Order-of-magnitude increase in laser-target coupling at near-relativistic intensities using compound parabolic concentrators.

Achieving a high conversion efficiency into relativistic electrons is central to short-pulse laser application and fundamentally relies on creating interaction regions with intensities ≫10^{18}W/cm^{2}. Small focal length optics are typically employed to achieve this goal; however, this solution is impractical for large kJ-class systems that are constrained by facility geometry, debris concerns, and component costs. We fielded target-mounted compound parabolic concentrators to overcome these limitations and achieved nearly an order-of-magnitude increase to the conversion efficiency and more than tripled electron temperature compared to flat targets. Particle-in-cell simulations demonstrate that plasma confinement within the cone and formation of turbulent laser fields that develop from cone wall reflections are responsible for the improved laser-to-target coupling. These passive target components can be used to improve the coupling efficiency for all high-intensity short-pulse laser applications, particularly at large facilities with long focal length optics.

Saturn-ring proton backlighters for the National Ignition Facility.

Proton radiography is a well-established technique for measuring electromagnetic fields in high-energy-density plasmas. Fusion reactions producing monoenergetic particles, such as D3He, are commonly used as a source, produced by a capsule implosion. Using smaller capsules for radiography applications is advantageous as the source size decreases, but on the National Ignition Facility (NIF), this can introduce complications from increasing blow-by light, since the phase plate focal spot size is much larger than the capsules. We report a demonstration of backlighter targets where a "Saturn" ring is placed around the capsule to block this light. The nuclear performance of the backlighters is unperturbed by the addition of a ring. We also test a ring with an equatorial cutout, which severely affects the proton emission and is not viable for radiography applications. These results demonstrate the general viability of Saturn ring backlighter targets for use on the NIF.

Production of relativistic electrons at subrelativistic laser intensities.

Relativistic electron temperatures were measured from kilojoule, subrelativistic laser-plasma interactions. Experiments show an order of magnitude higher temperatures than expected from a ponderomotive scaling, where temperatures of up to 2.2 MeV were generated using an intensity of 1×10^{18}W/cm^{2}. Two-dimensional particle-in-cell simulations suggest that electrons gain superponderomotive energies by stochastic acceleration as they sample a large area of rapidly changing laser phase. We demonstrate that such high temperatures are possible from subrelativistic intensities by using lasers with long pulse durations and large spatial scales.

Synthesis and biological activity of oxo-7H-benzo[e]perimidine-4-carboxylic acid derivatives as potent, nonpeptide corticotropin releasing factor (CRF) receptor antagonists.

A novel series of derivatives of oxo-7H-benzo[e]perimidine-4-carboxylic acid (I) potently displaced radioligand binding of 125I-CRF to both CRF1 and CRF2 receptors. The members of this series antagonized CRF-stimulated cAMP formation and CRF-stimulated corticotropin release from rat pituitary in vivo. These are the first nonpeptide antagonists to show activity at both CRF1 and CRF2 receptors.

Locus coeruleus electrophysiological activity and responsivity to corticotropin-releasing factor in inbred hypertensive and normotensive rats.

The spontaneously hypertensive rat (SHR) and its normotensive progenitor, the Wistar-Kyoto rat (WKY), have been shown to be differentially responsive to the behavioral and endocrine effects of both stress and corticotropin-releasing factor (CRF), both of which increase locus coeruleus (LC) electrophysiological activity. However, the effect of central administration of CRF in these rat strains has yet to be examined. In the present studies, LC electrophysiological responsivity to intracerebroventricular infusions of CRF was assessed in SHR, an inbred strain of WKY rats (the WKY[LJ] rat), and an outbred normotensive rat strain, Sprague-Dawley (SD) rats. Spontaneous LC discharge rate, mean arterial blood pressure and heart rate were also examined. LC activity was increased to the same extent in the three rat strains in response to a 3 microg dose of CRF. However, WKY(LJ) rats showed an exaggerated LC in response to a 1 microg dose of CRF in comparison to the other rat strains tested at this dose. Spontaneous discharge rates of individual LC neurons were lower in both SHR and WKY[LJ] rats than in SD rats. Further, the variability of the discharge rates of LC neurons was greater in WKY[LJ] rats than in the other two strains. These results indicate that the WKY[LJ] rat may provide a useful model for assessing the role of sensitivity to CRF in stress responsiveness.

Spinal nicotinic receptor expression in spontaneously hypertensive rats.

Intrathecal administration of nicotinic agonists previously has been shown to result in exaggerated pressor and heart rate responses as well as greater nociceptive behavior in adult (12-week-old) spontaneously hypertensive rats (SHR) than in age-matched normotensive Wistar-Kyoto rats (WKY). Paradoxical to these augmented responses to nicotinic agonists in SHR, nicotinic receptor number in the spinal cord as measured by cytisine binding sites is lower in adult SHR than normotensive WKY and Sprague-Dawley rats. Using the high-affinity agonist epibatidine, we found similar differences in receptor number between strains in both in vitro ligand binding experiments with spinal cord membranes and in situ autoradiographic analyses. Spinal nicotinic receptor number did not differ in 5-week-old prehypertensive SHR and age-matched WKY; however, receptor numbers were higher in young rats of both strains than in their adult counterparts. Antihypertensive treatment (25 mg/kg per day hydralazine PO) in 6-week-old SHR from 6 to 12 weeks of age markedly reduced the progressive rise in blood pressure yet did not alter nicotinic receptor number compared with untreated rats. Similar treatment of WKY with hydralazine produced a slight fall in blood pressure but no change in receptor number. Thus, normalization of blood pressure by hydralazine in SHR does not result in a return of receptor expression to levels seen in normotensive rats. Higher centrally mediated pressor activity or augmented postcoupling events after neuronal nicotinic receptor stimulation may slowly downregulate expression of spinal nicotinic receptors in this genetically hypertensive rat strain.

Central actions of corticotropin releasing factor on sensori-autonomic processing in normotensive and hypertensive rats.

The airpuff startle paradigm, a stress paradigm, elicits greater pressor and tachycardia responses in SHRLJ than WKYLJ which, unlike SHRLJ, also show bradycardia. CRF has been implicated in coordinating autonomic responses to stressors. The present studies explored the role of CRF, CRF antagonist D-PheCRF12-41 and chronic hydralazine in stress-induced cardiovascular responses. In SHRLJ CRF unmasked a bradycardia response, equal to WKYLJ receiving either aCSF or CRF, which was blocked by D-PheCRF12-41. CRF given to hydralazine-treated SHRLJ did not unmask a bradycardia. In WKYLJ CRF specifically lowered the pressor response on trial 1 compared to control, an effect abolished by the antagonist. WKYLJ receiving D-PheCRF12-41 prior to testing showed greater pressor and bradycardia responses when compared to control. In the WKYLJ CRF appears to exert an inhibitory role on the pressor and bradycardia responses while in the SHRLJ CRF exerts a permissive role on the bradycardia response which is lost when blood pressure is normalized with chronic hydralazine. CRF and D-PheCRF12-41 modify stress-induced cardiovascular responses in a strain-dependent dissimilar fashion. We conclude CRF has cardiovascular importance in the genetic hypertensive rat.

Peripheral beta adrenergic blockade modifies airpuff startle-induced heart rate responses.

Prior studies showed that repeated airpuff startle-reaction stimuli applied to normotensive inbred Wistar-Kyoto rats bred in La Jolla or Sprague-Dawley rats elicit pressor responses on all trials except trial-dependent bradycardia or tachycardia. However, hypertensive inbred spontaneously hypertensive rats bred in La Jolla exhibited no bradycardia. Peripheral methylatropine blocked bradycardia and unmasked tachycardia, which implies concurrent autonomic discharges on early trials. As shown here, vendor inbred Wistar-Kyoto rats from Charles River Laboratories (WKYCR) fail to show bradycardia. Because stress-induced parasympathetic responses are important to understanding arrhythmogenesis, we tested whether (WKYCR) and inbred spontaneously hypertensive rats from Charles River Laboratories (SHRCR) exhibit any parasympathetic activation by blunting sympathetic chronotropic responses with cardioselective beta-adrenoceptor antagonists. WKYCR or SHRCR were pretreated with either nonselective propranolol, beta 1-selective metoprolol, beta 1-selective celiprolol (with beta 2-receptor agonist activity) or ICI 118,551, a selective beta 2-receptor antagonist. Neither propranolol nor metoprolol affected resting HR in WKYCR, but both decreased HR in SHRCR, whereas celiprolol raised resting HR only in WKYCR. Although control WKYCR nor SHRCR exhibited bradycardia, bradycardia was unmasked in both by all beta 1-selective agents but not by ICI 118,551. However, ICI 118, 551 reduced tachycardia responses over all trials in WKYCR, which suggests beta 2-adrenoceptor involvement in the stress-induced tachycardia. Significant cardiac contributions to the pressor responses in both WKYCR and SHRCR were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Rheumatoid factors from the peripheral blood of two patients with rheumatoid arthritis are genetically heterogeneous and somatically mutated.

We report the DNA sequences of the heavy and light chain immunoglobulin genes of 11 monoclonal rheumatoid factor (RF)-secreting lines derived from the peripheral blood of two patients with rheumatoid arthritis (RA). It is evident from immunogenetic analysis of these lines that RA-associated RF activity can arise from a wide variety of heavy and light chain genes and gene combinations. Although the RF response from our two patients shows a bias in gene usage toward those genes used to encode monoclonal RF, particularly VkIII, relatively few of these RFs are reactive with the monoclonal antiidiotypes 6B6.6 and 17.109 that define VkIII germline-encoded light chains and the loss of this idiotypic reactivity is clearly related to somatic mutation. Finally, RFs derived from peripheral blood of RA patients show a similar heterogeneity of epitope binding to Fc as that seen for synovium-derived RF and some are clearly different in binding specificity from the restricted RF population found in patients with B cell malignancies. Somatic mutations as well as different VH/VL combinations contribute to the heterogeneity in the binding patterns of these RA-derived RF.