Showing papers by "University of Milan published in 1997"

Brain activity during observation of actions. Influence of action content and subject's strategy.

Abstract: PET was used to map brain regions that are associated with the observation of meaningful and meaningless hand actions. Subjects were scanned under four conditions which consisted of visually presented actions. In each of the four experimental conditions, they were instructed to watch the actions with one of two aims: to be able to recognize or to imitate them later. We found that differences in the meaning of the action, irrespective of the strategy used during observation, lead to different patterns of brain activity and clear left/right asymmetries. Meaningful actions strongly engaged the left hemisphere in frontal and temporal regions while meaningless actions involved mainly the right occipitoparietal pathway. Observing with the intent to recognize activated memory-encoding structures. In contrast, observation with the intent to imitate was associated with activation in the regions involved in the planning and in the generation of actions. Thus, the pattern of brain activation during observation of actions is dependent both on the nature of the required executive processing and the type of the extrinsic properties of the action presented.

Reproducibility testing of RAPD, AFLP and SSR markers in plants by a network of European laboratories

Abstract: A number of PCR-based techniques can be used to detect polymorphisms in plants. For their wide-scale usage in germplasm characterisation and breeding it is important that these marker technologies can be exchanged between laboratories, which in turn requires that they can be standardised to yield reproducible results, so that direct collation and comparison of the data are possible. This article describes a network experiment involving several European laboratories, in which the reproducibility of three popular molecular marker techniques was examined: random-amplified fragment length polymorphism (RAPD), amplified fragment length polymorphism (AFLP) and sequence-tagged microsatellites (SSR). For each technique, an optimal system was chosen, which had been standardised and routinely used by one laboratory. This system (genetic screening package) was distributed to different participating laboratories in the network and the results obtained compared with those of the original sender. Different experiences were gained in this exchange experiment with the different techniques. RAPDs proved difficult to reproduce. For AFLPs, a single-band difference was observed in one track, whilst SSR alleles were amplified by all laboratories, but small differences in their sizing were obtained.

Relationship Between Spectral Components of Cardiovascular Variabilities and Direct Measures of Muscle Sympathetic Nerve Activity in Humans

Abstract: Background Spectral analysis of RR interval and systolic arterial pressure variabilities may provide indirect markers of the balance between sympathetic and vagal cardiovascular control. Methods and Results We examined the relationship between power spectral measurements of variabilities in RR interval, systolic arterial pressure, and muscle sympathetic nerve activity (MSNA) obtained by microneurography over a range of blood pressures. In eight healthy human volunteers, MSNA, RR interval, intra-arterial pressure, and respiration were measured during blood pressure reductions induced by nitroprusside and during blood pressure increases induced by phenylephrine. Both low-frequency (LF; 0.10±0.01 Hz) and high-frequency (HF; 0.23±0.01 Hz) components were detected in MSNA variability. Increasing levels of MSNA were associated with a shift of the spectral power toward its LF component. Decreasing levels of MSNA were associated with a shift of MSNA spectral power toward the HF component. Over the range of pressu...

Intracellular Calcium Oscillations in Astrocytes: A Highly Plastic, Bidirectional Form of Communication between Neurons and Astrocytes In Situ

Abstract: The spatial–temporal characteristics of intracellular calcium ([Ca2+]i) changes elicited in neurons and astrocytes by various types of stimuli were investigated by means of confocal fluorescent microscopy in acute rat brain slices loaded with the Ca2+ indicator indo-1. Neurons and astrocytes from the visual cortex and CA1 hippocampal region were identified in situ on the basis of their morphological, electrophysiological, and pharmacological features. We show here that stimulation of neuronal afferents triggered periodic [Ca2+]i oscillations in astrocytes. The frequency of these oscillations was under a dynamic control by neuronal activity as it changed according to the pattern of stimulation. After repetitive episodes of neuronal stimulation as well as repetitive stimulation with a metabotropic glutamate receptor agonist, astrocytes displayed a long-lasting increase in [Ca2+]i oscillation frequency. Oscillating astrocytes were accompanied by repetitive [Ca2+]i elevations in adjacent neurons, most likely because of the release of glutamate via a tetanus toxin-resistant process. These results reveal that [Ca2+]i oscillations in astrocytes represent a highly plastic signaling system that underlies the reciprocal communication between neurons and astrocytes.

In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

Abstract: Following the identification of the C-C chemokines RANTES, MIP-1alpha and MIP-1beta as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1alpha and MIP-1 receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains and by simian immunodeficiency virus (SIV), whereas CXCR4, a receptor for the C-X-C chemokine SDF-1, is used by MT2-tropic HIV-1 and HIV-2, but not by SIV. Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain of gp120 were associated with the loss of sensitivity to C-C chemokines and the shift in co-receptor usage. These results suggest an adaptive evolution of HIV-1 in vivo, leading to escape from the control of the antiviral C-C chemokines.

How to use expert advice

Abstract: We analyze algorithms that predict a binary value by combining the predictions of several prediction strategies, called experts. Our analysis is for worst-case situations, i.e., we make no assumptions about the way the sequence of bits to be predicted is generated. We measure the performance of the algorithm by the difference between the expected number of mistakes it makes on the bit sequence and the expected number of mistakes made by the best expert on this sequence, where the expectation is taken with respect to the randomization in the predictins. We show that the minimum achievable difference is on the order of the square root of the number of mistakes of the best expert, and we give efficient algorithms that achieve this. Our upper and lower bounds have matching leading constants in most cases. We then show how this leads to certain kinds of pattern recognition/learning algorithms with performance bounds that improve on the best results currently know in this context. We also compare our analysis to the case in which log loss is used instead of the expected number of mistakes.

BeppoSAX, the wide band mission for X-ray astronomy

Abstract: The X-ray satellite SAX, a major program of the Italian Space Agency with participation of the Netherlands Agency for Aereospace Programs, was launched on April 30 1996 from Cape Canaveral. After launch it was renamed BeppoSAX in honour of Giuseppe (Beppo) Occhialini. The payload is characterized by a very wide spectral coverage from 0.1 to 300 keV, with well bal- anced performances both from its low and high energy instrumentation. Its sensitivity will allow the exploitation of the full band for weak sources (1/20 of 3C 273), open- ing new perspectives in the study of spectral shape and variability of several classes of objects. Furthermore, the presence of wide eld cameras will allow monitoring of the long term variability of sources down to 1 mCrab and the discovery of X-ray transient phenomena. In this paper we describe the main aspects of the mission, the operations, the scientic capabilities of the instruments and the sci- entic objectives.

Prognostic Significance of Vascular Endothelial Growth Factor Protein in Node-Negative Breast Carcinoma

Abstract: Background: The clinical outcome is generally positive for patients with node-negative breast carcinoma (i.e., those who do not have detectable metastases in the lymph nodes) who have been treated with surgery or surgery plus radiation therapy. In about 30% of the patients, however, the disease recurs, and they are at risk of death. Determination of valid new prognostic indicators would improve the ability to identify patients at high risk of recurrence. Breast cancer can entail substantial development of new blood vessels within the tumor tissue, and it is known that the growth and metastasis of solid tumors are dependent on such angiogenesis. The conversion of tumor cells to an angiogenic phenotype may be preceded by a change in the balance of angiogenic growth factors and angiogenesis inhibitors. Purpose: This study was conducted to determine if the levels of vascular endothelial growth factor (VEGF) protein, a potent endothelial growth factor and mediator of vascular permeability and angiogenesis, measured in the primary tumors of women with node-negative breast cancer are associated with known prognostic factors and patient survival. Methods: By use of a selective enzymatic immunoassay, levels of VEGF protein were measured in cytosolic extracts of primary tumor tissue surgically obtained from 260 women with node-negative breast carcinoma who had been treated with surgery with or without radiation therapy but not with adjuvant therapy and who had been followed for a median time of 66 months. The relationships between VEGF concentrations and other prognostic dichotomous variables or clinical outcome were tested by the use of the Kolmogorov-Smirnov test and univariate and multivariate Cox analyses, respectively. The relationship between VEGF and hormone receptors (i.e., those for estrogen and progesterone) was examined by the use of Spear-man's correlation analyses. All P values resulted from the use of two-sided statistical tests. Results: Tumors from 247 (95%) of the 260 patients had detectable VEGF, ranging in concentration from 5.0 to 6523 pg/mg protein (median, 126.25 pg/mg protein). No statistically significant associations were found between VEGF and the other prognostic factors (e.g., age, menopausal status, histologic tumor type, tumor size, and hormone receptors) examined. Levels of VEGF were found to be prognostic for both relapse-free and overall survival in univariate and multivariate analyses (likelihood ratio tests; all four P values <.001). In the multivariate analysis, the first-order interaction term of VEGF and estrogen receptor was also prognostic for overall survival (likelihood ratio test; P =.05). Conclusions: The results show that cytosolic levels of VEGF in tumor tissue samples are indicative of prognosis for patients with node-negative breast carcinoma.

A logical language for expressing authorizations

Abstract: A major drawback of existing access control systems is that they have all been developed with a specific access control policy in mind. This means that all protection requirements (i.e. accesses to be allowed or denied) must be specified in terms of the policy enforced by the system. While this may be trivial for some requirements, specification of other requirements may become quite complex or even impossible. The reason for this is that a single policy simply cannot capture the different protection requirements that users may need to enforce on different data. In this paper, we take a first step towards a model that is able to support different access control policies. We propose a logical language for the specification of authorizations on which such a model can be based. The Authorization Specification Language (ASL) allows users to specify, together with the authorizations, the policy according to which access control decisions are to be made. Policies are expressed by means of rules which enforce the derivation of authorizations, conflict resolution, access control and integrity constraint checking. We illustrate the power of our language by showing how different constraints that are sometimes required, but very seldom supported by existing access control systems, can be represented in our language.

High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma.

Abstract: Background We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma. Methods Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were randomly assigned to receive either MACOP-B (50 patients) or high-dose sequential therapy (48 patients). If the assigned treatment failed, the study design allowed patients to cross over to the other treatment group. Results After a median follow-up of 55 months, the patients given high-dose sequential therapy, as compared with those treated with MACOP-B, had significantly higher rates of complete response (96 percent vs. 70 percent, P = 0.001), freedom from disease progression (84 percent vs. 49 percent, P<0.001), freedom from relapse (88 percent vs. 70 ...

Interrater reliability and internal consistency of the structured clinical interview for DSM-IV axis II personality disorders (SCID-II), version 2.0.

Abstract: Interrater reliability and internal consistency of the SCID-II 2.0 was assessed in a sample of 231 consecutively admitted in- and outpatients using a pairwise interview design, with randomized rater pairing and blind interview assessment. Interrater reliability coefficients ranged from .48 to .98 for categorical diagnosis (Cohen kappa), and from .90 to .98 for dimensional judgements (Intraclass correlation coefficient). Internal consistency coefficients were satisfactory (.71-.94). The results suggest that the SCID-II 2.0 has adequate interrater and internal consistency reliability.

A role for the Ras signalling pathway in synaptic transmission and long-term memory

Abstract: Members of the Ras subfamily of small guanine-nucleotide-binding proteins are essential for controlling normal and malignant cell proliferation as well as cell differentiation. The neuronal-specific guanine-nucleotide-exchange factor, Ras-GRF/CDC25Mm, induces Ras signalling in response to Ca2+ influx and activation of G-protein-coupled receptors in vitro, suggesting that it plays a role in neurotransmission and plasticity in vivo. Here we report that mice lacking Ras-GRF are impaired in the process of memory consolidation, as revealed by emotional conditioning tasks that require the function of the amygdala; learning and short-term memory are intact. Electrophysiological measurements in the basolateral amygdala reveal that long-term plasticity is abnormal in mutant mice. In contrast, Ras-GRF mutants do not reveal major deficits in spatial learning tasks such as the Morris water maze, a test that requires hippocampal function. Consistent with apparently normal hippocampal functions, Ras-GRF mutants show normal NMDA (N-methyl-D-aspartate) receptor-dependent long-term potentiation in this structure. These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories.

Polarization properties of vertical-cavity surface-emitting lasers

Abstract: Polarization-state selection, polarization-state dynamics, and polarization switching of a quantum-well vertical-cavity surface-emitting laser (VCSEL) for the lowest order transverse spatial mode of the laser is explored using a recently developed model that incorporates material birefringence, the saturable dispersion characteristic of semiconductor physics, and the sensitivity of the transitions in the material to the vector character of the electric field amplitude. Three features contribute to the observed linearly polarized states of emission: linear birefringence, linear gain or loss anisotropies, and an intermediate relaxation rate for imbalances in the populations of the magnetic sublevels. In the absence of either birefringence or saturable dispersion, the gain or loss anisotropies dictate stability for the linearly polarized mode with higher net gain; hence, switching is only possible if the relative strength of the net gain for the two modes is reversed. When birefringence and saturable dispersion are both present, there are possibilities of bistability, monostability, and dynamical instability, including switching by destabilization of the mode with the higher gain to loss ratio in favor of the weaker mode. We compare our analytical and numerical results with recent experimental results on bistability and switchings caused by changes in the injection current and changes in the intensity of an injected optical signal.

Immunocompetence, ornamentation, and viability of male barn swallows (Hirundo rustica)

Abstract: Immunocompetence (i.e., the ability to produce an immune response to pathogens) can be predicted to influence the chances that organisms have to survive and reproduce. In this study we simulated a challenge to the immune systems of male barn swallows (Hirundo rustica) by injecting them intraperitoneally with a multigenic antigen, sheep red blood cells, and we analyzed long-term survival in relation to their immunocompetence. Males were assigned to four groups that differed for the treatment of the length of the outermost tail feathers, a sexually dimorphic ornamental character that is currently under directional sexual selection. Immunocompetence was measured as change of concentration of gamma globulins relative to plasma proteins. The intensity of the immune response was independent of age. Males that showed the highest short-term response to sheep red blood cells were more likely to survive until the breeding season following that in which they had been inoculated, a pattern consistently observed within each experimental group. Males with comparatively long tails were more likely to survive than those with short tails. To our knowledge, the results of this study are the first to demonstrate that immunocompetence can predict long-term survival in a free-ranging vertebrate. Moreover, they are compatible with current models of parasite-mediated sexual selection because long-tailed males are more immunocompetent than short-tailed ones, and females, by preferring to mate with the most ornamented males, may acquire the “good genes” for high immunocompetence and, hence, for high viability of their offspring.

HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

Abstract: HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their HIV-seropositive partners; antibodies were not detected in low-risk controls. Envelope protein (Env) peptide-stimulated interleukin-2 (IL-2) production by peripheral blood mononuclear cells (PBMCs) was detected in 9 out of 16 ESNs, 5 out of 16 HIV-infected patients and 1 out of 50 controls. Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression. These data demonstrate that a compartmentalized immune response to pathogens is possible in humans and raise the possibility of protective roles for cell-mediated immunity and mucosal IgA in HIV-seronegative individuals exposed to HIV.

Scale-sensitive dimensions, uniform convergence, and learnability

Abstract: Learnability in Valiant's PAC learning model has been shown to be strongly related to the existence of uniform laws of large numbers These laws define a distribution-free convergence property of means to expectations uniformly over classes of random variables Classes of real-valued functions enjoying such a property are also known as uniform Glivenko-Cantelli classes In this paper, we prove, through a generalization of Sauer's lemma that may be interesting in its own right, a new characterization of uniform Glivenko-Cantelli classes Our characterization yields Dudley, Gine´, and Zinn's previous characterization as a corollary Furthermore, it is the first based on a Gine´, and Zinn's previous characterization as a corollary Furthermore, it is the first based on a simple combinatorial quantity generalizing the Vapnik-Chervonenkis dimension We apply this result to obtain the weakest combinatorial condition known to imply PAC learnability in the statistical regression (or “agnostic”) framework Furthermore, we find a characterization of learnability in the probabilistic concept model, solving an open problem posed by Kearns and Schapire These results show that the accuracy parameter plays a crucial role in determining the effective complexity of the learner's hypothesis class

Absence of Low-Frequency Variability of Sympathetic Nerve Activity in Severe Heart Failure

Abstract: Background In normal humans, variability of blood pressure, RR interval, and sympathetic activity occurs predominantly at a low frequency (LF; 0.04 to 0.14 Hz) and a high frequency (HF; ±0.25 Hz). In conditions that increase sympathetic activation in normal humans, the LF component is increased relative to the HF component. Patients with heart failure have high levels of sympathetic activity. We tested the hypothesis that the LF component of sympathetic nerve activity variability is increased in heart failure. Methods and Results. We performed spectral analysis of simultaneous recordings of resting muscle sympathetic nerve activity (MSNA) and RR interval in 21 patients with chronic heart failure and 12 age-matched control subjects. MSNA was higher in patients with heart failure (62±4 bursts per minute) than in the normal subjects (39±4 bursts per minute; P<.01). LF components of RR interval and MSNA variability were lower in the heart failure patients versus the control subjects (P<.01). HF variability of...

Implant-retained mandibular overdentures with immediate loading. A retrospective multicenter study on 226 consecutive cases.

Abstract: A multicenter retrospective study has been conducted on 226 patients necessitating an implant-supported overdenture in the lower jaw. The patients were provided with 904 osseointegrated implants inserted in the interforaminal area of the mental symphisis (4 implants per patient). 4 titanium implant systems were used: TPS and ITI screw implants (Straumann Institute, Waldenburg, Switzerland); Ha-Ti screw implants (Mathys Dental Implants, Bettlach, Switzerland); NLS screw implants (Friatec, Mannheim, Germany). Immediately after implant placement, a U-shaped gold bar was fabricated and implants were immediately loaded with an implant-retained overdenture. Out of 226 patients treated, 194 were followed from a minimum of 2 years to a maximum of 13 years, with a mean follow-up of 6.4 years, whereas 32 patients dropped out during follow-up. The overall failure rate of implants was 3.1% (24/776 implants), whereas the failure rate of bars was 1.5% (3/194 bars). Results from this study showed that the success rate of immediately loaded implants is similar to that obtained in the case of delayed loading, after osseointegration has taken place. In contrast, this method shortens dental rehabilitation times with relevant satisfaction for patients.

Lung Function and Exercise Gas Exchange in Chronic Heart Failure

Abstract: Background The ventilatory response to exercise in patients with chronic heart failure (HF) is greater than normal for a given metabolic rate. The objective of the present study was to determine the mechanism(s) for the high ventilatory output in patients with chronic HF. Methods and Results Centers in Germany, Italy, Japan, and the United States participated in this study. Each center contributed studies on patients and normal subjects of similar age and sex. One hundred thirty patients with chronic HF and 52 healthy subjects participated. Spirometric and breath-by-breath gas exchange measurements were made during rest and increasing cycle exercise. Arterial blood was sampled for measurement of pH, Paco2, Pao2, and lactate during exercise in 85 patients. Resting forced expiratory volume in 1 second (FEV1) and vital capacity (VC) were proportionately reduced at all levels of impairment. Patients with more severe HF had greater tachypnea and a smaller tidal volume (Vt) at a given exercise expired volume per unit time (Ve). This was associated with an expiratory flow pattern characteristic of lung restriction. Ve and Vco2 as a function of Vo2 were increased during exercise in HF patients. The increases were greater the lower the peak Vo2 per kilogram of body weight. The ratio of Vd (physiological dead space) to Vt and the difference between arterial and end tidal Pco2 at peak Vo2 also increased inversely with peak Vo2/kg. In contrast, the difference between alveolar and arterial Po2 and PaCO2 were both normal, on average, at peak Vo2 regardless of the level of impairment. The more severe the exercise limitation, the higher the lactate and the lower the HCO3− at a given Vo2, although pH was tightly regulated. Conclusions The increase in Ve in chronic HF patients is caused by an increase in Vd/Vt due to high ventilation/perfusion mismatching, an increase in Vco2 relative to Vo2 resulting from HCO3− buffering of lactic acid, and a decrease in Paco2 due to tight regulation of arterial pH. With regard to the excessive Ve in HF patients, the increases in Vd/Vt and Vco2 relative to Vo2 are more important as the patient becomes more exercise limited. Regional hypoperfusion but not hypoventilation typifies lung gas exchange in HF. This and other mechanisms might account for the restrictive changes leading to exercise tachypnea in HF patients.

Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis

Abstract: We examined the effect of fluvastatin, the first entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that is structurally different from other vastatins, on tissue factor (TF) expression in human macrophages spontaneously differentiated in culture from blood monocytes. Fluvastatin decreased TF activity in a dose-dependent manner (1 to 5 mumol/L) in both unstimulated and lipopolysaccharide-stimulated macrophages, and this reduction paralleled the decrease in immunologically recognized TF protein. The same results were obtained with another lipophilic vastatin, simvastatin, but not with hydrophilic pravastatin. The reduction in TF expression was also observed in macrophages enriched in cholesterol after exposure to 50 micrograms/mL acetylated low density lipoprotein. The inhibitory effect of fluvastatin on TF activity and antigen was fully reversible by coincubation with 100 mumol/L mevalonate or 10 mumol/L all-trans-geranylgeraniol but not with dolichol, farnesol, or geraniol. Suppression of TF antigen and activity was accompanied by a diminution in TF mRNA levels, which was completely prevented by mevalonate. Furthermore, fluvastatin impaired bacterial lipopolysaccharide-induced binding of c-Rel/p65 heterodimers to a kappa B site in the TF promoter, indicating that this drug influences induction of the TF gene. We conclude that lipophilic vastatins inhibit TF expression in macrophages, and because this effect is prevented by mevalonate and geranylgeraniol, a geranylgeranylated protein plays a crucial role in the regulation of TF biosynthesis. The suppression of TF in macrophages by vastatins indicates a potential mechanism by which these drugs interfere with the formation and progression of atherosclerotic plaque as well as thrombotic events in hyperlipidemic patients.