Anisotropic exchange and spin-wave damping in pure and electron-doped Sr2_2IrO4_4

The collective magnetic excitations in the spin-orbit Mott insulator (Sr$_{1-x}$La$_x$)$_2$IrO$_4$ ($x=0,\,0.01,\,0.04,\, 0.1$) were investigated by means of resonant inelastic x-ray scattering. We report significant magnon energy gaps at both the crystallographic and antiferromagnetic zone centers at all doping levels, along with a remarkably pronounced momentum-dependent lifetime broadening. The spin-wave gap is accounted for by a significant anisotropy in the interactions between $J_\text{eff}=1/2$ isospins, thus marking the departure of Sr$_2$IrO$_4$ from the essentially isotropic Heisenberg model appropriate for the superconducting cuprates.Comment: 6 pages, 4 figure

Microstructural and geochemical constraints on the evolution of deep arc lithosphere

Mantle xenoliths from the Sierra Nevada, California, USA, sampled a vertical column (60–120 km) of lithosphere that formed during Mesozoic continental arc magmatism. This lithosphere experienced an anticlockwise P-T-t path resulting in rapid cooling that effectively “quenched in” features inherited from earlier high-temperature conditions. Here we combine new mineral chemistry data (water, trace element, and major element concentrations) with mineral crystallographic preferred orientations (CPOs) to investigate the relationship between melt infiltration and deformation. The peridotites record a refertilization trend with increasing depth, starting from shallow, coarse-protogranular, less-melt-infiltrated spinel peridotite with strong, orthorhombic olivine CPO to deep, fine-porphyroclastic, highly melt-infiltrated garnet peridotite with weak, axial-[010] olivine CPO. In contrast to the observed axial-[010] CPOs, subgrain boundary orientations and misorientation axes suggest the dominant activation of the (001)[100] slip system, suggesting deformation under moderately hydrous conditions. After accounting for effects of subsolidus cooling, we see coherent trends between mineral trace element abundance and water content, indicating that melt infiltration led to an increase in water content of the peridotites. However, measured olivine and pyroxene water contents in all peridotites (5–10 and 30–500 wt ppm, respectively) are lower than that required to promote dominant (001)[100] slip system observed in both natural and experimental samples. These results suggest that deformation occurred earlier along the P-T path, probably during or shortly after hydrous melt infiltration. Subsequent rapid cooling at 90 Ma led to water loss from olivine (owing to decreased solubility at low temperature), leaving behind a deep arc lithosphere that remained viscously coupled to the Farallon slab until the opening of the slab window in the late Cenozoic

Microstructural and geochemical constraints on the evolution of deep arc lithosphere

Mantle xenoliths from the Sierra Nevada, California, USA, sampled a vertical column (60–120 km) of lithosphere that formed during Mesozoic continental arc magmatism. This lithosphere experienced an anticlockwise P-T-t path resulting in rapid cooling that effectively “quenched in” features inherited from earlier high-temperature conditions. Here we combine new mineral chemistry data (water, trace element, and major element concentrations) with mineral crystallographic preferred orientations (CPOs) to investigate the relationship between melt infiltration and deformation. The peridotites record a refertilization trend with increasing depth, starting from shallow, coarse-protogranular, less-melt-infiltrated spinel peridotite with strong, orthorhombic olivine CPO to deep, fine-porphyroclastic, highly melt-infiltrated garnet peridotite with weak, axial-[010] olivine CPO. In contrast to the observed axial-[010] CPOs, subgrain boundary orientations and misorientation axes suggest the dominant activation of the (001)[100] slip system, suggesting deformation under moderately hydrous conditions. After accounting for effects of subsolidus cooling, we see coherent trends between mineral trace element abundance and water content, indicating that melt infiltration led to an increase in water content of the peridotites. However, measured olivine and pyroxene water contents in all peridotites (5–10 and 30–500 wt ppm, respectively) are lower than that required to promote dominant (001)[100] slip system observed in both natural and experimental samples. These results suggest that deformation occurred earlier along the P-T path, probably during or shortly after hydrous melt infiltration. Subsequent rapid cooling at 90 Ma led to water loss from olivine (owing to decreased solubility at low temperature), leaving behind a deep arc lithosphere that remained viscously coupled to the Farallon slab until the opening of the slab window in the late Cenozoic

Neither a novel tau proteinopathy nor an expansion of a phenotype: Reappraising clinicopathology-based nosology

The gold standard for classification of neurodegenerative diseases is postmortem histopathol-ogy; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia–ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann–Pick disease Type C. Postmortem evaluation unexpectedly demonstrated neurodegeneration with 4-repeat tau deposition in a distribution diagnostic of progressive supranuclear palsy (PSP). Whole-exome sequencing revealed a new het-erozygous variant in TGM6, associated with spinocerebellar ataxia type 35 (SCA35). This novel TGM6 variant reduced transglutaminase activity in vitro, suggesting it was pathogenic. This case could be interpreted as expanding: (1) the PSP phenotype to include a spinocerebellar variant; (2) SCA35 as a tau proteinopathy; or (3) TGM6 as a novel genetic variant underlying a SCA35 phenotype with PSP pathology. None of these interpretations seem adequate. We instead hypothesize that impairment in the crosslinking of tau by the TGM6-encoded transglutaminase enzyme may compromise tau functionally and structurally, leading to its aggregation in a pattern currently classified as PSP. The lessons from this case study encourage a reassessment of our clinicopathology-based nosology.Fil: Marsili, Luca. University of Cincinnati; Estados UnidosFil: Sharma, Jennifer. University of Cincinnati; Estados UnidosFil: Espay, Alberto J.. University of Cincinnati; Estados UnidosFil: Migazzi, Alice. Universita degli Studi di Trento; ItaliaFil: Abdelghany, Elhusseini. University of Cincinnati; Estados UnidosFil: Hill, Emily J.. University of Cincinnati; Estados UnidosFil: Duque, Kevin R.. University of Cincinnati; Estados UnidosFil: Hagen, Matthew C.. University of Cincinnati; Estados UnidosFil: Stephen, Christopher D.. Harvard Medical School; Estados UnidosFil: Kovacs, Gabor G.. University of Toronto; CanadáFil: Lang, Anthony E.. University of Toronto; CanadáFil: Hadjivassiliou, Marios. University Of Sheffield (university Of Sheffield);Fil: Basso, Manuela. Universita degli Studi di Trento; ItaliaFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Sturchio, Andrea. University of Cincinnati; Estados Unido

A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies

Immunotherapy promotes the attack of cancer cells by the immune system; however, it is difficult to detect early responses before changes in tumor size occur. Here, we report the rational design of a fluorogenic peptide able to detect picomolar concentrations of active granzyme B as a biomarker of immune-mediated anticancer action. Through a series of chemical iterations and molecular dynamics simulations, we synthesize a library of FRET peptides and identify probe H5 with an optimal fit into granzyme B. We demonstrate that probe H5 enables the real-time detection of T cell-mediated anticancer activity in mouse tumors and in tumors from lung cancer patients. Furthermore, we show image-based phenotypic screens, which reveal that the AKT kinase inhibitor AZD5363 shows immune-mediated anticancer activity. The reactivity of probe H5 may enable the monitoring of early responses to anticancer treatments using tissue biopsies

Natural orifice surgery: initial clinical experience

Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience. Under an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance. Nine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred. The limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access

Using imaging to combat a pandemic:rationale for developing the UK National COVID-19 Chest Imaging Database

No abstract available

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO