Doped carbon-based systems have been extensively studied over the past decade as active electrocatalysts for both the two-electron (2e–) and four-electron (4e–) oxygen reduction reactions (ORRs). ...However, the mechanisms for ORR are generally poorly understood. Here, we report an extensive experimental and first-principles theoretical study of the ORR at nitrogen-doped reduced graphene oxide (NrGO). We synthesize three distinct NrGO catalysts and investigate their chemical and structural properties in detail via X-ray photoelectron spectroscopy, infrared and Raman spectroscopies, high-resolution transmission electron microscopy, and thin-film electrical conductivity. ORR experiments include the pH dependences of 2e– versus 4e– ORR selectivity, ORR onset potentials, Tafel slopes, and H/D kinetic isotope effects. These experiments show very different ORR behavior for the three catalysts, in terms of both selectivity and the underlying mechanism, which proceeds either via coupled proton–electron transfers (CPETs) or non-CPETs. Reasonable structural models developed from density functional theory rationalize this behavior. The key determinant between CPET vs non-CPET mechanisms is the electron density at the Fermi level under operating ORR conditions. Regardless of the reaction mechanism or electrolyte pH, however, we identify the ORR active sites as sp2 carbons that are located next to oxide regions. This assignment highlights the importance of oxygen functional groups, while details of (modest) N-doping may still affect the overall catalytic activity, and likely also the selectivity, by modifying the general chemical environment around the active site.
Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic ...progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4
T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.
Spintronic elements based on spin transfer torque have emerged with potential for on‐chip memory, but they suffer from large energy dissipation due to the large current densities required. In ...contrast, an electric‐field‐driven magneto‐electric storage element can operate with capacitive displacement charge and potentially reach 1–10 µJ cm−2 switching operation. Here, magneto‐electric switching of a magnetoresistive element is shown, operating at or below 200 mV, with a pathway to get down to 100 mV. A combination of phase detuning is utilized via isovalent La substitution and thickness scaling in multiferroic BiFeO3 to scale the switching energy density to ≈10 µJ cm−2. This work provides a template to achieve attojoule‐class nonvolatile memories.
Spintronic elements based on spin transfer torque have emerged with potential for on‐chip memory, but they suffer from large energy dissipation. Magneto‐electric switching of a magnetoresistive element operating at or below 200 mV with a pathway to reduce a switching energy density to ≈10 µJ cm‐2 is shown. This work provides a template to achieve attojoule‐class nonvolatile memories.
Development and homeostasis of the cardiovascular system require intimate interactions between endothelial and smooth muscle cells, which form a seamless circulatory network. We show that histone ...deacetylase 7 (HDAC7) is specifically expressed in the vascular endothelium during early embryogenesis, where it maintains vascular integrity by repressing the expression of matrix metalloproteinase (MMP) 10, a secreted endoproteinase that degrades the extracellular matrix. Disruption of the
HDAC7 gene in mice results in embryonic lethality due to a failure in endothelial cell-cell adhesion and consequent dilatation and rupture of blood vessels. HDAC7 represses
MMP10 gene transcription by associating with myocyte enhancer factor-2 (MEF2), a direct activator of
MMP10 transcription and essential regulator of blood vessel development. These findings reveal an unexpected and specific role for HDAC7 in the maintenance of vascular integrity and have important implications for understanding the processes of angiogenesis and vascular remodeling during cardiovascular development and disease.
Despite the importance of carrier mobility, recent research efforts have been mainly focused on the improvement of volumetric capacitance in order to maximize the figure‐of‐merit, μC* (product of ...carrier mobility and volumetric capacitance), for high‐performance organic electrochemical transistors. Herein, high‐performance microfiber‐based organic electrochemical transistors with unprecedentedly large μC* using highly ordered crystalline poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) microfibers with very high carrier mobilities are reported. The strain engineering via uniaxial tension is employed in combination with solvent‐mediated crystallization in the course of drying coagulated fibers, resulting in the permanent preferential alignment of crystalline PEDOT:PSS domains along the fiber direction, which is verified by atomic force microscopy and transmission wide‐angle X‐ray scattering. The resultant strain‐engineered microfibers exhibit very high carrier mobility (12.9 cm2 V−1 s−1) without the trade‐off in volumetric capacitance (122 F cm−3) and hole density (5.8 × 1020 cm−3). Such advantageous electrical and electrochemical characteristics offer the benchmark parameter of μC* over ≈1500 F cm−1 V−1 s−1, which is the highest metric ever reported in the literature and can be beneficial for realizing a new class of substrate‐free fibrillar and/or textile bioelectronics in the configuration of electrochemical transistors and/or electrochemical ion pumps.
High‐performance microfiber‐based organic electrochemical transistors are reported, which display unprecedentedly large figure‐of‐merit (μC* ≈1500 F cm−1 V−1 s−1) using highly ordered crystalline PEDOT:PSS microfibers with enhanced carrier mobility (12.9 cm2 V−1 s−1) without the trade‐off in volumetric capacitance (122 F cm−3) owing to the highly anisotropic crystallite domain ordering along the fiber direction via uniaxial strain engineering in combination with solvent‐mediated crystallization.
Abstract
Magnetoelectric coupling at room temperature in multiferroic materials, such as BiFeO
3
, is one of the leading candidates to develop low-power spintronics and emerging memory technologies. ...Although extensive research activity has been devoted recently to exploring the physical properties, especially focusing on ferroelectricity and antiferromagnetism in chemically modified BiFeO
3
, a concrete understanding of the magnetoelectric coupling is yet to be fulfilled. We have discovered that La substitutions at the Bi-site lead to a progressive increase in the degeneracy of the potential energy landscape of the BiFeO
3
system exemplified by a rotation of the polar axis away from the 〈111〉
pc
towards the 〈112〉
pc
discretion. This is accompanied by corresponding rotation of the antiferromagnetic axis as well, thus maintaining the right-handed vectorial relationship between ferroelectric polarization, antiferromagnetic vector and the Dzyaloshinskii-Moriya vector. As a consequence, La-BiFeO
3
films exhibit a magnetoelectric coupling that is distinctly different from the undoped BiFeO
3
films.
High hyperdiploid acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. It is characterized by gain of chromosomes, typically +X, +4, +6, +10, +14, +17, +18, and +21, ...+21; little is known about additional genetic aberrations. Approximately 20% of the patients relapse; therefore it is clinically important to identify risk-stratifying markers. We used SNP array analysis to investigate a consecutive series of 74 cases of high hyperdiploid ALL. We show that the characteristic chromosomal gains are even more frequent than previously believed, indicating that karyotyping mistakes are common, and that almost 80% of the cases display additional abnormalities detectable by SNP array analysis. Subclonality analysis strongly implied that the numerical aberrations were primary and arose before structural events, suggesting that step-wise evolution of the leukemic clone is common. An association between duplication of 1q and +5 was seen (P = 0.003). Other frequent abnormalities included whole-chromosome uniparental isodisomies (wUPIDs) 9 and 11, gain of 17q not associated with isochromosome formation, extra gain of part of 21q, deletions of ETS variant 6 (ETV6), cyclin-dependent kinase inhibitor 2A (CKDN2A) and paired box 5 (PAX5), and PAN3 poly(A) specific ribonuclease subunit homolog (PAN3) microdeletions. Comparison of whole-chromosome and partial UPID9 suggested different pathogenetic outcomes, with the former not involving CDKN2A. Finally, two cases had partial deletions of AT rich interactive domain 5B (ARID5B), indicating that acquired as well as constitutional variants in this locus may be associated with pediatric ALL. Here we provide a comprehensive characterization of the genetic landscape of high hyperdiploid childhood ALL, including the heterogeneous pattern of secondary genetic events.
Rapid, nongenomic vascular cell and tissue responses to estrogen have been demonstrated for more than a decade. Although the pendulum continues to swing, accumulating evidence, both clinical and ...pre-clinical, support favorable effects of ovarian steroid hormones in the vascular system. These effects are mediated both by classical steroid hormone receptor-mediated transcriptional modulation, and largely by endothelial plasma membrane-associated estrogen receptor (ER)α, which when engaged triggers a signaling cascade resulting in release of cardioprotective nitric oxide (NO). In addition to full-length ERα (ER66), an N-terminus truncated ERα isoform, ER46, plays a key role in these rapid endothelial responses to 17β-estradiol (E2). We have recently determined that ER46 can be a Type I integral transmembrane molecule. In this review, we discuss ER isoforms, rapid E2-stimulated signaling in the endothelium, the importance of the ER46 transmembrane orientation, and the clinical context of this rapid endothelial signaling.
Numerous modified-carbon catalysts have been developed for the direct synthesis of hydrogen peroxide through electrochemical oxygen reduction. However, given the complex structure of most porous ...carbons and the poor oxygen reduction reaction (ORR) selectivity typically observed when they are used as catalysts, it is still unclear which carbon defects are responsible for the high two-electron ORR activity typically observed in these materials. Here, we study electrocatalytic peroxide formation activity of nitrogen-doped reduced graphene oxide (N-rGO) materials to relate carbon defects to electrocatalytic activity. To do so, we selected two N-rGO electrodes that selectively produce peroxide at all potentials studied (0.70–0.10 V vs RHE) under alkaline conditions. Oxygen reduction studies, combined with material characterization, especially solid-state 13carbon nuclear magnetic resonance coupled with magic angle spinning and cross-polarization, demonstrate that epoxy or ether groups in the N-rGO catalyst are likely associated with the active sites that form peroxide at the lowest overpotential in alkaline media.
Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of ...157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17) translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA) probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk), demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia.
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