Precise and Accurate Measurements of Strong-Field Photoionization and a Transferable Laser Intensity Calibration Standard.

Ionization of atoms and molecules in strong laser fields is a fundamental process in many fields of research, especially in the emerging field of attosecond science. So far, demonstrably accurate data have only been acquired for atomic hydrogen (H), a species that is accessible to few investigators. Here, we present measurements of the ionization yield for argon, krypton, and xenon with percent-level accuracy, calibrated using H, in a laser regime widely used in attosecond science. We derive a transferable calibration standard for laser peak intensity, accurate to 1.3%, that is based on a simple reference curve. In addition, our measurements provide a much needed benchmark for testing models of ionization in noble-gas atoms, such as the widely employed single-active electron approximation.

Transverse electron momentum distribution in tunneling and over the barrier ionization by laser pulses with varying ellipticity.

We study transverse electron momentum distribution in strong field atomic ionization driven by laser pulses with varying ellipticity. We show, both experimentally and theoretically, that the transverse electron momentum distribution in the tunneling and over the barrier ionization regimes evolves in a qualitatively different way when the ellipticity parameter describing polarization state of the driving laser pulse increases.

The interaction of excited atoms and few-cycle laser pulses.

This work describes the first observations of the ionisation of neon in a metastable atomic state utilising a strong-field, few-cycle light pulse. We compare the observations to theoretical predictions based on the Ammosov-Delone-Krainov (ADK) theory and a solution to the time-dependent Schrödinger equation (TDSE). The TDSE provides better agreement with the experimental data than the ADK theory. We optically pump the target atomic species and measure the ionisation rate as the a function of different steady-state populations in the fine structure of the target state which shows significant ionisation rate dependence on populations of spin-polarised states. The physical mechanism for this effect is unknown.

Impairments of mental rotation in Parkinson's disease.

It is controversial whether parkinsonian patients are impaired on visuospatial tasks. In the present study, patients and normal control subjects judged whether pairs of wire-frame figures in different orientations were the same or different. The orientation difference between the figures was either in the picture plane (around the z-axis, or two-dimensional) or in depth (around the y-axis, or three-dimensional). Reaction times and error rates were measured. For the two-dimensional task, there were no significant differences in errors between the two groups, though Parkinsonian subjects were significantly slower to respond than the control group. In the three-dimensional task, patients had a different pattern of reaction times from the controls and made significantly more errors, which were systematic at large angular differences. The results suggest a visuospatial deficit in Parkinson's disease, which reflects problems in some aspect of the perception of extra-personal space.

ELISA measurement of IgG subclass production in culture supernatants using monoclonal antibodies.

Specific and sensitive ELISA to quantitate the human IgG subclasses in cell culture supernatants are described. These assays detect a minimum of 5 ng/ml IgG1, 90 ng/ml IgG2, 8 ng/ml IgG3 and 8 ng/ml IgG4 and can generally measure IgG subclasses in lymphocyte cultures containing a minimum of 200 ng/ml of total IgG. The isotype specificity of these ELISA is demonstrated and each individual ELISA shown to react with a number of paraproteins of the relevant subclass independently of their light chain type or their (major Caucasian) allotype. These assays have been used to determine the IgG subclass response of normal human lymphocytes to pokeweed mitogen in vitro.

Analysis of the IgG subclass production from rheumatoid arthritis synovial cell cultures.

In man there are four subclasses of IgG which differ from each other with respect to their biological properties. Some evidence suggests that the production of IgG3 is unusually high in rheumatoid synovia. In this study secretion of IgG subclasses by synovial lymphocytes in vitro was measured using sensitive subclass-specific ELISAs. It was found that, in both synovial membrane- and synovial fluid-derived cell cultures, the general pattern of IgG subclass secretion was IgG1 greater than 2 greater than 3 greater than or equal to 4, and that, in most cultures, IgG3 was a minor subclass accounting, on average, for only 8% of the total IgG. This was similar to the percentage of this subclass in normal human serum and in culture supernatants from the patients' peripheral blood lymphocytes.

Levels of CD5+ B cells are not increased in probands or relatives in a family study of primary Sjögren's syndrome.

Levels of CD5+ B lymphocytes were assayed in a large family study of Primary Sjögren's syndrome. There was no significant difference in CD5 expression by index cases or their relatives when compared to controls. No association between CD5 expression, serological abnormalities or HLA haplotype was found and, furthermore, no evidence of linkage with HLA was observed. There was, however, variation in the expression of CD5+ B cells between the families. Levels in spouses were lower and reached statistical significance. The role for genetic and environmental factors influencing CD5 expression is discussed. Any genetic influence does not appear to involve the HLA region or genes in linkage disequilibrium.

The CD5+ B cell: a B cell lineage with a central role in autoimmune disease?

It is apparent that B cells are heterogeneous with respect to, for example, the antigens they express on their surface, and the stimuli to which they can respond. It is still unclear to what extent these differences relate to the stage of differentiation (eg. virgin B cells differing from activated B cells or memory cells), or whether distinct developmental lineages might exist. It has been proposed by some authors that, in the mouse, B cells expressing the ly-1 antigen constitute a separate lineage. In man also, a minor population of B cells expresses detectable levels of the CD5 antigen, but far less information is available about these cells. Interest in the CD5+ and ly-1+ B cell subpopulations has been further stimulated by the suggestion that these cells might play a special role in autoimmune disease. Although, in mouse, ly-1+ B cells differ in several respects from ly-1- B cells, the main evidence that they form a separate lineage derives from experiments in which ly-1+ B cells could not be reconstituted with adult bone marrow. It should be borne in mind that the situation is quite different in humans where, following bone marrow transplantation, CD5+ B cells are rapidly restored. Moreover, in the irradiated mice, at least in some of the experiments ly-1+ B cells were in fact reconstituted by adult bone marrow. Furthermore, at least in humans, expression of CD5 can sometimes be induced. There is, as yet, no good evidence that human CD5+ B cells form a distinct lineage, and it is possible that CD5 expression depends upon microenvironmental influences acting on the B cell during its differentiation. Several interesting properties have been attributed to ly-1+ B cells, including the ability to provide help to other B cells, and the secretion of autocrine factors. However there is also evidence that these features are not exclusive to B cells expressing ly-1. It has also been suggested that ly-1+ B cells might be long-lived. It is not yet known whether some of the properties of ly-1+ B cells might be a direct result of their expressing this antigen; this may become more clear when the function of CD5 is elucidated. The suggestion that the repertoire of ly-1+ B cells might be biased towards the expression of certain V genes is very interesting. Many of the hybridomas from neonatal mice produce antibodies which are multi-specific, and therefore well suited to form a first line of defence against potential pathogens.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of interferon-alpha therapy on immune parameters in immune thrombocytopenic purpura.

Interferon-alpha (IFN alpha) has been shown to increase platelet numbers in patients with immune thrombocytopenic purpura (ITP), but the basis for this effect is not known. In this study changes in immune function were monitored following administration of IFN alpha to seven patients whose ITP had proved refractory to conventional therapy. Patients' peripheral blood mononuclear cells were cultured with phytohaemagglutinin and culture supernatants assayed for cytokine production. Production of the Th1 cytokines IL-2 and IFN-gamma was low in patients compared to healthy controls, and amounts of these tended to increase after IFN alpha therapy. In two patients high levels of IL-10 were detectable in culture, and these were reduced after IFN alpha. In patients who had high serum concentrations of IL-4 or IL-10, these were also decreased following therapy. Natural killer cell activity, which was low in the patients prior to therapy, was increased following administration of IFN alpha. In those patients with detectable platelet-associated autoantibody to gpIIb/IIIa, the amounts were reduced after treatment. Two patients had an unusually high percentage of T cells expressing the gamma delta T cell receptor, which decreased after therapy. The findings are consistent with an increase in Th 1 activity and a decrease in autoantibody production following IFN alpha therapy, which may be related to the beneficial effects of this cytokine.

B cell differentiation and lymphocyte surface phenotype in late onset hypogammaglobulinaemia.

Lymphocyte function and cell surface phenotype were examined in fifteen patients with late onset hypogammaglobulinaemia. The percentage of surface immunoglobulin-positive B cells in fourteen of the fifteen patients was in the normal range. Patients' B cells expressed MHC class II antigens at normal levels. For one patient, there was relatively high sIgD and low sIgM expression on B cells; the rest of the patients did not differ from controls in surface immunoglobulin density. The proportion of B cells positive for CD5 in patients was comparable to normal controls, and considerably less than in cord blood. However, the pattern of immunoglobulin isotype secretion in vitro by patients' B cells closely paralleled responses of cord blood B cells. Spontaneous secretion of IgM and IgG by patients' B cells was very low. Following polyclonal activation in the presence of autologous T cells, cells from thirteen patients secreted IgM within the normal range in response to at least one activator. The response of patients' purified B cells to IL-2 and gamma-IFN was variable. For four of six tested, B cells cultured with IL-2 and gamma-IFN together with polyclonal activators secreted normal levels of IgM. B cells from the other two patients secreted little or no IgM in response to these cytokines. For fourteen patients, IgG secretion following polyclonal activation remained low both when B cells were cultured with T cells or with a combination of IL-2 and gamma-IFN. IgG subclass imbalance was seen in one patient, whose cells secreted an unusually high proportion of IgG3, and undetectable IgG2 and IgG4; this pattern was consistent whether T cell help was provided by autologous or allogeneic T cells. Similarly purified B cells from this patient showed deficient IgG2 and IgG4 production in response to IL-2 and gamma-IFN.

Modification of visual orientation illusions by drugs which influence dopamine and GABA neurones: differential effects on simultaneous and successive illusions.

The effects of haloperidol, nomifensine and lorazepam on the visual tilt illusion were studied in normal volunteers. Haloperidol and nomifensine produced no significant changes in the illusion, although in previous work they had been found to reduce and enhance, respectively, a closely related illusion, the tilt aftereffect. By contrast, lorazepam produced a dose-related increment in the size of the tilt illusion, but had no effect on the tilt aftereffect. The results are discussed in relation to proposed mechanisms which may underlie the two kinds of illusion. The differential effects of individual drugs on the two illusions may reflect their differing actions on two processes: lateral inhibition and adaptation in visual channels.

Spatial frequency and duration effects on the tilt illusion and orientation acuity.

The simultaneous tilt illusion and the decline in variance of orientation judgements (Andrews effect) were measured as a function of exposure duration and spatial frequency. The illusions increased in size (to more than 10 deg) with exposure times up to 30-100 msec, then declined. The Andrews effect was largest at the shortest exposure and asymptoted (for a particular spatial frequency) at about the same exposure duration at which the illusion peaked. The exposure duration at which the illusion peaked was longer if the subject was more dark adapted. When the subjects' rating of the perceptual clarity of the gratings was plotted against the size of the Andrews effect (for the same duration and spatial frequency), the data fell on a single function, whether the spatial frequency was 2, 5, or 10 c/deg. The functional significance of these effects is discussed.

Contrast, spatial frequency and test duration effects on the tilt aftereffect: implications for underlying mechanisms.

The tilt aftereffect (TAE) was measured with a forced-choice technique for gratings of different spatial frequencies, contrasts and adapting and test durations. At short test durations, a 2 c/deg grating gave a larger TAE than a 10 c/deg, while at long test durations the opposite occurred. Low contrast gratings tended to give smaller TAEs at short test durations, and larger TAEs at long durations, than high contrast. A longer adapting duration tended to produce larger TAEs at low contrast for any test duration, but larger TAEs at high contrast only at long test durations. We suggest that the spatial frequency effect reflects differential excitation by the test stimuli of transient and sustained channels, and that the contrast effects reflect both a non-linearity in the relationship between excitation and inhibition, and the adapting effects of the test grating.

Adaptation to peripheral flicker: relationship to contrast detection thresholds.

The time to disappearance of flicker of a temporally modulated uniform 1 degree field, steadily viewed with the temporal retina at an eccentricity of 12 degrees, was measured as a function of temporal frequency and depth of modulation (contrast). As found by others, for a fixed contrast, adaptation time declined as temporal frequency increased. To check whether this effect was genuinely temporal frequency-dependent, or reflected the amount above threshold of the adapting contrast, measurements were also made at contrasts which were multiples of the contrast threshold or matched across temporal frequencies. The results suggest that both temporal frequency and amount of adapting contrast above threshold are important in determining the speed of adaptation.

Object-name selection in psychiatric patients before and after neuroleptic therapy.

An object-name selection test was administered to 16 newly admitted schizo phrenic, non-schizophrenic psychotic and non-psychotic patients on admission when they were drug-free, and again 4-6 weeks later, following treatment with neuroleptics. Sixteen healthy, drug-free age-matched and sex-matched controls were similarly tested on two occasions 4-6 weeks apart. Schizophrenic and non-schizophrenic psychotic subjects made significantly more association-type errors than non-psychotic subjects and controls. A signifi cant reduction in association-type errors which was observed in both psychotic patient groups on the second testing occasion may be attributed to medication. The data suggest that overinclusive thinking, as measured by the object-name selection test, is a feature of both schizophrenic and non-schizophrenic psychosis. It is concluded that tests of overinclusion are therefore of limited diagnostic utility although they may be of value in monitoring response to treatment.

The perception of visual ambiguous figures in schizophrenia and Parkinson's disease.

The frequency of reversal and dominance of aspect of three versions of an ambiguous Schröder staircase were studied in patients with a diagnosis of either schizophrenia or Parkinson's Disease (PD), and in a mixed group of psychiatric patients before and after prolonged neuroleptic therapy. It was found that schizophrenics perceived the staircases from above for significantly less time, and had a (nonsignificant) tendency to have more reversals than controls. PD patients saw the staircases from above for significantly more time, and also had (nonsignificantly) more reversals than controls. In the psychiatric patients, long term neuroleptic therapy had no significant effect on either reversal rate or dominance of aspect. When the contrast and the luminance of the stimulus were manipulated, normal subjects reported significantly less reversals and significantly increased dominance of the superior aspect when the contrast of the stimulus was reduced. Changing the luminance had no significant effect. The implications of these results for visual abnormalities in schizophrenia and Parkinson's Disease are discussed.

Analysis of pigeon intestinal mucin allergens using a novel dot blot assay.

Many glycoproteins contain multiple glycosylation sites that can present multi-valent epitopes for antigenic recognition. Release of the oligosaccharides results in loss of avidity of antibody binding, which has been overcome by reforming clustered ligands, usually by reductive amination of free reducing oligosaccharides to poly-amine groups. We have adapted this approach to hydrazinolytic release of O-linked chains of mucin glycoproteins and 'one-pot' microscale coupling to poly-L-lysine (PLL). The conjugated PLL adheres to nitrocellulose membranes through washing procedures required for antibody or lectin overlay and detection. We show evidence for the applicability of this technique using lectin and antibody reactivity to the oligosaccharides of pigeon intestinal mucins, which have been implicated in the allergic disease pigeon fanciers' lung.

Use of a programmable calculator for rapid, low-cost processing of echocardiographic records.

A comparative study was performed to determine the accuracy of a programmable calculator with supplemental digitizer in echocardiographic analysis. Twenty separate measurements were collected per heart beat from five different dogs, taking five heart beats from each dog. The measurements were made by an echocardiographic technician (ET), echocomputer (EC), and by a programmable calculator (HP). In a triple comparison (ET-HP, ET-EC, HP-EC) there were no significant differences in the values obtained, suggesting that the programmable calculator can provide a highly accurate and rapid means of processing echocardiographic measurements, thereby providing the advantages of the echocomputer without the cost of such a device.