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Showing papers by "Sapienza University of Rome published in 1997"


Book ChapterDOI
01 Jan 1997
TL;DR: In this paper, a class of partial differential equations that generalize and are represented by Laplace's equation was studied. And the authors used the notation D i u, D ij u for partial derivatives with respect to x i and x i, x j and the summation convention on repeated indices.
Abstract: We study in this chapter a class of partial differential equations that generalize and are to a large extent represented by Laplace’s equation. These are the elliptic partial differential equations of second order. A linear partial differential operator L defined by $$ Lu{\text{: = }}{a_{ij}}\left( x \right){D_{ij}}u + {b_i}\left( x \right){D_i}u + c\left( x \right)u $$ is elliptic on Ω ⊂ ℝ n if the symmetric matrix [a ij ] is positive definite for each x ∈ Ω. We have used the notation D i u, D ij u for partial derivatives with respect to x i and x i , x j and the summation convention on repeated indices is used. A nonlinear operator Q, $$ Q\left( u \right): = {a_{ij}}\left( {x,u,Du} \right){D_{ij}}u + b\left( {x,u,Du} \right) $$ [D u = (D 1 u, ..., D n u)], is elliptic on a subset of ℝ n × ℝ × ℝ n ] if [a ij (x, u, p)] is positive definite for all (x, u, p) in this set. Operators of this form are called quasilinear. In all of our examples the domain of the coefficients of the operator Q will be Ω × ℝ × ℝ n for Ω a domain in ℝ n . The function u will be in C 2(Ω) unless explicitly stated otherwise.

8,299 citations


Journal ArticleDOI
TL;DR: Abnormal atrial histology was uniformly found in multiple biopsy specimens in all patients with LAF and was compatible with a diagnosis of myocarditis in 66% of patients and of noninflammatory localized cardiomyopathy in 17% and was represented by patchy fibrosis in 17%.
Abstract: Background Lone atrial fibrillation (LAF) is a common clinical syndrome, but its origin remains unknown. Methods and Results We performed endomyocardial biopsies of the right atrial septum (2 to 3 per patient; mean, 2.8) and of the two ventricles (6 per patient) in 12 patients (10 men, 2 women; mean age, 32 years) with paroxysmal LAF refractory to conventional antiarrhythmic treatment. As controls, we used endomyocardial biopsies (3 to 5 per patient; mean, 4.4) from the right atrial septum of 11 patients with Wolff-Parkinson-White syndrome (WPW) undergoing resection of the abnormal AV pathway. The weight of the biopsies ranged from 2.8 to 4.5 mg. Biopsy samples were processed for histology and electron microscopy and were read by a pathologist blinded to clinical data. All patients underwent two-dimensional Doppler echocardiography; cardiac catheterization; coronary angiography; and hormonal, virologic, and electrophysiological studies. All tests and WPW biopsies were normal, but all LAF atrial biopsy spe...

1,366 citations


Journal ArticleDOI
TL;DR: A registry containing information on the outcome of cord-blood transplantation from 1988 to 1996 was established, and younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors.
Abstract: Background Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Methods We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Results Among 78 recipients of cord blood from related donors, the Kaplan–Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-misma...

1,245 citations


Journal ArticleDOI
04 Apr 1997-Cell
TL;DR: P Pax-3 and Myf-5 define two distinct myogenic pathways, and MyoD acts genetically downstream of these genes for myogenesis in the body, and this genetic hierarchy does not appear to operate for head muscle formation.

834 citations


Journal ArticleDOI
TL;DR: Catalytic amounts of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) are used in combination with [bis(acetoxy)iodo]benzene (BAIB) as a stoichiometric oxidant in the conversion of primary and secondary alcohols to carbonyl compounds.
Abstract: Catalytic amounts of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) are used in combination with [bis(acetoxy)iodo]benzene (BAIB) as a stoichiometric oxidant in the conversion of primary and secondary alcohols to carbonyl compounds. This procedure works efficiently at room temperature in almost all common solvents and neat in some cases. This process exhibits a very high degree of selectivity for the oxidation of primary alcohols to aldehydes, without any noticeable overoxidation to carboxyl compounds, and a high chemoselectivity in the presence of either secondary alcohols or of other oxidizable moieties. This procedure allows an easy, convenient, high-yielding method for the oxidation of alcohols starting from commercially available compounds.

671 citations


Journal ArticleDOI
TL;DR: The response to rt-PA in patients with ischemic stroke can be predicted on the basis of initial CT findings of the extent of parenchymal hypoattenuation in the territory of the middle cerebral artery.
Abstract: PURPOSE: To determine whether the extent of subtle parenchymal hypoattenuation detected on computed tomographic (CT) scans obtained within 6 hours of ischemic stroke is a factor in predicting patients' response to thrombolytic treatment. MATERIALS AND METHODS: The baseline CT scans of 620 patients, who received either recombinant tissue plasminogen activator (rt-PA) or a placebo, in a double-blind, randomized multicenter trial were prospectively evaluated and assigned to one of three categories according to the extent of parenchymal hypoattenuation: none, 33% or less (small), or more than 33% (large) of the middle cerebral artery territory. The association between the extent of hypoattenuation on the baseline CT scans and the clinical outcome in the placebo-treated and the rt-PA-treated groups after 3 months was analyzed. RESULTS: In 215 patients with a small hypoattenuating area, treatment increased the chance of good outcome. In 336 patients with a normal CT scan and in 52 patients with a large hypoatte...

575 citations


Journal ArticleDOI
TL;DR: The risk of major bleeding during induction chemotherapy in adolescents and adults with acute myeloid leukemia (except acute promyelocytic leukemia, which the authors did not study) was similar with platelet-transfusion thresholds of 20,000 per cubic millimeter and 10,000 each.
Abstract: Background Prophylactic platelet transfusions are usually administered to patients receiving myelotoxic chemotherapy when their platelet count falls below 20,000 per cubic millimeter. Some observations suggest that lower platelet counts can be appropriate in patients in stable condition, but the safety of lower thresholds is uncertain. Methods We evaluated 255 adolescents and adults (age, 16 to 70 years) with newly diagnosed acute myeloid leukemia (but not acute promyelocytic leukemia), who were treated in 21 centers. One hundred thirty-five patients were randomly assigned to receive a transfusion when their platelet count fell below 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter in those with a temperature above 38°C, with active bleeding, or a need for invasive procedures), and 120 patients were assigned to receive a transfusion when their platelet count was less than 20,000 per cubic millimeter. Results Patients in the group with a threshold of 10,000 platelets per cubic millimet...

532 citations


Journal ArticleDOI
01 Aug 1997-Blood
TL;DR: This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RARα-positive APL and suggests that a remarkable cure rate can be obtained with this treatment.

494 citations


Journal ArticleDOI
20 Nov 1997-Nature
TL;DR: It is reported 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.
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.

479 citations


Journal ArticleDOI
10 Jan 1997-Science
TL;DR: TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway, which means SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis.
Abstract: Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor-associated factor 2 protein (TRAF2) is required for activation of the nuclear transcription factor nuclear factor kappa B. TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which blocks apoptosis, did not interfere with SAPK activation. Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis.

447 citations


Journal ArticleDOI
TL;DR: The authors argue that an evolutionary perspective, broadly defined, can easily accommodate both inducement effects and path-dependent patterns of technical change, and they also raise questions about the relative success of three interpretative perspectives which he calls 'induced', 'evolutionary' and 'path-dependent'.
Abstract: In a few pages, in the introductory article for this debate, Vernon Ruttan succeeds in the unlikely task of flagging many issues at the core of the economic interpretation of technological change (and by doing so he implicitly addresses also a few sensitive spots for the economic discipline at large). Here I will not attempt to provide any thorough view of what I consider the achievements and limitations of the current state-of-the-art (see, however, Freeman (I 994) for a critical survey which I largely share). Rather, I shall put forward a series of remarks which, hopefully, could be seen as part of a much wider, and still largely unexplored, research programme. As a premise, just note that some form of attention to technology-related phenomena has spread over the last 20-30 years from small enclaves of heterodox economists and economic historians to become an important concern even for quite mainstream theories of e.g. the firm, industrial organisation, macroeconomics, trade, growth, etc. From 'patent races' all the way to 'New Trade' and 'New Growth' theories and even Real Business Cycle macro models, technical change has drawn a consideration which is less by default than it was, say, in Robert Solow's original growth models orJoe Bain's barriers-to-entry views on industrial structures. And, in parallel, empirical studies at the levels of specific technologies, firms, sectors and countries have boomed (for overviews cf. Dosi (I988), Nelson (I993), Freeman (I982, I 994), Cohen (I 995) and Granstrand (I 994), among others). So, at least in this sense, those 'decreasing returns' to the economics of technical change suggested by Ruttan do not seem to have set in. However, Ruttan's paper raises also substantive questions about the relative success of three interpretative perspectives which he calls 'induced', 'evolutionary' and 'path-dependent'. In the following I shall argue that an evolutionary perspective, broadly defined, can easily accommodate both inducement effects and path-dependent patterns of technical change. Let me start from what I consider the major building blocks of an

Journal ArticleDOI
10 Apr 1997-Nature
TL;DR: It is shown that changes in apparent visual direction anticipate saccades and are not of the same size, or even in the same direction, for all parts of the visual field and there is a compression of visual space sufficient to reduce the spacing and even the apparent number of pattern elements.
Abstract: Saccadic eye movements, in which the eye moves rapidly between two resting positions, shift the position of our retinal images. If our perception of the world is to remain stable, the visual directions associated with retinal sites, and others they report to, must be updated to compensate for changes in the point of gaze. It has long been suspected that this compensation is achieved by a uniform shift of coordinates driven by an extra-retinal position signal, although some consider this to be unnecessary. Considerable effort has been devoted to a search for such a signal and to measuring its time course and accuracy. Here, by using multiple as well as single targets under normal viewing conditions, we show that changes in apparent visual direction anticipate saccades and are not of the same size, or even in the same direction, for all parts of the visual field. We also show that there is a compression of visual space sufficient to reduce the spacing and even the apparent number of pattern elements. The results are in part consistent with electrophysiological findings of anticipatory shifts in the receptive fields of neurons in parietal cortex and superior colliculi.

Journal Article
TL;DR: This analysis shows that the putative secondary/intermediate LHON mutations 4216, 4917, 13708, 15257, and 15812 are ancient polymorphisms, are associated in specific combinations, and define two common Caucasoid-specific haplotypes (haplogroups J and T).
Abstract: mtDNAs from 37 Italian subjects affected by Leber hereditary optic neuropathy (LHON) (28 were 11778 positive, 7 were 3460 positive, and 2 were 14484 positive) and from 99 Italian controls were screened for most of the mutations that currently are associated with LHON. High-resolution restriction-endonuclease analysis also was performed on all subjects, in order to define the phylogenetic relationships between the mtDNA haplotypes and the LHON mutations observed in patients and in controls. This analysis shows that the putative secondary/intermediate LHON mutations 4216, 4917, 13708, 15257, and 15812 are ancient polymorphisms, are associated in specific combinations, and define two common Caucasoid-specific haplotype groupings (haplogroups J and T). On the contrary, the same analysis shows that the primary mutations 11778, 3460, and 14484 are recent and are due to multiple mutational events. However, phylogenetic analysis also reveals a different evolutionary pattern for the three primary mutations. The 3460 mutations are distributed randomly along the phylogenetic trees, without any preferential association with the nine haplogroups (H, I, J, K, T, U, V, W, and X) that characterize European populations, whereas the 11778 and 14484 mutations show a strong preferential association with haplogroup J. This finding suggests that one ancient combination of haplogroup J-specific mutations increases both the penetrance of the two primary mutations 11778 and 14484 and the risk of disease expression.


Journal ArticleDOI
12 Sep 1997-Science
TL;DR: GD3 ganglioside mediates the propagation of CD95-generated apoptotic signals in hematopoietic cells and Pharmacological inhibition of GD3 synthesis and exposure to GD3 synthase antisense oligodeoxynucleotides preventedCD95-induced apoptosis.
Abstract: Gangliosides participate in development and tissue differentiation. Cross-linking of the apoptosis-inducing CD95 protein (also called Fas or APO-1) in lymphoid and myeloid tumor cells triggered GD3 ganglioside synthesis and transient accumulation. CD95-induced GD3 accumulation depended on integral receptor “death domains” and on activation of a family of cysteine proteases called caspases. Cell-permeating ceramides, which are potent inducers of apoptosis, also triggered GD3 synthesis. GD3 disrupted mitochondrial transmembrane potential (ΔΨm), and induced apoptosis, in a caspase-independent fashion. Transient overexpression of the GD3 synthase gene directly triggered apoptosis. Pharmacological inhibition of GD3 synthesis and exposure to GD3 synthase antisense oligodeoxynucleotides prevented CD95-induced apoptosis. Thus, GD3 ganglioside mediates the propagation of CD95-generated apoptotic signals in hematopoietic cells.

Journal ArticleDOI
TL;DR: The polymerase chain reaction was used to clone two distinct 550 bp-long DNA fragments of the gene encoding the Cryptosporidium oocyst wall protein (COWP) of C. wrairi, which showed 98% identity to the C. parvum homologue.
Abstract: Cryptosporidium wrairi was isolated from guinea pigs during a spontaneous outbreak of cryptosporidiosis. Despite the morphological and antigenic similarities to C. parvum, C. wrairi displayed a different host range and site of infection and may represent a separate species or sub-species. We used the polymerase chain reaction to clone two distinct 550 bp-long DNA fragments, Wc-I and Wc-II, of the gene encoding the Cryptosporidium oocyst wall protein (COWP) of C. wrairi, which showed 98% identity to the C. parvum homologue. Within Wc-I, polymorphic RsaI restriction sites were used to develop a polymerase chain reaction-restriction fragment length polymorphism method able to distinguish C. wrairi from C. parvum and to identify two groups of C. parvum isolates differentially associated with animal and human infections.

Journal ArticleDOI
TL;DR: In this article, a finite-size Lyapunov exponent was introduced to measure the growth rate of finite size perturbations, which coincides with the size of the perturbation.
Abstract: We investigate the predictability problem in dynamical systems with many degrees of freedom and a wide spectrum of temporal scales. In particular, we study the case of three-dimensional turbulence at high Reynolds numbers by introducing a finite-size Lyapunov exponent which measures the growth rate of finite-size perturbations. For sufficiently small perturbations this quantity coincides with the usual Lyapunov exponent. When the perturbation is still small compared to large-scale fluctuations, but large compared to fluctuations at the smallest dynamically active scales, the finite-size Lyapunov exponent is inversely proportional to the square of the perturbation size. Our results are supported by numerical experiments on shell models. We find that intermittency corrections do not change the scaling law of predictability. We also discuss the relation between the finite-size Lyapunov exponent and information entropy.

Journal ArticleDOI
TL;DR: The results indicate that 8-epi PGF2alpha and IPF2alpha-I, two distinct F2-isoprostanes and markers of oxidative stress in vivo, are present in human atherosclerotic plaque.
Abstract: F2-Isoprostanes are prostaglandin (PG) isomers formed in situ in cell membranes by peroxidation of arachidonic acid. 8-epi PGF2alpha and IPF2alpha-I are F2-isoprostanes produced in humans which circulate in plasma and are excreted in urine. Measurement of F2-isoprostanes may offer a sensitive, specific, and noninvasive method for measuring oxidant stress in clinical settings where reactive oxygen species are putatively involved. We determined whether isoprostanes were present in human atherosclerotic lesions, where lipid peroxidation is thought to occur in vivo. 8-epi PGF2alpha ranged from 1.310-3.450 pmol/micromol phospholipid in atherectomy specimens compared with 0.045-0.115 pmol/micromol phospholipid (P < 0.001) in vascular tissue devoid of atherosclerosis. Corresponding values of IPF2alpha-I were 5.6-13.8 vs. 0.16-0.44 pmol/micromol phospholipid (P < 0.001). Levels of the two isoprostanes in vascular tissue were highly correlated (r = 0.80, P < 0.0001). Immunohistochemical studies confirmed that foam cells adjacent to the lipid necrotic core of the plaque were markedly positive for 8-epi PGF2alpha. These cells were also reactive with anti-CD68, an epitope specific for human monocyte/macrophages. 8-epi PGF2alpha immunoreactivity was also detected in cells positive for anti-alpha-smooth muscle actin antibody, which specifically recognizes vascular smooth muscle cells. Our results indicate that 8-epi PGF2alpha and IPF2alpha-I, two distinct F2-isoprostanes and markers of oxidative stress in vivo, are present in human atherosclerotic plaque. Quantitation of these chemically stable products of lipid peroxidation in target tissues, as well as in biological fluids, may aid in the rational development of antioxidant drugs in humans.

Journal ArticleDOI
TL;DR: This work identifies several user types and match the VQS classes against them, in order to understand which kind of system may be suitable for each kind of user, and introduces a classification based on such features, namely the adopted visual representations and the interaction strategies.
Abstract: Visual query systems (VQSs) are query systems for databases that use visual representations to depict the domain of interest and express related requests. VQSs can be seen as an evolution of query languages adopted into database management systems; they are designed to improve the effectiveness of the human?computer communication. Thus, their most important features are those that determine the nature of the human?computer dialogue. In order to survey and compare existing VQSs used for querying traditional databases, we first introduce a classification based on such features, namely the adopted visual representations and the interaction strategies. We then identify several user types and match the VQS classes against them, in order to understand which kind of system may be suitable for each kind of user. We also report usability experiments which support our claims. Finally, some of the most important open problems in the VQS area are described.

Journal ArticleDOI
TL;DR: This study provides the first insight into two co‐operating partners in blue‐light signal transduction in any organism and describes the molecular tools with which to dissect this enigmatic process.
Abstract: A saturating genetic dissection of 'blind' mutants in Neurospora crassa has identified a total of two non-redundant loci (wc-1 and wc-2) each of which is required for blue-light perception/signal transduction. Previously, we demonstrated that WC1 is a putative zinc finger transcription factor able to bind specifically to a light-regulated promoter. Here, we present the cloning and characterization of the wc-2 gene. We demonstrate using mutation analysis and in vitro DNA-binding assays that WC2, the second partner of this light signal transduction system, encodes a functional zinc finger DNA-binding protein with putative PAS dimerization and transcription activation domains. This molecular genetic dissection of the second of two components of this light signal transduction system has enabled us to devise a model whereby WC1 and WC2 are proposed to interact via homologous PAS domains, bind to promoters of light-regulated genes and activate transcription. As such, this study provides the first insight into two co-operating partners in blue-light signal transduction in any organism and describes the molecular tools with which to dissect this enigmatic process.

Journal ArticleDOI
TL;DR: Flow cytometric analysis of freshly prepared human peripheral blood lymphocytes reveals that lipoic acid acts mainly to normalize a subpopulation of cells severely compromised in thiol status rather than to increase thiol content beyond physiological levels, suggesting it may have clinical relevance in restoration of severely glutathione deficient cells.
Abstract: Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a therapeutic agent, and is reported to have beneficial effects in disorders associated with oxidative stress, but its mechanism of action remains unclear. We present evidence that lipoic acid induces a substantial increase in cellular reduced glutathione in cultured human Jurkat T cells human erythrocytes, C6 glial cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect depends on metabolic reduction of lipoic acid to dihydrolipoic acid. Dihydrolipoic acid is released into the culture medium where it reduces cystine. Cysteine thus formed is readily taken up by the neutral amino acid transport system and utilized for glutathione synthesis. By this mechanism lipoic acid enables cystine to bypass the xc- transport system, which is weakly expressed in lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key enzyme of glutathione synthesis, gamma-glutamylcysteine synthetase, which is regulated by uptake-limited cysteine supply, to work at optimum conditions. Flow cytometric analysis of freshly prepared human peripheral blood lymphocytes, using monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly to normalize a subpopulation of cells severely compromised in thiol status rather than to increase thiol content beyond physiological levels. Hence lipoic acid may have clinical relevance in restoration of severely glutathione deficient cells.

Journal ArticleDOI
TL;DR: XAFS, IR, and UV−vis spectroscopies have been employed to investigate the local environment of CuI in CuI-ZSM-5 prepared by gas phase reaction of ZSM with CuCl.
Abstract: XAFS, IR, and UV−vis (diffuse reflectance and photoluminescence) spectroscopies have been employed to investigate the local environment of CuI in CuI-ZSM-5 prepared by gas phase reaction of H-ZSM-5 (SiO2/Al2O3 = 90−50) with CuCl The measurements confirm that the absolutely predominant copper species formed with this procedure are CuI:Cu species in other oxidation states are less than 1% Direct proof of the absence of both unreacted CuCl microaggregates and of copper clusters in the zeolite channels is also given CuI-ZSM-5 prepared in this way represents a model solid for investigating the structure of isolated CuI sites in zeolites EXAFS analysis reveal that, in vacuum conditions, Cu+ cations are surrounded by 25 ± 03 oxygens at 200 ± 002 A The combined use of EXAFS, IR, and photoluminescence UV−vis spectroscopies and computer graphic simulations allows to infer that Cu+ ions in CuI-ZSM-5 are located in two families of sites, indicated as I and II, (site II having the highest coordinative unsatur

Journal ArticleDOI
TL;DR: The increased percentage of spontaneous menarche is Turner's syndrome reported in the recent literature might be due to increased ascertainment by diligent screening for Turner’s syndrome in girls with short stature and mild or no Turner's Syndrome stigmata, even though they may be menstruating.
Abstract: The incidence of spontaneous puberty in Turner's syndrome is reported to be between 5-10% and, more recently in some series, as high as 20%. In an Italian retrospective multicenter study, of 522 patients older than 12 yr with Turner's syndrome, 84 patients (16, 1%) presented spontaneous pubertal development with menarche that occurred at a chronological age of 13.2 +/- 1.5 yr (mean +/- SD) and a bone age of 12.9 +/- 1.9 yr. Karyotype distribution in the whole group was as follows: 52.1% (272 patients) X-monosomy (45,X), 13.2% (69 patients) mosaicism characterized by X-monosomy and cellular line with no structural abnormalities of the second X, 19.9% (104 patients) mosaicism characterized by X-monosomy and cellular line with structural abnormalities of the second X, and 14.8% (77 patients) structural abnormalities of the second X. Menstrual cycles were still regular in 30 patients at 9.2 +/- 5.0 yr after menarche, 12 developed secondary amenorrhea 1.6 +/- 2.0 yr after menarche, and 19 had irregular menstrual cycles 0.9 +/- 1.8 yr after menarche. As signs of spontaneous puberty developed in 14.0% of X-monosomic patients and in 32.0% of patients with cell lines with more than one X, the presence of the second X seems to have a cardinal influence on the appearance of spontaneous puberty. Spontaneous pregnancy occurred in 3 patients (3.6%). The presence of chromosomal abnormalities and malformations in 2 of 3 pregnancies led us to agree with other investigators in discouraging unassisted pregnancies. Treatment with GH does not seem to exert any influence on either the age of onset or the prevalence of spontaneous pubertal development in Turner's syndrome. The increased percentage of spontaneous menarche is Turner's syndrome reported in the recent literature might be due to increased ascertainment by diligent screening for Turner's syndrome in girls with short stature and mild or no Turner's syndrome stigmata, even though they may be menstruating.

Journal ArticleDOI
TL;DR: An approach to structurally stable regulation that unifies and extends a number of existing results is described, and the issue of robust regulation is addressed, i.e. theissue of achieving regulation in the presence of parameter uncertainties ranging within a prescribed set.

Journal ArticleDOI
TL;DR: I. Introduction II.
Abstract: I. Introduction II. Neurohormones/Neuropeptides A. GH-releasing hormone (GHRH) B. Pituitary adenylate cyclase-activating peptide (PACAP) C. GnRH D. CRH E. Oxytocin (OT) F. Arginine vasopressin (AVP) G. TRH H. Somatostatin (SRIF) I. Opioids J. Substance-P (SP) K. Neuropeptide Y (NPY) III. Peptides Originally Identified in the Male Gonad A. Inhibin (INH) and activin (ACT) B. PModS IV. Growth Factors A. Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBs) B. Transforming growth factor-β (TGFβ) C. TGFα/EGF D. Fibroblast growth factor (FGF) E. Platelet-derived growth factor (PDGF) F. Nerve growth factor (NGF) G. Steel factor (SLF) H. Gastrin-releasing peptide (GRP) V. Immune Derived Cytokines A. Interleukins (ILs) B. Tumor necrosis factor-α (TNFα) VI. Vasoactive Peptides A. Endothelin (ET) B. Angiotensin-II (AT-II) C. Atrial natriuretic peptide (ANP) VII. Conclusions and Perspectives

Journal ArticleDOI
I. Abt1, T. Ahmed2, S. Aid3, Vladimir Andreev4  +564 moreInstitutions (28)
TL;DR: The H1 detector at the electron-proton storage ring HERA as mentioned in this paper was used from 1992 to the end of 1994, and a major upgrade of some components was undertaken.
Abstract: General aspects of the H1 detector at the electron-proton storage ring HERA as well as technical descriptions of the magnet, luminosity system, trigger, slow-control, data acquisition and off-line data handling are given. The three major components of the detector, the tracking, calorimeter and muon detectors, will be described in a forthcoming article. The present paper describes the detector that was used from 1992 to the end of 1994. After this a major upgrade of some components was undertaken. Some performance figures from luminosity runs at HERA during 1993 and 1994 are given.

Journal ArticleDOI
TL;DR: In this paper, the four longest European pollen records were linked and a terrestrial sequence of vegetation events and a coherent stratigraphic scheme for the last 500,000 years was derived, showing that the pollen sequences contain a higher degree of climate sensitivity than the oxygen isotope record.

Journal ArticleDOI
TL;DR: It is demonstrated that, in differentiating skeletal muscle cells, p300 physically interacts with the myogenic basic helix–loop–helix (bHLH) regulatory protein MyoD at its DNA binding sites, and p300 potentiates MyOD‐ and myogenin‐dependent activation of transcription from E‐box‐containing reporter genes.
Abstract: The nuclear phosphoprotein p300 is a new member of a family of 'co-activators' (which also includes the CREB binding protein CBP), that directly modulate transcription by interacting with components of the basal transcriptional machinery. Both p300 and CBP are targeted by the adenovirus E1A protein, and binding to p300 is required for E1A to inhibit terminal differentiation in both keratinocytes and myoblasts. Here we demonstrate that, in differentiating skeletal muscle cells, p300 physically interacts with the myogenic basic helix-loop-helix (bHLH) regulatory protein MyoD at its DNA binding sites. During muscle differentiation, MyoD plays a dual role: besides activating muscle-specific transcription, it induces permanent cell cycle arrest by up-regulating the cyclin-dependent kinase inhibitor p21. We show that p300 is involved in both these activities. Indeed, E1A mutants lacking the ability to bind p300 are greatly impaired in the repression of E-box-driven transcription, and p300 overexpression rescues the wild-type E1A-mediated repression. Moreover, p300 potentiates MyoD- and myogenin-dependent activation of transcription from E-box-containing reporter genes. We also provide evidence, obtained by microinjection of anti-p300 antibodies, that p300 is required for MyoD-dependent cell cycle arrest in either myogenic cells induced to differentiate or in MyoD-converted C3H10T1/2 fibroblasts, but is dispensable for maintenance of the postmitotic state of myotubes.

Journal ArticleDOI
TL;DR: In early onset MS patients with disease duration < 8 years, cases with EDSS > 6 were slightly more frequent than in the AOMS group and the frequency of cases for different levels of disability was similar for disease duration > 8 years.
Abstract: From the retrospective study of 3375 patients affected by clinically definite or probable multiple sclerosis (MS), 149 patients were collected with onset of the disease before the age of 16 years (4.4%). Female/male ratio was higher than that of the adult onset MS (AOMS) population (2.2 vs 1.6) particularly at ages of onset after 12 years (3.0, P = 0.007 vs AOMS). Among initial symptoms, those suggesting brainstem dysfunction (25%) were more frequent compared to other systems and compared to AOMs symptoms; motor and sensory disturbances were slightly less frequent (respectively 17.5% and 18.3%). Optic neuritis appeared in 16.5% of cases with onset in childhood and in 16.2% of cases with AOMS, cerebellar disturbances respectively in 9.1% and 7.7%. The first interattack-interval and the clinical course of early onset MS did not differ significantly from AOMS. In early onset MS patients with disease duration 6 were slightly more frequent than in the AOMS group (P = 0.04). The frequency of cases for different levels of disability was similar for disease duration > 8 years.

Journal ArticleDOI
TL;DR: Three chromosomal forms of Anopheles gambiae s.s., designated as Bamako, Mopti and Savanna, were studied for diagnostic PCR assays based on the analysis of the X‐linked ribosomal DNA and the results confirm previous observations indicating barriers to gene flow within An.
Abstract: Three chromosomal forms of Anopheles gambiae ss, designated as Bamako, Mopti and Savanna, were studied for diagnostic PCR assays based on the analysis of the X-linked ribosomal DNA (rDNA) The study was performed on a 13 kb fragment containing part of the 28S coding region and part of the intergenic spacer region The amplified material was cut with fourteen restriction enzymes to detect Restriction Fragment Length Polymorphisms (RFLPs) The enzymes Tru9I and HhaI produced patterns of DNA bands which differentiated Mopti from Savanna and Bamako; moreover, a distinct ‘hybrid’ pattern was recognized in the F1 female progeny from the cross of Mopti with either one of the other two chromosomal forms The diagnostic significance of the PCR-RFLP assay was verified on 203 karyotyped females from field samples collected in two villages in Mali and one village in Burkina Faso Agreement was observed between the chromosomal and the molecular identifications No ‘hybrid’ molecular patterns were detected even among carriers of rare heterokaryotypes hypothetically produced by crosses between Mopti and Savanna The results confirm previous observations indicating barriers to gene flow within An gambiae ss and supporting the specific status of the taxonomic units proposed on cytogenetic ground