Uv Multiphoton Induced Chemistry of Nitrobenzene in Solution

The technique of Multiphoton Induced Chemistry (MPIC) has been employed to initiate ion-molecule chemistry of organic molecules in solution. We report one of the first examples of the use of liquid phase multiphoton ionization (MPI) to prepare organic cations, which then react with the solvent in ionmolecule processes. The products obtained in this chemical sequence are significantly different from those observed in conventional or multiphoton-induced neutral chemistry in the same solvent. The particular example explored in this work is the reactivity of the nitrobenzene cation in methanol solvent. Products of the ion-molecule chemistry, detected by gas chromatography/mass spectrometry, are phenol and benzyl alcohol. These products depend upon the square of the laser intensity. It is shown by ionization current measurements in a conductance cell, that ionic species are produced as precursors to the observed products. The implications of this application of MPI are briefly discussed. A preliminary report on the unimolecular chemistry of the highly excited neutral molecule is also included. The product of this channel is nitrosobenzene. It is shown, in this case, that the reactive state is most likely a highly vibrationally excited ground state molecule, not the lowest triplet level invoked in conventional photochemistry

Photodissociation Dynamics of OCS near 214 nm Using Ion Imaging

The OCS photodissociation dynamics of the dominant S(1 D 2) channel near 214 nm have been studied using velocity map ion imaging. We report a CO vibrational branching ratio of 0.79:0.21 for v = 0:v = 1, indicating substantially higher vibrational excitation than that observed at slightly longer wavelengths. The CO rotational distribution is bimodal for both v = 0 and v = 1, although the bimodality is less pronounced than at longer wavelengths. Vector correlations, including rotational alignment, indicate that absorption to both the 21A′ (A) and 11A″ (B) states is important in the lower-j part of the rotational distribution, while only 21A′ state absorption contributes to the upper part; this conclusion is consistent with work at longer wavelengths. Classical trajectory calculations including surface hopping reproduce the measured CO rotational distributions and their dependence on wavelength well, though they underestimate the v = 1 population. The calculations indicate that the higher-j peak in the rotational distribution arises from molecules that begin on the 21A′ state but make nonadiabatic transitions to the 11A′ (X) state during the dissociation, while the lower-j peak arises from direct photodissociation on either the 21A′ or the 11A″ states, as found in previous work

Evaluating diverse electronic consultation programs with a common framework.

BackgroundElectronic consultation is an emerging mode of specialty care delivery that allows primary care providers and their patients to obtain specialist expertise without an in-person visit. While studies of individual programs have demonstrated benefits related to timely access to specialty care, electronic consultation programs have not achieved widespread use in the United States. The lack of common evaluation metrics across health systems and concerns related to the generalizability of existing evaluation efforts may be hampering further growth. We sought to identify gaps in knowledge related to the implementation of electronic consultation programs and develop a set of shared evaluation measures to promote further diffusion.MethodsUsing a case study approach, we apply the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) and the Quadruple Aim frameworks of evaluation to examine electronic consultation implementation across diverse delivery systems. Data are from 4 early adopter healthcare delivery systems (San Francisco Health Network, Mayo Clinic, Veterans Administration, Champlain Local Health Integration Network) that represent varied organizational structures, care for different patient populations, and have well-established multi-specialty electronic consultation programs. Data sources include published and unpublished quantitative data from each electronic consultation database and qualitative data from systems' end-users.ResultsOrganizational drivers of electronic consultation implementation were similar across the systems (challenges with timely and/or efficient access to specialty care), though unique system-level facilitators and barriers influenced reach, adoption and design. Effectiveness of implementation was consistent, with improved patient access to timely, perceived high-quality specialty expertise with few negative consequences, garnering high satisfaction among end-users. Data about patient-specific clinical outcomes are lacking, as are policies that provide guidance on the legal implications of electronic consultation and ideal remuneration strategies.ConclusionA core set of effectiveness and implementation metrics rooted in the Quadruple Aim may promote data-driven improvements and further diffusion of successful electronic consultation programs

Formal Specification and Testing of a Management Architecture

The importance of network and distributed systems management to supply and maintain services required by users has led to a demand for management facilities. Open network management is assisted by representing the system resources to be managed as objects, and providing standard services and protocols for interrogating and manipulating these objects. This paper examines the application of formal description techniques to the specification of managed objects by presenting a case study in the specification and testing of a management architecture. We describe a formal specification of a management architecture suitable for scheduling and distributing services across nodes in a distributed system. In addition, we show how formal specifications can be used to generate conformance tests for the management architecture

Quantitative spectroscopy of close binary stars

The method of spectral disentangling has now created the opportunity for studying the chemical composition in previously inaccessible components of binary and multiple stars. This in turn makes it possible to trace their chemical evolution, a vital aspect in understanding the evolution of stellar systems. We review different ways to reconstruct individual spectra from eclipsing and non-eclipsing systems, and then concentrate on some recent applications to detached binaries with high-mass and intermediate-mass stars, and Algol-type mass-transfer systems.Comment: To appear in the Proceedings of IAU Symposium 282 'From Interacting Binaries to Exoplanets: Essential Modeling Tools

Glycoproteomic studies of IgE from a novel hyper IgE syndrome linked to PGM3 mutation

International audienceGlycans serve as important regulators of antibody activities and half-lives. IgE is the most heavily glycosylated antibody, but in comparison to other antibodies little is known about its glycan structure function relationships. We therefore describe the site specific IgE glycosylation from a patient with a novel hyper IgE syndrome linked to mutations in PGM3, which is an enzyme involved in synthesizing UDP-GlcNAc, a sugar donor widely required for glycosylation. A two-step method was developed to prepare two IgE samples from less than 1 mL of serum collected from a patient with PGM3 mutation and a patient with atopic dermatitis as a control subject. Then, a glycoproteomic strategy was used to study the site-specific glycosylation. No glycosylation was found at Asn264, whilst high mannose glycans were only detected at Asn275, tri-antennary glycans were exclusively observed at Asn99 and Asn252, and non-fucosylated complex glycans were detected at Asn99. The results showed similar glycosylation profiles between the two IgE samples. These observations, together with previous knowledge of IgE glycosylation, imply that IgE glycosylation is similarly regulated among healthy control, allergy and PGM3 related hyper IgE syndrome

Power, norms and institutional change in the European Union: the protection of the free movement of goods

How do institutions of the European Union change? Using an institutionalist approach, this article highlights the interplay between power, cognitive limits, and the normative order that underpins institutional settings and assesses their impact upon the process of institutional change. Empirical evidence from recent attempts to reinforce the protection of the free movement of goods in the EU suggests that, under conditions of uncertainty, actors with ambiguous preferences assess attempts at institutional change on the basis of the historically defined normative order which holds a given institutional structure together. Hence, path dependent and incremental change occurs even when more ambitious and functionally superior proposals are on offer

Extremely metal-poor stars in classical dwarf spheroidal galaxies: Fornax, Sculptor and Sextans

We present the results of a dedicated search for extremely metal-poor stars in the Fornax, Sculptor and Sextans dSphs. Five stars were selected from two earlier VLT/Giraffe and HET/HRS surveys and subsequently followed up at high spectroscopic resolution with VLT/UVES. All of them turned out to have [Fe/H] <= -3 and three stars are below [Fe/H] -3.5. This constitutes the first evidence that the classical dSphs Fornax and Sextans join Sculptor in containing extremely metal-poor stars and suggests that all of the classical dSphs contain extremely metal-poor stars. One giant in Sculptor at [Fe/H]=-3.96 +- 0.10 is the most metal-poor star ever observed in an external galaxy. We carried out a detailed analysis of the chemical abundances of the alpha, iron peak, and the heavy elements, and we performed a comparison with the Milky Way halo and the ultra faint dwarf stellar populations. Carbon, barium and strontium show distinct features characterized by the early stages of galaxy formation and can constrain the origin of their nucleosynthesis.Comment: In A&A. This version corrects a few typographical errors in the coordinates of some of our stars (Table 1

Accurate masses and radii of normal stars: modern results and applications

This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke