Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

80% Valley Polarization of Free Carriers in Singly Oriented Single-Layer WS_{2} on Au(111).

We employ time- and angle-resolved photoemission spectroscopy to study the spin- and valley-selective photoexcitation and dynamics of free carriers at the K[over ¯] and K[over ¯]^{'} points in singly oriented single-layer WS_{2}/Au(111). Our results reveal that in the valence band maximum an ultimate valley polarization of free holes of 84% can be achieved upon excitation with circularly polarized light at room temperature. Notably, we observe a significantly smaller valley polarization for the photoexcited free electrons in the conduction band minimum. Clear differences in the carrier dynamics between electrons and holes imply intervalley scattering processes into dark states being responsible for the efficient depolarization of the excited electron population.

Observation of coherence in the time-reversed relativistic photoelectric effect.

The photoelectric effect has been studied in the regime of hard x rays and strong Coulomb fields via its time-reversed process of radiative recombination (RR). In the experiment, the relativistic electrons recombined into the 2p_{3/2} excited state of hydrogenlike uranium ions, and both the RR x rays and the subsequently emitted characteristic x rays were detected in coincidence. This allowed us to observe the coherence between the magnetic substates in a highly charged ion and to identify the contribution of the spin-orbit interaction to the RR process.

Electron- and proton-impact excitation of hydrogenlike uranium in relativistic collisions.

The K shell excitation of H-like uranium (U(91+)) in relativistic collisions with different gaseous targets has been studied at the experimental storage ring at GSI Darmstadt. By performing measurements with different targets as well as with different collision energies, we were able to observe for the first time the effect of electron-impact excitation (EIE) process in the heaviest hydrogenlike ion. The large fine-structure splitting in H-like uranium allowed us to unambiguously resolve excitation into different L shell levels. State-of-the-art calculations performed within the relativistic framework which include excitation mechanisms due to both protons (nucleus) and electrons are in good agreement with the experimental findings. Moreover, our experimental data clearly demonstrate the importance of including the generalized Breit interaction in the treatment of the EIE process.

Thermal and electrochemical decomposition of lithium peroxide in non-catalyzed carbon cathodes for Li-air batteries.

The decomposition of lithium peroxide during the charging process of lithium-air batteries is investigated. A novel preparation method for electrodes in the discharged state, i.e., prefilled with Li2O2 using polyethylene oxide as a binder, is presented. The composition and reactivity of Li2O2-prefilled electrodes are examined by thermal analysis coupled with on-line mass spectrometry. Voltage profiles and gas evolution during the charging process of Li2O2-prefilled electrodes in battery cells are correlated with the thermal decomposition process of Li2O2 and its impact on other electrode compounds. It is found that both thermal Li2O2 decomposition and the electrochemical decomposition of Li2O2 during charging enhance the oxidation of the electrolyte, the binder, and/or carbon, which is suggested to be due to the formation of "nascent" oxygen during Li2O2 decomposition into O2 and Li2O (thermally) or into O2 and lithium ions (electrochemically).

Spectral shape of the two-photon decay of the 2 1S0 state in he-like tin.

The spectral distribution of the 1s2s {1}S{0}-->1s{2} 1S0 two-photon decay of He-like tin was measured using a novel approach at the gas-jet target of the ESR storage ring. Relativistic collisions of Li-like projectiles with low-density gaseous matter have been exploited to selectively populate the desired 1s2s state. Compared to conventional techniques, this approach results in a substantial gain in statistical and systematic accuracy, which allowed us to achieve for the first time a sensitivity to relativistic effects on the two-photon decay spectral shape as well as to discriminate the measured spectrum for Sn from theoretical shapes for different elements along the He-isoelectronic sequence.

Anthropogenic modification of forests means only 40% of remaining forests have high ecosystem integrity.

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remain poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate a globally consistent, continuous index of forest condition as determined by the degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) has high landscape-level integrity (mostly found in Canada, Russia, the Amazon, Central Africa, and New Guinea) and only 27% of this area is found in nationally designated protected areas. Of the forest inside protected areas, only 56% has high landscape-level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.

Spondylolisthesis and posterior instability.

We present the case of a patient with a spondylolisthesis of L5 on S1 due to spondylolysis at the level L5/S1. The vertebral slip was fixed and no anterior instability was found. Using functional magnetic resonance imaging (MRI) in an upright MRI scanner, posterior instability at the level of the spondylolytic defect of L5 was demonstrated. A structure, probably the hypertrophic ligament flava, arising from the spondylolytic defect was displaced toward the L5 nerve root, and a bilateral contact of the displaced structure with the L5 nerve root was shown in extension of the spine. To our knowledge, this is the first case described of posterior instability in patients with spondylolisthesis. The clinical implications of posterior instability are unknown; however, it is thought that this disorder is common and that it can only be diagnosed using upright MRI.

The effects of aging and diabetes mellitus on human red and white cell calmodulin levels (chemotaxis/phagocytosis/calcium).

Both the calcium ion and calmodulin have been proposed to play a role in producing the intracellular effects of insulin. Abnormalities in calmodulin levels have previously been reported in tissues from diabetic animals. Thus, using a sensitive and specific radioimmunoassay, we measured calmodulin levels in red cells and polymorphonuclear leukocytes from humans with diabetes mellitus. Diabetic patients have significantly lower white cell calmodulin levels than age-matched controls. There were no significant differences in red cell calmodulin levels in diabetics compared with controls. Red cell calmodulin levels in normal subjects were decreased with advancing age. We conclude that the alteration in calmodulin levels in leukocytes from diabetics may be associated with the decreased neutrophil function that has been observed in diabetics.

Idiopathic acquired diffuse osteosclerosis in a young woman.

We describe a young woman who acquired a painful, diffuse osteosclerosis of the cervical, thoracic, and lumbar spine, pelvis, and long bones of the legs as an adult. Bone densitometry showed a large increase in apparent bone density. Skeletal radiographs demonstrated progressive endosteal and periosteal thickening of the cortices. A bone scan showed increased uptake of radiolabel. The serum total alkaline phosphatase and 1,25-(OH)2D3 levels were substantially elevated and the immunoreactive PTH was mildly elevated. Bone biopsy showed increased bone turnover, especially on endocortical and intracortical surfaces, but the structural indices were normal. By 4 years after presentation the bone pain had remitted and the serum alkaline phosphatase, 1,25-(OH)2D3, and PTH were normal. No cause for the occurrence of osteosclerosis in this patient could be found.

Regulation of the messenger ribonucleic acid for corticotropin-releasing factor in the paraventricular nucleus and other brain sites of the rat.

CRF, from the paraventricular nucleus of the hypothalamus (PVN), is the major hypothalamic releasing factor that controls pituitary ACTH. Recently, the mRNA for CRF and the CRF peptide have been detected in other brain sites. However, there is little information on the function and regulation of CRF in brain sites outside the paraventricular nucleus. We investigated the content of CRF mRNA in the PVN, the central nucleus of the amygdala (CN), the bed nucleus of the stria terminalis (BN), and the supraoptic nucleus (SON). Northern gel analysis showed that the mRNA for CRF is present in the BN, CN, and SON as well as the PVN, and that all are the same size. In response to adrenalectomy, the level of hybridizable mRNA increased 2.75-fold over 7 days in the PVN; there was no change in the CN, BN, or SON. High dose dexamethasone decreased, but did not eliminate, the PVN CRF mRNA; it was without effect in the other sites. Glucocorticoid replacement with constant low blood levels of corticosterone (5.6 +/- 0.3 micrograms/100 ml) suppressed plasma ACTH and decreased thymus weight while reducing, but not eliminating, PVN CRF mRNA. We conclude that the same sized mRNA for CRF is synthesized in the PVN, BN, CN, and SON, but only the PVN mRNA responds to alterations of peripheral glucocorticoid status. This may imply that only CRF from the PVN is involved in control of the hypothalamic-pituitary-adrenal axis.

Induction of the messenger ribonucleic acid for proenkephalin A in cultured murine CD4-positive thymocytes.

Although proenkephalin A (PEA) messenger RNA (mRNA) has been detected in many types of immune cells, little understanding exists about its role or the role of enkephalin peptides in immune responses. We have studied the expression of PEA mRNA during thymocyte maturation by identifying the subpopulation of thymocytes that expresses PEA mRNA. PEA mRNA was induced in unfractionated murine thymocytes after in vitro activation of these cells with the T cell mitogen, concanavalin A (Con-A). A slight induction of PEA mRNA was seen after 48 h of Con-A stimulation; however, the maximal response occurred after 72 h of culture with Con-A. Two PEA mRNA bands were present in unfractionated thymocytes which had been cultured with Con-A for 48 and 72 h. The predominant band was 1.4 kilobases (kb), and a second band was approximately 1.7 kb. Fractionation of thymocytes into CD4, CD8, and double negative subpopulations showed that only the 1.4 kb PEA mRNA was inducible in the mature CD4 subpopulation. Induction required the presence of antigen-presenting cells in addition to CD4 thymocytes. Neither the 1.4 kb nor the 1.7 kb PEA mRNA was induced in the CD8 or double negative subpopulations. In contrast to the action of Con-A on murine thymocytes, PEA mRNA was not induced by this mitogen in murine splenic mononuclear cells at 24, 48, or 72 h. The regulated expression of PEA mRNA in murine thymocytes, but not in peripheral T lymphocytes, suggests a role for PEA mRNA and its peptides in thymocyte maturation.

Protein kinase A regulates nicotinic cholinergic receptors and subunit messenger ribonucleic acids in PC 12 cells.

To delineate mechanisms regulating the expression of neuronal nicotinic cholinergic receptors (nAcChRs), we studied the cAMP-dependent second messenger system. PC 12 cells were grown in (Bu)2cAMP (0.001-1.0 mM) or vehicle for 7 days, and specific [3H] nicotine binding was measured. (Bu)2cAMP (0.1 mM) increased specific binding 2- and 4-fold at 3 and 7 days, respectively, whereas 1.0 mM enhanced binding 4-fold at both time intervals. Cells grown in 8-bromo-cAMP (1.0 mM) showed a 2-fold increase in [3H]nicotine binding at 3 days. Forskolin (10-100 microM), in combination with isobutyl-methylxanthine (1.0 mM), enhanced [3H]nicotine binding 2- to 3-fold at 7 days; forskolin or isobutyl-methylxanthine alone had no effect. Specific [3H] nicotine binding to PC 12 cell mutants (A126.1B2 and A123.7), deficient in cAMP-responsive protein kinase A types I and II, were unaffected by (Bu)2cAMP. Northern gel analysis of nAcChR subunit messenger RNAs showed that the alpha-3, alpha-5, and beta-4 subunits were significantly decreased by (Bu)2cAMP at 4 h. However, (Bu)2cAMP caused an increase in the beta-2 messenger RNA transcript at 4 h, which returned to baseline by 24 h. These studies indicate that the cAMP-protein kinase A system regulates expression of nAcChR by PC 12 cells. These studies also suggest that enhancement of [3H]nicotine binding by activated protein kinase A may not involve synthesis of new receptor subunit proteins.

Hepatic messenger ribonucleic acid activity profile of rats subjected to alterations in thyroidal and adrenocortical states: evidence for significant interaction.

We have previously established the value of 2-dimensional electrophoretic mRNA activity profiles for investigating the hepatic genomic response to several metabolic perturbations, such as thyroid hormone or GH treatment, diabetes, high carbohydrate diet, starvation, and uremia. We now report the effects of adrenalectomy and dexamethasone treatment, and compare these with alterations due to thyroidectomy and T3 treatment. Total rat hepatic RNA was isolated and translated in a reticulocyte lysate system. The [35S]methionine-labeled translated products were separated by 2-dimensional gel electrophoresis and quantified with computerized videodensitometry. Of 200 consistently quantifiable products, 14 (7%) were altered by adrenalectomy and dexamethasone, including 4 products (46, 47, 56, and 57) which have not been observed to change in previous studies from this laboratory. Adrenalectomy increased 5 and decreased 2 products, whereas dexamethasone increased 1 and decreased 8 products. Two products maintained the same directional shift in the transitions form adrenalectomy to control and from control to the dexamethasone-treated state. Thyroidectomy and T3 altered 13 products. Thyroidectomy increased 2 and decreased 7 products, whereas T3 treatment increased 6 and decreased 3 products. Four products maintained the same directional shift in the transitions from thyroidectomy to control and from control to the T3-treated state. In all of the manipulations performed (adrenalectomy, thyroidectomy, dexamethasone treatment, and T3 treatment), a total of 20 separate products changed. One third were affected by alterations of both the steroidal and thyroidal states. However, when adrenalectomy and thyroidectomy were compared, only 7% of the shifts were concordant, whereas 30% of the shifts were concordant when treatment with dexamethasone and T3 were compared. These results demonstrate that the mRNA activity response is highly specific for each hormonal manipulation. In addition, unanticipated interrelationships between steroidal and thyroidal states were observed. In some, the presence of T3 appears necessary for the suppressive effect of dexamethasone. Others show that T3 appears to inhibit a stimulatory effect of dexamethasone. Specificity of response to dexamethasone is emphasized by the lack of response to vitamin D, deoxycorticosterone, and dihydrotestosterone and by a different response to estradiol from dexamethasone.

Cortisol secretion by an incidentally discovered nonfunctional adrenal adenoma.

We describe a middle-aged man with late-onset multiple sclerosis and an incidentally discovered asymptomatic adrenal mass. He had no symptoms or signs of hypercortisolism. A 24-h profile revealed fluctuating serum cortisol values (between 15.1 and 4.7 micrograms/dl) and inappropriately low plasma ACTH values. Urinary cortisol excretion was 89 and 106 micrograms/day on two occasions. After a 4-h ACTH infusion, serum cortisol rose from 6.3 to 108 micrograms/dl. The serum dehydroepiandrosterone level, 33 ng/dl before ACTH stimulation, did not change. During dexamethasone administration, the lowest daily urinary cortisol excretion was 37 micrograms/day, and 17-ketosteroid excretion was 8 mg/day. The response to metyrapone showed a rise of serum 11-deoxycortisol to 25.6 micrograms/dl and of ACTH to 169.5 pg/ml. After removal of the tumor, most likely an adenoma, the circadian pattern of cortisol and ACTH was normal. During a 4-h ACTH infusion, the serum cortisol level rose from 10 to 27 micrograms/dl, and dehydroepiandrosterone rose from 62 to 90 ng/dl. During dexamethasone administration, daily urinary cortisol excretion decreased to 12 micrograms/day, and 17-ketosteroid excretion dropped to 3.9 mg/day. These data show that while the tumor appeared clinically to be nonfunctional, it was producing cortisol and possibly androgens autonomously, albeit at levels too low to cause complete suppression of the pituitary-adrenal axis.

Beta-endorphin attenuates the serum cortisol response to exogenous adrenocorticotropin.

Controversy surrounds the issue of whether beta-endorphin affects adrenal steroidogenesis. Recent work has both supported and refuted the claim that beta-endorphin stimulates a rise in serum aldosterone. We investigated the role of beta-endorphin in adrenal steroidogenesis by examining its potential modulation of the response of serum cortisol to exogenous ACTH (Cosyntropin). Four of five normal men received: 1) synthetic beta-endorphin (1 microgram/kg X min) for 30 min, followed by a bolus dose of 0.2 micrograms ACTH; 2) beta-endorphin (100 micrograms, iv), followed by 0.2 micrograms ACTH iv; 3) 0.2 micrograms ACTH iv; and 4) beta-endorphin (100 micrograms iv) alone. The integrated cortisol response to exogenous ACTH, calculated as the area under the cortisol response curve, was significantly less when the ACTH infusion was preceded by the 30-min beta-endorphin infusion than when administered alone [163 +/- 50 (SE) microgram/dl X min vs. 282 +/- 51 micrograms/dl X min, respectively; P less than 0.01]. By contrast, there was no difference between the integrated cortisol response to exogenous ACTH alone and exogenous ACTH after the bolus dose of beta-endorphin (282 +/- 51 vs. 293 +/- 39 micrograms/dl X min, respectively). Beta-Endorphin (30-min infusion or 100-micrograms bolus dose alone) caused no change in serum aldosterone, dehydroepiandrosterone, or PRA. Serum PRL levels, however, were raised significantly (P less than 0.05) by the 30-min infusion of beta-endorphin. The infusion and bolus doses of beta-endorphin raised plasma beta-endorphin levels to over 100,000 pg/ml and 5,000 pg/ml, respectively. We conclude that very high plasma levels of beta-endorphin may influence the response of cortisol to ACTH through a direct effect on the adrenal cortex. However, even in disease states such as Addison's and Nelson's diseases, such levels of plasma beta-endorphin are not known to be achieved.

The effects of chronic renal failure and hemodialysis on human red and white cell calmodulin levels.

Red blood cell (RBC) and polymorphonuclear white blood cell (WBC) calmodulin levels were measured in 25 uremic patients on regular hemodialysis. Uremic patients had significantly higher RBC [11.45 +/- 0.66 (+/-SE) fg/cell] and WBC (590.5 +/- 110 fg/cell) calmodulin levels than normal subjects (8.62 +/- 0.37 and 130 +/- 30 fg/cell; P less than 0.05). An extremely high RBC calmodulin level (20.58 fg/cell) was found in a patient with sickle cell anemia. Uremic patients on dialysis for 2 yr or more had lower RBC (10.99 +/- 0.58 fg/cell) and WBC (390 +/- 50 fg/cell) calmodulin levels than those who were on dialysis for less than 2 yr (RBC, 12.30 +/- 1.56 fg/cell; WBC, 943 +/- 256 fg/cell; P less than 0.05). There were no statistically significant differences in calmodulin levels when different subgroups of uremic patients were compared, e.g. patients with diabetes mellitus or those receiving supplemental vitamin D, anabolic steroids, or antihypertensive medications. We conclude that calmodulin levels are elevated in uremic patients on regular hemodialysis.

Use of the dexamethasone-adrenocorticotropin test to assess the requirement for continued glucocorticoid replacement therapy after pituitary surgery.

We assessed the need for continued glucocorticoid replacement therapy in postsurgical pituitary tumor patients using a dexamethasone-ACTH test. The patients received 1 mg dexamethasone, orally, at 2300 h and 250 micrograms synthetic ACTH (Cosyntropin), iv, at 0800 h the next morning. The mean +/- SD integrated cortisol response for a 2-h period of the 31 pituitary tumor patients [1264 +/- 924 micrograms X min/dl (34.87 +/- 25.49 mumol X min/liter)] was significantly less (P less than 0.005) than that of 25 normal subjects [3331 +/- 544 micrograms X min/dl (91.90 +/- 17.04 mumol X min/liter)]. Replacement glucocorticoids were abruptly discontinued in 11 patients with responses above 1450 micrograms X min/dl (40.01 mumol X min/liter). No clinical or laboratory evidence of adrenal insufficiency occurred as long as 15 months after discontinuation. Metyrapone tests, however, in the 11 glucocorticoid-withdrawn patients revealed a reduced mean +/- SD serum 11-deoxycortisol level compared with that of 10 normal subjects [8.9 +/- 4.7 vs. 15.6 +/- 5.0 micrograms/dl (0.26 +/- 0.13 vs. 0.45 +/- 0.16 mumol/liter); P less than 0.005]. Our results indicate that the dexamethasone-ACTH test is useful in identifying patients in whom replacement glucocorticoid therapy can be safely withdrawn under nonstressed conditions. The test can be simplified to one plasma cortisol level determined 30 min after ACTH administration.

Human corticotropin-releasing hormone in depression--correlation with thyrotropin secretion following thyrotropin-releasing hormone.

Twenty-two subjects (11 patients with major endogenous depression and 11 controls) received an intravenous test dose of 100 micrograms human corticotropin-releasing hormone (h-CRH). Corticotropin (ACTH), but not cortisol, responses were blunted in depressives. Basal cortisol secretion was higher in depressives than in controls and was negatively correlated to the corticotropin response following h-CRH. This finding indicates the integrity of the glucocorticoid-dependent negative feedback regulation in depression and supports the view that hypercortisolism in depression is primarily due to a suprapituitary disturbance. Comparison of ACTH responses after h-CRH with thyrotropin (TSH) output following thyrotropin-releasing hormone (TRH) revealed a positive correlation (r = 0.65, p less than 0.001). The concordance between ACTH and TSH responses after specific challenges suggests that regulation of both systems is at least in part under a common control.