Search

In this paper we describe our design, implementation, and initial results of a prototype connected-phonem-based speech recognition system on the Cell Broadband Engine[TM] (Cell/B.E.) processor. Automated speech recognition decodes speech samples into plaintext (other representations are possible) and must process samples at real-time rates. Fortunately, the computational tasks involved in this pipeline are highly data parallel and can receive significant hardware acceleration from vector-streaming architectures such as the Cell/B.E. Architecture. Identifying and exploiting these parallelism opportunities is challenging and critical to improving system performance. From our initial performance timings, we observed that a single Cell/B.E. processor can recognize speech from thousands of simultaneous voice channels in real time--a channel density that is orders of magnitude greater than the capacity of existing software speech recognizers based on CPUs (central processing units). This result emphasizes the potential for Cell/B.E. processor-based speech recognition and will likely lead to the development of production speech systems using Cell/B.E. processor clusters.

The development of the Global Position System (GPS) satellite network provides new opportunities to characterize atmospheric parameters using innovative techniques. The GPS Radio Occultation Technique (GPS RO) is one of the most recent and promising atmospheric remote sensing technique applied to GPS measurements. The GPS RO technique allows obtaining profiles of refractivity, temperature, pressure and water vapor in the neutral atmosphere and electron density in the ionosphere. In the last years, other missions confirmed the RO efficiency, like GPS/MET, COSMIC (Constellation Observing System for Meteorology, Ionosphere, and Climate), Formosa Satellite Mission 3 and the last Radio Occultation Sounder Antenna for the Atmosphere. In this work, water vapor mixing ratio profiles retrieved from COSMIC observations are presented and validated using ground based water vapor Raman lidar profiles. As far as we know, this is the first time water vapor mixing ratio profiles provided by COSMIC are compared with a ground based Raman lidar. COSMIC profiles used in this study are retrieved applying a one-dimensional variational method that make use of ECMWF low resolution analysis data as a guess of atmospheric water vapor. Raman lidar measurements of the water vapor mixing ratio profiles are provided by PEARL (Potenza EArlinet Raman Lidar) system running at CIAO, located in Potenza, South Italy. Performance of COSMIC retrieval are studied over a period of one year (2008) of systematic water vapor Raman lidar measurements. A possible strategy for reducing the impact of the co-location mismatch between satellite footprint and the lidar station is presented and the problem of the vertical resolution of COSMIC profiles respect to the Raman lidar is also discussed. The statistical analysis for the selected cases shows good performance of COSMIC in the identification of the vertical gradients of the water vapor field, even though the average difference between the Raman lidar and the COSMIC profiles suggests that caution should be taken in using COSMIC data as an absolute or reference measurement of water vapor, in particular in the low and middle troposphere.

Since cyclooxygenase (COX) isozymes discovery, many papers and reviews have been published to describe the structural bases of COX inhibition, and to debate on the therapeutic and adverse effects of worldwide clinically used nonsteroidal anti-inflammatory drugs (NSAIDs), included COX-2 selective inhibitors (well known as Coxibs). COX-2 inhibition has been widely investigated, whereas the role of COX-1 in human pathophysiology is mostly not yet well ascertained. As time goes on, the cliche that the constitutively expressed isoform COX-1 is only involved in normal physiological functions, such as platelet aggregation, gastric mucosa protection and renal electrolyte homeostasis is going to be shattered. Low-dose aspirin, behaving as a preferential inhibitor of platelet COX-1, allowed to enlighten the role exerted by this isoenzyme in many mammalian cell types. This review would elucidate the most recent findings on selective COX-1 inhibition and their relevance to human pathology such as cancer, neuro-inflammation, cardioprotection, fever and pain. It would also focus on the design and development of new highly selective COX-1 inhibitors, useful tools in pharmacological studies aimed at gaining a deeper insight of the role of COX-1 in human health and disease. Among the traditional NSAIDs, other then aspirin and indomethacin, only few examples of selective COX-1 inhibitors (SC-560, FR122047, mofezolac, P6 and TFAP) have been so far identified. This review has also the scope to stimulate the development of novel drugs, which activity is COX-1 mediated.

The aim of this work has been to test the reliability of a simple relation connecting the order of probe molecules dissolved in binary nematic mixtures with that exhibited in each nematic component at the same reduced temperatures. In order to do this, a large amount of 1 H-LXNMR experiments at different temperatures has been performed, utilizing as solutes 1 ,4-difluorobenzene, 1,4-dichlorobenzene, 1,4-dibromobenzene and naphthalene in I52, EBBA and I52/EBBA mixtures at variable mixing percentages (50/50, 20/80 and 80/20 mol%). The results confirm that the orientations of the solutes in the mixtures can be predicted in a satisfactory way as a function of the mixing ratios, independently of the solutes and the temperatures. Finally, as a stimulation for future studies, a conjecture about the observed discrepancies is suggested.

The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (Ki = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

Tyrphostins are low-molecular-weight synthetic inhibitors of protein tyrosine kinase, which block cell proliferation. Since platelet-derived growth factor (PDGF) is thought to figure prominently in disorders of vascular smooth muscle cells (VSMC), such as atherosclerosis, hypertension, and restenosis, we examined whether tyrphostins would inhibit PDGF-induced mitogenesis in VSMC. In this communication, we demonstrate that tyrphostins with the benzenemalononitrile nucleus inhibited PDGF-dependent growth of VSMC as well as PDGF-dependent DNA synthesis in these cells, with the concentrations for 50% inhibition ranging from 0.04 to 9 microM. Up to 30-fold higher tyrphostin concentrations were required to inhibit serum-stimulated DNA synthesis of VSMC. The effect of the tyrphostins is reversible, since on their removal a normal proliferative response to PDGF was resumed. Tyrphostins also inhibited PDGF-receptor autophosphorylation and PDGF-induced phosphorylation of intracellular substrates, including the phosphorylation of phospholipase C-gamma, with a potency ratio similar to their antimitogenic activity. The expression of c-fos mRNA, a mitogenic nuclear signal, was also reduced in PDGF-stimulated VSMC treated with tyrphostins at concentrations which inhibit PDGF-induced mitogenesis. It is concluded that tyrphostins are potent reversible inhibitors of PDGF-induced mitogenesis which act by inhibiting the tyrosine kinase activity of the PDGF receptor and the subsequent signaling cascade. Tyrphostins may be useful in the study and treatment of VSMC proliferation disorders.

The evolution of the main parameters (spot size, radius of curvature, and far-field divergence) of the beam provided by a high-gain, short-pulse Xe–Cl laser equipped with a plane-parallel Gaussian resonator has been investigated both theoretically and experimentally as a function of the number of round trips. It is shown that a theoretical analysis, formerly developed to study the growth of coherence of a Schell–Gauss model beam propagating through a periodic sequence of Gaussian apertures, provides a satisfactory description of the temporal evolution of the Xe–Cl laser beam. A good agreement between theoretical and experimental data has been found.

A theoretical analysis of the time evolution of spatial coherence in a large Fresnel-number laser cavity with use of the second-moment-analysis method and assuming quadratic (Gaussian) variable-reflectivity mirrors was found also to provide a satisfactory description of coherence growth inside a pulsed high-gain laser with use of either super-Gaussian or phase-unifying mirrors. The theoretical results are found to be in good agreement with the detailed experimental results from a high-gain, short-pulse Xe–Cl laser having a plane-parallel cavity equipped with both types of mirror.

A XeCl laser system without dispersive elements is used to investigate near threshold reflectivity and phase-conjugation (PC) fidelity of stimulated Brillouin scattering (SBS) mirrors with SF6 as the active medium. Using different focal-length lenses to focus the broadband laser radiation into the Brillouin medium, it was found that at threshold the effective interaction length for SBS is equal to the confocal parameter and that the SBS gain is equal to its steady-state value for monochromatic pumping. High PC-fidelity values ranging from 0.8–1.0 were found under most of the experimental conditions investigated.

An oscillator-amplifier XeCl laser system has been used to experimentally investigate the effectiveness of a liquid stimulated Brillouin scattering (SBS) mirror for correcting the spatial aberrations of broad-band laser radiation in a double-pass amplifier. It has been found that the SBS amplifier performance is strongly dependent on the intensity Ip exciting the Brillouin medium. A good beam reconstruction has been attained at Ip=1GW/cm2, whereas highly aberrated output beams have been delivered by the SBS amplifier for Ip>1 GW/cm2. By comparing the broad-band SBS amplifier performance to that of the same amplifier with a dielectrically coated flat mirror at one end, it has been found that the use of a SBS mirror is advantageous to obtain lower divergence output beams only for low energy pump beams (<1 mJ).

The temporal evolution of the beam-quality factor M^2 is investigated in plane-parallel cavities of different Fresnel numbers with a Gaussian reflectivity mirror and applied to a Xe–Cl excimer laser. The Fresnel number is changed by varying resonator length. Laser radiation of higher spatial coherence is provided by the cavity of greater length (2.5 m) and then of lower Fresnel number after the first transit. Indeed, the beam spatial coherence decreases with cavity length. It is also shown that the Gaussian mirror affects the properties of the oscillating laser radiation only at the very first cavity round trips. The near- and far-field spatial characteristics of the laser radiation do not vary after a few transits inside the cavity. Experimental results are supported by a theory formerly developed for the evolution of the parameters of Gaussian Schell-model beams propagating in Gaussian cavities.

In order to assess the involvement of alpha-2 adrenergic receptors in nociception, the in vitro potencies of seven alpha-2 adrenergic agonists (clonidine, guanabenz, guanfacine, BHT-920, ICI 106270, xylazine and lofexidine) were compared with their ability to prevent the writhing response elicited by i.p. administration of phenyl-p-guinone. Administration of each compound elicited antinociception, and this effect was attenuated by pretreatment with the alpha-2 adrenergic antagonists, yohimbine. The potency of these compounds to cause antinociception was correlated with their potency to displace [3H]clonidine from its binding site on brain membranes and with their ability to inhibit the twitch of the electrically stimulated vas deferens, suggesting an alpha-2 involvement in the antinociceptive action. In addition to causing antinociception, administration of these agonists also impaired rotorod performance in mice. These agonists were 2.5 to 72 times more potent in inhibiting writhing than in impairing rotorod performance, and, except for ICI 106270, there was a correlation between antinociceptive and ataxic potency. ICI 106270 was a notable exception to this correlation, however, producing only minimal ataxia, which unlike the other agonists was not reversed by yohimbine. These results indicate that alpha-2 adrenergic agonists can produce antinociception and further suggest that this may be dissociable from the ataxia.

The integrin receptor recognition sequence Arg-Gly-Asp was successfully used as a template from which to develop a series of potent, selective, orally active, peptide-based fibrinogen receptor antagonists with a long duration of action. Simple modifications centered on the Arg and Gly residues quickly led to a modified peptide (1) with significantly enhanced ability to inhibit in vitro platelet aggregation. Substitution of the guanidino group in 1 by piperidine provided 3, which showed not only a further increase in potency but also a modest degree of oral efficacy. Finally, exploration of the nature of the C-terminal amino acid, with respect to its side-chain functionality and the carboxy terminus, yielded a group of molecules that showed excellent in vitro potency for inhibiting platelet aggregation, excellent integrin selectivity, a high level of oral efficacy, and an extended duration of action.

The discovery and some of the basic structure−activity relationships of a series of novel nonpeptide inhibitors of blood coagulation Factor Xa is described. These inhibitors are functionalized β-alanines, exemplified by 2a. Docking experiments placing 2a in the active site of Factor Xa implied that the most expeditious route to enhancing in vitro potency was to modify the group occupying the S3 site of the enzyme. Increasing the hydrophobic contacts between the inhibitor and the enzyme in this region led to 8, which has served as the prototype for this series. In addition, an enantioselective synthesis of these substituted β-alanines was also developed.

We present a very compact and very reliable laser system formed of two discharge sections both with lateral UV preionization. The discharge electrodes are contained in a single vessel and form an oscillator-amplifier system. A single spark gap switches on both circuits. By applying a generalized self-filtering unstable resonator to the oscillator and injecting the laser beam into the single pass amplifier, an output beam of 105 mJ, with a brightness of 5.5×1013 W cm-2Sr-1 has been obtained. Moreover, by applying a pulse-forming network in one discharging circuit, the duration of the discharge breakdown has been increased and output laser pulses of 40 ns FWHM, and 80 ns base width duration (at 10% points) and of energy 100 mJ are obtained.

This study examined the cardioprotective effects and pharmacology of the novel adenosine A1/A2 receptor agonist ([1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3H-imida zo[4,5-b] pyridyl-3-yl] cyclopentane carboxamide) (AMP 579), in a model of myocardial infarction. Experiments were performed in pentobarbital-anesthetized pigs in which myocardial infarction was induced by a 40-min occlusion of the left anterior descending coronary artery, followed by 3 hr of reperfusion. This procedure resulted in approximately 20% of the left ventricle being made ischemic in all test groups. In untreated animals, an infarct size equal to 56 +/- 5% of the ischemic area was observed. Preconditioning, with two cycles of 5 min of ischemia followed by 10-min reperfusion, resulted in a 70% reduction in infarct size (17 +/- 5%) relative to risk area. Administration of AMP 579 30 min before ischemia (3 microg/kg i.v. followed by 0.3 microg/kg/min i.v. through 1 hr of reperfusion) did not change blood pressure, HR or coronary blood flow but resulted in marked cardioprotection: a 98% reduction in infarct size (1 +/- 1%) relative to risk area. Moreover, whereas approximately 90% of control pigs suffered ventricular fibrillation during ischemia, no fibrillation was observed in animals treated with AMP 579. Further experiments determined the effects of AMP 579 when administered 30 min after the onset of myocardial ischemia, 10 min before reperfusion. Two doses were studied: a low hemodynamically silent dose (3 microg/kg + 0.3 microg/kg/min through 1 hr of reperfusion) and a 10-fold higher dose that did cause reductions in blood pressure and HR. Both doses of AMP 579 produced a comparable cardioprotective effect, reducing infarct size to approximately 50% of that observed in control animals. The cardioprotective effect of AMP 579 was a consequence of adenosine receptor stimulation, because it was completely inhibited by pretreatment with the specific adenosine receptor antagonist CGS 15943 (1 mg/kg i.v.). However, the selective A1 receptor agonist GR 79236 (3 microg/kg + 0.3 microg/kg/min i.v.) did not reduce infarct size, which suggests that under these experimental conditions, stimulation of adenosine A2 receptors is important for the cardioprotective effect of AMP 579. The adenosine-regulating agent acadesine (5 mg/kg + 0.5 mg/kg/min i.v.) also failed to reduce infarct size. In conclusion, the novel adenosine A1/A2 receptor agonist AMP 579 produces marked cardioprotection whether administered before myocardial ischemia or reperfusion. Cardioprotection is not dependent on changes in afterload or myocardial oxygen demand and is a consequence of adenosine receptor stimulation. The pharmacological profile of AMP 579 in this model is consistent with its potential utility in the treatment of acute myocardial infarction.

We have compared two different methods of attenuating protein kinase C (PKC) activity in vascular smooth muscle. First, the effects of two purported PKC inhibitors, staurosporine (stauro) and H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride], were examined on contractility of isolated, intact canine femoral artery. In arterial rings stauro was equipotent in relaxing contractions induced by phenylephrine (PE), phorbol-12,13-dibutyrate (PDBu) and KCl (IC50, 0.31 +/- 0.19; 0.35 +/- 0.2; and 0.34 +/- 0.16 microM). H-7, in comparison, was markedly less potent than stauro (IC50, 0.67 +/- 0.2, 2.33 +/- 0.24; and 6.5 +/- 5.5 microM for PE, PDBu and KCl, respectively). Pretreatment of tissues with 1 microM stauro suppressed tension development almost completely when PE and PDBu were the contractile agonists, and partially in K(+)-depolarized rings. H-7, in contrast, had no inhibitory effect on agonist-induced contraction. Neither basal nor K(+)-stimulated calcium influx was affected by 10 microM stauro. Second, prolonged exposure of canine carotid arterial rings to PDBu (1-100 nM for 24 hr), a means of depleting PKC from the tissue, caused dose-dependent attenuation of agonist-induced contractions. Preincubation with 100 nM PDBu caused complete inhibition of tension induced by norepinephrine (NE) and serotonin and partial inhibition of PDBu- and KCl-induced contractions. Lowering the concentration of PDBu during preincubation to 30, 10 or 1 nM reduced markedly the inhibitory effects. The inactive phorbolester 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) had no effect on agonist-induced contractions. PKC activity was determined in rings contracted isometrically with PDBu or NE after prolonged exposure to vehicle, 4 alpha-PDD or PDBu.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the role of protein kinase C (PKC) in the control of vessel tone in vivo in genetic hypertension, the vascular effects of phorbol-12,13-dibutyrate (PDBu), a PKC activator, was measured in the autoperfused hindlimb of reserpinized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). PDBu infusion (1-3000 ng/kg/min) into the hindlimb elevated perfusion pressure in a dose-related manner. Vasoconstriction response characteristics (latency, T1/2 to peak effect, decay of effect) of PDBu were significantly longer (2- to 10-fold) than that produced by membrane receptor agonists; phenylephrine, SKF 89748, a lipophilic alpha-1 agonist, angiotensin II and 5-hydroxytryptamine. The tonic vasoconstriction induced by PDBu was not antagonized by prazosin, rauwolscine, cyproheptadine, [Sar1lle8]-angiotensin II but was inhibited reversibly by microbial PKC-inhibitors, K252a and staurosporine at concentrations (1.56-2.8 micrograms/kg/min) which did not block vasoconstriction by phenylephrine or 5-hydroxytryptamine. The EC50 for PDBu was identical in SHR and WKY. However, the maximal response to PDBu was significantly greater in SHR compared to WKY. Staurosporine lowered mean arterial pressure equally in SHR (20%) and WKY (17%) but reduced perfusion pressure in SHR (13%) to a slightly greater extent than in WKY (5%). Unlike the in vivo response, aortic rings removed from SHR were more sensitive to cumulative doses of PDBu than rings from WKY. It is concluded that PDBu-vasoconstriction in vivo is mediated largely through activation of PKC.(ABSTRACT TRUNCATED AT 250 WORDS)

The vasodilator activity of adenosine has been associated with selective stimulation of A2 receptors. In the present study, the vasorelaxant (VR) activity of an A1-selective agonist, CPA (cyclopentyladenosine), was examined in isolated porcine coronary arterial rings precontracted with prostaglandin F2 alpha and compared to the A2-selective agonist DPMA (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl] adenosine). DPMA, approximately 13-fold selective for the rat brain A2 receptor, relaxed isolated coronary arterial rings with an EC50 of 0.59 +/- 0.19 microM (n = 23) whereas CPA, 2200-fold selective for the rat brain A1 receptor, was approximately 5-fold less potent with an EC50 of 3.18 +/- 0.6 microM (n = 11). At low concentrations (10-300 nM) CPA caused vasoconstriction, indicative of the A1-selective nature of this agonist. CGS 15943 (100 nM), a nonselective adenosine antagonist, attenuated the VR activity of DPMA and CPA, causing a 9- and 12-fold rightward shift of the dose-response curves, respectively, whereas 8-cyclopentyl-1,3-dipropylxanthine (20 nM), a highly A1-selective blocker, had no such effect. Both adenosine antagonists abolished the vasoconstrictor response of CPA at low concentrations. The contributions of the cyclic GMP pathway to adenosine-induced VR was assessed using an inhibitor of endothelium-dependent relaxing factor (L-nitroarginine). L-nitroarginine had no effect on the EC50 for CPA-induced VR and, marginally, but not significantly, attenuated DPMA effects. Moreover, no elevation in cyclic GMP levels could be observed in tissues stimulated with CPA or DPMA.(ABSTRACT TRUNCATED AT 250 WORDS)

We have examined the interaction of zaprinast with mediators of guanylate cyclase on the relaxation of aortic smooth muscle. Zaprinast, a selective inhibitor of the low Km-cyclic GMP (cGMP) phosphodiesterase [low Km cGMP phosphodiesterase (PDE)], was equally effective in relaxing phenylephrine-contracted aortas from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) with an intact endothelium [EC50 = 7.6 (3.5-16.6) microM vs. 9.3 (4.1-21.3) microM, respectively]. In contrast, the vasorelaxant activity of zaprinast in intact and denuded phenylephrine-contracted guinea pig aortas, as well as denuded (SHR and WKY) aortas was minimal. Sodium nitroprusside and atriopeptin II were significantly (P less than .05) more potent as vasorelaxants in denuded SHR aortas when compared with denuded aortas from WKY. Pretreatment with zaprinast potentiated the vasorelaxant potency of sodium nitroprusside in both SHR and WKY aortas whereas atriopeptin II responses were potentiated only in WKY aortas. In studies with the low Km cGMP PDE, isolated via DEAE column chromatography, the apparent Km for cGMP and potency of zaprinast were approximately 2-fold greater (P less than .05) in WKY when compared with the same PDE isozyme isolated from SHR aortic preparations. However, the Vmax (picomoles per milligram per minute) for cGMP hydrolysis was greater in SHR than in WKY. In conclusion, these data show that, although there are no apparent differences in the influence of spontaneously released endothelium-derived relaxing factor from SHR and WKY aortas, reactivity differences to other agents known to stimulate guanylate cyclase activity exist between SHR and WKY denuded aortas.(ABSTRACT TRUNCATED AT 250 WORDS)

A one-dimensional code for the numerical simulation of negative branch unstable resonators with an intracavity aperture that are applied to high-gain, short-pulse XeCl lasers is described. The model predicts near- and far-field performance of the output laser beams. The intracavity aperture size is shown as an important parameter for control of the output beam energy and divergence. A comparison with experimental measurements is presented.

Near-diffraction-limited laser beams of high energy have been achieved with a long-pulse (110-ns) XeCl laser fitted with a super-Gaussian unstable cavity of magnification M = 2.7. It has been found that when the super-Gaussian output coupler is replaced with a hard-edge aluminized mirror of radius equal to the super-Gaussian mirror spot size, the output laser energy is reduced by 10%, whereas the beam divergence increases more than 50%.

Confocal and non-confocal negative branch unstable resonators with an intracavity spatial filter have been applied to a high-gain short-pulse UV preionized XeCl laser. The near- and far-field radiation characteristics have been investigated in both configurations. Laser beams of larger brightness have been obtained with non-confocal schemes. A maximum beam brightness of 1.3×1014 Wcm-2Sr-1 has been achieved.

A positive and a negative branch confocal unstable resonator with magnification |M| = 10 and with an intracavity spatial filter have been applied to a high-gain short-pulse u.v. pre-ionized XeCl laser. The performance of both resonators has been investigated and compared.

A stimulated Brillouin scattering mirror has been used to 'temporally tune' from nanoseconds to subnanoseconds the width of laser pulses generated by a free running XeCl oscillator, equipped with a super-Gaussian reflectivity unstable resonator. Pulse shortening techniques by stimulated Brillouin scattering (SBS) and by truncated SBS have been investigated. A maximum pulse shortening of about fifty has been achieved by truncated SBS.

The adhesion of pathogenic bacteria to the host surface is an essential step in the development of numerous infections, including dental caries. Attachment of Streptococcus mutans, the main etiological agent of human dental caries, to the tooth surface may be mediated by glucan synthesized by glucosyltransferase (GTF) and by cell surface proteins, such as P1, which bind to salivary receptors. Fimbriae on the surfaces of many microorganisms are known to function in bacterial adhesion. Previous studies in this laboratory have initially characterized the fibrillar surface of S. mutans. The purpose of this investigation was the comparison of the antigenic properties of fimbria preparations of S. mutans isolates from five caries-resistant (CR) and six caries-susceptible (CS) subjects. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of S. mutans fimbrial preparations revealed five major protein bands at 200, 175, 157, 86, and 66 kDa in preparations from CR and CS subjects. Immunoblot analysis indicated the presence of the same major bands recognized by anti-S. mutans fimbria antisera. Furthermore, the 175- and 157-kDa bands were recognized by antibodies to P1 and GTF, respectively. Immunoblot analysis with antisera to the fimbria preparation, to P1, or to GTF indicated that the levels of fimbria-reactive components and P1 and GTF antigens were higher in S. mutans fimbria preparations from CS subjects than in those from CR individuals. For example, four of six fimbria preparations from CS patients had demonstrable P1, and all had GTF. In contrast, only two of five CR fimbrial preparations exhibited P1 and GTF. Enzyme-linked immunosorbent assay demonstrated similar results for levels of GTF antigen in the fimbrial preparations from CR and CS subjects. The results suggest that differences between the compositions of S. mutans fimbriae in CR and CS individuals may play an important role in the virulence of this microorganism in dental caries.

The tricarboxylate carrier from eel liver mitochondria was purified by chromatography on hydroxyapatite and Matrix Gel Blue B and reconstituted into liposomes by removal of the detergent with Amberlite. Optimal transport activity was obtained by using a phospholipid concentration of 11.5 mg/ml, a Triton X-114/phospholipid ratio of 0.9, and ten passages through the same Amberlite column. The activity of the carrier was influenced by the phospholipid composition of the liposomes, being increased by cardiolipin and phosphatidylethanolamine and decreased by phosphatidylinositol. The reconstituted tricarboxylate carrier catalyzed a first-order reaction of citrate/citrate or citrate/malate exchange. The maximum transport rate of external [14C]citrate was 9.0 mmol/min per g of tricarboxylate carrier protein at 25°C and this value was virtually independent of the type of substrate present in the external or internal space of the liposomes. The half-saturation constant (Km) was 62 μMfor citrate and 541 μMfor malate. The activation energy of the citrate/citrate exchange reaction was 74 kJ/mol from 5 to 19°C and 31 kJ/mol from 19 to 35°C. The rate of the exchange had an external pH optimum of 8.

Thyroid function was evaluated in patients affected by Fisher-Evans syndrome (FES) and compared to that of patients affected only by autoimmune hemolytic anemia (AIHA) and to that of patients affected only by idiopathic thrombocytopenic purpura (ITP). The study population consisted of 20 patients with FES, 44 with AIHA and 20 with ITP. All patients were examined for thyroid function abnormalities and thyroid autoantibodies. Abnormal thyroid function test results were observed in 40, 25 and 10% of the patients, respectively. The prevalence of antithyroid antibodies (ATA) in FES was 25%; this is higher than the sum of the prevalences of ATA in patients affected only by AIHA (11.4%) or only by ITP (none). Subclinical primary hypothyroidism and hyperthyroxinemia with or without hypertriiodothyroninemia, with TSH serum levels below normal, were present in 20% and 10% of patients affected by FES, respectively. Of the former, 75% were positive for ATA. These results: i) confirm the high prevalence of abnormal thyroid test results in patients affected by AIHA, ITP and FES; ii) demonstrate the higher prevalence of autoimmune hypothyroidism in FES; iii) lead to the possibility of including FES as one of the multiple autoimmune syndromes.

Substance P (SP) receptors were described by the specific binding of [3H]SP to several neuronal and glial cell lines. The neuronal cell lines N18 and NG108-15 were found to contain few if any SP receptors (less than 5 fmol/mg of protein). The glial cell line LRM55 contained large numbers (Bmax = 707 fmol/mg of protein) of a single class of SP binding sites (Kd = 276 pM). [3H]SP binding could be inhibited by a number of c-terminal SP fragments and the tachykinins physalaemin, eledoisin and kassinin. The binding kinetics and pharmacology of these receptors are similar to those the authors have previously described in the brain. Activation of SP receptors was shown to inhibit cyclic AMP-dependent, beta adrenergic-stimulated taurine release from LRM55 glial cells. SP inhibition must occur by mechanisms affecting taurine release after adenylate cyclase activation, inasmuch as SP has no significant effect on beta adrenergic-stimulated increases or basal levels of intracellular cyclic AMP.

We tested the performance of a XeCl laser with unstable resonators using as an output coupler a phase unifying (PU) mirror, a super-Gaussian mirror, and a hard-edge mirror. The quantitative impact of the output coupler design on the energy extraction efficiency, near-field profile, far-field energy distribution, and spatial coherence time evolution has been investigated. Laser beams of larger brightness have been obtained with the PU unstable cavity. A faster growth of the laser beam spatial coherence has been observed with the PU cavity by time-resolved, far-field measurements.

An XeCl laser beam has been used to investigate stimulated Raman scattering in H2 and in various H2-foreign gas mixtures. Helium, neon, argon, and nitrogen have been tested as foreign gases. In all the investigated mixtures with 50% of H2, the energy conversion efficiency to the first Stokes (353 nm) was more than 70% higher than that obtained in H2 at the same total pressure (40 bar) and pump energy (60 mJ). The dependence of the energy conversion efficiency on pump beam divergence has also been investigated.

The unsaturated losses a, and the saturation intensityIs, were measured in an uv-preionized KrCl laser for optimized He and Ne based laser gas mixtures. The measurements were made as a function of the specific power loading and of the total pressure of the laser mixtures. Higher values for a andIs were found for the Ne-based laser mixture than for the He-based mixture. At 45 kV charging voltage and at 355 kPa of total pressure we measured a=0.053 cm-1 andIs=9.4MW/cm2 for the Ne based mixture, and a=0.035 cm-1 andIs=5.1MW/cm2 for the He based mixture.

Intensity-induced variations in the energy transmittivity and temporal shape of pulses emerging from a 200-µm-diameter core silica fibre have been investigated with a single-pulse XeCl laser. By coupling an XeCl laser pulse of 3mJ with a temporal width of 20 ns into a 30-m-long all-silica fibre, a total laser pulse of 1 mJ and 3 ns duration has been extracted at the fibre end. A pulse shortening larger than 80% has been observed. It is shown that the shape variations in the transmitted laser pulses are mainly due to stimulated Raman scattering processes. Substantial shape variations have been observed even at energy conversion efficiencies to the Stokes radiation of lower than 10%. The drop in energy transmittivity at higher fluences seems mainly due to two-photon absorption processes.

The performance of a high-gain, short-pulse XeCl amplifier fitted with a phase-conjugate (PC) cavity by stimulated Brillouin scattering and injected by a laser pulse provided by a XeCl oscillator without intracavity dispersive elements is investigated. A train of up to four pulses with pulse shortening was obtained from the PC cavity. The divergence of the PC cavity output beam was close to the diffraction limit and its spectral intensity distribution was equal to that provided by the free-running XeCl oscillator.

The performance of a long pulse XeCl laser, fitted with a negative branch unstable cavity using a phase-unifying (PU) mirror as output coupler, has been investigated. Laser beams with a divergence close to the diffraction limited value and with a relatively uniform intensity profile have been extracted by using an unstable cavity with magnification factor M = 2. It is shown that PU-unstable cavities are quite peculiar tools with respect to hard-edge unstable cavities, mainly for active media having a large cross section and requiring low magnification factors. Indeed, the beam divergence is increased by about 50% by replacing the phase-unifying mirror with a hard-edge aluminized mirror.