Glass transition of nanometric polymer films probed by picosecond ultrasonics.

The possibility to measure the glass transition temperature in poly(methyl methacrylate) (PMMA) films by picosecond ultrasonics with thicknesses ranging from 458 nm to 32 nm is demonstrated. A shift of the longitudinal acoustic eigenmodes towards lower frequencies with temperature is observed accompanied by a change in the temperature-frequency slopes at the glass transition temperature. The contributions to the frequency shift from changes in film thickness and sound velocity are discussed and the latter is extracted below the glass transition temperature. Finally, the advantages and disadvantages of the current approach in a comparison to other methods based on acoustic measurements in the GHz regime are reviewed.

Direct observation of electron propagation and dielectric screening on the atomic length scale.

The propagation and transport of electrons in crystals is a fundamental process pertaining to the functioning of most electronic devices. Microscopic theories describe this phenomenon as being based on the motion of Bloch wave packets. These wave packets are superpositions of individual Bloch states with the group velocity determined by the dispersion of the electronic band structure near the central wavevector in momentum space. This concept has been verified experimentally in artificial superlattices by the observation of Bloch oscillations--periodic oscillations of electrons in real and momentum space. Here we present a direct observation of electron wave packet motion in a real-space and real-time experiment, on length and time scales shorter than the Bloch oscillation amplitude and period. We show that attosecond metrology (1 as = 10(-18) seconds) now enables quantitative insight into weakly disturbed electron wave packet propagation on the atomic length scale without being hampered by scattering effects, which inevitably occur over macroscopic propagation length scales. We use sub-femtosecond (less than 10(-15) seconds) extreme-ultraviolet light pulses to launch photoelectron wave packets inside a tungsten crystal that is covered by magnesium films of varied, well-defined thicknesses of a few ångströms. Probing the moment of arrival of the wave packets at the surface with attosecond precision reveals free-electron-like, ballistic propagation behaviour inside the magnesium adlayer--constituting the semi-classical limit of Bloch wave packet motion. Real-time access to electron transport through atomic layers and interfaces promises unprecedented insight into phenomena that may enable the scaling of electronic and photonic circuits to atomic dimensions. In addition, this experiment allows us to determine the penetration depth of electrical fields at optical frequencies at solid interfaces on the atomic scale.

Challenging the sleep homeostat: sleep in depression is not premature aging.

OBJECTIVES: The close relationship between major depression and sleep disturbances led to the hypothesis of a deficiency in homeostatic sleep pressure in depression (S-deficiency hypothesis). Many observed changes of sleep characteristics in depression are also present in healthy aging, leading to the premise that sleep in depression resembles premature aging. In this study, we aimed at quantifying the homeostatic sleep-wake regulation in young women with major depression and healthy young and older controls under high sleep pressure conditions. METHODS: After an 8-h baseline night nine depressed women, eight healthy young, and eight healthy older women underwent a 40-h sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, were analyzed during the recovery night. RESULTS: Young depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation, particularly in frontal brain regions. In contrast, healthy older women exhibited not only attenuated SWA values compared to the other two groups, but also an absence of the frontal SWA predominance. CONCLUSIONS: Homeostatic sleep regulation and sleep architecture in young depressed women are not equal to premature aging. Moreover, our findings demonstrate that young moderately depressed women exhibit no deficiency in the sleep homeostatic process S as predicted by the S-deficiency hypothesis, but, rather, live on an elevated level of homeostatic sleep pressure.

A flexible apparatus for attosecond photoelectron spectroscopy of solids and surfaces.

We describe an apparatus for attosecond photoelectron spectroscopy of solids and surfaces, which combines the generation of isolated attosecond extreme-ultraviolet (XUV) laser pulses by high harmonic generation in gases with time-resolved photoelectron detection and surface science techniques in an ultrahigh vacuum environment. This versatile setup provides isolated attosecond pulses with photon energies of up to 140 eV and few-cycle near infrared pulses for studying ultrafast electron dynamics in a large variety of surfaces and interfaces. The samples can be prepared and characterized on an atomic scale in a dedicated flexible surface science end station. The extensive possibilities offered by this apparatus are demonstrated by applying attosecond XUV pulses with a central photon energy of ∼125 eV in an attosecond streaking experiment of a xenon multilayer grown on a Re(0001) substrate.

Versatile apparatus for attosecond metrology and spectroscopy.

We present the AS-2 Attosecond Beamline at the Joint Laboratory for Attosecond Physics of the Max-Planck-Institut für Quantenoptik and Ludwig-Maximilians-Universität for time resolved pump/probe experiments with attosecond resolution. High harmonic generation and subsequent filtering of the generated extreme ultraviolet (XUV) continuum by means of metal filters and XUV multilayer mirrors serve for the generation of isolated attosecond laser pulses. After high harmonic generation, the remaining fundamental laser pulse is spatially separated from the attosecond XUV pulse, to what is to our knowledge for the first time, by means of a perforated mirror in a Mach-Zehnder interferometer. Active stabilization of this interferometer guarantees the necessary temporal resolution for tracking attosecond dynamics in real time. As a proof-of-principle, photoelectron streaking experiments are performed and experimental techniques for their realization are summarized. Finally we highlight the potential of the presented beamline system for future experiments in comparison with previously demonstrated attosecond beamlines.

Delay in photoemission.

Photoemission from atoms is assumed to occur instantly in response to incident radiation and provides the basis for setting the zero of time in clocking atomic-scale electron motion. We used attosecond metrology to reveal a delay of 21 +/- 5 attoseconds in the emission of electrons liberated from the 2p orbitals of neon atoms with respect to those released from the 2s orbital by the same 100-electron volt light pulse. Small differences in the timing of photoemission from different quantum states provide a probe for modeling many-electron dynamics. Theoretical models refined with the help of attosecond timing metrology may provide insight into electron correlations and allow the setting of the zero of time in atomic-scale chronoscopy with a precision of a few attoseconds.

Single-cycle nonlinear optics.

Nonlinear optics plays a central role in the advancement of optical science and laser-based technologies. We report on the confinement of the nonlinear interaction of light with matter to a single wave cycle and demonstrate its utility for time-resolved and strong-field science. The electric field of 3.3-femtosecond, 0.72-micron laser pulses with a controlled and measured waveform ionizes atoms near the crests of the central wave cycle, with ionization being virtually switched off outside this interval. Isolated sub-100-attosecond pulses of extreme ultraviolet light (photon energy approximately 80 electron volts), containing approximately 0.5 nanojoule of energy, emerge from the interaction with a conversion efficiency of approximately 10(-6). These tools enable the study of the precision control of electron motion with light fields and electron-electron interactions with a resolution approaching the atomic unit of time ( approximately 24 attoseconds).

Characterization of polymorphisms in the toxin A and B genes of Clostridium difficile.

We have used six independent polymerase chain reactions (A1-A3 and B1-B3) for amplification of the entire sequence of the two toxin genes tcdA and tcdB of several Clostridium difficile strains. With this approach we have detected (1) restriction site polymorphisms which are distributed all over the genes, and (2) deletions that could be found only in tcdA. Characteristic differences between strains were mainly focused to the 5' third of tcdB (B1 fragment) and/or the 3' third of tcdA (A3 fragment). The possible use of our approach for typing of C. difficile toxin genes is discussed.

Identification of phosphatidate phosphohydrolase purified from rat liver membranes on SDS-polyacrylamide gel electrophoresis.

Phosphatidate phosphohydrolase (PAP; EC 3.1.3.4) insensitive to N-ethylmaleimide was partially purified from rat liver membranes by a combination of chromatographic methods, immunoabsorption and glycerol gradient centrifugation. The specific activity was increased more than 600-fold over that of the membrane extract. Enzyme antibodies precipitating more than 80% of PAP were obtained and used for the identification of PAP protein on SDS-polyacrylamide gels employing the immunodetection method of Muilerman et al. [(1982) Anal. Biochem. 120, 46-51]. By this approach PAP was localized as a 31 kDa polypeptide.

Brain abscess. A study of 45 consecutive cases.

Clinical features, findings of diagnostic studies, results of therapy, and prognostic factors were analyzed in 45 patients with brain abscesses. The number of patients diagnosed yearly has increased since CT scanning became available, but despite the enhanced sensitivity, the time from either onset of symptoms or hospital admission until initiation of therapy was not decreased and there was no dramatic effect upon morbidity or mortality in this series. Infections of paranasal sinuses, ears, lungs, and odontogenic foci were predisposing factors in approximately 70% of cases. Single abscesses, present in 75% of patients, were distributed equally in both hemispheres, with more than half in the frontal and parietal lobes. Common signs and symptoms included headache, fever, chills, seizures, nausea, vomiting, altered sensorium, nuchal rigidity, and localizing neurologic signs. Blood cultures were positive in 11%. Lumbar puncture rarely provided data from which a diagnosis could be established; CSF cultures were positive in only 7% of patients, and there was a 15% temporally associated incidence of brain herniation and death. Diagnostic information was most readily obtained using imaging techniques such as CT and 99mTc scanning, and arteriography was invasive and of no added value. CT scans are however, often initially negative in patients presenting with clinical signs of meningitis presumably following rupture of an abscess into the subarachnoid space, and the average time for changes to appear on CT scan is 9 days. It is, therefore, recommended that when the clinical assessment suggests the possibility of brain abscess the patient be treated empirically with antibiotics and that lumbar puncture be performed only after thoughtful assessment of the risk-to-benefit ratio for each patient. Causative organisms were isolated from more than 80% of abscesses despite prior antibiotic treatment; more than half grew a single pathogen, most commonly streptococci. Anaerobic and microaerophilic bacteria accounted for 62% of all isolates, and were the only organisms in 33% of patients. Computerized tomographic scans in 30 patients showed "ring-enhancing" lesions, nodular enhancement, or areas of low attenuation. Complete resolution of abscesses on CT scans rarely occurred during hospitalization and took as long as 5 months. Decrease in the size of abscesses on CT scan correlated well with clinical improvement and was seen within a week when abscesses were excised, but was often not obvious for 6 to 8 weeks if antibiotics were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)

IgE responses in human schistosomiasis. I. Quantitation of specific IgE by radioimmunoassay and correlation of results with skin test and basophil histamine release.

We have developed a non-competitive solid-phase radioimmunoassay (SPRIA) to quantitate human IgE antibodies to Schistosoma mansoni antigens that was capable of accurately measuring IgE antibodies in both high and low titer sera. Ninety sera from "early" or "chronic" schistosomiasis patients were studied. Both levels of parasite-specific IgE antibodies and the proportion of the total IgE response that was parasite-specific were significantly lower in "early infection" sera than in sera of patients with chronic infections. The SPRIA to adult worm antigen was compared with basophil histamine release and direct intradermal skin testing also performed with the adult antigen. Both tests showed significant correlations with the SPRIA in detecting specific anti-parasite antibody.

Modulation of the host response in human schistosomiasis. IV. Parasite antigen induces release of histamine that inhibits lymphocyte responsiveness in vitro.

Several mechanisms underlying the suppression of in vitro lymphocyte transformation responses to parasite antigens in human schistosomiasis have been previously described, but the role that immediate hypersensitivity reactions may have in regulating these lymphocyte transformation responses has been little explored. Using Hypaque-Ficoll-separated peripheral blood mononuclear cells (PBMC) from patients with schistosome infections, we found that histamine release could be demonstrated routinely in lymphocyte cultures challenged with adult worm, egg, or cercarial antigens. Release occurred within 1 hr of stimulation, and histamine persisted in the cultures for 6 days at levels of 10(-6) to 10(-7) M. That such concentrations were capable of suppressing LT responses in vitro was shown by the addition of exogenous histamine to modified PBMC culture systems from 10 normal individuals and eight patients with Schistosoma mansoni or Schistosoma mekongi infections. Responses to phytohemagglutinin, streptokinase-streptodornase, and tetanus were equivalently suppressed in both groups (50.8 +/- 6% in normals and 55.9 +/- 6.2% in patients), and the doses required for maximal suppression were similar. Passage of PBMC from infected patients over nylon wool, in addition to removing adherent suppressor cells, also markedly reduced the number of histamine-containing basophils (74 +/- 4.5% removed). The enhanced responsiveness to parasite antigen by PBMC depleted by nylon wool passage was abrogated by the addition of exogenous histamine to the cultures. These results indicate that in routine PBMC cultures 'nonspecific' lymphocyte suppression by histamine liberated from basophils in an antigen-specific fashion may help to account for the specific suppression of lymphocyte responses to parasite antigens so characteristic of patients with schistosome and other helminth infections.

Specificity of antibody and cellular immune responses in human schistosomiasis.

Thirty patients infected with Schistosoma mekongi, S. mansoni or S. japonicum had cell-mediated immune responses assessed by lymphocyte transformation in vitro (LT), immediate hypersensitivity responses determined by basophil histamine release in vitro (HR) and IgG antibody responses evaluated in an enzyme-linked immunosorbent assay (ELISA). Species specificity was evaluated with antigens obtained from adult worms or eggs of the three schistosome species. Though cross-reactivity was present in all tests, homologous antigens elicited responses significantly greater than those to heterologous antigens in all comparisons of parasite specific IgG and IgE antibody in these groups of patients. A similar generalization could be made for the lymphocyte responses to the same antigen preparations, but statistically significant differences were achieved only in certain comparisons.

Treatment of Schistosoma mekongi with praziquantel: a double-blind study.

Praziquantel is a newly developed drug effective in the treatment of schistosomiasis. In order to assess the efficacy and toxicity of praziquantel in the treatment of Schistosoma mekongi, 11 infected Laotian refugees, all belonging to a single extended family, were treated in a double-blind crossover trial with praziquantel and placebo. Initially, one group of five received praziquantel 60 mg/kg body weight in three divided doses orally while the remainder received an identically appearing placebo. Patients were evaluated clinically before, during and following therapy for 2 days. After 2.5 months the patients were re-evaluated and subjected to the opposite treatment, and final follow-up took place 5-7 months later. Three other patients were treated using an open protocol. All but one person was cured (91%). This patient failed to show a decrease in egg excretion 2.5 weeks after praziquantel therapy and was lost to follow-up thereafter. Side effects were common and consisted primarily of abdominal pain, malaise, and fever. These were generally mild and transient. No abnormal laboratory findings were associated with praziquantel therapy. At the final evaluation 6/6 patients with initial hepatomegaly showed a decrease in liver size.

Schistosoma mekongi infection in man: cellular immune responses and modulating mechanisms.

Cell-mediated immune responses (CMI), as assessed by lymphocyte proliferation in vitro, were evaluated in 11 Laotian patients harbouring asymptomatic chronic infections by Schistosoma mekongi, a schistosome closely related to S. japonicum. When the mononuclear cells of these patients were cultured in autologous plasma, lymphocyte responses to schistosome antigens were essentially nil, not differing from those of unexposed North American controls. Specific lymphocyte proliferation, however, was seen both after the removal of mononuclear cells that were nylon-wool-adherent and after substitution of the autologous serum in the culture with normal AB serum. Our data suggest that the CMI responses of humans with chronic S. mekongi infections are 'modulated' by adherent suppressor cells and serum-suppressive factors, and that modulation of CMI supports the stable host-parasite relationship in a similar fashion to that described for chronic human Schistosoma mansoni infection.

Changes in EEG, blood levels, mood scales and performance scores during long term treatment with diazepam, phenobarbital or placebo in patients.

1. The patient population consisting of fifteen patients was divided into three groups, namely: diazepam group, phenobarbital group and placebo group. After three weeks the medicated groups were switched to placebo for a week and the placebo group was given phenobarbital. 2. The parameters to be assessed once a week comprised frequency-analyzed EEG recordings, performance in two attention tests and subjectively estimated mood modalities. 3. The EEG analysis suggested that EEG patterns: a) were drug-dependent, with a differential distribution for each drug of the four frequency bands analyzed; b) showed no change during the three-week treatment period; c) changed on cessation of medication or on switch from placebo to active medication; d) were task-dependent and changed in a systematic way with the level of activation (stress, vigilance or relaxation). 4. The results would allow a better understanding of the clinical course, the choice of therapeutic measures and of the underlying mechanisms of action.