Blazar spectral variability as explained by a twisted inhomogeneous jet.

Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.

Comparison of MEG and EEG on the basis of somatic evoked responses elicited by stimulation of the snout in the juvenile swine.

OBJECTIVE: Some basic characteristics of magnetoencephalographic (MEG) and electroencephalographic (EEG) signals were studied by comparing somatic evoked fields (SEFs) and potentials (SEPs) elicited by electrical stimulations of different areas of the snout in piglets. METHODS: SEFs were measured with and without an intact skull, whereas SEPs were measured on the skull and cortex (Electrocorticograms - ECoG) and within the cortex of the same animal. RESULTS: The SEFs above the skull and dura were very similar to each other in temporal waveform and spatial topography, indicating small effects of the skull. They both revealed very similar somatotopic projections of the snout. The SEPs on the skull and cortex were, in contrast, clearly different in their amplitudes as well as temporal and spatial morphologies, indicating significant effects of the skull. However, an early component of the SEP on the skull revealed a somatotopic representation of the snout, indicating that EEG can be also useful for inferring cortical projection areas. Discrepancies in their maps were due to predominance of the potentials produced by currents in the gyral cortex. The projection sites inferred from SEFs were quite accurate in comparison to those inferred from ECoGs and intracortical SEPs. CONCLUSION: The similarities and differences clearly point out the complementary nature of MEG and EEG.

Experimental analysis of distortion of magnetoencephalography signals by the skull.

OBJECTIVES: Magnetoencephalography (MEG) signals are, on theoretical grounds, thought to be relatively undistorted by the skull in contrast to electroencephalographic (EEG) signals. This assumption was experimentally tested in an animal preparation with a brain similar to the human brain in many respects. METHODS: Possible skull effects on MEG were evaluated directly using an in vivo porcine preparation, by measuring the somatic evoked magnetic field (SEF) above the skull with and without the skull under, otherwise, the same condition. RESULTS: The SEF was virtually undistorted by the skull with no obvious visible change in its waveform and amplitude under these two conditions. However, there was some small, but significant attenuation when the skull was removed, the distortion being greater for deeper sources. CONCLUSION: Our results are consistent with a theoretical expectation that the skull should be virtually 'transparent' to the magnetic fields for shallow sources, but less so for fields generated by deeper sources.

A placebo-controlled flow cytometric study of the effect of low-dose prednisolone treatment on sperm-bound antibody levels.

In this placebo-controlled study the effect of short term, low-dose prednisolone treatment on sperm-bound antibody levels was investigated using an objective flow cytometric (FCM) measurement. Twenty infertile men, positive for antisperm antibodies by the mixed antiglobulin reaction (MAR) test, were treated with either 20 mg/day prednisolone (n = 10) or placebo (n = 10) for 3 weeks. The two groups were similar with respect to sperm count, motility and antibody levels. The proportion of spermatozoa positive for IgG and IgA antibodies and the antibody load, expressed as the number of IgG and IgA antibody molecules bound per spermatozoa were measured by FCM. The study showed that, overall, the antibody levels measured before and after treatment with low-dose prednisolone or with placebo were not statistically different. However, in the prednisolone group a marked decrease in the proportion of spermatozoa positive for IgG and IgA antibodies was observed in two of the patients. An examination of the FCM data of these two patients revealed that, in their ejaculates, only the spermatozoa with low to moderate amounts of sperm-bound antibodies had responded to prednisolone treatment, while spermatozoa with high levels of sperm antibodies had remained resistant to prednisolone. These results point to the existence of an as-yet-undefined subset of prednisolone-responsive, antibody--positive spermatozoa.

Low-dose prednisolone does not improve the outcome of in-vitro fertilization in male immunological infertility.

Early reports of male immunological infertility suggested a decline in antisperm antibody concentrations in some patients after even short-term (10 day) therapy with low-dose prednisolone. In the present study, 53 men with positive results in spermatozoal mixed antiglobulin reaction (MAR) and serum tray agglutination tests (TAT), were randomized to receive either 20 mg of prednisolone or placebo daily for 2 weeks prior to in-vitro fertilization (IVF) treatment. The antibody levels were also monitored by flow cytometry (FCM). There were no significant differences between these groups as regards fertilization rates (35% with prednisolone; 39% with placebo) and pregnancy rates (29%; 32%). No significant changes occurred in either MAR or FCM results in relation to therapy. Patients with fertilization rates of < 10% had significantly higher immunoglobulin G (IgG) MAR values compared with those with better fertilization, whereas there was no relationship between IgA levels and fertilization results. As regards FCM, the results were similar, but without statistical significance. In conclusion, IVF is a good course of action in severe male immune infertility, but low-dose prednisolone therapy does not lower the sperm-bound antibody numbers and does not improve the IVF outcome.

Treatment of severe male immunological infertility by intracytoplasmic sperm injection.

A total of 29 infertile couples (group A) with male antisperm antibodies detected by the mixed antiglobulin reaction (MAR) and partly by flow cytometry (n = 21) were treated using an intracytoplasmic sperm injection (ICSI) technique to assist fertilization. In all, 22 of them had shown a poor fertilization rate (6%) in previous in-vitro fertilization (IVF) treatments. The fertilization and cleavage rates in ICSI, 79 and 89% respectively, were similar to those in a MAR-negative group (group B; n = 20) injected because of male infertility (68 and 93% respectively). A third group (group C; n = 37) with male immune infertility was treated by conventional IVF. All these couples had at least one oocyte fertilized, but the overall fertilization rate (44%) in group C was significantly poorer (P < 0.001) than that in the two ICSI groups. However, the embryo quality was lower in group A compared with that in the other groups. A total of 13 pregnancies resulted in group A (46%), of which five ended in miscarriage. None of the six pregnancies (30%) in group B aborted during the first trimester. These results reveal, for the first time, that ICSI offers a good chance of fertilization for couples with male immunological infertility. However, post-fertilization events may compromise these results because of factors not yet clearly understood.

Intra-uterine insemination versus cyclic, low-dose prednisolone in couples with male antisperm antibodies.

A total of 46 couples with male immunological infertility entered the trial at the infertility clinic of the Family Federation of Finland. The men all showed a positive mixed antiglobulin reaction to immunoglobulin G in their semen; 31 men were also tested for sperm-bound IgA immunoglobulins by flow cytometry. Serum antisperm antibodies were checked in a tray agglutination test. The women showed normal reproductive endocrinology and at least one patent Fallopian tube. The couples were randomized to undergo either up to three intra-uterine inseminations (IUI), or timed intercourse with cyclic, low-dose (20 mg) prednisolone therapy of the men. Cross-over was carried out if no pregnancy occurred in the first stage. Timing of ovulation was based on urinary luteinizing hormone assay and transvaginal ultrasonographic measurements. In all, 40 couples either completed the study or the female partner conceived. IUI was significantly better (P = 0.04) with nine pregnancies than timed intercourse with prednisolone (one pregnancy). There were no significant associations between antibody levels, sperm count or motility versus the incidence of pregnancy. In male immunological infertility, well-timed IUI is an effective treatment method: results are obtained rapidly and steroidal side-effects can be avoided.

Comparison of flow cytometric measurement of seminal antisperm antibodies with the mixed antiglobulin reaction and the serum tray agglutination test.

OBJECTIVE: To compare the mixed antiglobulin reaction (MAR) and the serum tray agglutination test (TAT) with the flow cytometric (FCM) measurement of sperm antibodies. To evaluate by FCM the correlation in sperm antibody parameters between paired semen ejaculates obtained 2 to 4 weeks apart and the effect of washing on sperm antibody levels. SETTING: University-based infertility clinic. PATIENTS: The TAT and FCM were done on 81 patients with a positive immunoglobulin (Ig)G-MAR test. The correlation of sperm antibody parameters between paired semen samples was done in 16 men. A few samples were used to study the effect of washing on sperm antibody parameters. MAIN OUTCOME MEASURES: The proportion of spermatozoa positive for IgG and IgA antibodies as well as the number of antibody molecules per spermatozoa measured by FCM. RESULTS: In general, the degree of MAR positivity but not that of the TAT correlated with the sperm antibody load. With reference to FCM the MAR test had an 1% false positive rate, whereas the serum TAT had a 25% false negative rate. Correlation between FCM measurements of paired semen samples was good. Washing the spermatozoa once removed the loosely bound antibodies; further washes were not useful. CONCLUSION: Flow cytometry is a reliable technique that correlates with the MAR test. In patients with a strongly positive MAR, FCM is useful to identify patients with a low sperm antibody load. It is speculated that patients with a low sperm antibody load may respond better to IVF treatment.

Epididymal sperm aspiration and use of donor spermatozoa when necessary for in-vitro fertilization, and vasoepididymostomy: an acceptable combination in the treatment of obstructive azoospermia.

Infertility due to obstructive azoospermia in 24 men was treated with a combination of scrotal exploration, microsurgical sperm aspiration and vasoepididymostomy, at the same operation. In-vitro fertilization (IVF) and embryo transfer were performed using epididymal spermatozoa. Donor spermatozoa were used if no motile epididymal spermatozoa were obtained. With this combination, emotionally and economically acceptable pregnancy rates were achieved: 24% per aspiration, 43% per embryo transfer, and 25% per couple. One twin pregnancy resulting in the birth of two healthy female infants and one ongoing twin pregnancy were achieved with epididymal spermatozoa; four pregnancies (one twin, two singletons, one abortion) were achieved with donor spermatozoa.

In-vitro fertilization in the presence of antisperm antibodies detected by the mixed antiglobulin reaction (MAR) and the tray agglutination test (TAT).

Data from 33 couples suffering from male immune infertility, who underwent 47 in-vitro fertilization (IVF) cycles between January 1989 and August 1991, were retrospectively analysed. The serum of all the 33 male partners had elevated tray agglutination test (TAT) titres (> or = 1:16) and positive mixed antiglobulin reaction (IgG MAR) test results in their semen. There was a slight correlation between these tests in semen and serum. Fertilization rates were analysed in three sperm MAR subcategories. Only the strongly positive MAR group (values > or = 90%) revealed a significant reduction in fertilization rate compared to the other MAR groups. However, this was not observed with increasing serum TAT titres. Fertilization rates were decreased in asthenozoospermic (20.1%) compared to normozoospermic (34.0%) male partners. This occurred also with couples not affected by immunological factors, but when antisperm antibodies were present, the fertilization rates were significantly poorer irrespective of whether the sperm motility was normal or decreased. Once fertilization occurred, the pregnancy rate was not affected by the severity of immunological factors. In assisted reproduction the sperm preparation techniques may reduce the inhibiting effects of antibodies bound to the spermatozoa, and when there are several oocytes to be inseminated, the chance of fertilization rises.

Quality of life before and after liver transplantation: experiences with 7 patients with primary biliary cirrhosis in a 2-year follow-up.

Seven patients with end-stage primary biliary cirrhosis were evaluated both before and 1 and 2 years after liver transplantation using a clinical psychiatric interview and the self-rating questionaire SCL-90. Neuropsychological tests were done before and 1 year after operation. Preoperatively, all patients had a poor general condition and overall quality of life. Flattening of emotions and reactions, regression, disturbances of verbal memory and cognitive function, and dependence on close relatives were observed. One year after transplantation, 6 patients had a much better overall quality of life, and with five patients it improved still further during the 2nd year, but only 2 patients felt that their life situation had fully stabilised. However, nearly all of them experienced phases of moderate or even severe depression or anxiety during those 2 years. On neuropsychological tests patients appeared to be near their normal level. The only patient who died during this follow-up (some months after transplantation) had in her life history a prominent sense of insecurity and mistrust. It seems to take more than a year for the majority of patients to give up the regressive mode of experience and turn to adult interests in life again, as well as psychologically experience the new liver as part of oneself.

Vertical and horizontal coding of space in the monkey dorsolateral prefrontal cortex.

Single cell activity in the dorsolateral prefrontal cortex was recorded in a monkey performing a delayed alternation (DA) task in 3 directions, to the left, to the right, and upwards. Among the 127 units studied in all three directions, 18 neurons were spatially selective in one direction (to the left, to the right or upwards), 37 neurons in two directions and 8 neurons in each 3 directions during the performance of the DA task. Of the 9 neurons that were spatially selective upwards, 8 had a specific pattern of activity during the delay period and one during the response period. When several spatial directions are studied in a DA task, as in this work, it becomes evident that the prefrontal cortex contains a large number of spatially selective neurons. The results of this study suggest that there is a spatial memory map in the prefrontal cortex which is needed not only when a DA task is performed to the left and to the right but also in the upward direction.

EGF- and TGF-alpha-like peptides in human fetal gut.

The presence of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) immunoreactivities in fetal human tissues was studied immunohistochemically at different gestational ages. EGF and TGF alpha immunoreactivities were detected from the 20th gestational wk. EGF immunoreactivity was limited to the small intestine, but TGF alpha immunoreactive cells were present in the colon also. According to radioreceptor assay, the intestine of a 19-wk-old human fetus contained 10 times more EGF receptor-binding substance than EGF, as measured by immunofluorometric assay. Chromatographic analysis suggests that TGF alpha-like peptides account for at least part of this activity, as so argues in favor of the presence of TGF alpha- and EGF-like peptides in the human fetal gut. Whether they are synthesized in the fetus is yet unknown.