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The spatial shaping of light beams is the process of redistributing the irradiance of a light beam. A correct beam shaping is essential to optimize a large number of laser-material processing applications and laser-material interaction studies. In this paper, after introducing the basic equations of the classical beam integration method to reshape and homogenize laser beams, we detail the design elements, the experimental performance and the main parameters of a novel transfocal homogenizer that is able to homogenize and reshape any light beam. Then we discuss the reliability of existing international standard parameters to evaluate the ”goodness” of nearly flat-top shaped laser beams. Finally, we present examples of successful applications of this new homogenizer technology to ultraviolet irradiation experiments.

Low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex results in lasting changes of excitatory neurotransmission. We investigated the effects of suprathreshold 1 Hz rTMS on brain derived neurotrophic factor (BDNF) plasma levels in 10 healthy subjects and effects of either 1 Hz or 20 Hz rTMS in four amyotrophic lateral sclerosis (ALS) patients. BDNF levels were progressively decreased by 1 Hz rTMS in healthy subjects; there was no effect of 1 Hz rTMS on BDNF plasma levels in ALS patients, an effect probably due to the loss of motor cortex pyramidal cells. High frequency rTMS determined a transitory decrease in BDNF plasma levels. Cumulatively these findings suggest that rTMS might influence the BDNF production by interfering with neuronal activity.

Subanaesthetic doses of the N‐methyl‐d‐aspartate (NMDA) antagonist ketamine have been shown to determine a dual modulating effect on glutamatergic transmission in experimental animals, blocking NMDA receptor activity and enhancing non‐NMDA transmission through an increase in the release of endogenous glutamate. Little is known about the effects of ketamine on the excitability of the human central nervous system. The effects of subanaesthetic, graded incremental doses of ketamine (0.01, 0.02 and 0.04 mg kg−1min−1, i.v.) on the excitability of cortical networks of the human motor cortex were examined with a range of transcranial magnetic and electric stimulation protocols in seven normal subjects. Administration of ketamine at increasing doses produced a progressive reduction in the mean resting motor threshold (RMT) (F(3, 18) = 22.33, P< 0.001) and active motor threshold (AMT) (F(3, 18) = 12.17, P< 0.001). Before ketamine administration, mean RMT ±s.d. was 49 ± 3.3 % of maximum stimulator output and at the highest infusion level it was 42.6 ± 2.6 % (P< 0.001). Before ketamine administration, AMT ±s.d. was 38 ± 3.3 % of maximum stimulator output and at the highest infusion level it was 33 ± 4.4 % (P< 0.002). Ketamine also led to an increase in the amplitude of EMG responses evoked by magnetic stimulation at rest; this increase was a function of ketamine dosage (F(3, 18) = 5.29, P= 0.009). In contrast to responses evoked by magnetic stimulation, responses evoked by electric stimulation were not modified by ketamine. The differential effect of ketamine on responses evoked by magnetic and electric stimulation demonstrates that subanaesthetic doses of ketamine enhance the recruitment of excitatory cortical networks in motor cortex. Transcranial magnetic stimulation produces a high‐frequency repetitive discharge of pyramidal neurones and for this reason probably depends mostly on short‐lasting AMPA transmission. An increase in this transmission might facilitate the repetitive discharge of pyramidal cells after transcranial magnetic stimulation which, in turn, results in larger motor responses and lower thresholds. We suggest that the enhancement of human motor cortex excitability to transcranial magnetic stimulation is the effect of an increase in glutamatergic transmission at non‐NMDA receptors similar to that described in experimental studies.

We test the hypothesis that interaction between the human basal ganglia and cerebral cortex involves activity in multiple functional circuits characterized by their frequency of oscillation, phase characteristics, dopamine dependency and topography. To this end we took recordings from macroelectrodes (MEs) inserted into the subthalamic nucleus (STN) in eight awake patients following functional neurosurgery for Parkinson’s disease. An EEG was also recorded, as were the signals from MEs in the globus pallidus interna (GPi) in two of the cases. Coherence between EEG and ME potentials was apparent in three major frequency bands, 2–10 Hz, 10–30 Hz and 70–85 Hz. These rhythmic activities differed in their cortical topography, although coherence was always strongest over the midline. Coherence between EEG and ME potentials in the 70–85 Hz band was only recorded in patients treated with levodopa. Cortical activity phase led that in the basal ganglia in those oscillatory activities with frequencies <30 Hz. In contrast, STN and GPi phase led cortex in the 70–85 Hz band. The temporal differences in the way in which cortical activity led or lagged behind that in STN/GPi were similar, around 20 ms, regardless of the overall direction of information flow and frequency band. We conclude that the basal ganglia may receive multiple cortical inputs at frequencies <30 Hz and, in the presence of dopaminergic activity, produce a high frequency drive back to the cerebral cortex, in particular the supplementary motor area (SMA).

There is a wealth of data suggesting that behavioural events are reflected in the basal ganglia through phasic changes in the discharge of individual neurones. Here we investigate whether events are also reflected in momentary changes in the degree of synchronization between neuronal elements. We simultaneously recorded local potentials (LPs) from the subthalamic nucleus (STN) and/or ipsilateral globus pallidus interna (GPi) or scalp EEG during voluntary movements of a hand‐held joystick in six awake patients following neurosurgery for Parkinson’s disease. Without medication the power within the STN and the coherence between the STN and the GPi were dominated by activity with a frequency of <30 Hz. This coupling was attenuated by movement. In the presence of exogenous dopaminergic stimulation, power within the STN and coherence between the STN and the GPi was dominated by activity at 70–85 Hz, which increased with movement. The movement‐related changes in coherence between the STN and EEG showed a similar pattern of pharmacological dependence, as seen subcortically. Movement‐related frequency‐specific changes in synchronization occur in the basal ganglia and extend to involve subcortico‐cortical motor loops. The dynamic organization of activities in the frequency domain might provide a means for temporal co‐ordination within and across different processing streams in the basal ganglia. This organization is critically dependent on the level of dopaminergic activity.

1Descending corticospinal volleys evoked after transcranial magnetic or electrical stimulation of the leg area of the motor cortex were recorded from an electrode in the spinal epidural space of six conscious patients who had electrodes implanted for treatment of chronic pain, and from one anaesthetised patient undergoing surgery for a spinal tumour.2At threshold, the shortest‐latency volley (L1 volley) was evoked by stimulation with an anode 2 cm lateral to the vertex. Anodal stimulation at the vertex also elicited a volley at this latency in two patients, but in the other patients the first volley evoked appeared 1—1.3 ms later (L2 volley), at the same latency as the initial volley evoked by magnetic stimulation. High‐intensity stimulation of any type could evoke both the L1 and L2 waves as well as later ones (L3, L4, etc.) that had a periodicity of about 1.5 ms.3Voluntary contraction increased the amplitude of the L2 and later volleys, but had no effect on the L1 volley.4Intracortical inhibition between pairs of magnetic stimuli resulted in clear suppression of the L4 and later waves. The L2 and L3 waves were unaffected.5In the anaesthetised patient the L1 volley occurred 1.7 ms later than the volley produced by transmastoid stimulation of the corticospinal pathways in the brainstem.6The L1 volley is likely to be a D wave produced by the direct activation of pyramidal axons in the subcortical white matter; the L2 and later volleys are likely to be I waves produced by the trans‐synaptic activation of corticospinal neurones. The implication is that electrical stimulation with an anode at the vertex is more likely to evoke I waves preferentially than stimulation over the hand area. A more secure way to ensure D wave activation of corticospinal fibres from the leg area is to place the anode 2 cm lateral to the vertex.

The shadow monochromatic backlighting (SMB) scheme, a modification of the well-known soft X-ray monochromatic backlighting scheme, is proposed. It is based on a spherical crystal as the dispersive element and extends the traditional scheme by allowing one to work with a wide range of Bragg angles and thus in a wide spectral range. The advantages of the new scheme are demonstrated experimentally and supported numerically by ray-tracing simulations. In the experiments, the X-ray backlighter source is a laser-produced plasma, created by the interaction of an ultrashort pulse, Ti:Sapphire laser (120 fs, 3–5 mJ, 1016 W/cm2 on target) or a short wavelength XeCl laser (10 ns, 1–2 J, 1013 W/cm2 on target) with various solid targets (Dy, Ni + Cr, BaF2). In both experiments, the X-ray sources are well localized spatially (~20 μm) and are spectrally tunable in a relatively wide wavelength range (λ = 8–15 Å). High quality monochromatic (δλ/λ ~ 10−5–10−3) images with high spatial resolution (up to ~4 μm) over a large field of view (a few square millimeters) were obtained. Utilization of spherically bent crystals to obtain high-resolution, large field, monochromatic images in a wide range of Bragg angles (35° &lt; Θ &lt; 90°) is demonstrated for the first time.

A microfiltration (MF) membrane bioreactor was developed for an efficient production of a recombinant thermostable α-glucosidase (rSsGA) from Sulfolobus solfataricus MT-4. The aim of the membrane bioreactor was to improve the control of the concentration of key components in the growth of genetic engineered microorganisms, such as Escherichia coli. The influence of medium composition was studied in relation to cell growth and α-glucosidase production. The addition of components such as yeast extract and tryptone resulted in a higher enzyme production. High cell density cultivation of E. coli BL21(DE3) on semidefined medium, exploiting a microfiltration bioreactor, was studied in order to optimize rSsGA production. In addition to medium composition, the inducer employed (either isopropyl β-D-thiogalactopyranoside or lactose), the induction duration, and the cultivation mode influenced both the final biomass and the enzyme yield. The MF bioreactor allowed a cell concentration of 50 g/L dry weight and a corresponding α-glucosidase production of 11,500 U/L. The improvement obtained in the enzyme production combining genetic engineering and the microfiltration strategy was estimated to be 2,000-fold the wild-type strain. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 70: 670–676, 2000.

The early scalp somatosensory evoked potentials (SEPs) to median and tibial nerve stimulation were recorded at rest and during voluntary movement of the stimulated hand and foot, respectively. Both tibial and median nerve SEP distributions at rest could be explained by four-dipole models, in which one dipole was activated at the same latency as the subcortical far field and the three remaining dipolar sources were located in the perirolandic region contralateral to the stimulated side. Voluntary movement reduced all cortical dipoles in strength, while the subcortical one remained unchanged, suggesting that the effect of movement occurs above the cervicomedullary junction. In animals, cutaneous inputs are suppressed during movement and we therefore interpreted the depression of activity in the primary somatosensory cortex induced by movement as due to selective “gating” of cutaneous afferents. Because the reduction in strength of the cortical dipoles was generally lower during passive than active movement, both centrifugal and centripetal mechanisms probably contribute to the phenomenon of “gating.” © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1510–1519, 1999

Abstract: A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below threshold for obtaining electromyographical (EMG) responses in active hand muscles can suppress responses evoked in the same muscles at rest by a suprathreshold magnetic test stimulus given 1–5 ms later. In order to define the mechanism of this inhibitory effect, we recorded descending volleys produced by single and paired magnetic transcranial stimulation of motor cortex through high cervical, epidural electrodes implanted for pain relief in two conscious subjects with no abnormality of the central nervous system. The conditioning stimulus evoked no recognisable descending activity in the spinal cord, whilst the test stimulus evoked 3–4 waves of activity (I-waves). Conditioning stimulation suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus. Inhibition of the descending spinal volleys was most pronounced at ISI 1 ms and had disappeared by ISI 5 ms. It was evident for all components following the I1-wave, while the I1-wave itself was not inhibited at all. We conclude that a small conditioning magnetic stimulus can suppress the excitability of human motor cortex, probably by activating local cortico-cortical inhibitory circuits.

1The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of three conscious human subjects. These volleys were termed direct (D) and indirect (I) waves according to their latency.2We measured the size and number of volleys elicited by magnetic stimulation at various intensities with subjects at rest and during 20 or 100 % maximum contraction of the contralateral first dorsal interosseous muscle (FDI). Surface EMG activity was also recorded.3Electrical stimulation evoked a D‐wave volley. Magnetic stimulation at intensities up to about 15 % of stimulator output above threshold evoked only I‐waves. At higher intensities, a D‐wave could be seen in two of the three subjects.4At all intensities tested, voluntary contraction increased the number and size of the I‐waves, particularly during maximum contractions. However, there was only a small effect on the threshold for evoking descending activity. Voluntary contraction produced large changes in the size of EMG responses recorded from FDI.5Because the recorded epidural activity is destined for muscles other than the FDI, it is impossible to say to what extent increased activity contributes to voluntary facilitation of EMG responses. Indeed, our results suggest that the main factor responsible for enhancing EMG responses in the transition from rest to activity is likely to be increased excitability of spinal motoneurones, rather than increases in the corticospinal volley. The latter may be more important in producing EMG facilitation at different levels of voluntary contraction.

We studied tibial nerve somatosensory evoked potentials (SEPs) in 22 patients with progressive clinical signs of sensory and motor involvemcnt of the lower limbs. Magnetic resonance imaging (MRI) in 21 patients revealed lesions of the thoracolumbar cord in 18 and of the cauda equina in the remaining three. SEP recordings enabled us to clearly differentiate the response generated by the dorsal horns of the lumbosacral cord from the activity generated in the cauda equina dorsal roots. Neurophysiologic findings strongly correlated with the lesion site demonstrated by the MRI (cauda equina, lumbosacral cord, or thoracic cord immediately above the lumbar enlargement). The N24 cord potential was absent with a normal cauda equina response in 10 of 12 patients with MRI signs of lumbosacral cord lesions. Clinical examination often failed to localize the spinal cord as the lesion site, suggesting pure peripheral involvement in six of the 12 patients with MRI signs of lumbosacral cord lesions.

We studied somatosensory potentials (SEPs) evoked by stimulation of radial, median, and ulnar nerves in 11 patients with MRI evidence of cervical spondylosis. All patients presented with progressive spastic paraparesis that was either isolated or associated with lower motor neuron signs in the upper limbs, with preserved joint, touch, pain, and temperature sensations in the four limbs. In all patients, scalp SEPs reflecting tho activity of the dorsal column system up to the parietal cortex were normal while segmental cervical cord dysfunction was manifested by an abnormal spinal N13 potential in 95 of radial, 90 of median, and 54 of ulnar nerve SEPs. These subclinical abnormalities of the spinal N13 SEP probably result from reduced blood supply due to compression of the anterior spinal artery in patients with cervical spondylotic myelopathy.

Two immunotoxins were prepared using monoclonal antibodies (mAb) directed towards two distinct epitopes of the gp185 HER-2 extracellular domain, and the type I ribosome inactivating protein (RIP) plant toxin saporin 6. Cell protein synthesis inhibition assay reveals that the immunotoxins display a potent and specific cytotoxicity that is characterized by a slow rate, since the time required to inhibit incorporation of radiolabeled leucine completely ranges from 36 h to 60 h depending on the target cell line and the immunotoxin. Because this feature may hamper the immunotherapeutic use of these conjugates we analysed this further by studying the early phases of internalization of immunotoxins by immunoelectron microscopy. The results of this study have demonstrated that the distribution pattern of the immunotoxins and of the unconjugated mAb over the cell surface overlaps. Similarly the mAb and immunotoxins are internalized into the cell by two different pathways: via clathrin-coated pits or via smaller uncoated pits and vesicles. A higher degree of internalization is achieved when the two immunotoxins are used in combination. Unlike the slow kinetics of cell intoxication the process of immunotoxin endocytosis is characterized by a rapid rate of internalization (above 40% at 5 min in the SK-BR-3 cell line). Although these findings provide no clue to explain the mechanisms of the slow rate of cytotoxicity of the two immunotoxins their rapid internalization indicates that these reagents can be exploited in immunotherapeutic approches to gp185 HER-2-expressing malignancies.

We studied 6 patients with adrenomyeloneuropathy (AMN) showing mild signs of central nervous system involvement. All patients underwent brain and spinal magnetic resonance imaging (MRI) and somatosensory (SEP) and motor (MEP) evoked potential study. Whereas SEPs and MEPs were abnormal in all patients, only 1 patient showed brain MRI abnormalities; spinal MRI showed hypotrophy without focal abnormalities in 4 of 6 patients. Median nerve SEPs, which were recorded with noncephalic reference montage, revealed delayed or absent scalp P14 far-field potential in all patients and abnormal spinal N13 in 2. Moreover, tibial nerve SEPs revealed abnormalities of the subcortical P30 response in all 4 patients in whom scalp-to-ear recording was employed. These findings strongly suggest that in the early stages of disease neurological dysfunction is localized in the spinal cord, where it is difficult to assess using MRI. However, SEPs and MEPs, which show a typical pattern of abnormality in these patients, could be useful in disclosing signs of long tract involvement and in monitoring treatment. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1249–1257, 1997

A target of Fe-40 at.-%Al intermetallic alloy with ordered B2 structure was subjected to laser melting processing by a high energy XeCI excimer pulse (wavelength 308 nm, pulse length 120 ns) in low pressure air. The total thickness of the laser affected zone (LAZ) was ~ 150 nm. The modified surface showed an increased roughness and the presence of cracking. The X-ray photoelectron spectroscopy (XPS) measurements revealed a strong enrichment in the aluminium concentration within the LAZ, as well as relatively high contents of oxygen and nitrogen incorporated in the near surface region. Both angle resolved and depth profile XPS analyses suggested that oxides, nitrides, and oxynitrides were mainly present within the LAZ as discrete particles in the metallic matrix rather than as surface layers. Significant surface hardness reduction was observed after laser treatment, which has been interpreted to be due to partial suppression of B2 lattice ordering. Electrochemical measurements in borate buffer solution showed a reduced anodic activity of the laser processed aluminide in the potential range between the open circuit potential and 0.1 V saturated calomel electrode, whereas at higher anodic overpotentials no substantial differences in behaviourwere observed with respect to the untreated Fe–40Al surfaces. Such consequences of the excimer laser treatment may be explained by mechanisms involving aluminium enrichment and nitride formation processes inside the LAZ.

Transcranial stimulation was performed in 4 patients with Duchenne muscular dystrophy and 4 control subjects. The patients' central motor conduction time was normal. The threshold for evoking electromyographic responses using electrical anodal stimulation was the same in both groups, but the threshold for stimulation with a circular magnetic coil at the vertex was higher in the patients. This is compatible with reduced cortical excitability that may be related to the deficiency of brain synaptic dystrophin. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:662–664, 1998.

Two patients with spinal infarction and one patient with the previously unreported complication of spinal transient ischaemic attack associated with cocaine misuse are reported. Spinal MRI documented an infarction in the territory of the anterior spinal artery in the first two patients and was completely normal in the patient with a transient ischaemic attack. Motor evoked potentials were abnormal in all three patients.

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Patients with traumatic lesion of the anterior cruciate ligament often experience knee instability, which, recent studies suggest, is probably due to reduced knee proprioception. We studied knee proprioception and somatosensory evoked potentials (SEPs) after stimulation of the common peroneal nerve at the knee above the articular branches subserving the sensory innervation of the anterior cruciate ligament, in 19 patients with traumatic anterior cruciate ligament lesion. Ten patients showed decreased position sense of the knee, and of these, seven presented loss of cortical P27 potential while preserving lemniscal P20 and spinal N14 responses to common peroneal nerve stimulation on the side of the anterior cruciate ligament lesion. All our patients had normal SEPs to stimulation of the posterior tibial nerve at both the ankle and the knee. We suggest that in patients showing SEP abnormalities, the dysfunction of the central somatosensory conduction is located above the medial lemniscus and is limited to common peroneal nerve somatosensory pathways. Therefore, it is likely that in the seven patients showing SEP abnormalities, the loss of the knee mechanoreceptors was followed by remodelling of the CNS above the medial lemniscus. In five patients with P27 absence after common peroneal nerve stimulation, we also recorded SEPs after stimulation of the peroneal nerve at the ankle and obtained a normal cortical positive response; moreover, in our healthy subjects, cortical responses were significantly higher in amplitude after peroneal nerve than after common peroneal nerve stimulation. These findings strongly suggest that proprioceptive afferent inputs from the knee are more effective than distal afferent inputs in generating the greater part of the common peroneal nerve cortical SEPs. Since common peroneal nerve stimulation probably allows selective recording of the responses produced by the activation of the cortical representation of the knee, minor lesions with a reduction in the number of knee mechanoceptors could result in SEP changes after common peroneal nerve stimulation.