Showing papers by "University of Cagliari published in 1999"
TL;DR: In this paper, the authors describe a multi-agent model of financial markets which supports the idea that scaling arises from mutual interactions of participants, and they find that it generates such behaviour as a result of interactions between agents.
Abstract: Financial prices have been found to exhibit some universal characteristics1,2,3,4,5,6 that resemble the scaling laws characterizing physical systems in which large numbers of units interact. This raises the question of whether scaling in finance emerges in a similar way — from the interactions of a large ensemble of market participants. However, such an explanation is in contradiction to the prevalent ‘efficient market hypothesis’7 in economics, which assumes that the movements of financial prices are an immediate and unbiased reflection of incoming news about future earning prospects. Within this hypothesis, scaling in price changes would simply reflect similar scaling in the ‘input’ signals that influence them. Here we describe a multi-agent model of financial markets which supports the idea that scaling arises from mutual interactions of participants. Although the ‘news arrival process’ in our model lacks both power-law scaling and any temporal dependence in volatility, we find that it generates such behaviour as a result of interactions between agents.
1,504 citations
TL;DR: The results of this study confirmed the possibility of using thyme essential oils or some of their components in food systems to prevent the growth of foodborne bacteria and extend the shelf‐life of processed foods.
Abstract: Essential oils and their components are becoming increasingly popular as naturally occurring antimicrobial agents. In this work the chemical composition and the antimicrobial properties of Thymus essential oils and of their main components were determined. Three essential oils obtained from different species of Thymus growing wild in Sardinia and a commercial sample of Thymus capitatus oil were analysed. The essential oil components were identified by GC/MS analysis. The antimicrobial activity of the oils and components was determined against a panel of standard reference strains and multiple strains of food-derived spoilage and pathogenic bacteria, using a broth microdilution method. The GC/MS analysis showed that the major constituents of the oils were monoterpene hydrocarbons and phenolic monoterpenes, but the concentration of these compounds varied greatly among the oils examined. The results of the antimicrobial assay showed that essential oils extracted from Sardinian Thymus species have an antimicrobial activity comparable to the one observed in other thyme oils. It seems also confirmed that the antimicrobial properties of thyme essential oils are mainly related to their high phenolic content. Among the single compounds tested carvacrol and thymol turned out to be the most efficient against both reference strains and food-derived bacteria. The results of this study confirmed the possibility of using thyme essential oils or some of their components in food systems to prevent the growth of foodborne bacteria and extend the shelf-life of processed foods.
1,043 citations
TL;DR: A role in associative stimulus-reward learning can provide an explanation for the extinction-like impairment of primary reinforcement that led Wise to propose the "anhedonia hypothesis" as mentioned in this paper, where addictive drugs share with natural rewards the property of stimulating dopamine transmission preferentially in the nucleus accumbens shell.
556 citations
TL;DR: In this article, the authors discuss the background theory, role of spontaneous polarization in this context, and the practical implications of built-in polarization fields in nitride nanostructures.
Abstract: Huge built-in electric fields have been predicted to exist in wurtzite III-V nitrides thin films and multilayers. Such fields originate from heterointerface discontinuities of the macroscopic bulk polarization of the nitrides. Here we discuss the background theory, the role of spontaneous polarization in this context, and the practical implications of built-in polarization fields in nitride nanostructures. To support our arguments, we present detailed self-consistent tight-binding simulations of typical nitride quantum well structures in which polarization effects are dominant.
469 citations
TL;DR: It is hypothesized that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction and further studies will be conducted to investigate other attributes of this novel dairy product.
Abstract: Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product.
458 citations
TL;DR: Monitoring the changes in dopamine transmission in the nucleus accumbens shell and core during appetitive and consummatory phases of behaviour motivated by food suggests that phasic dopamine Transmission in each compartment of the nucleus Accumbens subserves different roles in motivated behaviour.
426 citations
TL;DR: In the present survey of an iodine-deficient community, a progressive increase with age of goiter prevalence, thyroid nodularity, and functional autonomy was observed, twice as high as that reported in iodine-sufficient areas, mainly due to an increased frequency of toxic nodular goiter.
Abstract: We carefully assessed thyroid status and goiter by ultrasound in 1411 subjects virtually representing the entire resident population of Pescopagano, an iodine-deficient village of Southern Italy. Median urinary iodine excretion was 55 microg/L. The prevalence of goiter was 16.0% in children and 59.8% in adults. Thyroid nodularity was 0.5% in children and progressively increased with age to 28.5% in the 56- to 65-yr-old group. The prevalence of present or past hyperthyroidism was 2.9%, including 9 cases with toxic diffuse goiter and 20 with toxic nodular goiter. Functional autonomy was rare in children, progressively increased with age up to 15.4% in the elderly, and was related to nodular goiter. The prevalences of overt and subclinical hypothyroidism in the adults were 0.2% and 3.8%, respectively. Serum autoantibodies to thyroglobulin and thyroperoxidase were detected in 12.6% of the entire population. The prevalence of diffuse autoimmune thyroiditis was 3.5%, being very low in children. Thyroid cancer was found in only 1 case. In conclusion, in the present survey of an iodine-deficient community, a progressive increase with age of goiter prevalence, thyroid nodularity, and functional autonomy was observed. Hyperthyroidism was twice as high as that reported in iodine-sufficient areas, mainly due to an increased frequency of toxic nodular goiter. Although low titer serum thyroid antibodies were relatively frequent, the prevalences of both overt and subclinical autoimmune hypothyroidism were not different from those observed in iodine-sufficient areas.
403 citations
TL;DR: In this paper, the authors tested the hypothesis that blood flow velocity could be recorded in the left anterior descending coronary artery (LAD) during transthoracic echocardiography by using second harmonic echo Doppler modality along with contrast enhancement (intravenous Levovist) at rest and after pharmacologically induced maximal vasodilation to assess coronary flow reserve (CFR) with a totally noninvasive approach.
Abstract: Background—We tested the hypothesis that blood flow velocity could be recorded in the left anterior descending coronary artery (LAD) during transthoracic echocardiography by use of second harmonic echo Doppler modality along with contrast enhancement (intravenous Levovist) at rest and after pharmacologically induced maximal vasodilation to assess coronary flow reserve (CFR) with a totally noninvasive approach. Methods and Results—Fifty-six consecutive patients undergoing coronary angiography underwent transthoracic contrast-enhanced pulsed-wave Doppler recording of blood flow velocity in the LAD by use of harmonic color Doppler as a guide at rest and after maximal vasodilation by dipyridamole infusion. Contrast enhancement with the harmonic mode greatly improved the success rate of recording adequate pulsed-wave Doppler signal in the LAD. CFR was (mean±SD) 1.54±0.7 in patients with (group 1) and 2.79±0.9 in patients without (group 2) significant LAD stenosis (lumen narrowing >70%) (P<0.001); sensitivity a...
355 citations
TL;DR: In this paper, the performance of the electrodes was evaluated in terms of faradaic yield and fraction of toxic intermediates removed during the electrolysis of 2-chlorophenol at Ti/PbO2 and Ti/SnO2 anodes.
Abstract: Electrochemical oxidation of 2-chlorophenol was studied at Ti/PbO2 and Ti/SnO2 anodes. The performance of the electrodes was evaluated in terms of faradaic yield and fraction of toxic intermediates removed during the electrolysis. Results showed that, although similar average faradaic yields were obtained using Ti/PbO2 or Ti/SnO2 anodes, the latter material is preferred because of its better ability to oxidise toxic compounds. An effective electrochemical treatment (ηF≅50%) may be accomplished, in which electrolysis at Ti/SnO2 can be stopped when, in spite of a relatively high COD, only a small amount of easily biodegradable oxalic acid is present in the effluent.
307 citations
TL;DR: In this paper, the role of spontaneous and piezoelectric polarization in determining built-in fields in III-V nitride nanostructures has been investigated and clarified.
Abstract: Macroscopic polarization plays a major role in determining the optical and electrical properties of nitride nanostructures via polarization-induced built-in electrostatic fields. While currently fashionable, this field of endeavour is still by far in its early infancy. Here we contribute some clarifications on the conceptual issues involved in determining built-in fields in III–V nitride nanostructures, sorting out in particular the roles of spontaneous and piezoelectric polarization.
305 citations
01 Jan 1999
TL;DR: In this paper, a collection of control algorithms which are able to give rise to 2-sliding modes have been presented, and for each of them the sufficient convergence conditions are given.
Abstract: In this paper a collection of control algorithms which are able to give rise to 2-sliding modes have been presented, and for each of them the sufficient convergence conditions are given. Furthermore, the real sliding behaviour is briefly considered, and, in some cases, the upper bound of the convergence time is given.
TL;DR: The results show that the phasic responsiveness of NAc DA transmission to an unfamiliar palatable food is under strong modulatory control by primary (consummatory) and secondary (appetitive) stimuli, and that the sign and extent of this control depends on the nature of the appetitive stimulus, delay of reward and motivational state (deprivation).
Abstract: We have previously shown in non-deprived rats that feeding of an unfamiliar palatable food (Fonzies(R)) phasically stimulates in vivo dopamine (DA) transmission in the medial nucleus accumbens (NAc) and this effect undergoes habituation after a previous (24 h) Fonzies meal (Bassareo & Di Chiara 1997, J Neurosci, 17, 851-861) The present study shows that an unfamiliar food (Kinder(R)) with a taste and composition (milk chocolate) different from that of Fonzies, also induces a release of DA in the NAc subjected to one-trial habituation Habituation was taste specific as no cross-habituation was observed between Fonzies and Kinder In undeprived rats, a 40-min exposure to an intrinsic appetitive stimulus (food smell arising from a Fonzies-filled plastic box) also prevented the increase in dialysate DA associated with Fonzies feeding, and this effect was partially reversed by food deprivation Food deprivation also prevented habituation of Fonzies-induced increase of dialysate DA in the NAc Predictive association of an empty plastic box to Fonzies feeding resulted in the acquisition of appetitive properties by the box and in facilitation (rather than inhibition) of the phasic responsiveness of DA transmission to Fonzies feeding A 10-min pre-exposure to appetitive olfactory stimuli intrinsic to Fonzies still prevented, like a 40-min pre-exposure, the NAc DA response to Fonzies feeding; however, a 5-min pre-exposure to these appetitive stimuli did not prevent the DA response in the NAc These results show that the phasic responsiveness of NAc DA transmission to an unfamiliar palatable food is under strong modulatory control by primary (consummatory) and secondary (appetitive) stimuli, and that the sign and extent of this control depends on the nature of the appetitive stimulus, delay of reward and motivational state (deprivation)
TL;DR: CMS reciprocally affected DA responsiveness to motivational stimuli, facilitating or inducing a stimulatory DA response to aversive stimuli but blunting stimulatory responses to rewarding stimuli.
TL;DR: Addiction is the expression of the excessive control over behavior acquired by drug‐related stimuli as a result of abnormal strenghtening of stimulus‐drug contingencies by nondecremental drug‐induced stimulation of dopamine transmission in the nucleus accumbens shell.
Abstract: Conventional reinforcers phasically stimulate dopamine transmission in the nucleus accumbens shell. This property undergoes one-trial habituation consistent with a role of nucleus accumbens shell dopamine in associative learning. Experimental studies with place- and taste-conditioning paradigms confirm this role. Addictive drugs share with conventional reinforcers the property of stimulating dopamine transmission in the nucleus accumbens shell. This response, however, undergoes one-trial habituation in the case of conventional reinforcers but not of drugs. Resistance to habituation allows drugs to repetitively activate dopamine transmission in the shell upon repeated self-administration. This process abnormally facilitates associative learning, leading to the attribution of excessive motivational value to discrete stimuli or contexts predictive of drug availability. Addiction is therefore the expression of the excessive control over behavior acquired by drug-related stimuli as a result of abnormal strenghtening of stimulus-drug contingencies by nondecremental drug-induced stimulation of dopamine transmission in the nucleus accumbens shell.
TL;DR: Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Dopplers flow wire CFR measurements.
TL;DR: To investigate whether the severity of GHD was correlated with the degree of bone mass and turnover impairment, BMD at the lumbar spine and femoral neck was evaluated and circulating IGF-I, IGF-binding protein-3, and osteocalcin levels, and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were evaluated.
Abstract: Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD) or with multiple pituitary hormone deficiencies (MPHD). To investigate whether the severity of GHD was correlated with the degree of bone mass and turnover impairment, we evaluated BMD at the lumbar spine and femoral neck; circulating insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and osteocalcin levels, and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels in 101 adult hypopituitary patients and 35 sex- and age-matched healthy subjects. On the basis of the GH response to arginine plus GHRH (ARG+/-GHRH), patients were subdivided into 4 groups: group 1 included 41 patients with a GH peak below 3 microg/L (0.9 +/- 0.08 microg/L), defined as very severe GHD; group 2 included 25 patients with a GH peak between 3.1-9 microg/L (4.7 +/- 0.4 microg/L), defined as severe GHD; group 3 included 18 patients with a GH peak between 9.1-16.5 microg/L (11.0 +/- 0.3 microg/L), defined as partial GHD; and group 4 included 17 patients with a GH peak above 16.5 microg/L (28.3 +/- 4.3 microg/L), defined as non-GHD. In all 35 controls (group 5), the GH response after ARG+/-GHRH was above 16.5 microg/L (40.7 +/- 2.2 microg/L). In patients in group 1, circulating IGF-I (P < 0.001), IGFBP-3 (P < 0.05), osteocalcin (P < 0.001), and urinary Ntx levels (P < 0.001) were lower than those in group 3-5, which were not different from each other; the t score at the lumbar spine (-1.99 +/- 0.2) and that at the femoral neck (-1.86 +/- 0.3) were lower than those in groups 3 (-0.5 +/- 0.7, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), 4 (-0.5 +/- 0.2, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), and 5 (-0.5 +/- 0.2, P < 0.001 and 0.0 +/- 0.02, P < 0.001, respectively). In patients in group 2, circulating IGF-I and IGFBP-3 levels were not different from those in group 1, whereas the t scores at the lumbar spine (-1.22 +/- 0.3) and femoral neck (-0.9 +/- 0.3) were significantly higher and lower, respectively, than those in groups 1 and 5 (P < 0.05) but not those in groups 3 and 4, and serum osteocalcin and urinary Ntx levels were significant higher than those in group 1 and lower than those in groups 3-5 (P < 0.001). To evaluate the effect of isolated GHD vs. MPHD, patients were subdivided according to the number of their hormonal deficits, such as panhypopituitarism with (10 patients) or without (31 patients) diabetes insipidus, GHD with 1 or more additional pituitary deficit(s) (36 patients), isolated GHD (7 patients), 1-2 pituitary hormone deficit(s) without GHD (10 patients), and normal anterior pituitary function (7 patients). The t score at the lumbar spine and femoral neck and the biochemical parameters of bone turnover were not significantly different among the different subgroups with similar GH secretions. A significant correlation was found between the GH peak after ARG+GHRH and IGF-I, osteocalcin, urinary Ntx levels, and the t score at the lumbar spine, but not that at the femoral neck level. A significant correlation was also found between plasma IGF-I levels and the t score at the lumbar spine and femoral neck, serum osteocalcin, and urinary Ntx. Multiple correlation analysis revealed that the t score at the lumbar spine, but not that at the femoral neck, was more strongly predicted by plasma IGF-I levels (t = 3.376; P < 0.005) than by the GH peak after ARG+GHRH (t = -0.968; P = 0.338). In conclusion, a significant reduction of BMD associated with abnormalities of bone turnover parameters was found only in patients with very severe or severe GHD, whereas normal BMD values were found in non-GHD hypopituitary patients. These abnormalities were consistently present in all patients with GHD regardless of the presence of additional hormone deficits, suggesting that GHD plays a central role in the development of osteopenia in hypopituitary patients.
TL;DR: In this paper, the authors investigate the process of spatial agglomeration of innovation and production activities and assess the extent to which the degree of specialisation or diversity externalities in the area may affect the innovative output in a particular local industry.
Abstract: The aim of the paper is to investigate the process of spatial agglomeration of innovation and production activities and to assess the extent to which the degree of specialisation or diversity externalities in the area may affect the innovative output in a particular local industry. The analysis is carried out thanks to an original databank on innovation and production activity across 85 industrial sectors and 784 Italian Local Labour Systems, which are groupings of municipalities characterised by a high degree of self-contained flows of commuting workers. According to the global and local indicators of spatial association there are clear signs of spatial correlation in the distribution of innovation activities. The econometric analysis shows that the two types of externalities – specialisation and urbanisation economies – are both effective. Moreover, we find evidence for knowledge spillovers since technological activities of a local industry influence positively innovations of the same sectors in contiguous areas.
TL;DR: The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implications.
Abstract: In this study it was investigated whether the oral administration of melatonin (1 mg) in comparison to placebo was able to reduce blood pressure, vascular reactivity, and catecholamines in men, as previously reported in young women. The administration of melatonin significantly reduced blood pressure, the pulsatility index in the internal carotid artery, and catecholamines levels within 90 minutes. The effect of melatonin on the artery pulsatility index was related to baseline values, being greater in men with higher baseline values. The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implications.
TL;DR: It is suggested that rats behaviorally sensitized to morphine show opposite changes in the stimulant effect of morphine in the nucleus accumbens shell and core and in the dorsal caudate-putamen, suggesting that sensitization of the dopamine system to a given agent does not necessarily extend to drugs of abuse of different pharmacological classes.
TL;DR: TheCLA dose-response effect on arachidonic acid suppression corresponded closely with the CLA dose- response effect on cancer protection in the mammary gland, and optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the breast gland.
Abstract: Previous research suggested that conjugated linoleic acid (CLA) feeding during the period of pubescent mammary gland development in the rat resulted in diminished mammary epithelial branching which might account for the reduction in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the objectives of the present study was to investigate the modulation of TEB density by increasing levels of dietary CLA and to determine how this might affect the risk of methylnitrosourea-induced mammary carcinogenesis. The data show a graded and parallel reduction in TEB density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was observed when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the mammary gland. Since both CLA and linoleic acid are likely to share the same enzyme system for chain desaturation and elongation, it is possible that increased CLA intake may interfere with the further metabolism of linoleic acid. Fatty acid analysis of total lipid showed that CLA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5-2% CLA. There was no perturbation in tissue linoleic acid, however, linoleic acid metabolites (including 18:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA. Of particular interest was the significant drop in 20:4 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoid biosynthesis. Thus the CLA dose-response effect on arachidonic acid suppression corresponded closely with the CLA dose-response effect on cancer protection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA.
TL;DR: In this article, the authors evaluated the feasibility in detecting blood flow in the left anterior descending coronary artery (LAD) using transthoracic color Doppler imaging (in both second harmonic and fundamental mode) along with contrast enhancement and to verify if this new noninvasive method along with adenosine is safe, rapid and effective in assessing coronary flow reserve (CFR).
TL;DR: In this paper, structural and vibrational features of polyiodides and donor-I2 adducts are used to remove the arbitrariness in considering discrete/non discrete entities and to provide a unified picture of the bonding in these species.
TL;DR: Hydroxytyrosol was highly protective against the peroxynitrite-dependent nitration of tyrosine and DNA damage by peroxlynitrite in vitro and could conceivably provide a defense against damage by oxidants in vivo.
TL;DR: The results suggest that the neurosteroids may play a role in the anxiolytic and rewarding effects of alcohol in sP rats.
TL;DR: There is no evidence that patients with a pre-existing mood or anxiety disorder were more likely than other patients to interrupt the interferon-α therapy.
TL;DR: In this paper, the interaction of iron oxide with the silica matrix in a Fe2O3-SiO2 nanocomposite prepared by a sol-gel method was investigated using Near-, Mid-, and Far-IR, and 29Si MAS-, and 1H NMR techniques.
TL;DR: In this paper, the optimal number and location of switching devices for both radial and meshed power distribution systems was found based on the Bellmann's optimality principle, combined with thinning techniques, yielding the optimal solution in a few ms for real size problems.
Abstract: Automatic devices that locate and automatically sectionalize faulted branches in MV power distribution systems restrict drastically the extent of disruption caused by long power interruptions when properly positioned. Some algorithms and automatic calculation procedures are proposed for determining the optimum number and location of automatic sectionalizing switching devices. Using these algorithms, the optimal solution can be found for both radial and meshed systems. The procedure is based on Bellmann's optimality principle which, combined with thinning techniques, yields the optimal solution in a few ms for real size problems.
TL;DR: In this paper, the authors present a detailed discussion of the asymptotic symmetries of anti-de-Sitter space in two dimensions and their relationship with the conformal group in one dimension.
TL;DR: The results demonstrate that the changes in the plasticity of GABA(A) receptors that occur in rat brain during pregnancy and after delivery are related to the physiological changes in plasma and brain concentrations of neurosteroids.
TL;DR: The high frequency, the expected prevention by preclinical diagnosis and early treatment of the devastating effect of WD on the nervous system and liver tissue, and the feasibility to detect most of molecular defects by DNA analysis indicate that WD in the Sardinian population should be added to the list of diseases currently detected by newborn screening.
Abstract: Wilson disease (WD) in the Sardinian population has an approximate incidence of 1:7,000 live births. Mutation analysis of the WD gene in this population reported in our previous articles led us to the characterization of two common mutations and a group of 13 rare mutations accounting for the molecular defect of 8.5, 7.9, and 15.1% of the WD chromosomes. However, molecular analysis of the WD chromosomes containing the most common haplotype, which accounts for 60.5% of the WD chromosomes, failed to define the disease-causing mutation. In this study, we characterized the promoter and the 5' UTR of the WD gene sequence and carried out a mutation analysis in this DNA region from patients with the most common haplotype. The promoter is contained in a GC-rich island and shows a TATA and a CAAT consensus sequence as well as potential binding sites for transcription factors and metal response elements. In all the analyzed 92 chromosomes with this haplotype, we detected a single mutation consisting of a 15-nt deletion from position -441 to position -427 relative to the translation start site. Expression assays demonstrated a 75% reduction in the transcriptional activity of the mutated sequence compared to the normal control. By adding this mutation to those that have been already characterized, we have now defined the molecular defect in 92% of the WD chromosomes in Sardinians. The high frequency, the expected prevention by preclinical diagnosis and early treatment of the devastating effect of WD on the nervous system and liver tissue, and the feasibility to detect most of molecular defects by DNA analysis indicate that WD in the Sardinian population should be added to the list of diseases currently detected by newborn screening.