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Organic light-emitting diodes (OLEDs) are a revolutionary light-emitting display technology that has been successfully commercialized in mobile phones and televisions1,2. The injected charges form both singlet and triplet excitons, and for high efficiency it is important to enable triplets as well as singlets to emit light. At present, materials that harvest triplets by thermally activated delayed fluorescence (TADF) are a very active field of research as an alternative to phosphorescent emitters that usually use heavy metal atoms3,4. Although excellent progress has been made, in most TADF OLEDs there is a severe decrease of efficiency as the drive current is increased, known as efficiency roll-off. So far, much of the literature suggests that efficiency roll-off should be reduced by minimizing the energy difference between singlet and triplet excited states (ΔEST) to maximize the rate of conversion of triplets to singlets by means of reverse intersystem crossing (kRISC)5–20. We analyse the efficiency roll-off in a wide range of TADF OLEDs and find that neither of these parameters fully accounts for the reported efficiency roll-off. By considering the dynamic equilibrium between singlets and triplets in TADF materials, we propose a figure of merit for materials design to reduce efficiency roll-off and discuss its correlation with reported data of TADF OLEDs. Our new figure of merit will guide the design and development of TADF materials that can reduce efficiency roll-off. It will help improve the efficiency of TADF OLEDs at realistic display operating conditions and expand the use of TADF materials to applications that require high brightness, such as lighting, augmented reality and lasing.

Our understanding of the climatic teleconnections that drove ice-age cycles has been limited by a paucity of well-dated tropical records of glaciation that span several glacial–interglacial intervals. Glacial deposits offer discrete snapshots of glacier extent but cannot provide the continuous records required for detailed interhemispheric comparisons. By contrast, lakes located within glaciated catchments can provide continuous archives of upstream glacial activity, but few such records extend beyond the last glacial cycle. Here a piston core from Lake Junín in the uppermost Amazon basin provides the first, to our knowledge, continuous, independently dated archive of tropical glaciation spanning 700,000 years. We find that tropical glaciers tracked changes in global ice volume and followed a clear approximately 100,000-year periodicity. An enhancement in the extent of tropical Andean glaciers relative to global ice volume occurred between 200,000 and 400,000 years ago, during sustained intervals of regionally elevated hydrologic balance that modified the regular approximately 23,000-year pacing of monsoon-driven precipitation. Millennial-scale variations in the extent of tropical Andean glaciers during the last glacial cycle were driven by variations in regional monsoon strength that were linked to temperature perturbations in Greenland ice cores1; these interhemispheric connections may have existed during previous glacial cycles.

The development of intestinal organoids from single adult intestinal stem cells in vitro recapitulates the regenerative capacity of the intestinal epithelium1,2. Here we unravel the mechanisms that orchestrate both organoid formation and the regeneration of intestinal tissue, using an image-based screen to assay an annotated library of compounds. We generate multivariate feature profiles for hundreds of thousands of organoids to quantitatively describe their phenotypic landscape. We then use these phenotypic fingerprints to infer regulatory genetic interactions, establishing a new approach to the mapping of genetic interactions in an emergent system. This allows us to identify genes that regulate cell-fate transitions and maintain the balance between regeneration and homeostasis, unravelling previously unknown roles for several pathways, among them retinoic acid signalling. We then characterize a crucial role for retinoic acid nuclear receptors in controlling exit from the regenerative state and driving enterocyte differentiation. By combining quantitative imaging with RNA sequencing, we show the role of endogenous retinoic acid metabolism in initiating transcriptional programs that guide the cell-fate transitions of intestinal epithelium, and we identify an inhibitor of the retinoid X receptor that improves intestinal regeneration in vivo.

Asteroseismology probes the internal structures of stars by using their natural pulsation frequencies1. It relies on identifying sequences of pulsation modes that can be compared with theoretical models, which has been done successfully for many classes of pulsators, including low-mass solar-type stars2, red giants3, high-mass stars4and white dwarfs5. However, a large group of pulsating stars of intermediate mass—the so-called δ Scuti stars—have rich pulsation spectra for which systematic mode identification has not hitherto been possible6,7. This arises because only a seemingly random subset of possible modes are excited and because rapid rotation tends to spoil regular patterns8–10. Here we report the detection of remarkably regular sequences of high-frequency pulsation modes in 60 intermediate-mass main-sequence stars, which enables definitive mode identification. The space motions of some of these stars indicate that they are members of known associations of young stars, as confirmed by modelling of their pulsation spectra.

The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5+crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5+CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5+CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5+CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5+CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5+CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation.

The crystal structures of a human IgG antibody molecule Kol and a human Fc fragment have been determined at 4-Å and 3.5-Å resolution respectively, by isomorphous replacement. The electron-density maps were interpreted in terms of immunoglobulin domains based on the Rei and McPC 603 models (Kol) and by model-building (Fc). The Fab parts of Kol have a different quaternary structure from that observed in isolated crystalline Fab fragments, there being no longitudinal V–C contact in Kol. The Fc part C terminal to the hinge is disordered in the Kol crystals. It is suggested that the Kol molecule is flexible in solution, whereas fragments are rigid. In the Fc fragment both CH3 and CH2 show the immunoglobulin fold. The CH3 dimer aggregates as CH1-CLwhile CH2 are widely separated from each other. The carbohydrate bound to Fc is in fixed position. From these structures a hypothetical liganded antibody molecule has been constructed, which is assumed to be rigid.

The microinjection of selected antibodies into the cytosol or nucleus of living cells is proving a useful technique for investigating the function of intracellular proteins1–5. The rationale underlying this approach is that, in binding to its antigenic determinant, the antibody may mask or disrupt the activity mediated by the region of the protein near the determinant. This technique, however, cannot be used to identify functions related to antigenic determinants of proteins within the lumen of the endoplasmic reticulum (ER), or Golgi compartments, since both regions are inaccessible to direct microinjection and since the movement of proteins into these areas from the cytosol occurs during but not after their translation6. In theory, this constraint could be overcome if the mRNAs specifying the antibody were injected into the cell containing the target antigenic determinant. After the vectorial and co-translational transfer of its constituent chains through the membrane, the antibody would then be assembled within the lumen of the ER thereby being in a position to bind to its antigenic determinants. We demonstrate here a successful example of such an approach.

The three-dimensional structure of plastocyanin, a ‘blue’ or ‘Type 1’ copper-protein, has been determined at a resolution of 2.7 Å. The copper atom has a highly distorted tetrahedral coordination geometry. It is coordinated by a cysteine thiol group, a methionine thioether group, and two histidine imidazole groups.

The secretion of immunoglobulins from mouse plasmacytoma cell lines is a valuable model for the study of mechanisms of protein secretion from eukaryotic cells. Some cells do not synthesize heavy chain immunoglobulin while retaining the ability to synthesize though not to secrete the complementary light chain1–3. In the MOPC 21 variant tine, NS1, it is absence of heavy chain that prevents secretion4–6. A reciprocal dependence, that is, a requirement of light chain for heavy chain secretion, has not been tested directly because no variants producing normal heavy chain alone have been detected4,7–9. In view of the known insolubility characteristics of isolated heavy chains in vitro10–12, this failure has led to the idea that free heavy chains would be toxic to the cell7,9. Recently, Xenopus laevis oocytes have been shown to provide a surrogate system for studying protein secretion after microinjection of the encoding mRNA13,14. Using this technique we demonstrate here that tetrameric mouse immunoglobulin is assembled and secreted by the oocyte but that free light chains are not secreted. Moreover, using purified heavy chain mRNA we show that heavy chain dimers accumulate in the oocyte and are not secreted unless light chain mRNA is also injected.

THE final stage of blood coagulation, the conversion of fibrinogen to fibrin by thrombin, is associated with the release of two acidic peptides designated A and B in the bovine system1. These peptides have been fully characterized by physico-chemical, chemical, and enzyme methods, and the exact ammo-acid sequence has been determined2. Laki3has shown that the peptides released from fibrinogen affect the frog heart, and experiments carried out in this laboratory have shown that bovine peptide B (Fig. 1) in a concentration of 4 × 10−5moles/l. produces a slow contraction of the rabbit carotid artery strip, while in a concentration of 1.6 × 10−6moles/l. the peptide markedly potentiated the bradykinin-induced contraction of the isolated oestrous rat uterus. The present experiments were undertaken to ascertain whether bovine peptide B had any vasopressor effect in vivo.

A NUMBER of unrelated groups of planktonic animals have developed the curious arrangement of upwardly directed eyes combined with downwardly directed photophores; this has been described and discussed by Hardy1, who has suggested a number of possible explanations.

OPHIUTROIDS are known1,2to eat a wide range of food, including phytoplankton, zooplankton, polychaetes and detritus; carrion-eating can now be added to the list, for it has recently been observed in this laboratory on the part of Ophiocomina nigra (Abild.), Ophiothrix fragilis(Abild.), Ophiura texturata Lam. and O. abilda Forbes. In aquaria these brittle-stars were seen to eat on one occasion a dead lesser weever (Trachinus viper C. and V.), and on another a small dead cephalopod (Sepiola atlantica d'Orb.). Each ophiuroid's stomach was scarcely everted at all while feeding, but the long tube-feet round the mouth made strong tugging movements, breaking off small pieces from the prey which were later found in the ophiuroid's stomach.

THE past winter has been unusually cold and stormy in Ontario, and, as a result, an uneven strip of ice 100 to 200 yards wide has accumulated along the lake shore, sometimes forming mounds twenty or thirty feet high. Many of these mounds are conical, and have a crater-like opening communicating with the water. In stormy weather every wave hurls a column of spray and ice fragments through the opening. The ejecta freeze fast as they fall, and add to the height of the cone. In high winds the coast seems fringed with miniature volcanoes in active eruption. After a time the crater becomes clogged with ice, and the volcano may be looked on as extinct. Often a second crater is formed just to seaward of the first, and growing upon its ruins.