Gapped Collective Charge Excitations and Interlayer Hopping in Cuprate Superconductors.

We use resonant inelastic x-ray scattering to probe the propagation of plasmons in the electron-doped cuprate superconductor Sr_{0.9}La_{0.1}CuO_{2}. We detect a plasmon gap of ∼120 meV at the two-dimensional Brillouin zone center, indicating that low-energy plasmons in Sr_{0.9}La_{0.1}CuO_{2} are not strictly acoustic. The plasmon dispersion, including the gap, is accurately captured by layered t-J-V model calculations. A similar analysis performed on recent resonant inelastic x-ray scattering data from other cuprates suggests that the plasmon gap is generic and its size is related to the magnitude of the interlayer hopping t_{z}. Our work signifies the three dimensionality of the charge dynamics in layered cuprates and provides a new method to determine t_{z}.

Publisher Correction: Electronic structure of the parent compound of superconducting infinite-layer nickelates.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Electronic structure of the parent compound of superconducting infinite-layer nickelates.

The search continues for nickel oxide-based materials with electronic properties similar to cuprate high-temperature superconductors1-10. The recent discovery of superconductivity in the doped infinite-layer nickelate NdNiO2 (refs. 11,12) has strengthened these efforts. Here, we use X-ray spectroscopy and density functional theory to show that the electronic structure of LaNiO2 and NdNiO2, while similar to the cuprates, includes significant distinctions. Unlike cuprates, the rare-earth spacer layer in the infinite-layer nickelate supports a weakly interacting three-dimensional 5d metallic state, which hybridizes with a quasi-two-dimensional, strongly correlated state with [Formula: see text] symmetry in the NiO2 layers. Thus, the infinite-layer nickelate can be regarded as a sibling of the rare-earth intermetallics13-15, which are well known for heavy fermion behaviour, where the NiO2 correlated layers play an analogous role to the 4f states in rare-earth heavy fermion compounds. This Kondo- or Anderson-lattice-like 'oxide-intermetallic' replaces the Mott insulator as the reference state from which superconductivity emerges upon doping.

Strong Superexchange in a d

The discovery of superconductivity in a d^{9-δ} nickelate has inspired disparate theoretical perspectives regarding the essential physics of this class of materials. A key issue is the magnitude of the magnetic superexchange, which relates to whether cuprate-like high-temperature nickelate superconductivity could be realized. We address this question using Ni L-edge and O K-edge spectroscopy of the reduced d^{9-1/3} trilayer nickelates R_{4}Ni_{3}O_{8} (where R=La, Pr) and associated theoretical modeling. A magnon energy scale of ∼80 meV resulting from a nearest-neighbor magnetic exchange of J=69(4) meV is observed, proving that d^{9-δ} nickelates can host a large superexchange. This value, along with that of the Ni-O hybridization estimated from our O K-edge data, implies that trilayer nickelates represent an intermediate case between the infinite-layer nickelates and the cuprates. Layered nickelates thus provide a route to testing the relevance of superexchange to nickelate superconductivity.

Efficacy and safety of hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs.

OBJECTIVE: To evaluate the Safety and Efficacy of Hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs. MATERIALS AND METHODS: This was a double blind, placebo controlled, parallel group study in 304 inadequately controlled type 2 diabetes (T2DM) subjects with two oral antidiabetic drugs (glimepiride 4 mg and metformin 500 mg) were randomised to hydroxychloroquine (HCQ) 200 mg, 300 mg, 400 mg once daily (OD) or placebo. Dose of hydroxychloroquine was selected as per body weight of the subject. Primary end point was glycated haemoglobin (HbA1c) change at week 12 from baseline. Secondary endpoint was change in fasting plasma glucose (FPG), post prandial plasma glucose (PPG), body weight and any adverse reaction including no of hypoglycemic events, as well as a change in the percentage of subjects with A1C < 7.0% and > 6.5% after 12 weeks of treatment.. In follow-up of 400 mg once daily was once again divided to 200 mg twice daily (BD) to study the effect on tolerability profile for further 12 weeks. RESULTS: Hydroxychloroquine was associated with significant reduction in HbA1c from baseline (7-8.5%) in 12 weeks -0.78%, -0.91% and 1.2% for hydroxychloroquine 200 mg, 300 mg and 400 mg OD, respectively, versus 0.13% with placebo (P < 0.005). FPG and PPG were reduced by -25 to -38 mg/dl and 34-53 mg/dl, respectively. Body weight also reduced in each group of HCQ. Hypoglycemia was reported only with 300 mg (1.2%) and 400 mg (2.1%) group of HCQ. It was observed that patients who complains with mild GI disturbance with HCQ 400 mg glycemic efficacy was maintained with 200 mg BD with significant relief of the symptoms. CONCLUSION: Hydroxychloroquine added to sulphonylurea and metformin, improves glycemic control significantly in T2DM patients. Glycemic effect of different dose of hydroxychloroquine is dose dependent. The safety/tolerability profile of hydroxychloroquine was favourable except GI disturbance which is more frequent with 400 mg. This can be avoided with 200 mg BD without compromise on efficacy.

Strongly Correlated Charge Density Wave in La_{2-x}Sr_{x}CuO_{4} Evidenced by Doping-Dependent Phonon Anomaly.

The discovery of charge-density-wave-related effects in the resonant inelastic x-ray scattering spectra of cuprates holds the tantalizing promise of clarifying the interactions that stabilize the electronic order. Here, we report a comprehensive resonant inelastic x-ray scattering study of La_{2-x}Sr_{x}CuO_{4} finding that charge-density wave effects persist up to a remarkably high doping level of x=0.21 before disappearing at x=0.25. The inelastic excitation spectra remain essentially unchanged with doping despite crossing a topological transition in the Fermi surface. This indicates that the spectra contain little or no direct coupling to electronic excitations near the Fermi surface, rather they are dominated by the resonant cross section for phonons and charge-density-wave-induced phonon softening. We interpret our results in terms of a charge-density wave that is generated by strong correlations and a phonon response that is driven by the charge-density-wave-induced modification of the lattice.

Hopping-Induced Ground-State Magnetism in 6H Perovskite Iridates.

Investigation of elementary excitations has advanced our understanding of many-body physics governing most physical properties of matter. Recently spin-orbit excitons have drawn much attention, whose condensates near phase transitions exhibit Higgs mode oscillations, a long-sought-after physical phenomenon [A. Jain, et al., Nat. Phys. 13, 633 (2017)NPAHAX1745-247310.1038/nphys4077]. These critical transition points, resulting from competing spin-orbit coupling (SOC), local crystalline symmetry, and exchange interactions, are not obvious in iridium-based materials, where SOC prevails in general. Here, we present results of resonant inelastic x-ray scattering on a spin-orbital liquid Ba_{3}ZnIr_{2}O_{9} and three other 6H-hexagonal perovskite iridates that show magnetism, contrary to the nonmagnetic singlet ground state expected due to strong SOC. Our results show that substantial hopping between closely placed Ir^{5+} ions within Ir_{2}O_{9} dimers in these 6H iridates modifies spin-orbit coupled states and reduces spin-orbit excitation energies. Here, we are forced to use at least a two-site model to match the excitation spectrum going in-line with the strong intradimer hopping. Apart from SOC, low-energy physics of iridates is thus critically dependent on hopping and may not be ignored even for systems having moderate hopping, where the excitation spectra can be explained using an atomic model. SOC, which is generally found to be 0.4-0.5 eV in iridates, is scaled in effect down to ∼0.26 eV for the 6H systems, sustaining the hope of achieving quantum criticality by tuning Ir-Ir separation.

Tear metabolite changes in keratoconus.

While efforts have been made over the years, the exact cause of keratoconus (KC) remains unknown. The aim of this study was to identify alterations in endogenous metabolites in the tears of KC patients compared with age-matched healthy subjects. Three groups were tested: 1) Age-matched controls with no eye disease (N = 15), 2) KC - patients wearing Rigid Gas permeable lenses (N = 16), and 3) KC - No Correction (N = 14). All samples were processed for metabolomics analysis using LC-MS/MS. We identified a total of 296 different metabolites of which >40 were significantly regulated between groups. Glycolysis and gluconeogenesis had significant changes, such as 3-phosphoglycerate and 1,3 diphosphateglycerate. As a result the citric acid cycle (TCA) was also affected with notable changes in Isocitrate, aconitate, malate, and acetylphosphate, up regulated in Group 2 and/or 3. Urea cycle was also affected, especially in Group 3 where ornithine and aspartate were up-regulated by at least 3 fold. The oxidation state was also severely affected. Groups 2 and 3 were under severe oxidative stress causing multiple metabolites to be regulated when compared to Group 1. Group 2 and 3, both showed significant down regulation in GSH-to-GSSG ratio when compared to Group 1. Another indicator of oxidative stress, the ratio of lactate - pyruvate was also affected with Groups 2 and 3 showing at least a 2-fold up regulation. Overall, our data indicate that levels of metabolites related to urea cycle, TCA cycle and oxidative stress are highly altered in KC patients.

Quadrupolar magnetic excitations in an isotropic spin-1 antiferromagnet.

The microscopic origins of emergent behaviours in condensed matter systems are encoded in their excitations. In ordinary magnetic materials, single spin-flips give rise to collective dipolar magnetic excitations called magnons. Likewise, multiple spin-flips can give rise to multipolar magnetic excitations in magnetic materials with spin S ≥ 1. Unfortunately, since most experimental probes are governed by dipolar selection rules, collective multipolar excitations have generally remained elusive. For instance, only dipolar magnetic excitations have been observed in isotropic S = 1 Haldane spin systems. Here, we unveil a hidden quadrupolar constituent of the spin dynamics in antiferromagnetic S = 1 Haldane chain material Y2BaNiO5 using Ni L3-edge resonant inelastic x-ray scattering. Our results demonstrate that pure quadrupolar magnetic excitations can be probed without direct interactions with dipolar excitations or anisotropic perturbations. Originating from on-site double spin-flip processes, the quadrupolar magnetic excitations in Y2BaNiO5 show a remarkable dual nature of collective dispersion. While one component propagates as non-interacting entities, the other behaves as a bound quadrupolar magnetic wave. This result highlights the rich and largely unexplored physics of higher-order magnetic excitations.

Salvage Using Polatuzumab Vedotin Based Therapy in Relapsed Refractory Large B-Cell Lymphomas: Early Experience from a Real-World Middle-Income Setting Using Named-Patient Compassionate Access Program.

Polatuzumab vedotin is a novel immunotherapy antibody-drug conjugate targeting CD79b. It has been used in relapsed/refractory (R/R) large B-cell lymphomas since its FDA approval in 2019. Presently, this drug is unaffordable or unavailable for patients in Lower-Middle Income Countries (LMIC) like India. This is a retrospective study of adult (> 18 years) patients with R/R large B-cell lymphoma failing two prior lines of therapy, who received Polatuzumab based salvage therapy on a compassionate or named-patient access program. Between May 2019 and April 2022, 10 patients received Polatuzumab vedotin, and 9 were evaluable. The most common regimen used was Polatuzumab-Bendamustine-Rituximab. Out of 43 infusions administered, the adverse event profile was manageable [One grade-2 infusion reaction, 4 patients developed grade 3-4 hematological toxicity and none had grade 3-4 non-hematological toxicities]. Ten infusions were administered in the day care service. After a median of 4.5 cycles (range 1-8), 4 patients achieved CR, 2 had partial response (PR), and 3 had progressive disease (PD). With a median follow up of 491 days (range 8-1048 days), four patients are alive (three in CR and one in PR), three patients have died and three patients were lost to follow up. Early real-world experience from a LMIC setting demonstrates feasibility and a favourable safety profile of Polatuzumab vedotin based approach, along with encouraging response rates in a subset of patients.

Resonant inelastic x-ray spectroscopy on UO2 as a test case for actinide materials.

Resonant inelastic x-ray spectroscopy at the uranium N4 absorption edge at 778 eV has been used to reveal the excitations in UO2 up to 1 eV. The earlier (1989) studies by neutron inelastic scattering of the crystal-field states within the 3H4 multiplet are confirmed. In addition, the first excited state of the 3F2 multiplet at ∼520 meV has been established, and there is a weak signal corresponding to the next excited state at ∼920 meV. This represents a successful application of soft x-ray spectroscopy to an actinide sample, and resolves an open question in UO2 that has been discussed for 50 years. The technique is described and important caveats are drawn about possible future applications.

Magnetic excitations in infinite-layer nickelates.

The discovery of superconductivity in infinite-layer nickelates brings us tantalizingly close to a material class that mirrors the cuprate superconductors. We measured the magnetic excitations in these nickelates using resonant inelastic x-ray scattering at the Ni L 3-edge. Undoped NdNiO2 possesses a branch of dispersive excitations with a bandwidth of approximately 200 milli-electron volts, which is reminiscent of the spin wave of strongly coupled, antiferromagnetically aligned spins on a square lattice. The substantial damping of these modes indicates the importance of coupling to rare-earth itinerant electrons. Upon doping, the spectral weight and energy decrease slightly, whereas the modes become overdamped. Our results highlight the role of Mottness in infinite-layer nickelates.

Gamma-Ray and Radio-Frequency Radiation from Thunderstorms Observed from Space and Ground.

Terrestrial gamma ray flashes (TGFs) are a class of enigmatic electrical discharges in the Earth's atmosphere. In this study, we analyze an unprecedentedly large dataset comprised of 2188 TGFs whose signatures were simultaneously measured using space- and ground-based detectors over a five-year period. The Gamma-ray Burst Monitor (GBM) on board the Fermi spacecraft provided the energetic radiation measurements. Radio frequency (RF) measurements were obtained from the Global Lightning Dataset (GLD360). Here we show the existence of two categories of TGFs - those that were accompanied by quasi-simultaneous electromagnetic pulses (EMPs) detected by the GLD360 and those without such simultaneous EMPs. We examined, for the first time, the dependence of the TGF-associated EMP-peak-amplitude on the horizontal offset distance between the Fermi spacecraft and the TGF source. TGFs detected by the GBM with sources at farther horizontal distances are expected to be intrinsically brighter and were found to be associated with EMPs having larger median peak-amplitudes. This provides independent evidence that the EMPs and TGFs are produced by the same phenomenon, rather than the EMPs being from "regular" lightning in TGF-producing thunderstorms.

Ultrastructure and adenosine triphosphatase activity of red and white muscle fibers of the caudal region of a fish, Salmo gairdneri.

Electron microscopy, together with quantitation using a tracing device linked to a digital computer, reveals that the red and white muscle fibers of Salmo gairdneri differ in diameter, organization of myofibrils, dimensions of myofilaments, volumes and surface areas of T system and sarcoplasmic reticulum, morphology of mitochondria, and content of mitochondria, lipid, and glycogen. Biochemical studies show that the ATPase activity of white fibers is three times that of the red fibers. Actomyosin content of red fibers is higher than that of the white fibers. The functional significance of these differences between two fiber types is discussed.

Intercellular adhesion: coconstruction of contractile heart tissue by cells of different species.

Dissociated embryonic rat myocardial cells and chick myocardial cells labeled with radioactive isotope coaggregate and establish intercellular junctions. These bispecific cells reconstruct synchronously beating myocardial tissue within 24 hours of culture.

DNA synthesis and mitosis in adult amphibian cardiac muscle cells in vitro.

High-resolution autoradiography and fine structural analysis of adult newt heart tissue in long-term culture revealed that tritiated thymidine was concentrated in the nuclei of dedifferentiated myocardial cells. Mitotic chromosomes were observed in some of these cells. This demonstrates that adult amphibian myocardial cells in vitro are capable of DNA synthesis and mitosis.

Replication timing of genes and middle repetitive sequences.

DNA replication in mammals is temporally bimodal. "Housekeeping" genes, which are active in all cells, replicate during the first half of the S phase of cell growth. Tissue-specific genes replicate early in those cells in which they are potentially expressed, and they usually replicate late in tissues in which they are not expressed. Replication during the first half of the S phase is, therefore, a necessary but not sufficient condition for gene transcription. A change in the replication timing of a tissue-specific gene appears to reflect the commitment of that gene to transcriptional competence or to quiescence during ontogeny. Most families of middle repetitive sequences replicate either early or late. These data are consistent with a model in which two functionally distinct genomes coexist in the nucleus.

A comparative study of macrobenthic community from harbours along the central west coast of India.

Harbours are heavily stressed coastal habitats characterised by high concentration of contaminant and low diversity of benthic community. The west coast of India harbours most of the major harbours compared to the east coast. Very few studies have compared the macrobenthic community between different Indian harbours. The present study was therefore conducted in three important harbour (Ratnagiri, Goa, Karwar) along the central west coast of India. The paper discusses the health status of the three harbours diagnosed using various biotic indices. Sediment samples were collected using van Veen grab (0.11 m(2)) on board CRV Sagar Sukti. A total of 55 macrobenthic taxa were identified and were numerically dominated by polychaete. Biomass was high (0.14-145.7 g m(-2)) and was made largely by echiurans (>80%). Overall, polychaete dominated the macrobenthic diversity. Opportunistic P.pinnata, Notomastus sp. and Mediomastus sp., dominated the macrobenthic community responding to the increased in the harbour. Biotic indices (Polychaete:Amphipod ratio, ABC curve and geometric class abundance) and the dominance of opportunistic species indicate that, the three harbours are under stress from anthropogenic activities.

A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. METHODS: Based on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. KEY RESULTS: Suggestive GWAS signals (P ≤ 5.0 × 10-6 ) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P = 3.1 × 10-10 ) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. CONCLUSION & INFERENCES: Our results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.

The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells.

The damaged-DNA binding protein DDB consists of two subunits, DDB1 (127 kDa) and DDB2 (48 kDa). Mutations in the DDB2 subunit have been detected in patients suffering from the repair deficiency disease xeroderma pigmentosum (group E). In addition, recent studies suggested a role for DDB2 in global genomic repair. DDB2 also exhibits transcriptional activity. We showed that expression of DDB1 and DDB2 stimulated the activity of the cell cycle regulatory transcription factor E2F1. Here we show that DDB2 is a cell cycle-regulated protein. It is present at a low level in growth-arrested primary fibroblasts, and after release the level peaks at the G(1)/S boundary. The cell cycle regulation of DDB2 involves posttranscriptional mechanisms. Moreover, we find that an inhibitor of 26S proteasome increases the level of DDB2, suggesting that it is regulated by the ubiquitin-proteasome pathway. Our previous study indicated that the cullin family protein Cul-4A associates with the DDB2 subunit. Because cullins are involved in the ubiquitin-proteasome pathway, we investigated the role of Cul-4A in regulating DDB2. Here we show that DDB2 is a specific target of Cul-4A. Coexpression of Cul-4A, but not Cul-1 or other highly related cullins, increases the ubiquitination and the decay rate of DDB2. A naturally occurring mutant of DDB2 (2RO), which does not bind Cul-4A, is not affected by coexpression of Cul-4A. Studies presented here identify a specific function of the Cul-4A gene, which is amplified and overexpressed in breast cancers.