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Biomedical subjects

G Parisi

Publications and source records attributed to G Parisi.

At least 19 recordsLinked to original sources
PubMed2001

Zero-temperature responses of a 3D spin glass in a magnetic field.

We probe the energy landscape of the 3D Edwards-Anderson spin glass in a magnetic field to test for a spin glass ordering. We find that the spin glass susceptibility is anomalously large on the lattice sizes we can reach. Our data suggest that a transition from the spin glass to the paramagnetic phase takes place at B(c) approximately 0.65, though the possibility B(c) = 0 cannot be excluded. We also discuss the question of the nature of the putative frozen phase.

Journal Article↗
PubMed2001

Vibrational spectrum of topologically disordered systems.

The topological nature of the disorder of glasses and supercooled liquids strongly affects their high-frequency dynamics. In order to understand its main features, we analytically studied a simple topologically disordered model, where the particles oscillate around randomly distributed centers, interacting through a generic pair potential. We present results of a resummation of the perturbative expansion in the inverse particle density for the dynamic structure factor and density of states. This gives accurate results for the range of densities found in real systems.

Journal Article↗
PubMed2001

Topological description of the aging dynamics in simple glasses.

We numerically investigate the aging dynamics of a monatomic Lennard-Jones glass, focusing on the topology of the potential energy landscape which, to this aim, has been partitioned in basins of attraction of stationary points (saddles and minima). The analysis of the stationary points visited during the aging dynamics shows the existence of two distinct regimes: (i) at short times the system visits basins of saddles whose energies and orders decrease with t; (ii) at long times the system mainly lies in basins pertaining to minima of slowly decreasing energy. The long time dynamics can be represented by a simple random walk on a network of minima with a jump probability proportional to the inverse of the waiting time.

Journal Article↗
PubMed2001

Effects of a bulk perturbation on the ground state of 3D Ising spin glasses.

We compute and analyze couples of ground states of 3D spin glasses before and after applying a volume perturbation which adds to the Hamiltonian a repulsion from the true ground state. The physical picture based on replica symmetry breaking is in excellent agreement with the observed behavior.

Journal Article↗
PubMed2001

Fast Monte Carlo algorithm for supercooled soft spheres.

We present a nonlocal Monte Carlo algorithm with particle swaps that greatly accelerates thermalization of soft sphere binary mixtures in the glassy region. Our first results show that thermalization of systems of hundreds of particles is achievable, and find behavior compatible with a thermodynamic glass transition.

Journal Article↗
PubMed2001

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Aged↗
PubMed2001

Latent coeliac disease in a child with epilepsy, cerebral calcifications, drug-induced systemic lupus erythematosus and intestinal folic acid malabsorption associated with impairment of folic acid transport across the blood-brain barrier.

UNLABELLED: A 15-year-old boy with epilepsy and cerebral calcifications, treated with valproic acid, ethyl phenylbarbiturate and ethosuximide, was referred for drug induced systemic lupus erythematosus. Anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests were both positive (EMA titre 1:50). Endoscopic duodenal biopsy showed intense chronic inflammation without villous atrophy or crypt hyperplasia. The child was discharged with a gluten-containing diet. The follow-up showed an increase in EMA titre (1:200) and the persistence of AGA. After 15 months, a second endoscopic intestinal biopsy showed flat mucosa and villous atrophy. Three serum folic acid determinations showed 1.8, 2.4, 2.0 ng/ml (reference range 2.5-16.9 ng/ml) prior to the two intestinal biopsies, but returned to normal levels (11.8 ng/ml) after a gluten-free diet and oral supplementation together. Two years later, the frequency of epileptic seizures was unchanged despite ongoing anti-epileptic treatment and a gluten-free diet. As cerebral calcification and epilepsy are reminiscent of the findings in congenital folate malabsorption, oral loading tests with 5 mg folic acid were carried out and showed impaired intestinal absorption and a defect in the transport across the blood-brain barrier. Low CSF folate levels (13.9 and 12.6 ng/ml, reference range 15-40 ng/ml) and an alteration in the CSF/serum folate ratio (1.43 and 1.16, normal ratio 3:1) were also found as well as increased levels of cystathionine both in CSF (40 micromol/l, reference range 18-28 micromol/l) and in serum (32 micromol/l, reference value <0.10 micromol/l). CONCLUSION: Impairment of intestinal folic acid absorption with a defect in folic acid transport across the blood-brain barrier has been demonstrated in a case of epilepsy and cerebral calcifications associated with coeliac disease.

Adolescent↗
PubMed2001

Structural constraints and emergence of sequence patterns in protein evolution.

The aim of this work was to study the relationship between structure conservation and sequence divergence in protein evolution. To this end, we developed a model of structurally constrained protein evolution (SCPE) in which trial sequences, generated by random mutations at gene level, are selected against departure from a reference three-dimensional structure. Since at the mutational level SCPE is completely unbiased, any emergent sequence pattern will be due exclusively to structural constraints. In this first report, it is shown that SCPE correctly predicts the characteristic hexapeptide motif of the left-handed parallel beta helix (LbetaH) domain of UDP-N-acetylglucosamine acyltransferases (LpxA).

Acyltransferases↗
PubMed2000

Off-equilibrium effective temperature in monatomic Lennard-Jones glass.

The off-equilibrium dynamics of a monatomic Lennard-Jones glass is numerically investigated after sudden isothermal density jumps (crunch) from well equilibrated liquid configurations towards the glassy state. The generalized fluctuation-dissipation relation has been studied and the temperature dependence of the violation factor m is found in agreement with the one step replica symmetry breaking scenario, i.e., at low temperature m(T) is found proportional to T up to an off-equilibrium effective temperature T(eff), where m(T(eff)) = 1. We report T(eff) as a function of the density and compare it with the glass transition temperature T(g) as determined by equilibrium calculations.

Journal Article↗
PubMed2000

Glassy transition in a disordered model for the RNA secondary structure.

We numerically study a disordered model for the RNA secondary structure and we find that it undergoes a phase transition, with a breaking of the replica symmetry in the low temperature region (as in spin glasses). Our results are based on the exact evaluation of the partition function.

Models, Chemical↗
PubMed2000

Thermodynamical liquid-glass transition in a lennard-jones binary mixture

We use results derived in the framework of the replica approach to study the liquid-glass thermodynamic transition. The main results are derived without using replicas and applied to the study of the Lennard-Jones binary mixture introduced by Kob and Andersen. We find that there is a phase transition due to the entropy crisis. We compute both analytically and numerically the value of the phase transition point T(K) and the specific heat in the low temperature phase.

Journal Article↗
PubMed2000

Evolutionary analysis of gamma-carbonic anhydrase and structurally related proteins.

We studied the evolutionary relationships between gamma-carbonic anhydrase (gamma-CA) and a very diverse group of proteins that share the sequence motif characteristic of the left-handed parallel beta-helix (LbetaH) fold. This sequence motif is characterized by the imperfect tandem repetition of short hexapeptide units, which makes it difficult to obtain a reliable alignment based on sequence information alone. To solve this problem, we used a structural alignment of three members of the group with known crystallographic structures as a seed to obtain a reliable sequence alignment. Then, we applied protein maximum-parsimony and maximum-likelihood phylogenetic inference methods to this alignment. We found that gamma-CA belongs to a diverse superfamily of proteins that share the LbetaH domain. This superfamily is composed mainly of acyltransferases. The most remarkable feature of the phylogenetic tree obtained is that its main branches group together functionally related proteins, so that the coarse topology can be rather easily explained in terms of functional diversification. Regarding the main branch of the tree containing gamma-CA, we found that, in addition to the group of its closest relatives that had already been studied, gamma-CA is closely related to the tetrahydrodipicolinate N-succinyltransferases.

Acyltransferases↗
PubMed2000

High-dose interferon plus ribavirin in chronic hepatitis C not responding to recombinant alpha-interferon.

BACKGROUND: Recently, the combination treatment of recombinant alpha-interferon plus ribavirin has been proposed for chronic hepatitis C patients unresponsive to previous therapy with recombinant alpha-interferon alone. AIM: To determine the effectiveness of the combination therapy for the re-treatment of chronic hepatitis C patients unresponsive to previous interferon therapy. Immediate and long-term follow-up data are reported. PATIENTS AND METHODS: A series of 100 patients with chronic hepatitis C not responding to recombinant alpha-interferon 3 MU tiw, were randomly assigned to two groups of 50 patients each: Group A, treated with recombinant alpha-interferon therapy for an additional six months but at a double dosage (6 MU tiw) in association with ribavirin. Group B, same treatment as group A but without ribavirin. All patients responsive to therapy were then followed-up for at least 12 months. At the end of the treatment and at the end of the follow-up period, we distinguished between complete responses (return to normal of alanine aminotransferase with undetectable serum HCV-RNA] and biochemical responses (return to normal of alanine aminotransferase still with detectable viraemia). RESULTS: Side-effects were observed only in patients treated with recombinant alpha-interferon plus ribavirin: 12% discontinued the therapy due to haemolytic anaemia. In group A, the percentages of end-of-treatment complete response, end-of-treatment biochemical response, sustained complete response, and sustained biochemical response, were 38%, 20%, 8%, and 14%, respectively, whilst in group B, these percentages were 12%, 16%, 6%, and 16%, respectively. CONCLUSION: The results indicate that in patients with chronic hepatitis C unresponsive to previous recombinant alpha-interferon therapy, re-treatment with higher recombinant alpha-interferon doses, either alone or in combination with ribavirin, lead to mild long-term benefit. However, the satisfactory end of treatment complete response in group A suggests that a significant percentage of patients are sensitive to the combination therapy; and that a more aggressive therapeutic protocol in this selected subset of patients could result in a larger number of long-lasting responses leading, in turn, to a more favourable cost-effect ratio.

Alanine Transaminase↗
PubMed2000

Interferon plus ribavirin in chronic hepatitis C non-responders to recombinant alpha-interferon.

The aim of this study was to evaluate the most appropriate therapeutic protocol for patients with chronic hepatitis C not responding to a previous course of recombinant interferon alpha-2b (rIFN). Sixty patients were randomly assigned to two groups of 30 subjects each: group A was treated with double dose of the same type of rIFN (6 MU t.i.w.) plus ribavirin for 6 months; group B was treated with the same rIFN dose and duration as group A, but without ribavirin. An end of treatment complete response (ETCR) was defined as alanine transaminase (ALT) normalization with undetectable serum HCV-RNA at the end of the treatment, while an end of treatment biochemical response (ETBR) as ALT normalization with still detectable viraemia. The two groups were homogeneous. The patients with ETCR or ETBR were than followed-up for at least 1 year. A sustained biochemical response (SBR) was defined as the persistence of normal ALT with still detectable viraemia after a 12-month follow-up, and a sustained complete response (SCR) as the persistence of normal ALT with undetectable viraemia. Side-effects were only observed in patients treated with rIFN plus ribavirin: four cases (13%) discontinued the therapy owing to haemolytic anaemia. Combination therapy induced an ETCR in 11 patients (37%) and an ETBR in six (20%), while a SCR was observed in two subjects (7%) and a SBR in four (13%). The use of a double dose of rIFN alone obtained an ETCR in four cases (13%) and an ETBR in five (17%), with a SCR in two (7%) and a SBR in three (10%). Hence, both combination therapy and single treatment with higher rIFN doses were unable to show statistically significant long-term benefits in patients with chronic hepatitis C resistant to a previous course of rIFN treatment.

Adult↗
PubMed2000

Does the initial location of Crohn's disease have an influence on the time-to-relapse in patients under maintenance treatment with oral mesalamine?

The aim of this study was to determine the possible influence of the initial location of Crohn's disease (CD) on the time-to-relapse in patients with quiescent CD treated only with oral mesalamine (5-ASA). We divided 74 consecutive patients in clinical remission into three groups according to the initial location of CD. Group A consisted of 30 cases with an ileal location; group B, 18 with ileocolonic location; and group C, 26 with a colonic location. The patients entered the study if they were in clinical and endoscopic remission for at least 3 months. Relapse was defined by CD Activity Index > or = 150, CD Endoscopic Index of Severity > or =4, and by an abnormal increase of C-reactive protein, white blood cell count, and erythrocyte sedimentation rate; moreover, if it was confirmed by x-ray and/or endoscopy. Time-to-relapse was defined as the interval between the date of enrollment and the date of relapse. The patients with an ileal location showed a relapse within 5 years, with a time-to-relapse of 1 year in 26% of cases, 2 years in 85%, 3 years in 92%, and 4 years in 96%. The patients with ileocolonic location showed a relapse within 4 years, with time-to-relapse of 1 year in 39% of cases, 2 years in 89%, and 3 years in 94%. The cases with a colonic location showed a relapse within 6 years, with time-to-relapse of 1 year in 33% of cases, 2 years in 71%, 3 years in 79%, and 4 years in 87%. Surgical treatment was necessary in 37% of the cases with an ileal location, in 44% with ileocolonic location, and 17% with a colonic location. In conclusion, even if our data lack a statistical significance, we have found that the initial anatomic involvement is not a valid parameter to predict the relapse risk in a homogeneous group under continuous treatment with oral 5-ASA, although ileocolonic location seems to have a more aggressive course.

Administration, Oral↗
PubMed2000

Potential energy landscape and long-time dynamics in a simple model glass

We analyze the properties of a Lennard-Jones system at the level of the potential energy landscape. After an exhaustive investigation of the topological features of the landscape of the systems, obtained by studying small size samples, we describe the dynamics of the systems in multidimensional configurational space by means of a simple model. This considers the configurational space as a connected network of minima where the dynamics proceeds by jumps described by an appropriate master equation. Using this model we are able to reproduce the long-time dynamics and the low temperature regime. We investigate both the equilibrium regime and the off-equilibrium one, finding those typical glassy behaviors usually observed in the experiments such as (i) a stretched exponential relaxation, (ii) a temperature-dependent stretching parameter, (iii) a breakdown of the Stokes-Einstein relation, and (iv) the appearance of a critical temperature below which one observes a deviation from the fluctuation-dissipation relation as a consequence of the lack of equilibrium in the system.

Journal Article↗