A new view of electrochemistry at highly oriented pyrolytic graphite

Major new insights on electrochemical processes at graphite electrodes are reported, following extensive investigations of two of the most studied redox couples, Fe(CN)64–/3– and Ru(NH3)63+/2+. Experiments have been carried out on five different grades of highly oriented pyrolytic graphite (HOPG) that vary in step-edge height and surface coverage. Significantly, the same electrochemical characteristic is observed on all surfaces, independent of surface quality: initial cyclic voltammetry (CV) is close to reversible on freshly cleaved surfaces (>400 measurements for Fe(CN)64–/3– and >100 for Ru(NH3)63+/2+), in marked contrast to previous studies that have found very slow electron transfer (ET) kinetics, with an interpretation that ET only occurs at step edges. Significantly, high spatial resolution electrochemical imaging with scanning electrochemical cell microscopy, on the highest quality mechanically cleaved HOPG, demonstrates definitively that the pristine basal surface supports fast ET, and that ET is not confined to step edges. However, the history of the HOPG surface strongly influences the electrochemical behavior. Thus, Fe(CN)64–/3– shows markedly diminished ET kinetics with either extended exposure of the HOPG surface to the ambient environment or repeated CV measurements. In situ atomic force microscopy (AFM) reveals that the deterioration in apparent ET kinetics is coupled with the deposition of material on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the local surface conductivity of HOPG deteriorates significantly with time. These observations and new insights are not only important for graphite, but have significant implications for electrochemistry at related carbon materials such as graphene and carbon nanotubes

Photochemistry of Furyl- and Thienyldiazomethanes: Spectroscopic Characterization of Triplet 3-Thienylcarbene

Photolysis (λ \u3e 543 nm) of 3-thienyldiazomethane (1), matrix isolated in Ar or N2 at 10 K, yields triplet 3-thienylcarbene (13) and α-thial-methylenecyclopropene (9). Carbene 13 was characterized by IR, UV/vis, and EPR spectroscopy. The conformational isomers of 3-thienylcarbene (s-E and s-Z) exhibit an unusually large difference in zero-field splitting parameters in the triplet EPR spectrum (|D/hc| = 0.508 cm–1, |E/hc| = 0.0554 cm–1; |D/hc| = 0.579 cm–1, |E/hc| = 0.0315 cm–1). Natural Bond Orbital (NBO) calculations reveal substantially differing spin densities in the 3-thienyl ring at the positions adjacent to the carbene center, which is one factor contributing to the large difference in D values. NBO calculations also reveal a stabilizing interaction between the sp orbital of the carbene carbon in the s-Z rotamer of 13 and the antibonding σ orbital between sulfur and the neighboring carbon—an interaction that is not observed in the s-E rotamer of 13. In contrast to the EPR spectra, the electronic absorption spectra of the rotamers of triplet 3-thienylcarbene (13) are indistinguishable under our experimental conditions. The carbene exhibits a weak electronic absorption in the visible spectrum (λmax = 467 nm) that is characteristic of triplet arylcarbenes. Although studies of 2-thienyldiazomethane (2), 3-furyldiazomethane (3), or 2-furyldiazomethane (4) provided further insight into the photochemical interconversions among C5H4S or C5H4O isomers, these studies did not lead to the spectroscopic detection of the corresponding triplet carbenes (2-thienylcarbene (11), 3-furylcarbene (23), or 2-furylcarbene (22), respectively)

Materials characterisation part II: tip geometry of the Vickers indenter for microindentation tests

This is the second of two papers by the authors associated with materials characterisation methods based on hardness testing. It is important to have knowledge of the tip geometry of the indenter employed in the hardness test as this affects the correctness of the value of contact area parameter used to determine the mechanical properties. In this paper, outcomes of a study concerned with the tip geometry of the Vickers microindenter are presented. Results from experiment are compared with results from published works and the most current accepted analytical models. A new non-contact methodology based on a residual imprint imaging process is developed and further compared with other methods using experimental and numerical analyses over a wide range of material properties. For confirmation, an assessment was undertaken using numerical dimensional analysis which permitted a large range of materials to be explored. It is shown that the proposed method is more accurate compared with other methods regardless of the mechanical properties of the material. The outcomes demonstrate that measuring contact area with the new method enhanced the overall relative error in the resulting mechanical properties including hardness and Young’s modulus of elasticity. It is also shown that the value of the contact area using actual indenter geometry obtained from experimental load-displacement analysis or FEM numerical analysis is more accurate than the value obtained from the assumption of perfect indenter geometry and hence can be used for materials with low strain hardening property. © 2017 Springer-Verlag Londo

Effect of C-2 substitution on the stability of non-traditional cephalosporins in mouse plasma

A systematic study of the stability of a set of cephalosporins in mouse plasma reveals that cephalosporins lacking an acidic moiety at C-2 may be vulnerable to β-lactam cleavage in mouse plasma

Exploring the relationship between homosexuality and sport among the teammates of a small, Midwestern Catholic college soccer team.

Despite decreasing homophobia, openly gay male athletes are still rare in organized, competitive teamsports. In this action research, we explore two aspects of homosexuality and sport: (1) the effect of a gay male soccer player coming out to his teammates; and (2) the effect of having an openly gay researcher in the field. This is, therefore, the first-ever first-hand account of an athlete's coming-out process with researchers in the field. Even though this is action research and, therefore, not generalizable, we highlight that this research contributes to the body of literature on sexuality and sport because we document the interactions of straight athletes with a gay player and a gay researcher among the heterosexual players at a small, Catholic college in the American Midwest. We use interviews to show that players were accepting of homosexuality before the beginning of this research and show that discussions with these two gay men further promoted players' perspectives on homosexuality. This led to an increase in the team's social cohesion and a decrease in heteronormativity

Apraxia in progressive nonfluent aphasia

The clinical and neuroanatomical correlates of specific apraxias in neurodegenerative disease are not well understood. Here we addressed this issue in progressive nonfluent aphasia (PNFA), a canonical subtype of frontotemporal lobar degeneration that has been consistently associated with apraxia of speech (AOS) and in some cases orofacial apraxia, limb apraxia and/or parkinsonism. Sixteen patients with PNFA according to current consensus criteria were studied. Three patients had a corticobasal syndrome (CBS) and two a progressive supranuclear palsy (PSP) syndrome. Speech, orofacial and limb praxis functions were assessed using the Apraxia Battery for Adults-2 and a voxel-based morphometry (VBM) analysis was conducted on brain MRI scans from the patient cohort in order to identify neuroanatomical correlates. All patients had AOS based on reduced diadochokinetic rate, 69% of cases had an abnormal orofacial apraxia score and 44% of cases (including the three CBS cases and one case with PSP) had an abnormal limb apraxia score. Severity of orofacial apraxia (but not AOS or limb apraxia) correlated with estimated clinical disease duration. The VBM analysis identified distinct neuroanatomical bases for each form of apraxia: the severity of AOS correlated with left posterior inferior frontal lobe atrophy; orofacial apraxia with left middle frontal, premotor and supplementary motor cortical atrophy; and limb apraxia with left inferior parietal lobe atrophy. Our findings show that apraxia of various kinds can be a clinical issue in PNFA and demonstrate that specific apraxias are clinically and anatomically dissociable within this population of patients

Erythropoietin Blockade Inhibits the Induction of Tumor Angiogenesis and Progression

BACKGROUND: The induction of tumor angiogenesis, a pathologic process critical for tumor progression, is mediated by multiple regulatory factors released by tumor and host cells. We investigated the role of the hematopoietic cytokine erythropoietin as an angiogenic factor that modulates tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: Fluorescently-labeled rodent mammary carcinoma cells were injected into dorsal skin-fold window chambers in mice, an angiogenesis model that allows direct, non-invasive, serial visualization and real-time assessment of tumor cells and neovascularization simultaneously using intravital microscopy and computerized image analysis during the initial stages of tumorigenesis. Erythropoietin or its antagonist proteins were co-injected with tumor cells into window chambers. In vivo growth of cells engineered to stably express a constitutively active erythropoietin receptor EPOR-R129C or the erythropoietin antagonist R103A-EPO were analyzed in window chambers and in the mammary fat pads of athymic nude mice. Co-injection of erythropoietin with tumor cells or expression of EPOR-R129C in tumor cells significantly stimulated tumor neovascularization and growth in window chambers. Co-injection of erythropoietin antagonist proteins (soluble EPOR or anti-EPO antibody) with tumor cells or stable expression of antagonist R103A-EPO protein secreted from tumor cells inhibited angiogenesis and impaired tumor growth. In orthotopic tumor xenograft studies, EPOR-R129C expression significantly promoted tumor growth associated with increased expression of Ki67 proliferation antigen, enhanced microvessel density, decreased tumor hypoxia, and increased phosphorylation of extracellular-regulated kinases ERK1/2. R103A-EPO antagonist expression in mammary carcinoma cells was associated with near-complete disruption of primary tumor formation in the mammary fat pad. CONCLUSIONS/SIGNIFICANCE: These data indicate that erythropoietin is an important angiogenic factor that regulates the induction of tumor cell-induced neovascularization and growth during the initial stages of tumorigenesis. The suppression of tumor angiogenesis and progression by erythropoietin blockade suggests that erythropoietin may constitute a potential target for the therapeutic modulation of angiogenesis in cancer

Structure of a Classical MHC Class I Molecule That Binds “Non-Classical” Ligands

The chicken MHC YF1*7.1 X-ray structures reveal that this protein binds lipids and thus represents a "hybrid" class I complex with features of classical as well as non-classical MHC molecules

Dual-Pharmacophore Pyrithione-Containing Cephalosporins Kill Both Replicating and Nonreplicating Mycobacterium tuberculosis

The historical view of β-lactams as ineffective antimycobacterials has given way to growing interest in the activity of this class against Mycobacterium tuberculosis (Mtb) in the presence of a β-lactamase inhibitor. However, most antimycobacterial β-lactams kill Mtb only or best when the bacilli are replicating. Here, a screen of 1904 β-lactams led to the identification of cephalosporins substituted with a pyrithione moiety at C3′ that are active against Mtb under both replicating and nonreplicating conditions, neither activity requiring a β-lactamase inhibitor. Studies showed that activity against nonreplicating Mtb required the in situ release of the pyrithione, independent of the known class A β-lactamase, BlaC. In contrast, replicating Mtb could be killed both by released pyrithione and by the parent β-lactam. Thus, the antimycobacterial activity of pyrithione-containing cephalosporins arises from two mechanisms that kill mycobacteria in different metabolic states

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms