuel technology, i.e., UO₂ fuel with less than 5% ²³⁵U enrichment. The core consists of 89 fuel assemblies employing the 17×17 Westinghouse Robust Fuel Assembly (RFA) design and Standard Fuel dimensions. The adopted design enables to meet all the objectives of the first IRIS core, including over 3-year cycle length with low soluble boron concentration, within the envelope of licensed, readily available fuel technology. Alternative fuel designs are investigated for the subsequent waves of IRIS reactors in pursuit of further improving the fuel utilization and/or extending the cycle length. In particular, an increase in the lattice pitch from the current 0.496 in. for the Standard Fuel to 0.523 in. is among the objectives of this study. The larger fuel pitch and increased moderator-to-fuel volume ratio that it entails fosters better neutron thermalization in an altogether under-moderated lattice thereby offering the potential for considerable increase of fuel utilization and cycle length, up to 5% in the two-batch fuel management scheme considered for IRIS. However, the improved moderation also favors higher values of the Moderator Temperature Coefficient, MTC, which must be properly counteracted to avoid undesired repercussions on the plant safety parameters or controllability during transient operations. This paper investigates counterbalancing the increase in the MTC caused by the enhanced moderation lattice by adopting a suitable choice of fuel burnable absorber (BA). In particular, a fuel design combining erbia, which benefits MTC due to its resonant behavior but leads to residual reactivity penalty, and IFBA, which maximizes cycle length, is pursued. In the proposed approach, IFBA provides the bulk of the hold-down, with no penalty on cycle length, while the amount of erbia is adjusted to obtain the desired margin in the core peaking power and MTC. Preliminary economic analysis proves that within the IRIS design envelope, the combined BA fuel together with the enhanced moderation lattice offer the potential for considerable fuel cycle cost savings when compared to the current core design based on the Westinghouse Standard 17×17 lattice with IFBA. Therefore a combined BA fuel with the enhanced moderation lattice is a promising option to consider for future developments of the IRIS core.     

A survey of antibiotic resistance in Micrococcaceae isolated from Italian dry fermented sausages

The transfer of bacteria that are resistant to antimicrobial agents or resistance genes from animals to humans via the food chain is increasingly a problem. Therefore, it is important to determine the species and the numbers of bacteria involved in this phenomenon. For this purpose, 148 strains of microstaphylococci were isolated from three types of Italian dry fermented sausages. Eight of 148 strains belonged to the genera Kocuria and Micrococcus. The remaining 140 strains belonged to 11 different species of the genus Staphylococcus. The species most frequently isolated was Staphylococcus xylosus, followed by Staphylococcus saprophyticus and Staphylococcus aureus. Antibiotic resistance levels differed among the species and depended on the strain origin. Microstaphylococci were generally susceptible to beta-lactams, but 12 strains were resistant to methicillin, 8 were resistant to oxacillin, and 9 were resistant to penicillin G. No resistance was observed for aminoglicosides and cephalosporines. Many strains were resistant to sulfonamide, colistin suphate, tetracyclin, and bacitracin. Two strains of S. aureus, four strains of S. xylosus, and one strain of Staphylococcus sciuri were able to grow in the presence of 8 microg of vancomycin per g, but all strains were susceptible to teicoplanin. Twenty-two microstaphylococci were resistant to at least five of the tested antibiotics. The multiresistant strain S. aureus 899 was unaffected by eight antibiotics, including vancomycin and methicillin, indicating that a more prudent use of antibiotics in animal husbandry and better hygienic conditions during production should be encouraged because they can play a major role in reducing the incidence of such multiresistant microorganisms and the possible spread of the genetic elements of their resistance.     

A precise computation of stress intensity factor on the front of a convex planar crack

In this paper, we consider a general integral expression for mode I stress intensity factor along the fronts of convex planar cracks. For this integral approximation, we develop a simple numerical quadrature formula on every convex set Ω which allows a precise estimation of the error. This permits the use of extrapolation techniques for the accurate computation of the integral. Copyright © 2002 John Wiley & Sons, Ltd.     

Steric factors controlling the surface hybridization of PCR amplified sequences

This study elucidated the hybridization behavior of surface-bound oligonucleotides to their longer PCR-amplified targets. The screen-printed gold surface of disposable electrodes was the platform onto which thiol-tethered oligonucleotides (21-mer) were immobilized by chemisorption. As a model case, approximately 600-bp amplicons were studied. Surface hybridization was monitored by means of an enzyme-linked assay with electrochemical detection. Use of different surface-tethered probe sequences over a wide range of surface densities was explored to achieve the highest duplex yield. Both the surface coverage by the probe and its relative position on the target strand were found to control the efficiency of capture of the target sequence. Interfacial hybridization occurred with the highest efficiency for a probe coverage of approximately 2.9 x 10(12) molecules/cm2 and when the 3' end of the amplicon was involved. An unusual (bell-shaped) response/amplicon concentration profile was additionally found. It was hypothesised that when the amount of solution-phase target is relatively high, random collisions make reannealing of the approximately 600-bp strands favored over formation of the surface-tethered probe-amplicon complex. This paper also describes a strategy to enhance the sensitivity of enzyme-linked hybridization assays. Such a strategy relies on formation, around the long target sequence, of dendritic-like structures, which could offer multiple anchoring points for the enzyme conjugate. The results shown in this work might have great significance for the practical application of hybridization to oligonucleotide chips.     

Preliminary geochemical model of the Cerro Prieto geothermal field

The distribution of the Na-K-Ca index values in the geothermal aquifer of Cerro Prieto indicates a probable cold-water recharge in the northern and western parts of the present producing field. In the central part of the field, the distribution of Na-K-Ca values is very irregular, due to the effect of percolation or the vertical descending flow of colder waters caused by apparent over-exploitation.The large area with indices varying between 0·5 and 0·7 to the east, southeast, and south of the field confirm the presence of hotter geothermal waters than those observed in the present producing field. The limits of this hot aquifer have not yet been determined toward the east and southeast.The temperature distribution in the Cerro Prieto aquifer confirms the conclusions reached using the Na-K-Ca index. The maximum temperature calculated was in well M-53 (350°C) and the minimum was in M-9 (250°C), when wells M-6 and M-1A, which have lower temperatures, are not taken into account.The chloride distribution in the aquifer confirms the recharge of colder, less saline waters in the northern and western parts of the field. It was surprising to find that the chloride content in the aquifer was lower in the eastern part (M-53) than in the present field, even though the temperature is higher. Another interesting fact is the extremely low chloride content found in well M-101, with temperatures around 290°C.The distribution of potassium and silica in the aquifer was not as useful for the interpretation of fluid movement as originally expected. Discrepancies were found with respect to the interpretations based on the Na - K - Ca index and the chloride content.In regard to the changes in the Na - K - Ca index, in temperature, and in chloride content during the exploitation of the field, a gradual increase in Na - K - Ca index values was observed in wells with high and low enthalpy. In exceptional cases these values decrease or remain constant. This increase in the index has represented a 10 to 20°C temperature decrease with respect to the original values existing at the beginning of the exploitation of the field (1973). The chloride content in the aquifer has decreased at different rates, from 670 mg/l per year in M-26 to 371 mg/1 per year in well M-42, even though in some wells (M-20) it has increased and in others (M-5) it has remained almost constant.In order to decrease the rate of temperature and pressure reduction in the present producing field, it is recommended that production of low enthalpy wells be suspended and be replaced by new wells located in the periphery of the field, preferably to the southwest and northeast. Thus, the production area would at least be doubled, in an attempt to avoid the percolation or vertical flow, which is apparently causing the cooling of the reservoir.Another measure, which could help prevent a rapid drawdown, is to exploit the deeper hot aquifers that apparently exist in the center of the field. This would first have to be confirmed by an exploratory well or by deepening one of the present wells.