Showing papers by "University of Florence published in 1996"

Macroscopic quantum tunnelling of magnetization in a single crystal of nanomagnets

Abstract: THE precise manner in which quantum-mechanical behaviour at the microscopic level underlies classical behaviour at the macroscopic level remains unclear, despite seventy years of theoretical investigation. Experimentally, the crossover between these regimes can be explored by looking for signatures of quantum-mechanical behaviour—such as tunneling—in macroscopic systems1. Magnetic systems (such as small grains, spin glasses and thin films) are often investigated in this way2–12 because transitions between different magnetic states can be closely monitored. But transitions between states can be induced by thermal fluctuations, as well as by tunnelling, and definitive identification of macroscopic tunnelling events in these complex systems is therefore difficult13. Here we report the results of low-temperature experiments on a single crystal composed of super-paramagnetic manganese clusters (Mn12-ac), which clearly demonstrate the existence of quantum-mechanical tunnelling of the bulk magnetization. In an applied magnetic field, the magnetization shows hysteresis loops with a distinct 'staircase' structure: the steps occur at values of the applied field where the energies of different collective spin states of the manganese clusters coincide. At these special values of the field, relaxation from one spin state to another is enhanced above the thermally activated rate by the action of resonant quantum-mechanical tunnelling. These observations corroborate the results of similar experiments performed recently on a system of oriented crystallites made from a powdered sample4.

Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium

Abstract: Vascular endothelial growth factor (VEGF) is a secreted protein that is a specific growth factor for endothelial cells. We have recently demonstrated that nitric oxide (NO) donors and vasoactive peptides promoting NO-mediated vasorelaxation induce angiogenesis in vivo as well as endothelial cell growth and motility in vitro; in contrast, inhibitors of NO synthase suppress angiogenesis. In this study we investigated the role of NO in mediating the mitogenic effect of VEGF on cultured microvascular endothelium isolated from coronary postcapillary venules. VEGF induced a dose-dependent increase in cell proliferation and DNA synthesis. The role of NO was determined by monitoring proliferation or guanosine 3',5'-cyclic monophosphate (cGMP) levels in the presence and absence of NO synthase blockers. The proliferative effect evoked by VEGF was reduced by pretreatment of the cells with NO synthase inhibitors. Exposure of the cells to VEGF induced a significant increment in cGMP levels. This effect was potentiated by superoxide dismutase addition and was abolished by NO synthase inhibitors. VEGF stimulates proliferation of postcapillary endothelial cells through the production of NO and cGMP accumulation.

A pencil beam algorithm for proton dose calculations

Abstract: The sharp lateral penumbra and the rapid fall-off of dose at the end of range of a proton beam are among the major advantages of proton radiation therapy. These beam characteristics depend on the position and characteristics of upstream beam-modifying devices such as apertures and compensating boluses. The extent of separation, if any, between these beam-modifying devices and the patient is particularly critical in this respect. We have developed a pencil beam algorithm for proton dose calculations which takes accurate account of the effects of materials upstream of the patient and of the air gap between them and the patient. The model includes a new approach to picking the locations of the pencil beams so as to more accurately model the penumbra and to more effectively account for the multiple-scattering effects of the media around the point of interest. We also present a faster broad-beam version of the algorithm which gives a reasonably accurate penumbra. Predictions of the algorithm and results from experiments performed in a large-field proton beam are presented. In general the algorithm agrees well with the measurements.

Magnetic molecular materials

Abstract: The strategies currently developed for the synthesis of molecular based magnetic materials are reviewed. After a brief introduction resuming the conditions which are required to observe spontaneous magnetization, the organic, inorganic, organometallic approaches are illustrated. Particular attention is devoted to the metal-radical approach, in which the materials are assembled using transition metal complexes and stable organic radicals as building blocks.

The Dipole Formalism for the Calculation of QCD Jet Cross Sections at Next-to-Leading Order

Abstract: In order to make quantitative predictions for jet cross sections in perturbative QCD, it is essential to calculate them to next-to-leading accuracy. This has traditionally been an extremely laborious process. Using a new formalism, imaginatively called the dipole formalism, we are able to construct a completely general algorithm for next-to-leading order calculations of arbitrary jet quantities in arbitrary processes. In this paper we present the basic ideas behind the algorithm and illustrate them with a simple example.

Superparamagnetic-like behavior in an octanuclear iron cluster

Abstract: Using high-frequency EPR spectroscopy we have found that a cluster comprising eight iron(III) ions, Fe8, which is essentially flat, has a ground S = 10 state and an Ising-type anisotropy. For the first time both ac susceptibility and Mossbauer spectroscopy could be used in order to monitor the relaxation time of the magnetization, which was found to follow a thermally activated behavior, as in a superparamagnet, with τ0 = 1.9 × 10−7 s and an energy barrier of 22.2 K. The set of data allowed us to conclude that the origin of the anisotropy in nanosize molecular clusters is associated with the single ion contributions and not with the shape of the clusters.

Alzheimer's Disease Associated with Mutations in Presenilin 2 is Rare and Variably Penetrant

Abstract: Missense mutations in the presenilin 2 (PS-2) gene on chromosome 1 were sought by direct nucleotide sequence analysis of the open reading frame of 60 pedigrees with familial Alzheimer's disease (FAD) In the majority of these pedigrees, PS-1 and beta-amyloid precursor protein (beta APP) gene mutations had been excluded While no additional PS-2 pathogenic mutations were detected, four silent nucleotide substitutions and alternative splicing of nucleotides 1338-1340 (Glu325) were observed Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years) This variability is not attributable to differences in ApoE genotypes These results suggest (i) that, in contrast to mutations in PS-1, mutations in PS-2 are a relatively rare cause of FAD; (ii) that other genetic or environmental factor modify the AD phenotype associated with PS-2 mutations; and (iii) that still other FAD susceptibility genes remain to be identified

Long-lasting memory t cell responses following self-limited acute hepatitis b

Abstract: The molecular and cellular basis of long-term T cell mem- ory against viral antigens is still largely undefined. To char- acterize anti-viral protection by memory T cells against non-cytopathic viruses able to cause acute self-limited and chronic infections, such as the hepatitis B virus (HBV), we studied HLA class II restricted responses against HBV struc- tural antigens in 17 patients with acute hepatitis B, during the acute stage of infection and 2.2 to 13 yr after clinical resolu- tion of disease. Results indicate that: (a) significant T cell proliferative responses to HBV nucleocapsid antigens were detectable in all patients during the acute phase of infection and in 14/17 also 2-13 yr after clinical resolution of disease; b) long-lasting T cell responses were sustained by CD45RO 1 T cells, predominantly expressing the phenotype of recently activated cells; c) limiting dilution analysis showed that in some patients the frequency of HBV-specific T cells was comparable to that observed in the acute stage of infection and, usually, higher than in patients with chronic HBV in- fection; d) the same amino acid sequences were recognized by T cells in the acute and recovery phases of infection; and e) HBV-DNA was detectable by nested-PCR in approxi- mately half of the subjects. In conclusion, our results show that vigorous anti-viral T cell responses are detectable in vitro several years after clin- ical recovery from acute hepatitis B. Detection of minute amounts of virus in some recovered subjects suggests that long-term maintenance of an active anti-viral T cell re- sponse could be important not only for protection against reinfection but also for keeping the persisting virus under tight control. ( J. Clin. Invest. 1996. 98:1185-1194.) Key words: viremiacytokinestetanustoxoidHBV nucleo- capsid antigensHBV envelope antigens

Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis.

Abstract: Expression of platelet-derived growth factor (PDGF) and its receptor (R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry. In normal liver, PDGF and PDGF-R subunit expression was limited to a few mesenchymal cells of the portal tract stroma and vessels. In cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co-distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa. These aspects were paralleled by a marked overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities in a wide range of mesenchymal cells in fibrous septa and in perisinusoidal alpha-smooth-muscle-actin-positive cells. In general expression and distribution of PDGF-R subunits appeared to be related to the activation of different mesenchymal cell types involved in the fibroproliferative process. Therefore, we evaluated the expression of PDGF-R subunits in liver tissue specimens with increasing degrees of necroinflammatory activity. The results of this additional study confirmed that expression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition. Our results, providing evidence for a functional involvement of PDGF/PDGF-R in liver fibrogenesis, greatly support the results of previous in vitro studies and direct attention toward pharmacological strategies able to affect the series of signaling events arising from the autophosphorylation of PDGF-R subunits.

Human CD8+ T lymphocyte subsets that express HLA class I-specific inhibitory receptors represent oligoclonally or monoclonally expanded cell populations

Abstract: A small percentage of human T lymphocytes, predominantly CD8+ T cells, express receptors for HLA class 1 molecules of natural killer type (NK-R) that are inhibitory for T-cell antigen receptor (TCR)-mediated functions. In the present study, it is demonstrated that the various NK-R molecules typically expressed by NK cells are also expressed on periheral blood T lymphocytes. These CD3+ NK-R+ cells have a cell surface phenotype typical of memory cells as indicated by the expression of CD45RO and CD29 and by the lack of CD28 and CD45RA. Furthermore, by the combined use of anti-TCR V beta-specific antibodies and a semiquantitative polymerase chain reaction assay, the TCR repertoire in this CD3+ NK-R+ cell subset was found to be skewed; in fact, one or two V beta families were largely represented, and most of the other V beta s were barely detected. In addition, analysis of recombinant clones of the largely represented V beta families demonstrated that these V beta s were oligoclonally or monoclonally expanded.

Comments on "A possibilistic approach to clustering"

Abstract: In this comment, we report a difficulty with the-application of the possibilistic approach to fuzzy clustering (PCM) proposed by Keller and Krishnapuram (1993). In applying this algorithm we found that it has the undesirable tendency to produce coincidental clusters. Results illustrating this tendency are reported and a possible explanation for the PCM behavior is suggested.

A General Algorithm for Calculating Jet Cross Sections in NLO QCD

Abstract: We present a new general algorithm for calculating arbitrary jet cross sections in arbitrary scattering processes to next-to-leading accuracy in perturbative QCD. The algorithm is based on the subtraction method. The key ingredients are new factorization formulae, called dipole formulae, which implement in a Lorentz covariant way both the usual soft and collinear approximations, smoothly interpolating the two. The corresponding dipole phase space obeys exact factorization, so that the dipole contributions to the cross section can be exactly integrated analytically over the whole of phase space. We obtain explicit analytic results for any jet observable in any scattering or fragmentation process in lepton, lepton-hadron or hadron-hadron collisions. All the analytical formulae necessary to construct a numerical program for next-to-leading order QCD calculations are provided. The algorithm is straightforwardly implementable in general purpose Monte Carlo programs.

Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats

Abstract: 1. The effects of histamine and agents at histamine receptors on spontaneous and 100 mM K(+)-evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving, rats, and on cognitive tests are described. 2. Local administration of histamine (0.1-100 microM) failed to affect spontaneous but inhibited 100 mM K(+)-stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)-alpha-methylhistamine (RAMH) (0.1-10 microM), imetit (0.01-10 microM) and immepip (0.01-10 microM) mimicked the effect of histamine. 3. Neither 2-thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K(+)-evoked release of acetylcholine. 4. The inhibitory effect of 100 microM histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors. 5. The H3 receptor-induced inhibition of K(+)-evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX). 6. The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg-1) and RAMH (5 mg kg-1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K(+)-evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response. 7. These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

Aniracetam restores object recognition impaired by age, scopolamine, and nucleus basalis lesions.

Abstract: Object recognition was investigated in adult and aging male rats in a two-trials, unrewarded, test that assessed a form of working-episodic memory. Exploration time in the first trial, in which two copies of the same object were presented, was recorded. In the second trial, in which one of the familiar objects and a new object were presented, the time spent exploring the two objects was separately recorded and a discrimination index was calculated. Adult rats explored the new object longer than the familiar object when the intertrial time ranged from 1 to 60 min. Rats older than 20 months of age did not discriminate between familiar and new objects. Object discrimination was lost in adult rats after scopolamine (0.2 mg/kg SC) administration and with lesions of the nucleus basalis, resulting in a 40% decrease in cortical ChAT activity. Both aniracetam (25, 50, 100 mg/kg os) and oxiracetam (50 mg/kg os) restored object recognition in aging rats, in rats treated with scopolamine, and with lesions of the nucleus basalis. In the rat, object discrimination appears to depend on the integrity of the cholinergic system, and nootropic drugs can correct its disruption.

Humus and Enzyme Activity

Abstract: Publisher Summary A level of extracellular enzyme activity exists in soil. Enzymes secreted by living cells during normal cell activity, leaked from extant cells, or released from lysed cells, are short-lived unless they are adsorbed by soil colloids or inglobated by humic molecules. This level of extracellular enzyme activity indicates the biological capacity of the soil for the enzymatic conversion of the substrate, which is independent of the extant microbial activity; it also has an important role in the ecology of microorganisms. The activity of enzymes associated with mineral or organic colloids is one of the various activities contributing to the overall activity of the enzyme in soil. The extraction of humus–enzyme complexes from soil in good yields is obtained with solutions employed in extracting humic substances. The intrinsically high electron density of inorganic colloids masks the enzyme reaction product, while the humus material nonspecifically adsorbs the trapping agent becoming electron-dense. Using the electron probe microanalysis overcomes these problems. The chapter analyzes that if extracellular enzymes are observed in the humified organic matter, the comparison of data from extraction–purification experiments with observations by the electron probe microanalyses may prove useful.

Sequential approximation of feasible parameter sets for identification with set membership uncertainty

Abstract: In this paper the problem of approximating the feasible parameter set for identification of a system in a set membership setting is considered. The system model is linear in the unknown parameters. A recursive procedure providing an approximation of the parameter set of interest through parallelotopes is presented, and an efficient algorithm is proposed. Its computational complexity is similar to that of the commonly used ellipsoidal approximation schemes. Numerical results are also reported on some simulation experiments conducted to assess the performance of the proposed algorithm.

Thermally activated carrier transfer and luminescence line shape in self‐organized InAs quantum dots

Abstract: We investigated the temperature dependence (10–180 K) of the photoluminescence (PL) emission spectrum of self‐organized InAs/GaAs quantum dots grown under different conditions. The temperature dependence of the PL intensity is determined by two thermally activated processes: (i) quenching due to the escape of carriers from the quantum dots and (ii) carrier transfer between dots via wetting layer states. The existence of different dot families is confirmed by the deconvolution of the spectra in gaussian components with full width half maxima of 20–30 meV. The transfer of excitation is responsible for the sigmoidal temperature dependence of the peak energies of undeconvoluted PL bands.

Benign Paroxysmal Positional Vertigo of the Horizontal Canal: A Form of Canalolithiasis with Variable Clinical Features

Abstract: Benign paroxysmal positional vertigo of the horizontal semicircular canal (HC-BPPV) is a well-defined syndrome characterized by direction-changing horizontal positional nystagmus. We report the clinical features of 5 patients who illustrate the possible variables of the syndrome. In most cases, nystagmus is geotropic and more intense when the pathological ear is lowermost; less often the syndrome presents with apogeotropic nystagmus that is more intense when the affected ear is uppermost. The nystagmus pattern may vary in time in the same patient, changing from apogeotropic to geotropic even in observations at short intervals. In some patients, the features indicate involvement of more than one canal, either simultaneously or in succession. It is sustained that the clinical findings can be explained by movement of endolymph caused by displacement of otoconia in the semicircular canals and that variants are due to different positions of the otoconia within the canals.

Extracellular calcium negatively modulates tyrosine phosphorylation and tyrosine kinase activity during capacitation of human spermatozoa.

Abstract: Capacitation of spermatozoa, a complex process occurring after sperm ejaculation, is required to obtain fertilization of the oocyte in vivo and in vitro. Although most of the biochemical/biophysical events that occur during capacitation in vitro have been characterized, the molecular mechanisms underlying these complex events are still obscure. Increases of intracellular free Ca 2+ concentrations ([Ca 2+ ] i ) and protein tyrosine phosphorylation have previously been demonstrated during in vitro capacitation of human spermatozoa. In the present study we investigated the relationship between extracellular/intracellular Ca 2+ , protein tyrosine phosphorylation, and tyrosine kinase and phosphatase activities during sperm capacitation. We report that the increase in tyrosine phosphorylation of several protein bands that occurs during sperm capacitation is independent of the presence of Ca 2+ in the external medium and, at least partially, of the increase in [Ca 2+ ] i occurring during the process. Indeed, the spontaneous increase in phosphorylation was still present in Ca 2+ -free/EGTA-containing-medium and in the presence of the intracellular Ca 2+ chelator BAPTA/AM. Moreover, phosphorylation of proteins and protein tyrosine kinase (PTK) activity was enhanced if spermatozoa were incubated in Ca 2+ -free medium, suggesting the presence of Ca 2+ -inhibited tyrosine kinase(s) in human sperm. This hypothesis is further substantiated by the lower tyrosine phosphorylation observed after incubation with the ionophore A23187 and the endoplasmic Ca 2+ -ATPase inhibitor thapsigargin, which promote Ca 2+ influx in human sperm. The ability of the cells to undergo acrosome reaction in response to progesterone, which can be considered a functional endpoint of capacitation, was highly compromised when spermatozoa were incubated in Ca 2+ -free medium or in the presence of EGTA, confirming that Ca 2+ is required for sperm capacitation. Conversely, in the presence of erbstatin, a inhibitor of tyrosine kinase activity, which blunts tyrosine phosphorylation during capacitation, response to progesterone was maintained, suggesting that tyrosine phosphorylation must be kept at a low level (physiologically by the presence of Ca 2+ in the external medium, or pharmacologically by the presence of erbstatin) in order to obtain response to progesterone. This mechanism may be important in vivo during sperm transit in the female genital tract to ensure appropriate timing of full capacitation in the proximity of the oocyte.

Occurrence and Properties of the Hyperpolarization-Activated Current If in Ventricular Myocytes From Normotensive and Hypertensive Rats During Aging

Abstract: Background Cellular electrophysiological alterations may contribute to arrhythmogenesis in cardiac hypertrophy. An I f -like current occurs in left ventricular myocytes (LVMs) isolated from the hypertrophied heart of old spontaneously hypertensive rats (SHR). Factors that influence I f occurrence during development of cardiac hypertrophy were studied by determining its presence, amplitude, characteristics, and β-adrenoceptor modulation. Methods and Results Patch-clamped LVMs from young (2 to 3 months old) or old (18 to 24 months old) normotensive Wistar-Kyoto rats (WKY) and SHR were used. A diastolic depolarization phase was present in old SHR. An I f -like current occurred in >90% of LVMs from old SHR and WKY and in ≈15% of LVMs from young rats ( P f were similar in old rats, with the midpoint at −92.9±2.9 mV in WKY (n=42) and −88.1±1.5 mV in SHR (n=25); maximal specific conductance was 54.4±1.7 in SHR and 20.1±0.5 picosiemens/picofarad in WKY ( P f amplitude was linearly related to membrane capacitance, an index of cell size ( r =.53, P f density. In both old WKY and old SHR, 0.1 μmol/L (−)-isoproterenol increased I f amplitude by shifting its activation curve toward more positive potentials. Conclusions In LVMs from both WKY and SHR, the occurrence of I f increases with aging. Density appears linearly related to the severity of cardiac hypertrophy and increases with β-adrenoceptor stimulation, which suggests that I f may contribute to an increased propensity of the hypertrophied heart for arrhythmias.

Hepatitis C Virus Genotype Analysis in Patients with Type II Mixed Cryoglobulinemia

Abstract: Objective: To investigate the possible role of HCV variants in the pathogenesis of mixed cryoglobulinemia. Setting: Medical service (rheumatology and hepatology units) of urban, university-affiliat...

Hydraulic conductance, light interception and needle nutrient concentration in Scots pine stands and their relations with net primary productivity.

Abstract: Aboveground xylem hydraulic conductance was determined in Scots pine (Pinus sylvestris L.) trees and stands from 7 to about 60 years of age. At the stand scale, leaf area index and net primary productivity (NPP, above- plus belowground) increased and reached a plateau at about 25-30 and 15-20 years, respectively; both parameters declined in mature stands. Stand hydraulic conductance followed a similar trend to NPP, with a maximum at about 15-20 years and a pronounced reduction in old stands. At the tree scale, annual biomass growth per unit of leaf area (growth efficiency) declined with tree age, whereas aboveground sapwood volume per unit leaf area, which is linearly related to maintenance respiration costs, steadily increased. Radiation interception per unit leaf area increased significantly with reduced leaf area index of mature stands, despite increased foliage clumping in the canopies of mature trees. Needle nutrient concentration did not change in the chronosequence. Tree hydraulic conductance per unit leaf area was strongly and positively correlated with growth efficiency. We discuss our findings in the context of growth reductions in mature and old trees, and suggest that increased hydraulic resistance and maintenance respiration costs may be the main causes of reduced carbon gain in mature and old trees.