2-Diazo-1-(4-hydroxyphenyl)ethanone: A Versatile Photochemical and Synthetic Reagent

α-Diazo arylketones are well-known substrates for Wolff rearrangement to phenylacetic acids through a ketene intermediate by either thermal or photochemical activation. Likewise, α-substituted p-hydroxyphenacyl (pHP) esters are substrates for photo-Favorskii rerrangements to phenylacetic acids by a different pathway that purportedly involves a cyclopropanone intermediate. In this paper, we show that the photolysis of a series of α-diazo-p-hydroxyacetophenones and p-hydroxyphenacyl (pHP) α-esters both generate the identical rearranged phenylacetates as major products. Since α-diazo-p-hydroxyacetophenone (1a, pHP N2) contains all the necessary functionalities for either Wolff or Favorskii rearrangement, we were prompted to probe this intriguing mechanistic dichotomy under conditions favorable to the photo-Favorskii reangement, i.e., photolysis in hydroxylic media. An investigation of the mechanism for conversion of 1a to p-hydroxyphenyl acetic acid (4a) using time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of a ketene intermediate that is subsequently trapped by solvent or nucleophiles. The photoreaction of 1a is quenched by oxygen and sensitized by triplet sensitizers and the quantum yields for 1a–c range from 0.19 to a robust 0.25. The lifetime of the triplet, determined by Stern-Volmer quenching, is 15 ns with a rate for appearance of 4a of k = 7,1 × 106 s−1 in aq. acetonitrile (1:1 v:v). These studies establish that the primary rearrangement pathway for 1a involves ketene formation in accordance with the photo-Wolff rearrangement. Furthermore we have also demonstrated the synthetic utility of 1a as an esterification and etherification reagent with a variety of substituted α-diazo-p-hydroxyacetophenones, using them as synthons for efficiently coupling it to acids and phenols to produce pHP protect substrates

Closed-form sums for some perturbation series involving associated Laguerre polynomials

Infinite series sum_{n=1}^infty {(alpha/2)_n / (n n!)}_1F_1(-n, gamma, x^2), where_1F_1(-n, gamma, x^2)={n!_(gamma)_n}L_n^(gamma-1)(x^2), appear in the first-order perturbation correction for the wavefunction of the generalized spiked harmonic oscillator Hamiltonian H = -d^2/dx^2 + B x^2 + A/x^2 + lambda/x^alpha 0 0, A >= 0. It is proved that the series is convergent for all x > 0 and 2 gamma > alpha, where gamma = 1 + (1/2)sqrt(1+4A). Closed-form sums are presented for these series for the cases alpha = 2, 4, and 6. A general formula for finding the sum for alpha/2 = 2 + m, m = 0,1,2, ..., in terms of associated Laguerre polynomials, is also provided.Comment: 16 page

A Tale of 3 Dwarfs: No Extreme Cluster Formation in Extreme Star-Forming Galaxies

Nearly all current simulations predict that outcomes of the star formation process, such as the fraction of stars that form in bound clusters (Gamma), depend on the intensity of star formation activity (SigmaSFR) in the host galaxy. The exact shape and strength of the predicted correlations, however, vary from simulation to simulation. Observational results also remain unclear at this time, because most works have mixed estimates made from very young clusters for galaxies with higher SigmaSFR with those from older clusters for galaxies with lower SigmaSFR. The three blue compact dwarf (BCD) galaxies ESO185-IG13, ESO338-IG04, and Haro11 have played a central role on the observational side because they have some of the highest known SigmaSFR and published values of Gamma. We present new estimates of Gamma for these BCDs in three age intervals (1-10 Myr, 10-100 Myr, 100-400 Myr), based on age-dating which includes Halpha photometry to better discriminate between clusters younger and older than ~10 Myr. We find significantly lower values for Gamma (1-10 Myr) than published previously. The likely reason for the discrepancy is that previous estimates appear to be based on age-reddening results that underestimated ages and overestimated reddening for many clusters, artificially boosting Gamma (1-10 Myr). We also find that fewer stars remain in clusters over time, with ~15-39% in 1-10 Myr, ~5-7% in 10-100 Myr, and ~1-2% in 100-400 Myr clusters. We find no evidence that Gamma increases with SigmaSFR. These results imply that cluster formation efficiency does not vary with star formation intensity in the host galaxy. If confirmed, our results will help guide future assumptions in galaxy-scale simulations of cluster formation and evolution.Comment: Accepted for publication in Ap

Modelling and experimental study on β-phase depletion behaviour of HVOF sprayed free-standing CoNiCrA1Y coatings during oxidation

This paper investigates the β-phase depletion behaviour during oxidation of free-standing CoNiCrA1Y (Co-31.7%Ni-20.8%Cr-8.1%A1-0.5%Y, all in wt%) bond coats prepared by high velocity oxy-fuel (HVOF) thermal spraying. The microstructure of the coatings was characterised using scanning electron microscopy with energy dispersive X-ray (EDX) analysis and electron backscatter diffraction (EBSD). It comprises a two phase structure of fcc γ-Ni and bcc β-NiA1, with grain sizes varying largely from 0.5 to 2 μm for both phases. Isothermal oxidation tests of the free-standing coatings were carried out at 1100 °C for times up to 250 h. The β phase depletion behaviour at the surface was measured and was also simulated using Thermo-Calc and DICTRA software. An A1 flux function derived from an oxide growth model was employed as the boundary condition in the diffusion model. The diffusion calculations were performed using the TTNi7 thermodynamic database together with the MOB2 mobility database. Reasonable agreement was achieved between the measured and the predicted element concentration and phase fraction profiles after various time periods. Grain boundary diffusion is likely to be important to element diffusion in this HVOF sprayed CoNiCrA1Y coating due to the sub-micron grains

An analytical approach to the β-phase coarsening behaviour in a thermally sprayed CoNiCrAlY bond coat alloy

This paper investigates the β-phase coarsening behaviour during isothermal heat treatment of free-standing CoNiCrAlY (Co-31.7%Ni-20.8%Cr-8.1%Al-0.5%Y, all in wt%) coatings prepared by high velocity oxy-fuel (HVOF) thermal spraying. The microstructure of the coatings was characterised using scanning electron microscopy with energy dispersive X-ray (EDX) analysis and electron backscatter diffraction (EBSD). It comprises a two phase structure of fcc γ-Ni matrix and bcc β-NiAl precipitates. The volume fraction of the γ-Ni and the β-NiAl phases were measured to be around 70% and 30% respectively, with grain sizes varying largely from 0.5 to 2 μm for both phases. Isothermal heat treatments of the free-standing coatings were carried out at 1100 C for times up to 250 h. The β-phase coarsening behaviour during isothermal heat treatments was analysed by quantitative metallography. It is shown that the coarsening behaviour of β phase in the CoNiCrAlY alloy followed the classical Lifshitz-Slyozov-Wagner (LSW) theory of Ostwald ripening. By incorporating a dimensionless factor which correlates with volume fraction of the β phase, a modified LSW model coupled with formulaic interfacial energy and effective diffusion coefficient of the CoNiCrAlY alloy was utilised to interpret the coarsening behaviour of the β phase. The coarsening rate coefficient obtained from the modified LSW model shows good agreement with the corresponding experimental result

Morphology and characteristics of radio pulsars

This review describes the observational properties of radio pulsars, fast rotating neutron stars, emitting radio waves. After the introduction we give a list of milestones in pulsar research. The following chapters concentrate on pulsar morphology: the characteristic pulsar parameters such as pulse shape, pulsar spectrum, polarization and time dependence. We give information on the evolution of pulsars with frequency since this has a direct connection with the emission heights, as postulated in the radius to frequency mapping (RFM) concept. We deal successively with the properties of normal (slow) pulsars and of millisecond (fast-recycled) pulsars. The final chapters give the distribution characteristics of the presently catalogued 1300 objects.Comment: 33 pages, PDF with 30 PostScript figures, see http://springerlink.metapress.com/link.asp?id=d6k3a6wunb138dpl Accepted by Astronomy & Astrophysivs Review

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial

BACKGROUND AND OBJECTIVES: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM. METHODS: After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints included change from baseline to week 24 on the distance walked on the 6-minute walk test (6MWT) and total fatigue on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA). Secondary endpoints included most bothersome symptom score on the PMMSA, NeuroQoL Fatigue Short-Form scores, and the patient global impression and clinician global impression of PMM symptoms. RESULTS: Participants (N = 218) were randomized (n = 109 elamipretide; n = 109 placebo). The m0ean age was 45.6 years (64% women; 94% White). Most of the participants (n = 162 [74%]) had mitochondrial DNA (mtDNA) alteration, with the remainder having nuclear DNA (nDNA) defects. At screening, the most frequent bothersome PMM symptom on the PMMSA was tiredness during activities (28.9%). At baseline, the mean distance walked on the 6MWT was 336.7 ± 81.2 meters, the mean score for total fatigue on the PMMSA was 10.6 ± 2.5, and the mean T score for the Neuro-QoL Fatigue Short-Form was 54.7 ± 7.5. The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score (TFS). Between the participants receiving elamipretide and those receiving placebo, the difference in the least squares mean (SE) from baseline to week 24 on distance walked on the 6MWT was -3.2 (95% CI -18.7 to 12.3; p = 0.69) meters, and on the PMMSA, the total fatigue score was -0.07 (95% CI -0.10 to 0.26; p = 0.37). Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity. DISCUSSION: Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated. TRIAL REGISTRATION INFORMATION: Trial registered with clinicaltrials.gov, Clinical Trials Identifier: NCT03323749; submitted on October 12, 2017; first patient enrolled October 9, 2017. CLINICALTRIALS: gov/ct2/show/NCT03323749?term = elamipretide&draw = 2&rank = 9. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks compared with placebo in patients with primary mitochondrial myopathy

Decreased Brain Volume in Adults with Childhood Lead Exposure

Using magnetic resonance imaging to assess brain volumes, Kim Cecil and colleagues find that inner-city children with higher blood lead levels showed regions of decreased gray matter as adults

The full value of vaccine assessments concept - current opportunities and recommendations

For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities

The Full Value of Vaccine Assessments Concept—Current Opportunities and Recommendations

For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities