Lifshitz transition enabling superconducting dome around a charge-order critical point.

Superconductivity often emerges as a dome around a quantum critical point (QCP) where long-range order is suppressed to zero temperature, mostly in magnetically ordered materials. However, the emergence of superconductivity at charge-order QCPs remains shrouded in mystery, despite its relevance to high-temperature superconductors and other exotic phases of matter. Here, we present resistance measurements proving that a dome of superconductivity surrounds the putative charge-density-wave QCP in pristine samples of titanium diselenide tuned with hydrostatic pressure. In addition, our quantum oscillation measurements combined with electronic structure calculations show that superconductivity sets in precisely when large electron and hole pockets suddenly appear through an abrupt change of the Fermi surface topology, also known as a Lifshitz transition. Combined with the known repulsive interaction, this suggests that unconventional s± superconductivity is mediated by charge-density-wave fluctuations in titanium diselenide. These results highlight the importance of the electronic ground state and charge fluctuations in enabling unconventional superconductivity.

Co-operative activation of skeletal muscle thin filaments by rigor crossbridges. The effect of troponin C extraction.

When Ca2+ binds to troponin C (TnC), all 26 troponin-tropomyosin (Tn-Tm) complexes of a regulatory strand change in concert from the inactive to the active configuration. To see if the complexes respond similarly when they are activated by rigor crossbridges in the absence of Ca2+, we determined the slope (ns) of the bell-shaped pS/tension (pS = -log [MgATP], where S = MgATP2-) relationship between pS 5, where the tension is maximal, and pS 2.3, where fibers are fully relaxed. In control skinned rabbit psoas fibers the ns value is greater than 4; it progressively decreases with TnC extraction. This decrease in ns with TnC extraction is analogous to the decrease in the slope (Hill coefficient) of the pCa/tension (pCa = -log [Ca2+]) relationship with extraction. Complete TnC extraction reduces the maximum substrate-induced tension by only 25%; in contrast, it reduces the maximum Ca2+ induced tension to zero. The effects of TnC extraction on the slope of the pS/tension curve are explained by the assumptions that (1) extracted Tn-Tm complexes no longer change in concert with their neighbors but change independently of them, and (2) co-operative signals cannot cross extracted Tn-Tm complexes. The ns value, therefore, like the nH, is a direct function of the number of contiguous, intact, Tn-Tm complexes in a stretch of a regulatory strand. To describe qualitatively the bi-phasic pS/tension relationship, the mono-phasic pCa/tension relationship, and the effects of TnC extraction on them, we introduce a version of the concerted-transition formalism which includes two activating ligands, Ca2+ and rigor crossbridges.

[Physical performance in pregnancy]. / Körperliche Leistungsfähigkeit im Verlauf der Schwangerschaft.

To evaluate their physical efficiency, 14 healthy untrained women were examined during pregnancy weeks 16-20, 25-29 and 34-38 and 5 to 10 weeks post partum, by spiroergometry at various exercise levels on the bicycle ergometer. Besides the spiroergometric values, circulatory parameters were measured and serum analyses were carried out. The physical efficiency of the subjects was by no means reduced in the stages of pregnancy investigated. Indeed, several factors indicated an improvement of performance. Thus common features were found regarding the physiological effects of pregnancy and endurance training: increase of the maximum oxygen uptake, lower lactate production when the aerobic/anaerobic threshold was exceeded at high exercise intensity, as well as a relatively lower pulse under exercise. The increased metabolic fat utilisation for energy production in physical work is likewise similar to the effect of endurance training. Many pregnant women occasionally feel that they have reduced physical efficiency. Pregnant subjects were subjected to a standardised exercise test to appraise these complaints objectively. The study carried out was intended to answer the question as to whether the specific processes of adaptation of the cardiopulmonary system in pregnancy would lead to an impairment of physical efficiency. Furthermore, the question was to be answered as to whether the altered metabolic conditions of pregnant women under exercise will influence energy production from carbohydrate and fat metabolism.

Synthesis and pharmacological studies of 4,4-disubstituted piperidines: a new class of compounds with potent analgesic properties.

A series of 4,4-disubstituted piperidines has been synthesized and evaluated for analgesic activity. Several of these analogues show analgesic potency comparable to morphine in the mouse writhing and tail-flick tests. A number of compounds exhibit high affinity for [3H]naloxone binding sites in rat brain membranes. Among the most potent derivatives are compounds 15 and 48. Although opiate-like, attempts to modify this activity with various substituents have failed to produce antagonistic properties. A few of these analogues also show marked long-lasting serotonin antagonism in the guinea pig serotonin toxicity test and the DL-5-hydroxytryptophan induced head-twitch model in the mouse.

Opiate antagonistic properties of an octapeptide somatostatin analog.

The somatostatin analog D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-NH-CH(CH2OH)CHOHCH3 (SMS 201-995) displaces [3h[naloxone from its binding sites (IC50, 38 +/- 60 nM), being more than 200 times more potent than somatostatin. As measured by the difference between [3H]dihydromorphine, [3H][D-Ala2,D-Leu5]enkephalin, and (-)-[3H]bremazocine binding, SMS 201-995 appears to be highly specific for the opiate mu binding site. Electrophysiological data from hippocampal cultures and results from animal studies (tail flick, mydriasis) demonstrate the opiate antagonistic properties of SMS 201-995. SMS 201-995 is an opiate mu antagonist with a peptide structure. That this property is displayed by a somatostatin analog is somewhat unexpected.

Analgesic properties of the GABA-mimetic THIP.

The analgesic properties of the muscimol analogue THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) in laboratory animals were compared with those of baclofen, morphine and muscimol. THIP was active orally and parenterally and resembled muscimol qualitatively in its actions. Quantitatively, THIP and baclofen were 2--3 times less potent than morphine and 5--15 times less potent than muscimol. The analgesic effects of THIP, baclofen and muscimol were not reversed by naloxone or bicuculline.

Investigations of the analgesic and morphine-like properties of azidomorphine.

In equianalgesic doses, azidomorphine is reported by J. Knoll, S. Fürst and K. Kelemen (The pharmacology of azidomorphine and azidocodeine. J. Pharm. Pharmacol. 25: 929-939, 1973) to be less likely than morphine to cause physical dependence. As the separation of the analgesic from the dependence-producing properties would represent an important contribution to the development of potent analgesic drugs, we have compared the effects of azidomorphine and morphine in a number of experiments in laboratory animals. In analgesic studies, azidomorphine was more potent than morphine in all tests and by every route of administration. However, the differences between the analgesic effects of azidomorphine and morphine were much smaller after oral than after parenteral administration. In the rhesus monkey, the programmed administration of azidomorphine over a period of 9 weeks produced physical dependence. In addition, azidomorphine was self-administered by the rhesus monkey over 3 weeks producing marked opiate-like physical dependence. It is concluded that the introduction of the azido group into the morphine molecule leads to a marked increase in analgesic activity compared with the parent drug but which does not decrease the ability to produce physical dependence.