Thymosin β4 is differentially expressed in the cerebrospinal fluid of Creutzfeldt‐Jakob disease patients: a MALDI‐TOF MS protein profiling study

MALDI‐TOF protein profiling analysis permits the detection of peptides and small proteins in complex protein mixtures with great accuracy. We applied this analysis to cerebrospinal fluid (CSF) from 15 patients affected by Creutzfeldt‐Jakob disease (CJD). We compared the levels of the normalized ion signals of 11 sporadic and 4 genetic CJD forms with those from ten healthy control subjects and eight non‐CJD relapsing‐remitting multiple sclerosis patients. In so doing, we detected 61 differentially expressed ion signals in CJD samples compared to controls. Among the 61 signals, 3 signals had significantly increased levels with high statistical significance (p <0.0001) and were located at 3238.3 m/z, 4963.7 m/z, and 8565.3 m/z. We characterized the 5.0 and 8.6 kDa proteins as thymosin β4 N‐acetylated and free ubiquitin, respectively, while the 3.2‐kDa peptide remained uncharacterized. Although elevated ubiquitin levels have previously been described in CJD, we have demonstrated for the first time the involvement of thymosin β4 in a neurodegenerative disease. To support the validity of thymosin β4 levels obtained by MALDI‐TOF analysis, an independent enzyme immunoassay analysis was performed. Moreover, a validation cohort consisting of CSF from three CJD patients, five healthy subjects, and six non‐CJD relapsing‐remitting multiple sclerosis patients was analyzed in a similar way, yielding superimposable results. We propose that thymosin β4 is a potential new candidate marker for the ante mortem diagnosis of CJD disease.     

QFD: The problem of comparing technical/engineering design requirements

An approach based on multiple-criteria decision aid (MCDA) methods has been introduced for the prioritization of technical/engineering design requirements during the quality function deployment (QFD) process. The proposed method allows the avoidance of the rigid procedure under which the relationship matrix coefficients are turned from an ordinal into a cardinal scale. A comparison analysis is carried out between the traditional approach and the proposed one. A numerical example is also provided so as to highlight the main differences between the two methods.     

Preface by the section editor

This special section is devoted to some of the novel approaches to hardware-like system verification that are currently being used in industry or the object of fielded research. The topics presented in this special section are based on a selection of the papers which appeared originally in the Proceedings of CHARME 2001, the Eleventh Advanced Research Working Conference on Correct Hardware Design and Verification Methods which took place in Livingston, Scotland, UK in September 2001. They are by no means a complete account of the numerous ways in which hardware and hardware-like systems are being subject to rigorous investigation, but they represent an interesting sample of today’s problems and of the techniques oriented around new uses of verification techniques. Published online: 10 April 2003     

Nanoconfined mixed Li and Mg borohydrides as materials for solid state hydrogen storage

Several mixtures of LiBH₄ and Mg(BH₄)₂ borohydrides in different stoichiometric ratios (1:0, 2:1, 1:1, 1:2, 0:1), prepared by high energy ball milling, have been investigated with X-ray powder diffraction and thermal programmed desorption (TPD) volumetric analysis to test the dehydrogenation kinetics in correlation with the physical mixture composition. Afterwards mixed and unmixed borohydrides were dispersed on high specific surface area ball milled graphite by means of the solvent infiltration technique. BET and statistical thickness methods were used to characterize the support surface properties, and SEM micrographs gave a better understanding of the preparation techniques. It has been observed by TPD volumetric measurements that the confinement of the reactive borohydrides on the nanoporous supports leads to a lower dehydrogenation temperature compared to unsupported borohydrides. Moreover, a further decrease of the dehydrogenation temperature has been observed by increasing the specific surface area of the support and the pores volume and by using the prepared mixtures instead of pure materials. The dehydrogenation process seems to be favoured by the heterogeneous nucleation on the graphite surface of decomposition products or intermediate phases from melted liquid borohydrides.     

The value of quality clues in the wine market: evidences from Lazio,Italy

The purpose of the paper is to contribute to understanding the role and effectiveness of different quality clues in the creation of value for the main wines of the Lazio region. The study presents a hedonic price model. An ordinary least squares and a quantile regression models were estimated. The latter is able to detect additional patterns related to the effects of the covariates. Prices are regressed on wine color, sub-regional area of origin, the type of certification of origin, and on experts' evaluation. The analysis is based on data released by three major Italian wine guides: Gambero Rosso, l'Espresso, and AIS (Italian Sommelier Association). Results show that: (i) white and red wines follow two different price patterns; (ii) prices are correlated with experts' evaluation; (iii) the impact of the latter is higher when other quality clues, such as geographical indications, are less effective; (iv) the role of different quality clues varies at different price levels and it is different for red and white wines; overall, wines from the Lazio region are associated with poor to mediocre quality levels. This may explain the decline in reputation and in market share that these wines are experiencing after centuries of popularity.     

A constraint-based variability modeling framework

Constraint-based variability modeling is a flexible, declarative approach to managing solution-space variability. Product variants are defined in a top-down manner by successively restricting the admissible combinations of product artifacts until a specific product variant is determined. In this paper, we illustrate the range of constraint-based variability modeling by discussing two of its extreme flavors: constraint-guarded variability modeling and constraint-driven variability modeling. The former applies model checking to establish the global consistency of product variants which are built by manual specification of variations points, whereas the latter uses synthesis technology to fully automatically generate product variants that satisfy all given constraints. Each flavor is illustrated by means of a concrete case study.     

Application of nine air-dried Capsicum annum cultivars as food preservative: Micronutrient content,antioxidant activity,and foodborne pathogens inhibitory effects

Capsicum annum cultivars Yellow cayenne, Portafortuna, Idealino, Sole, Duemila, Pellegrino, Fantasia, Loco, and Effix were investigated for their antioxidant properties and foodborne pathogens inhibitory activity. The total phenols, flavonoids, anthocyanins, capsaicinoids, carotenoids, ascorbic acid, and vitamin E content were also determined. Duemila and Portafortuna cultivars showed the highest total phenol content with values of 924.3 and 935.0 mg of chlorogenic acid equivalents/100 g dried weight, respectively. Idealino pepper presented the highest capsaicin content (2932.1 μg/g dried weight). The antioxidant capacity was evaluated by using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid test, 2,2-diphenyl-1-picrylhydrazyl test, and ferric reducing ability power assay. Both Pellegrino and Idealino samples exhibited a promising radical scavenging ability against 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical with IC₅₀ values of 45.2 and 45.7 μg/mL, respectively. All the extracts were able to inhibit the growth of Staphylococcus aureus and Listeria monocytogenes investigated strains. The most active are Effix and Fantasia peppers with minimal inhibitory concentration between 12.5 and 25.0 mg/mL, respectively. Overall, these results support the use of these pepper species as dried extract in food preservation.     

Dietary krill oil increases docosahexaenoic acid and reduces 2-arachidonoylglycerol but not N-acylethanolamine levels in the brain of obese Zucker rats

Evidence suggests that dietary long chain polyunsaturated fatty acids (LCPUFAs), and particularly those belonging to the n-3 family, may influence the brain fatty acid profile and, thereby, the biosynthesis of endocannabinoids in rodents. However, the doses used are usually quite high and not comparable with human intake. Recently, we have shown that relatively low doses of dietary n-3 LCPUFAs (4 weeks), in the form of either fish or krill oil, balanced for EPA and DHA content, and against a control diet with no EPA and DHA and similar contents of oleic, linoleic and α-linolenic acids, lower the concentrations of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in the visceral adipose tissue, and of AEA in the liver and heart, of obese Zucker rats. This, in turn, is associated with lower levels of arachidonic acid in membrane phospholipids and with amelioration of some metabolic syndrome parameters. We investigated here whether in Zucker rats, under the same conditions, fish and krill oil are also able to influence LCPUFA and endocannabinoid profiles in brain. Only krill oil was able to increase significantly DHA levels in brain phospholipids, with no changes in arachidonic acid. DHA increase was associated with lower levels of 2-AG in the brain, whereas AEA and its congeners, N-palmitoylethanolamine and N-oleoylethanolamine, were unchanged. We conclude that, despite the strong impact of dietary n-3 fatty acid on endocannabinoid levels previously observed in peripheral tissues, in the brain only 2-AG is affected by dietary krill oil, suggesting that the beneficial effect of the latter on the metabolic syndrome is mostly exerted by modifying peripheral endocannabinoids. Nevertheless, possible effects of dietary krill oil in the brain through modification of 2-AG levels deserve further investigation.     

Poly(DL-lactide-co-ε-caprolactone) and poly(DL-lactide-co-glycolide) blends for biomedical application: Physical properties,cell compatibility,and in vitro degradation behavior

Poly(DL-lactide-co-ε-caprolactone) (PLCL) and poly(DL-lactide-co-glycolide) (PLGA) blends of various compositions were prepared. Fractured sections of PLCL/PLGA blends did not evidence phase separation and blend glass transition temperatures suggested some degree of blend compatibility. The elastic modulus showed a negative deviation from the additive law of mixture. Superior biocompatibility in terms of fibroblast NIH 3T3 cell adhesion and proliferation, better mechanical properties, and a more homogeneous phase were obtained with PLCL/PLGA 25/75 blend. Rapid degradation of PLCL phase (4–8 weeks) in PLCL/PLGA 25/75 blend led to a porous structure, which makes it a potential candidate for drug delivery systems.