Thermionic microwave gun for terahertz and synchrotron light sources.

Conventional thermionic microwave and radio frequency (RF) guns can offer high average beam current, which is important for synchrotron light and terahertz (THz) radiation source facilities, as well as for industrial applications. For example, the Advanced Photon Source at Argonne National Laboratory is a national synchrotron-radiation light source research facility that utilizes thermionic RF guns. However, these existing thermionic guns are bulky, difficult to handle and install, easily detuned, very sensitive to thermal expansion, and due for a major upgrade and replacement. In this paper, we present the design of a new, more stable, and reliable gun with optimized electromagnetic performance, improved thermal engineering, and a more robust cathode mounting technique, which is a critical step to improve the performance of existing and future light sources, industrial accelerators, and electron beam-driven THz sources. We will also present a fabricated gun prototype and show results of high-power and beam tests.

Cortical map plasticity as a function of vagus nerve stimulation rate.

BACKGROUND: Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an external event can reorganize the sensory or motor cortex. A 30 Hz train of sixteen VNS pulses paired with a tone significantly increases the number of neurons in primary auditory cortex (A1) that respond to tones near the paired tone frequency. The effective range of VNS pulse rates for driving cortical map plasticity has not been defined. OBJECTIVE/HYPOTHESIS: This project investigated the effects of VNS rate on cortical plasticity. We expected that VNS pulse rate would affect the degree of plasticity caused by VNS-tone pairing. METHODS: Rats received sixteen pulses of VNS delivered at a low (7.5 Hz), moderate (30 Hz), or high (120 Hz) rate paired with 9 kHz tones 300 times per day over a 20 day period. RESULTS: More A1 neurons responded to the paired tone frequency in rats from the moderate rate VNS group compared to naïve controls. The response strength was also increased in these rats. In contrast, rats that received high or low rate VNS failed to exhibit a significant increase in the number of neurons tuned to sounds near 9 kHz. CONCLUSION: Our results demonstrate that the degree of cortical plasticity caused by VNS-tone pairing is an inverted-U function of VNS pulse rate. The apparent high temporal precision of VNS-tone pairing helps identify optimal VNS parameters to achieve the beneficial effects from restoration of sensory or motor function.

Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Children of preschool age often have episodes of virus-associated wheeze, and research assessing efficacy of corticosteroids for paediatric wheeze exacerbations is inconclusive. METHODS: This non-inferiority, randomised, double-blind, placebo-controlled trial was to compare the efficacy of placebo versus oral prednisolone in children aged 24-72 months presenting with virus-associated wheeze at the paediatric emergency department of Princess Margaret Hospital in Perth, WA, Australia. Eligible participants were randomly assigned (1:1) using a computer-generated random number program to receive placebo or prednisolone (1 mg/kg per day) for 3 days. The primary outcome was total length of stay in hospital until ready for discharge. Following an analysis to test the hypothesis that placebo is non-inferior to prednisolone, a post-hoc superiority analysis was done to test the hypothesis that prednisolone was superior to placebo. A non-inferiority margin of 10% was used to establish non-inferiority. Efficacy analyses were on a modified intention-to-treat basis, whereby patients were excluded from the final efficacy analysis if consent was withdrawn, two doses of study drug were vomited, or paperwork was lost. All participants were included in safety analyses. This study is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12612000394842. FINDINGS: Between June 11, 2012, and June 10, 2015, we screened 3727 patients for eligibility. 624 eligible patients were randomly assigned to treatment, and 605 patients were included in the modified intention-to-treat analysis (300 patients from the placebo group, 305 patients from the prednisolone group). The median length of stay until ready for discharge was longer in the placebo group (540 min [IQR 124-971]) than in the prednisolone group (370 min [121-709]); placebo was inferior to prednisolone. In the post-hoc superiority analysis of 605 patients, the unadjusted ratio of geometric mean for length of stay was 0·79 (95% CI 0·64-0·97; p=0·0227) for the prednisolone group relative to the placebo group. No serious adverse events were reported during the study or follow-up period. One child in the placebo group had a non-specific maculopapular rash, which resolved spontaneously. Two children (one from each group) were reported to be hyperactive during follow-up assessments. INTERPRETATION: Oral prednisolone had a clear benefit over placebo at reducing the length of stay in children presenting to a paediatric emergency department with virus-associated wheeze and was well tolerated. FUNDING: Western Australian Department of Health.

Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity.

BACKGROUND: Pairing sensory or motor events with vagus nerve stimulation (VNS) can reorganize sensory or motor cortex. Repeatedly pairing a tone with a brief period of VNS increases the proportion of primary auditory cortex (A1) responding to the frequency of the paired tone. However, the relationship between VNS intensity and cortical map plasticity is not known. OBJECTIVE/HYPOTHESIS: The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity. METHODS: The rats were exposed to a 9 kHz tone paired with VNS at intensities of 0.4, 0.8, 1.2, or 1.6 mA. RESULTS: In rats that received moderate (0.4-0.8 mA) intensity VNS, 75% more cortical neurons were tuned to frequencies near the paired tone frequency. A two-fold effective range is broader than expected based on previous VNS studies. Rats that received high (1.2-1.6 mA) intensity VNS had significantly fewer neurons tuned to the same frequency range compared to the moderate intensity group. CONCLUSION: This result is consistent with previous results documenting that VNS is memory enhancing as a non-monotonic relationship of VNS intensity.

A short-pulse X-ray beamline for spectroscopy and scattering.

Experimental facilities for picosecond X-ray spectroscopy and scattering based on RF deflection of stored electron beams face a series of optical design challenges. Beamlines designed around such a source enable time-resolved diffraction, spectroscopy and imaging studies in chemical, condensed matter and nanoscale materials science using few-picosecond-duration pulses possessing the stability, high repetition rate and spectral range of synchrotron light sources. The RF-deflected chirped electron beam produces a vertical fan of undulator radiation with a correlation between angle and time. The duration of the X-ray pulses delivered to experiments is selected by a vertical aperture. In addition to the radiation at the fundamental photon energy in the central cone, the undulator also emits the same photon energy in concentric rings around the central cone, which can potentially compromise the time resolution of experiments. A detailed analysis of this issue is presented for the proposed SPXSS beamline for the Advanced Photon Source. An optical design that minimizes the effects of off-axis radiation in lengthening the duration of pulses and provides variable X-ray pulse duration between 2.4 and 16 ps is presented.

Degraded auditory processing in a rat model of autism limits the speech representation in non-primary auditory cortex.

Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood. Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children. Prenatal VPA exposure in rats causes numerous neural and behavioral abnormalities that mimic autism. We predicted that VPA exposure may lead to auditory processing impairments which may contribute to the deficits in communication observed in individuals with autism. In this study, we document auditory cortex responses in rats prenatally exposed to VPA. We recorded local field potentials and multiunit responses to speech sounds in primary auditory cortex, anterior auditory field, ventral auditory field. and posterior auditory field in VPA exposed and control rats. Prenatal VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in secondary, but not primary auditory cortex. This result parallels findings in humans and suggests that secondary auditory fields may be more sensitive to environmental disturbances and may provide insight into possible mechanisms related to auditory deficits in individuals with autism.

Optical design of the Short Pulse Soft X-ray Spectroscopy beamline at the Advanced Photon Source.

The Short Pulse X-ray facility planned for the Advanced Photon Source (APS) upgrade will provide two sectors with photon beams having picosecond pulse duration. The Short Pulse Soft X-ray Spectroscopy (SPSXS) beamline will cover the 150-2000 eV energy range using an APS bending magnet. SPSXS is designed to take full advantage of this new timing capability in addition to providing circular polarized radiation. Since the correlation between time and electron momentum is in the vertical plane, the monochromator disperses in the horizontal plane. The beamline is designed to maximize flux and preserve the time resolution by minimizing the number of optical components. The optical design allows the pulse duration to be varied from 1.5 to 100 ps full width at half-maximum (FWHM) without affecting the energy resolution, and the resolution to be changed with minimal effect on the pulse duration. More than 10(9) photons s(-1) will reach the sample with a resolving power of 2000 and a pulse duration of ∼2 ps for photon energies between 150 and 1750 eV. The spot size expected at the sample position will vary with pulse duration and exit slit opening. At 900 eV and at a resolving power of 2000 the spot will be ∼10 µm × 10 µm with a pulse duration of 2.3 ps FWHM.

Optical design of the short pulse x-ray imaging and microscopy time-angle correlated diffraction beamline at the Advanced Photon Source.

The short pulse x-ray imaging and microscopy beamline is one of the two x-ray beamlines that will take full advantage of the short pulse x-ray source in the Advanced Photon Source (APS) upgrade. A horizontally diffracting double crystal monochromator which includes a sagittally focusing second crystal will collect most of the photons generated when the chirped electron beam traverses the undulator. A Kirkpatrick-Baez mirror system after the monochromator will deliver to the sample a beam which has an approximately linear correlation between time and vertical beam angle. The correlation at the sample position has a slope of 0.052 ps/µrad extending over an angular range of 800 µrad for a cavity deflection voltage of 2 MV. The expected time resolution of the whole system is 2.6 ps. The total flux expected at the sample position at 10 keV with a 0.9 eV energy resolution is 5.7 × 10(12) photons/s at a spot having horizontal and vertical full width at half maximum of 33 µm horizontal by 14 µm vertical. This new beamline will enable novel time-dispersed diffraction experiments on small samples using the full repetition rate of the APS.

Mitochondrial quality, dynamics and functional capacity in Parkinson's disease cybrid cell lines selected for Lewy body expression.

BACKGROUND: Lewy bodies (LB) are a neuropathological hallmark of Parkinson's disease (PD) and other synucleinopathies. The role their formation plays in disease pathogenesis is not well understood, in part because studies of LB have been limited to examination of post-mortem tissue. LB formation may be detrimental to neuronal survival or merely an adaptive response to other ongoing pathological processes. In a human cytoplasmic hybrid (cybrid) neural cell model that expresses mitochondrial DNA from PD patients, we observed spontaneous formation of intracellular protein aggregates ("cybrid LB" or CLB) that replicate morphological and biochemical properties of native, cortical LB. We studied mitochondrial morphology, bioenergetics and biogenesis signaling by creating stable sub-clones of three PD cybrid cell lines derived from cells expressing CLB. RESULTS: Cloning based on CLB expression had a differential effect on mitochondrial morphology, movement and oxygen utilization in each of three sub-cloned lines, but no long-term change in CLB expression. In one line (PD63(CLB)), mitochondrial function declined compared to the original PD cybrid line (PD63(Orig)) due to low levels of mtDNA in nucleoids. In another cell line (PD61(Orig)), the reverse was true, and cellular and mitochondrial function improved after sub-cloning for CLB expression (PD61(CLB)). In the third cell line (PD67(Orig)), there was no change in function after selection for CLB expression (PD67(CLB)). CONCLUSIONS: Expression of mitochondrial DNA derived from PD patients in cybrid cell lines induced the spontaneous formation of CLB. The creation of three sub-cloned cybrid lines from cells expressing CLB resulted in differential phenotypic changes in mitochondrial and cellular function. These changes were driven by the expression of patient derived mitochondrial DNA in nucleoids, rather than by the presence of CLB. Our studies suggest that mitochondrial DNA plays an important role in cellular and mitochondrial dysfunction in PD. Additional studies will be needed to assess the direct effect of CLB expression on cellular and mitochondrial function.

Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy.

BACKGROUND: It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT). The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC) enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT). Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm2) for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined. RESULTS: The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM) was significantly reduced (p < 0.02) compared to mitochondrial movement in disease free CNT cybrid neuronal cells (0.232 +/- 0.017 SEM). For two hours after LLLT, the average velocity of mitochondrial movement in PD cybrid neurites was significantly (p < 0.003) increased (to 0.224 +/- 0.02 SEM) and restored to levels comparable to CNT. Mitochondrial movement in CNT cybrid neurites was unaltered by LLLT (0.232 +/- 0.017 SEM). Assembly of complexes in the mtETC was reduced and oxygen utilization was altered in PD cybrid neuronal cells. PD cybrid neuronal cell lines with the most dysfunctional mtETC assembly and oxygen utilization profiles were least responsive to LLLT. CONCLUSION: The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.

Relationships among molecular genetic and respiratory properties of Parkinson's disease cybrid cells show similarities to Parkinson's brain tissues.

We have studied sporadic Parkinson's disease (sPD) from expression of patient mitochondrial DNA (mtDNA) in neural cells devoid of their own mtDNA, the "cybrid" model. In spite of reproducing several properties of sPD brain, it remains unclear whether sPD cybrid cells reflect more complex sPD brain bioenergetic pathophysiology. We characterized and correlated respiration of intact sPD cybrid cells with electron transport chain (ETC) protein assembly, complex I ETC gene expression and ETC protein levels in sPD brain. We also assayed expression for multiple ETC genes coded by mtDNA and nuclear DNA (nDNA) in sPD cybrid cells and brain. sPD cybrid cells have reduced levels of mtDNA genes, variable compensatory normalization of mitochondrial gene expression and show robust correlations with mitochondrial ETC gene expression in sPD brains. Relationships among ETC protein levels predict impaired complex I-mediated respiration in sPD brain. That sPD cybrid cells and sPD brain samples show very correlated regulation of nDNA and mtDNA ETC transcriptomes suggests similar bioenergetic physiologies. We propose that further insights into sPD pathogenesis will follow elucidation of mechanisms leading to reduced mtDNA gene levels in sPD cybrids. This will require characterization of the abnormalities and dynamics of mtDNA changes propagated through sPD cybrids over time.

Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells.

BACKGROUND: Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins. RESULTS: We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes. CONCLUSION: Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.

Paediatric acute asthma management in Australia and New Zealand: practice patterns in the context of clinical practice guidelines.

OBJECTIVES: To compare clinical practice guideline (CPG) recommendations and reported physician management of acute paediatric asthma in the 11 largest paediatric emergency departments, all of which have CPGs, in Australia (n = 9) and New Zealand (n = 2). All 11 sites participate in the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network. METHODS: (a) A review of CPGs for acute childhood asthma from all PREDICT sites. (b) A standardised anonymous survey of senior emergency doctors at PREDICT sites investigating management of acute childhood asthma. RESULTS: CPGs for mild to moderate asthma were similar across sites and based on salbutamol delivery by metered dose inhaler with spacer and oral prednisolone. In severe to critical asthma, differences between sites were common and related to recommendations for: ipratropium use; metered-dose inhaler versus nebulised delivery of salbutamol in severe asthma; use of intravenous aminophylline, intravenous magnesium and dosing of intravenous salbutamol in critical asthma. The questionnaire (78 of 83 doctors responded) also revealed significant differences between doctors in the treatment of moderate to severe asthma. Ipratropium was used for moderate asthma by 42%. For severe to critical asthma, nebulised delivery of salbutamol was preferred by 79% of doctors over metered dose inhalers. For critical asthma, doctors reported using intravenous aminophylline in 45%, intravenous magnesium in 55%, and intravenous salbutamol in 87% of cases. Thirty-nine different dosing regimens for intravenous salbutamol were reported. CONCLUSIONS: CPG recommendations and reported physician practice for mild to moderate paediatric asthma management were broadly similar across PREDICT sites and consistent with national guidelines. Practice was highly variable for severe to critical asthma and probably reflects limitations of available evidence. Areas of controversy, in particular the comparative efficacy of intravenous bronchodilators, would benefit from multi-centre trials. Collaborative development of CPGs should be considered.

Differentiated Alzheimer's disease transmitochondrial cybrid cell lines exhibit reduced organelle movement.

The axonal transport and function of organelles like mitochondria and lysosomes may be impaired and play an important role in the pathogenesis of Alzheimer's disease (AD). Unique cybrid cell lines that model AD pathology were created by fusing platelets containing mitochondria from age-matched AD and control volunteers with mitochondrial DNA-free SH-SY5Y human neuroblastoma cells. These cybrid lines were differentiated to form process-bearing neuronal cells. Mitochondria and lysosomes in the neurites of each cybrid line were fluorescently labeled to determine the kinetics of organelle movement. The mitochondria in AD cybrid neurites were elongate, whereas the mitochondria in control cybrid neurites were short and more punctate. The mean velocity of mitochondrial movement, as well as the percentage of moving mitochondria, was significantly reduced in AD cybrids. The velocity of lysosomal movement was also reduced in the processes of AD cybrid cells, suggesting that the axonal transport machinery may be compromised in cybrid cell lines that contain mitochondrial DNA derived from AD patients. Reduced mitochondrial and lysosomal movement in susceptible neurons may compromise function in metabolically demanding structures like synaptic terminals and participate in the terminal degeneration that is characteristic of AD.

Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: a randomised double blind crossover study.

INTRODUCTION: The ideal analgesic agent for burns wound dressings in paediatric patients would be one that is easy to administer, well tolerated, and produces rapid onset of analgesia with a short duration of action and minimal side-effects to allow rapid resumption of activities and oral intake. We compared our current treatment of oral morphine to intranasal fentanyl in an attempt to find an agent closer to the ideal. METHODS: A randomised double blind two-treatment crossover study comparing intranasal administration of fentanyl (INF) to orally administered morphine (OM). Children with burn injury aged up to 15 years and weighing 10-75 kg were included. Primary end-point was pain scores. Secondary end-points were time to resumption of age-appropriate activities, time to resumption of fluid intake, sedation and cooperation. Routine observations and vital signs were also recorded. RESULTS: Twenty-four patients were studied with a median age of 4.5 years (interquartile range 1.8-9.0 years) and a median weight of 18.4 kg (interquartile range 12.9-33.2kg). Mean pain difference scores (OM-INF) ranged from -0.500 (95% CI=-1.653 to 0.653) at baseline to -0.625 (05% CI=-1.863 to 0.613) for a retrospective rating of worst pain experienced during the dressing procedure. All measurements were within a pre-defined range of equivalent efficacy. The median time to resumption of fluid intake was 108 min (range 44-175 min) with OM and 140 min (range 60-210 min) with INF. These differences were not statistically significant. Fewer patients experienced mild side-effects with INF compared to OM (n=5 versus n=10). No patients experienced depressed respirations or oxygen saturations. SUMMARY: Intranasal fentanyl was shown to be equivalent to oral morphine in the provision of analgesia for burn wound dressing changes in this cohort of paediatric patients. It was concluded that intranasal fentanyl is a suitable analgesic agent for use in paediatric burns dressing changes either by itself or in combination with oral morphine as a top up titratable agent.

Parkinson's disease transgenic mitochondrial cybrids generate Lewy inclusion bodies.

Many models of Parkinson's disease (PD) have succeeded in replicating dopaminergic neuron loss or alpha-synuclein aggregation but not the formation of classical Lewy bodies, the pathological hallmark of PD. Our cybrid model of sporadic PD was created by introducing the mitochondrial genes from PD patients into neuroblastoma cells that lack mitochondrial DNA. Previous studies using cybrids have shown that information encoded by mitochondrial DNA in patients contributes to many pathogenic features of sporadic PD. In this paper, we report the generation of fibrillar and vesicular inclusions in a long-term cybrid cell culture model that replicates the essential antigenic and structural features of Lewy bodies in PD brain without the need for exogenous protein expression or inhibition of mitochondrial or proteasomal function. The inclusions generated by PD cybrid cells stained with eosin, thioflavin S, and antibodies to alpha-synuclein, ubiquitin, parkin, synphilin-1, neurofilament, beta-tubulin, the proteasome, nitrotyrosine, and cytochrome c. Future studies of these cybrids will enable us to better understand how Lewy bodies form and what role they play in the pathogenesis of PD.

Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture.

We created and studied new cybrid cell lines from sporadic Alzheimer's disease (SAD) or control (CTL) subjects to assess mitochondrial abnormalities just after metabolic selection ("early passage") and again six passages later ("late passage"). Cytochrome oxidase (CO) activities in early passage SAD cybrids created independently from the same platelet samples were highly correlated. Early passage SAD and CTL cybrids showed equivalent mitochondrial morphologies. Late passage SAD cybrids showed increased mitochondrial number, reduced mitochondrial size, and an approximately eightfold increase in morphologically abnormal mitochondria. Deficiency of SAD cybrid mitochondrial membrane potentials (DeltaPsi(M)) increased with passage. Mitochondrial bromodeoxyuridine (BrdU) uptake to estimate mitochondrial DNA (mtDNA) synthesis did not change with passage in CTL but increased in SAD cybrids. With time in culture, SAD mtDNA appears to replicate faster in cybrids, yielding cells with relative worsening of bioenergetic function. Metabolically deleterious SAD mitochondrial genes, like those in yeast, may have a replicative advantage over nondeleterious mitochondrial genes that assume dominance in CTL cybrids.

Evidence for microbunching "sidebands" in a saturated free-electron laser using coherent optical transition radiation.

We report the first measurements of z-dependent coherent optical transition radiation (COTR) due to electron-beam microbunching at high gains ( >10(4)) including saturation of a self-amplified spontaneous emission free-electron laser (FEL). In these experiments the fundamental wavelength was near 530 nm, and the COTR spectra exhibit the transition from simple spectra to complex spectra ( 5% spectral width) after saturation. The COTR intensity growth and angular distribution data are reported as well as the evidence for transverse spectral dependencies and an "effective" core of the beam being involved in microbunching.