Performance Scaling in Magnetized Liner Inertial Fusion Experiments.

We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1×10^{13} (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.

Experimental demonstration of fusion-relevant conditions in magnetized liner inertial fusion.

This Letter presents results from the first fully integrated experiments testing the magnetized liner inertial fusion concept [S. A. Slutz et al., Phys. Plasmas 17, 056303 (2010)], in which a cylinder of deuterium gas with a preimposed 10 Taxial magnetic field is heated by Z beamlet, a 2.5 kJ, 1 TW laser, and magnetically imploded by a 19 MA, 100 ns rise time current on the Z facility. Despite a predicted peak implosion velocity of only 70 km = s, the fuel reaches a stagnation temperature of approximately 3 keV, with T(e) ≈ T(i), and produces up to 2 x 10(12) thermonuclear deuterium-deuterium neutrons. X-ray emission indicates a hot fuel region with full width at half maximum ranging from 60 to 120 µm over a 6 mm height and lasting approximately 2 ns. Greater than 10(10) secondary deuterium-tritium neutrons were observed, indicating significant fuel magnetization given that the estimated radial areal density of the plasma is only 2 mg = cm(2).

Understanding fuel magnetization and mix using secondary nuclear reactions in magneto-inertial fusion.

Magnetizing the fuel in inertial confinement fusion relaxes ignition requirements by reducing thermal conductivity and changing the physics of burn product confinement. Diagnosing the level of fuel magnetization during burn is critical to understanding target performance in magneto-inertial fusion (MIF) implosions. In pure deuterium fusion plasma, 1.01 MeV tritons are emitted during deuterium-deuterium fusion and can undergo secondary deuterium-tritium reactions before exiting the fuel. Increasing the fuel magnetization elongates the path lengths through the fuel of some of the tritons, enhancing their probability of reaction. Based on this feature, a method to diagnose fuel magnetization using the ratio of overall deuterium-tritium to deuterium-deuterium neutron yields is developed. Analysis of anisotropies in the secondary neutron energy spectra further constrain the measurement. Secondary reactions also are shown to provide an upper bound for the volumetric fuel-pusher mix in MIF. The analysis is applied to recent MIF experiments [M. R. Gomez et al., Phys. Rev. Lett. 113, 155003 (2014)] on the Z Pulsed Power Facility, indicating that significant magnetic confinement of charged burn products was achieved and suggesting a relatively low-mix environment. Both of these are essential features of future ignition-scale MIF designs.

Demonstration of improved laser preheat with a cryogenically cooled magnetized liner inertial fusion platform.

We report on progress implementing and testing cryogenically cooled platforms for Magnetized Liner Inertial Fusion (MagLIF) experiments. Two cryogenically cooled experimental platforms were developed: an integrated platform fielded on the Z pulsed power generator that combines magnetization, laser preheat, and pulsed-power-driven fuel compression and a laser-only platform in a separate chamber that enables measurements of the laser preheat energy using shadowgraphy measurements. The laser-only experiments suggest that ∼89% ± 10% of the incident energy is coupled to the fuel in cooled targets across the energy range tested, significantly higher than previous warm experiments that achieved at most 67% coupling and in line with simulation predictions. The laser preheat configuration was applied to a cryogenically cooled integrated experiment that used a novel cryostat configuration that cooled the MagLIF liner from both ends. The integrated experiment, z3576, coupled 2.32 ± 0.25 kJ preheat energy to the fuel, the highest to-date, demonstrated excellent temperature control and nominal current delivery, and produced one of the highest pressure stagnations as determined by a Bayesian analysis of the data.

Penetrating radiography of imploding and stagnating beryllium liners on the Z accelerator.

The implosions of initially solid beryllium liners (tubes) have been imaged with penetrating radiography through to stagnation. These novel radiographic data reveal a high degree of azimuthal correlation in the evolving magneto-Rayleigh-Taylor structure at times just prior to (and during) stagnation, providing stringent constraints on the simulation tools used by the broader high energy density physics and inertial confinement fusion communities. To emphasize this point, comparisons to 2D and 3D radiation magnetohydrodynamics simulations are also presented. Both agreement and substantial disagreement have been found, depending on how the liner's initial outer surface finish was modeled. The various models tested, and the physical implications of these models are discussed. These comparisons exemplify the importance of the experimental data obtained.

Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin, all as add-on to metformin monotherapy in Type 2 diabetes mellitus.

AIM: To investigate the cost-effectiveness of liraglutide as add-on to metformin vs. glimepiride or sitagliptin in patients with Type 2 diabetes uncontrolled with first-line metformin. METHODS: Data were sourced from a clinical trial comparing liraglutide vs. glimepiride, both in combination with metformin, and a clinical trial comparing liraglutide vs. sitagliptin, both as add-on to metformin. Only the subgroup of patients in whom liraglutide was added to metformin monotherapy was included in the cost-utility analysis. The CORE Diabetes Model was used to simulate outcomes and costs with liraglutide 1.2 and 1.8 mg vs. glimepiride and vs. sitagliptin over patients' lifetimes. Treatment effects were taken directly from the trials. Costs and outcomes were discounted at 3.5% per annum and costs were accounted from a third-party payer (UK National Health System) perspective. RESULTS: Treatment with liraglutide 1.2 and 1.8 mg resulted, respectively, in mean increases in quality-adjusted life expectancy of 0.32 ± 0.15 and 0.28 ± 0.14 quality-adjusted life years vs. glimepiride, and 0.19 ± 0.15 and 0.31 ± 0.15 quality-adjusted life years vs. sitagliptin, and was associated with higher costs of £ 3003 ± £ 678 and £ 4688 ± £ 639 vs. glimepiride, and £ 1842 ± £ 751 and £ 3224 ± £ 683 vs. sitagliptin, over a patient's lifetime. Both liraglutide doses were cost-effective, with incremental cost-effectiveness ratios of £ 9449 and £ 16,501 per quality-adjusted life year gained vs. glimepiride, and £ 9851 and £ 10,465 per quality-adjusted life year gained vs. sitagliptin, respectively. CONCLUSIONS: Liraglutide, added to metformin monotherapy, is a cost-effective option for the treatment of Type 2 diabetes in a UK setting.

Muscle metabolic, enzymatic and transporter responses to a session of prolonged cycling.

A single session of prolonged work was employed to investigate changes in selected metabolic, transporter and enzymatic properties in muscle. Ten active but untrained volunteers (weight = 73.9 ± 4.2 kg) with a peak aerobic power [Formula: see text] of 2.95 ± 0.27 l min(-1), cycled for 2 h at 62 ± 1.3% [Formula: see text] Tissue extraction from the vastus lateralis occurred prior to (E1-Pre) and following (E1-Post) exercise and on 3 consecutive days of recovery (R1, R2, R3). The exercise resulted in decreases (P < 0.05) in ATP (-9.3%) and creatine phosphate (-49%) and increases in lactate (+100%), calculated free ADP (+253%) and free AMP (+1,207%), all of which recovered to E1-Pre by R1. Glycogen concentration, which was depressed (P < 0.05) by 75% at E1-Post, did not recover until R3. Compared to E1-Pre, the cycling also resulted in decreases (P < 0.05) in the activities of cytochrome c oxidase, phosphorylase, and hexokinase but not in citrate synthase (CS) or 3-hydroxy-CoA dehydrogenase at E1-Post. With the exception of CS, which was elevated (P < 0.05) at R3, all enzyme activities were not different from E1-Pre during recovery. For the glucose (GLUT1, GLUT4) and monocarboxylate (MCT1, MCT4) transporters, changes in expression levels (P < 0.05) were only observed for GLUT1 at R1 (+42%) and R3 (+33%). It is concluded that the metabolic stress produced by prolonged exercise is reversed by 1 day of recovery. One day of exercise also resulted in a potential upregulation in the citric acid cycle and glucose transport capabilities, adaptations which are expressed at variable recovery durations.

Measurements of magneto-Rayleigh-Taylor instability growth during the implosion of initially solid Al tubes driven by the 20-MA, 100-ns Z facility.

The first controlled experiments measuring the growth of the magneto-Rayleigh-Taylor instability in fast (∼100 ns) Z-pinch plasmas are reported. Sinusoidal perturbations on the surface of an initially solid Al tube (liner) with wavelengths of 25-400 µm were used to seed the instability. Radiographs with 15 µm resolution captured the evolution of the outer liner surface. Comparisons with numerical radiation magnetohydrodynamic simulations show remarkably good agreement down to 50 µm wavelengths.

A spherical crystal diffraction imager for Sandia's Z Pulsed Power Facility.

Sandia's Z Pulsed Power Facility is able to dynamically compress matter to extreme states with exceptional uniformity, duration, and size, which are ideal for investigating fundamental material properties of high energy density conditions. X-ray diffraction (XRD) is a key atomic scale probe since it provides direct observation of the compression and strain of the crystal lattice and is used to detect, identify, and quantify phase transitions. Because of the destructive nature of Z-Dynamic Material Property (DMP) experiments and low signal vs background emission levels of XRD, it is very challenging to detect a diffraction signal close to the Z-DMP load and to recover the data. We have developed a new Spherical Crystal Diffraction Imager (SCDI) diagnostic to relay and image the diffracted x-ray pattern away from the load debris field. The SCDI diagnostic utilizes the Z-Beamlet laser to generate 6.2-keV Mn-Heα x rays to probe a shock-compressed material on the Z-DMP load. A spherically bent crystal composed of highly oriented pyrolytic graphite is used to collect and focus the diffracted x rays into a 1-in. thick tungsten housing, where an image plate is used to record the data.

Failure of hypoxia to exaggerate the metabolic stress in working muscle following short-term training.

This study investigated the effects of hypoxia (experiment 1) and the effects of hypoxia following short-term training (experiment 2) on metabolism in working muscle. In experiment 1, eight males with a peak aerobic power (VO2peak) of 45 +/- 1.7 ml x kg(-1) x min(-1) (x +/- SE) cycled for 15 min at 66.1 +/- 2.1% VO2peak while breathing room air [normoxia (N)] or 14% O(2) [hypoxia (H)]. In experiment 2, nine males with a VO2peak of 43.3 +/- 1.6 ml x kg(-1) x min(-1) performed a similar protocol at 60.7 +/- 1.4% VO2peak during N and during H following 5 days of submaximal exercise training (H + T). Tissue samples extracted from the vastus lateralis before exercise and at 1, 3, and 15 min of exercise indicated that compared with N, H resulted in lower (P < 0.05) concentrations (mmol/kg dry wt) of creatine phosphate and higher (P < 0.05) concentrations of creatine, inorganic phosphate, and lactate, regardless of exercise time. When the exercise was performed at H + T and compared with N, no differences were observed in creatine phosphate, creatine, inorganic phosphate, and lactate, regardless of duration. Given the well-documented effects of the short-term training model on elevating VO2 kinetics and attenuating the alterations in high-energy phosphate metabolism and lactate accumulation, it would appear that the mechanism underlying the reversal of these adaptations during H is linked to a more rapid increase in oxidative phosphorylation, mediated by increased oxygen delivery and/or mitochondrial activation.

Time-dependent effects of short-term training on muscle metabolism during the early phase of exercise.

In this study, we investigated the hypothesis that the metabolic adaptations observed during steady-state exercise soon after the onset of training would be displayed during the nonsteady period of moderate exercise and would occur in the absence of increases in peak aerobic power (Vo2peak) and in muscle oxidative potential. Nine untrained males [age = 20.8 +/- 0.70 (SE) yr] performed a cycle task at 62% Vo2peak before (Pre-T) and after (Post-T) training for 2 h/day for 5 days at task intensity. Tissue samples extracted from the vastus lateralis at 0 min (before exercise) and at 10, 60, and 180 s of exercise, indicated that at Pre-T, reductions (P < 0.05) in phosphocreatine and increases (P < 0.05) in creatine, inorganic phosphate, calculated free ADP, and free AMP occurred at 60 and 180 s but not at 10 s. At Post-T, the concentrations of all metabolites were blunted (P < 0.05) at 60 s. Training also reduced (P < 0.05) the increase in lactate and the lactate-to-pyruvate ratio observed during exercise at Pre-T. These adaptations occurred in the absence of change in Vo2peak (47.8 +/- 1.7 vs. 49.2 +/- 1.7 mlxkg(-1)xmin(-1)) and in the activities (molxkg protein(-1)xh(-1)) of succinic dehydrogenase (3.48 +/- 0.21 vs. 3.77 +/- 0.35) and citrate synthase (7.48 +/- 0.61 vs. 8.52 +/- 0.65) but not cytochrome oxidase (70.8 +/- 5.1 vs. 79.6 +/- 6.6 U/g protein; P < 0.05). It is concluded that the tighter metabolic control observed following short-term training is initially expressed during the nonsteady state, probably as a result of increases in oxidative phosphorylation that is not dependent on changes in Vo2peak while the role of oxidative potential remains uncertain.

Detecting colorectal cancer by 1H magnetic resonance spectroscopy of fecal extracts.

Colorectal cancer is one of the most common cancers in the western world. Its early detection has been found to improve the prognosis of the patient, providing a wide window of opportunity for successful therapeutic interventions. However, current diagnostic techniques all have some limitations; there is a need to develop a better technique for routine screening purposes. We present a new methodology based on magnetic resonance spectroscopy of fecal extracts for the non-invasive detection of colorectal cancer. Five hundred twenty-three human subjects (412 with no colonic neoplasia and 111 with colorectal cancer, who were scheduled for colonoscopy or surgery) were recruited to donate a single sample of stool. One-dimensional (1)H magnetic resonance spectroscopy (MRS) experiments were performed on the supernatant of aqueous dispersions of the stool samples. Using a statistical classification strategy, several multivariate classifiers were developed. Applying the preprocessing, feature selection and classifier development stages of the Statistical Classification Strategy led to approximately 87% average balanced sensitivity and specificity for both training and monitoring sets, improving to approximately 92% when only crisp results, i.e. class assignment probabilities > or =75%, are considered. These results indicate that (1)H magnetic resonance spectroscopy of human fecal extracts, combined with appropriate data analysis methodology, has the potential to detect colorectal neoplasia accurately and reliably, and could be a useful addition to the current screening tools.

Proton magnetic resonance of transfer RNA.

The temperature dependence of the areas under the proton magnetic resonance spectra of unfractionated yeast transfer RNA in 1.0 molar NaCl is a consequence of salt-induced aggregation and does not constitute a monitor of the melting of secondary molecular structure. Such melting can be observed by following the widths of the resonances in the various regions of the spectra. Peaks attributable to dihydrouracil and the methyl groups of the methylated bases are detected in the spectra of unfractionated transfer RNA and alanine transfer RNA.

Novel complex polar lipids from the methanogenic archaebacterium Methanospirillum hungatei.

The methanogenic archaebacterium Methanospirillum hungatei contains two unusual phosphoglycolipids that account for 64 percent of the total cellular lipids. These lipids are derivatives of the dibiphytanyl diglycerol tetraether, previously identified in methanogens. One of the free hydroxyls of this tetraether is esterified with glycerophosphoric acid, and the other is linked glycosidically to a disaccharide. The two phosphoglycolipids may function as covalently bonded lipid bilayers to impart stability and rigidity to methanogen membranes.

Detection of cholangiocarcinoma with magnetic resonance spectroscopy of bile in patients with and without primary sclerosing cholangitis.

BACKGROUND: Early detection of cholangiocarcinoma (CC) is very difficult, especially in patients with primary sclerosing cholangitis (PSC) who are at increased risk of developing CC. PURPOSE: To evaluate 1H magnetic resonance spectroscopy ((1)H-MRS) of bile as a diagnostic marker for CC in patients with and without PSC. MATERIAL AND METHODS: The institutional review board approved the study, and all patients gave informed consent. Bile from 49 patients was sampled and investigated using 1H-MRS. MR spectra of bile samples from 45 patients (18 female; age range 22-87 years, mean age 57 years) were analyzed both conventionally and using computerized multivariate analysis. Sixteen of the patients had CC, 18 had PSC, and 11 had other benign findings. RESULTS: The spectra of bile from CC patients differed from the benign group in the levels of phosphatidylcholine, bile acids, lipid, and cholesterol. It was possible to distinguish CC from benign conditions in all patients with malignancy. Two benign non-PSC patients were misclassified as malignant. The sensitivity, specificity, and accuracy were 88.9%, 87.1%, and 87.8%, respectively. CONCLUSION: With 1H-MRS of bile, cholangiocarcinoma could be discriminated from benign biliary conditions with or without PSC.

Phase modulation failsafe system for multi-kJ lasers based on optical heterodyne detection.

Amplification of the transverse scattered component of stimulated Brillouin scattering (SBS) can contribute to optical damage in the large aperture optics of multi-kJ lasers. Because increased laser bandwidth from optical phase modulation (PM) can suppress SBS, high energy laser amplifiers are injected with PM light. Phase modulation distributes the single-frequency spectrum of a master oscillator laser among individual PM sidebands, so a sufficiently high modulation index ß can maintain the fluence for all spectral components below the SBS threshold. To avoid injection of single frequency light in the event of a PM failure, a high-speed PM failsafe system (PMFS) must be employed. Because PM is easily converted to AM, essentially all PM failsafes detect AM, with the one described here employing a novel configuration where optical heterodyne detection converts PM to AM, followed by passive AM power detection. Although the PMFS is currently configured for continuous monitoring, it can also detect PM for pulse durations ≥2 ns and could be modified to accommodate shorter pulses. This PMFS was deployed on the Z-Beamlet Laser (ZBL) at Sandia National Laboratories, as required by an energy upgrade to support programs at Sandia's Z Facility such as magnetized liner inertial fusion. Depending on the origin of a PM failure, the PMFS responds in as little as 7 ns. In the event of an instantaneous failure during initiation of a laser shot, this response time translates to a 30-50 ns margin of safety by blocking a pulse from leaving ZBL's regenerative amplifier, which prevents injection of single frequency light into the main amplification chain. The performance of the PMFS, without the need for operator interaction, conforms to the principles of engineered safety.

Polycapillary x-ray lenses for single-shot, laser-driven powder diffraction.

X-ray diffraction measurements to characterize phase transitions of dynamically compressed high-Z matter at Mbar pressures require both sufficient photon energy and fluence to create data with high fidelity in a single shot. Large-scale laser systems can be used to generate x-ray sources above 10 keV utilizing line radiation of mid-Z elements. However, the laser-to-x-ray energy conversion efficiency at these energies is low, and thermal x-rays or hot electrons result in unwanted background. We employ polycapillary x-ray lenses in powder x-ray diffraction measurements using solid target x-ray emission from either the Z-Beamlet long-pulse or the Z-Petawatt (ZPW) short-pulse laser systems at Sandia National Laboratories. Polycapillary lenses allow for a 100-fold fluence increase compared to a conventional pinhole aperture while simultaneously reducing the background significantly. This enables diffraction measurements up to 16 keV at the few-photon signal level as well as diffraction experiments with ZPW at full intensity.

Protection of muscle membrane excitability during prolonged cycle exercise with glucose supplementation.

To determine if exercise-induced depressions in neuromuscular function are altered with oral glucose supplementation, 15 untrained participants (Vo2 peak = 45 +/- 2 ml x kg(-1) x min(-1), mean +/- SE) performed prolonged cycle exercise at approximately 60% Vo2 peak on two occasions: without glucose supplementation (NG) and with oral glucose supplementation (G). The oral G began at 30 min of exercise and was administered every 15 min (total ingested = 1.23 +/- 0.11 g carbohydrate/kg body mass). Quadriceps isometric properties and membrane excitability were assessed prior to exercise, after 90 min of exercise, and at fatigue. Cycle time to fatigue was greater (P < 0.05) in G compared with NG (137 +/- 7 vs. 115 +/- 6 min). Progressive reductions (P < 0.05) in maximal voluntary contraction (MVC, N) were observed for NG at 90 min (441 +/- 29) and at fatigue (344 +/- 33) compared with pre-exercise (666 +/- 30). At fatigue in G, the reduction in MVC was not as pronounced (P < 0.05) as in NG. Motor unit activation assessed with the interpolated twitch technique during an MVC following exercise was not different between conditions. During cycling, the G condition also resulted in a higher (P < 0.05) muscle compound potential (M-wave) amplitude (mV) at both 90 min (+50%) and at fatigue (+87%) compared with NG. Similar effects were also found M-wave area (mV/ms). These results suggest that the ergogenic effect of glucose supplementation occurs not as a result of decreased neural activation but to improved muscle function, possibly as a consequence of protection of muscle membrane excitability.

Muscle metabolic, SR Ca(2+) -cycling responses to prolonged cycling, with and without glucose supplementation.

This study investigated the effects of prolonged exercise, with and without glucose supplementation, on metabolism and sarcoplasmic reticulum (SR) Ca(2+)-handling properties in working vastus lateralis muscle. Fifteen untrained volunteers [peak O(2) consumption (Vo(2peak)) = 3.45 +/- 0.17 l/min; mean +/- SE] cycled at approximately 60% Vo(2peak) on two occasions, during which they were provided with either an artificially sweetened placebo beverage (NG) or a 6% glucose (G) beverage (~1.00 g carbohydrate/kg body mass). Beverage supplementation started at 30 min of exercise and continued every 15 min thereafter. SR Ca(2+) handling, metabolic, and substrate responses were assessed in tissue extracted from the vastus lateralis at rest, after 30 min and 90 min of exercise, and at fatigue in both conditions. Plasma glucose during G was 15-23% higher (P < 0.05) than those observed during NG following 60 min of exercise until fatigue. Cycle time to fatigue was increased (P < 0.05) by approximately 19% during G (137 +/- 7 min) compared with NG (115 +/- 6 min). Prolonged exercise reduced (P < 0.05) maximal Ca(2+)-ATPase activity (-18.4%), SR Ca(2+) uptake (-27%), and both Phase 1 (-22.2%) and Phase 2 (-34.2%) Ca(2+)-release rates during NG. The exercise-induced reductions in SR Ca(2+)-cycling properties were not altered during G. The metabolic responses to exercise were all unaltered by glucose supplementation, since no differences in respiratory exchange ratios, carbohydrate and lipid oxidation rates, and muscle metabolite and glycogen contents were observed between NG and G. These results indicate that the maintenance of blood glucose homeostasis by glucose supplementation is without effect in modifying the muscle metabolic, endogenous glycogen, or SR Ca(2+)-handling responses.

Identification of a multiprotein complex interacting with the c-fos serum response element.

The serum response element (SRE) is essential for serum and growth factor stimulation of the c-fos gene. We have examined the nuclear proteins, obtained from tissues with elevated expression of the c-fos gene (proliferating rat liver and hepatocarcinoma), that bind to the SRE sequence. A synthetic oligonucleotide containing the SRE sequence from the mouse c-fos gene promoter (-299 to -322) was radioactively labeled, used as a probe for the mobility shift assay and Southwestern (DNA-protein) blotting, and also used for sequence-specific affinity chromatography. We have identified a group of nuclear proteins of molecular sizes 36, 45, 62, 67, 72, and 112 kDa capable of interacting with the SRE sequence. The 36-, 67-, and 112-kDa proteins have DNA-binding properties, but the presence of the others in the SRE-protein complex could be the result of protein-protein interaction. All of these protein factors were present in nuclei obtained from intact and proliferating rat liver as well as from 5123tc Morris hepatoma. The DNA-binding activity (on Southwestern blots) of the 67- and 112-kDa proteins was not affected by alkaline phosphatase treatment, but the ability of the dephosphorylated nuclear proteins to form the complex with the SRE sequence under gel shift assay conditions was severely impaired. The same alkaline phosphatase treatment completely abolished the DNA-binding properties of the c-fos cyclic AMP-responsive element-specific proteins. Therefore, transcriptional activation of the c-fos gene at the SRE must require the presence of a multiprotein complex the formation of which is governed by phosphorylation. The binding of the 67- and 62-kDa proteins to the c-fos SRE has been previously reported; however, the 36-. 45-, 72-, and 112-kDa proteins are novel factors involved in the multifaceted regulation of c-fos gene expression in vivo.