Sallard.—Les Amygdalites Aigues. ("The Acute Inflammations of the Tonsil.") Paris: Rueff et Cie. 1892. Bibliothèque Médicale: Charcot-Debove.

n/

On "Aerial Goitre" and "Tracheocele."

n/

Entrepreneurial marketing in the digital age: A study of the SME tourism industry

This paper contributes to developing research enquiry relating to research at the Marketing and Entrepreneurship Interface (MEI) from the small and medium-sized firm (SME) marketing perspective. The paper presents findings emanating from a digital destinations project based on the south coast of England and a new, ongoing project on implementing digital marketing strategies in the context of small owner-managed firms. This area of research advances knowledge in several areas and is significant to the developing research of Entrepreneurial Marketing (EM) for a number of reasons. Firstly, there are still gaps in knowledge relating to the study of entrepreneurs (Li, 2008; Thomas et al., 2011) and the challenges associated with use of digital marketing and social media, including Twitter, Facebook etc. (Kim et al., 2011; Peltier et al., 2012). In addition there are reported difficulties with the embedding of e-marketing in SMEs for a number of reasons, notably employee resistance, a lack of technological ‘know how’ (Leeflang et al., 2014; Martin & Matlay, 2003) and, a lack of marketing competency, along with all the other associated limitations of a small business (Xiang & Gretzel, 2010) such as lack of finance, lack of business resource (Thompson et al., 2013). Third, these firms are geographically remote, in a rural region where they are situationally embedded and dependant on the overall effectiveness of destination marketing and where small tourism businesses often rely on a range of stakeholder relationships and agents to help promote their businesses via traditional (administrative) marketing approaches (Getz & Carlsen, 2005). Rurality also creates additional challenges with weak transport links and poor Internet connections while coastal tourist visits are often dependent on good weather and influenced by seasonality (Getz & Nilsson, 2004). Finally the fourth key challenge for entrepreneurs is detecting who they need to target their marketing towards, as digital marketing offers entrepreneurs an unbridled opportunity to market globally

Proton-in-Flight Mechanism for the Spontaneous Hydrolysis of N -Methyl O -Phenyl Sulfamate: Implications for the Design of Steroid Sulfatase Inhibitors

The hydrolysis of N-methyl O-phenyl sulfamate (1) has been studied as a model for steroid sulfatase inhibitors such as Coumate, 667 Coumate and EMATE. At neutral pH, simulating physiological conditions, hydrolysis of 1 involves an intramolecular proton transfer from nitrogen to the bridging oxygen atom of the leaving group. Remarkably, this proton transfer is estimated to accelerate the decomposition of 1 by a factor of 1011. Examination of existing kinetic data reveals that the sulfatase PaAstA catalyzes the hydrolysis of sulfamate esters with moderate efficiencies of ~104; whereas, the catalytic rate acceleration generated by the enzyme for its cognate substrate is on the order of ~1015. Rate constants for hydrolysis of a wide range of sulfuryl esters, ArOSO2X−, are shown to be correlated by a two parameter equation based on pKaArOH and pKaArOSO2XH

Method to reduce microbial bloom in poultry hatchery

Spore forming bacteria and Lactic Acid Bacteria for application in poultry hatcher cabinets to alter the bacterial bloom towards a more beneficial microbiota, positively affecting performance parameters such as mortality, body weight gain and feed conversion ratio throughout production

A persistent pesticide residue and the unusual catalytic proficiency of a dehalogenating enzyme

The soil of potato fields in The Netherlands harbors bacteria with the ability to metabolize 3-chloroacrylic acid, generated by the degradation of a pesticide (1,3-dichloropropene) that entered the environment in 1946. From examination of rate constants at elevated temperatures, we infer that the half-time at 25°C for spontaneous hydrolytic dechlorination of trans-3-chloroacrylic acid is 10,000 years, several orders of magnitude longer than half-times for spontaneous decomposition of other environmental pollutants such as 1,2-dichloroethane (72 years), paraoxon (13 months), atrazine (5 months), and aziridine (52 h). With thermodynamic parameters for activation similar to those for the spontaneous hydration of fumarate at pH 6.8, this slow reaction proceeds at a constant rate through the pH range between 2 and 12. However, at the active site of the enzyme 3-chloroacrylate dehalogenase (CaaD), isolated from a pseudomonad growing in these soils, hydrolytic dechlorination proceeds with a half-time of 0.18 s. Neither kcat nor kcat/Km is reduced by increasing solvent viscosity with trehalose, implying that the rate of enzymatic dechlorination is controlled by chemical events in catalysis rather than by diffusion-limited substrate binding or product release. CaaD achieves an ≈1012-fold rate enhancement, matching or surpassing the rate enhancements produced by many enzymes that act on more conventional biological substrates. One of those enzymes is 4-oxalocrotonate tautomerase, with which CaaD seems to share a common evolutionary origin

Mucosal adjuvants and delivery systems

Adjuvants comprising chitosan cross-linked with an aldehyde or mannosylated chitosan are provided herein. Methods of making the adjuvants and methods of combining or linking the adjuvants with antigens are also provided. The adjuvant-antigen combinations can be used in vaccine formulations and the vaccine formulations can be used in methods to vaccinate animals against the source of the antigen or to enhance the immune response in a subject

An interpretation of fluctuations in enzyme catalysis rate, spectral diffusion, and radiative component of lifetimes in terms of electric field fluctuations

Time-dependent fluctuations in the catalysis rate ({delta}k(t)) observed in single-enzyme experiments were found in a particular study to have an autocorrelation function decaying on the same time scale as that of spectral diffusion {delta}{omega}0(t). To interpret this similarity, the present analysis focuses on a factor in enzyme catalysis, the local electrostatic interaction energy (E) at the active site and its effect on the activation free energy barrier. We consider the slow fluctuations of the electrostatic interaction energy ({delta}E(t)) as a contributor to {delta}k(t) and relate the latter to {delta}{omega}0(t). The resulting relation between {delta}k(t) and {delta}{omega}0(t) is a dynamic analog of the solvatochromism used in interpreting solvent effects on organic reaction rates. The effect of the postulated {delta}E(t) on fluctuations in the radiative component ({delta}{gamma}Formula(t)) of the fluorescence decay of chromophores in proteins also is examined, and a relation between {delta}{gamma}Formula(t) and {delta}{omega}0(t) is obtained. Experimental tests will determine whether the correlation functions for {delta}k(t), {delta}{omega}0(t), and {delta}{gamma}Formula are indeed similar for any enzyme. Measurements of dielectric dispersion, {varepsilon}({omega}), for the enzyme discussed elsewhere will provide further insight into the correlation function for {delta}E(t). They also will determine whether fluctuations in the nonradiative component {gamma}Formula of the lifetime decay has a different origin, fluctuations in distance for example

Synthesis and Conformational Analysis of Locked Carbocyclic Analogues of 1,3-Diazepinone Riboside, a High-Affinity Cytidine Deaminase Inhibitor

Cytidine deaminase (CDA) catalyzes the deamination of cytidine via a hydrated transition-state intermediate that results from the nucleophilic attack of zinc-bound water at the active site. Nucleoside analogues where the leaving NH3 group is replaced by a proton and prevent conversion of the transition state to product are very potent inhibitors of the enzyme. However, stable carbocyclic versions of these analogues are less effective as the role of the ribose in facilitating formation of hydrated species is abolished. The discovery that a 1,3-diazepinone riboside (4) operated as a tight-binding inhibitor of CDA independent of hydration provided the opportunity to study novel inhibitors built as conformationally locked, carbocyclic 1,3-diazepinone nucleosides to determine the enzyme’s conformational preference for a specific form of sugar pucker. This work describes the synthesis of two target bicyclo[3.1.0]hexane nucleosides, locked as north (5) and south (6) conformers, as well as a flexible analogue (7) built with a cyclopentane ring. The seven-membered 1,3-diazepinone ring in all the three targets was built from the corresponding benzoyl-protected carbocyclic bis-allyl ureas by ring-closing metathesis. The results demonstrate CDA’s binding preference for a south sugar pucker in agreement with the high-resolution crystal structures of other CDA inhibitors bound at the active site