Tunable sub-luminal propagation of narrowband x-ray pulses

Group velocity control is demonstrated for x-ray photons of 14.4 keV energy via a direct measurement of the temporal delay imposed on spectrally narrow x-ray pulses. Sub-luminal light propagation is achieved by inducing a steep positive linear dispersion in the optical response of ${}^{57}$Fe M\"ossbauer nuclei embedded in a thin film planar x-ray cavity. The direct detection of the temporal pulse delay is enabled by generating frequency-tunable spectrally narrow x-ray pulses from broadband pulsed synchrotron radiation. Our theoretical model is in good agreement with the experimental data.Comment: 8 pages, 4 figure

Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab

Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone

Coherent control of collective nuclear quantum states via transient magnons

Ultrafast and precise control of quantum systems at x-ray energies involves photons with oscillation periods below 1 as. Coherent dynamic control of quantum systems at these energies is one of the major challenges in hard x-ray quantum optics. Here, we demonstrate that the phase of a quantum system embedded in a solid can be coherently controlled via a quasi-particle with subattosecond accuracy. In particular, we tune the quantum phase of a collectively excited nuclear state via transient magnons with a precision of 1 zs and a timing stability below 50 ys. These small temporal shifts are monitored interferometrically via quantum beats between different hyperfine-split levels. The experiment demonstrates zeptosecond interferometry and shows that transient quasi-particles enable accurate control of quantum systems embedded in condensed matter environments

Semiconductor microlasers with intracavity microfluidics for biomedical analyses

Recently demonstrated microfluidic chips have the potential to be useful bioanalytical tools for DNA, protein, and cellular studies. To realize this potential, means for introducing fluids, separating their components, and detection must be integrated onto the chip. The authors have investigated semiconductor laser microcavity spectroscopy as a means for ultrasensitive detection of various fluids, cells, and particulates. Two methods for implementing this laser device are illustrated. A scanning method for reading the light signals from a static fluid in the microcavity is presented. The device has a microfabricated flow structure formed between two surfaces, a vertical cavity surface-emitting laser and a glass dielectric mirror. The resonance frequencies of this Fabry-Perot microcavity are very sensitive to the dielectric properties of the fluids confined inside the cavity. Further, the resonance linewidth or cavity Q is sensitive to the optical length of the cavity, light absorption, and light scattering from the fluid and the surfaces forming the cavity. If cells or particulates are present in the fluid they confine light transverse to the cavity length and develop additional sub-frequencies between the Fabry-Perot frequencies. Thus, the spectrum of light emitted from or transmitted through the cavity comprises a wealth of information about the cavity contents

Innate Immune Activation by Checkpoint Inhibition in Human Patient-Derived Lung Cancer Tissues

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with 13C6-Glc/13C5,15N2-Gln, multiplex immunofluorescence, and digital spatial profiling (DSP) were employed to interrogate metabolic and functional responses to Pembrolizumab and/or WGP. Primary and BM PD-1+ lung cancer OTC responded to Pembrolizumab and Pembrolizumab + WGP treatments, respectively. Pembrolizumab activated innate immune metabolism and functions in primary OTC, which were accompanied by tissue damage. DSP analysis indicated an overall decrease in immunosuppressive macrophages and T cells but revealed microheterogeneity in immune responses and tissue damage. Two TMEs with altered cancer cell properties showed resistance. Pembrolizumab or WGP alone had negligible effects on BM-lung cancer OTC but Pembrolizumab + WGP blocked central metabolism with increased pro-inflammatory effector release and tissue damage. In-depth metabolic analysis and multiplex TME imaging of lung cancer OTC demonstrated overall innate immune activation by Pembrolizumab but heterogeneous responses in the native TME of a patient with primary NSCLC. Metabolic and functional analysis also revealed synergistic action of Pembrolizumab and WGP in OTC of metastatic NSCLC

Discontinuous properties of current-induced magnetic domain wall depinning

The current-induced motion of magnetic domain walls (DWs) confined to nanostructures is of great interest for fundamental studies as well as for technological applications in spintronic devices. Here, we present magnetic images showing the depinning properties of pulse-current-driven domain walls in well-shaped Permalloy nanowires obtained using photoemission electron microscopy combined with X-ray magnetic circular dichroism. In the vicinity of the threshold current density (J th = 4.2 × 10 11 â.A.m-2) for the DW motion, discontinuous DW depinning and motion have been observed as a sequence of "Barkhausen jumps". A one-dimensional analytical model with a piecewise parabolic pinning potential has been introduced to reproduce the DW hopping between two nearest neighbour sites, which reveals the dynamical nature of the current-driven DW motion in the depinning regime

Tunable energy transfer between dipolar-coupled magnetic disks by stimulated vortex gyration

A wide variety of coupled harmonic oscillators exist in nature1. Coupling between different oscillators allows for the possibility of mutual energy transfer between them2-4 and the information-signal propagation5,6. Low-energy input signals and their transport with low-energy dissipation are the key technical factors in the design of information processing devices7. Here, utilizing the concept of coupled oscillators, we experimentally demonstrated a robust new mechanism for energy transfer between spatially separated dipolar-coupled magnetic disks - stimulated vortex gyration. Direct experimental evidence was obtained by time-resolved soft X-ray microscopy. The rate of energy transfer from one disk to the other was deduced from the two normal modes' frequency splitting caused by dipolar interaction. This mechanism provides the advantages of tunable energy transfer rate, low-power input signal, and low-energy dissipation for magnetic elements with negligible damping. Coupled vortex-state disks are promising candidates for information-signal processing devices that operate above room temperature

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin