Insights into enzymatic halogenation from computational studies

The halogenases are a group of enzymes that have only come to the fore over the last 10 years thanks to the discovery and characterization of several novel representatives. They have revealed the fascinating variety of distinct chemical mechanisms that nature utilizes to activate halogens and introduce them into organic substrates. Computational studies using a range of approaches have already elucidated many details of the mechanisms of these enzymes, often in synergistic combination with experiment. This Review summarizes the main insights gained from these studies. It also seeks to identify open questions that are amenable to computational investigations. The studies discussed herein serve to illustrate some of the limitations of the current computational approaches and the challenges encountered in computational mechanistic enzymology

Convenient Labelling Technique for Mass Spectrometry - Acid Catalyzed Deuterium and Oxygen-18 Exchange via Gas-liquid Chromatography

Mass spectrometry labelling technique - acid catalyzed deuterium and oxygen 18 exchange by gas-liquid chromatograph

Phase-locking in the multidimensional Frenkel-Kontorova model

We consider the multidimensional Frenkel-Kontorova model with one degree of freedom which is a variational problem for real functions on the lattice Zn

Equilibrium form of crystals and stable norm

The equilibrium form of a crystal is the shape which minimizes the total surface tension for a given volume. The surface tension itself is considered to be a function of the orientation of the crystal face within the crystal lattice. This function of orientation is identified with the stable norm on the second homology classes of a Riemannian 3-torus. Minimizing the total surface tension of the crystal leads to an equilibrium form which corresponds to the dual unit ball of the stable norm. We outline the connection between surface tension and stable norm and interpret the differentiability properties of the stable norm in terms of the crystal shape. The differentiability properties, in particular, prove Sohnke's reciprocity law estimating the size of crystal faces

An investigation into the unusual linkage isomerization and nitrite reduction activity of a novel tris(2-pyridyl) copper complex

The copper-containing nitrite reductases (CuNIRs) are a class of enzymes that mediate the reduction of nitrite to nitric oxide in biological systems. Metal–ligand complexes that reproduce the salient features of the active site of CuNIRs are therefore of fundamental interest, both for elucidating the possible mode of action of the enzymes and for developing biomimetic catalysts for nitrite reduction. Herein, we describe the synthesis and characterization of a new tris(2-pyridyl) copper complex ([Cu1(NO2)2]) that binds two molecules of nitrite, and displays all three of the common binding modes for NO2−, with one nitrite bound in an asymmetric quasi-bidentate κ2-ONO manner and the other bound in a monodentate fashion with a linkage isomerism between the κ1-ONO and κ1-NO2 binding modes. We use density functional theory to help rationalize the presence of all three of these linkage isomers in one compound, before assessing the redox activity of [Cu1(NO2)2]. These latter studies show that the complex is not a competent nitrite reduction electrocatalyst in non-aqueous solvent, even in the presence of additional proton donors, a finding which may have implications for the design of biomimetic catalysts for nitrite reduction

Linguistic theory and the analysis of minority languages: native, immigrant and heritage Spanish

In this paper we aim to contribute to the emerging field of heritage studies by investigating whether Spanish heritage speakers in Canada, namely the second or subsequent generation of Spanish speakers who grew up as English-Spanish bilinguals, differ from native Spanish speakers (those who have always lived in a Spanishspeaking country) and from immigrant Spanish speakers (those who immigrated to Canada as adults) with respect to their grammatical competence and to their processing strategies. Taking as a point of departure recent proposals from linguistic theory, we provide a description of Spanish restrictive relative clauses with so-called resumptive pronouns (Es una mujer que nunca LA vimos llorar) in order to determine whether and how our three groups of speakers differ in terms of the grammatical intuitions and processing resources they display when confronted with this type of constructions. We discuss to what extent language attrition, influence from English (in the case of both immigrant and heritage speakers), or incomplete acquisition (in the case of heritage speakers) may be behind the characteristics of the immigrant and the heritage speakers’ linguistic behaviour. We argue that sophisticated experimental tasks provide a better tool than global proficiency tests to compare these three groups of speakers. The ultimate aim of this study is to provide a framework for analyzing the status of the minority languages spoken by immigrant communities.Este artículo quiere contribuir al emergente campo de los estudios de la herencia (heritage), investigando si los hablantes de herencia de español en Canadá (los hablantes de español de segunda o posterior generación que crecieron como bilingües de inglés-español) se diferencian de los hablantes de español nativos (aquellos que han vivido siempre en un país de habla hispana) y de los inmigrantes hablantes de español (los que inmigraron a Canadá como adultos), con respecto a su capacidad gramatical y a sus estrategias de procedimiento. Tomando como punto de partida las propuestas más recientes de la teoría lingüística, presentamos una descripción de las cláusulas relativas restrictivas con pronombres de reasuntivos en español ('Es una mujer que nunca LA vimos llorar') con el fin de determinar las diferencias entre los tres grupos de hablantes en términos de intuiciones gramaticales y de recursos de procesamiento que utilizan al enfrentarse a este tipo de construcciones. Se discute en qué medida la erosión de la lengua, por influencia del inglés (en el caso de los hablantes inmigrantes y de herencia), o una adquisición incompleta (en el caso de los hablantes de herencia) pueden estar detrás del comportamiento lingüístico. Se discute también si las pruebas experimentales sofisticadas son mejores herramientas, para comparar los tres grupos de hablantes, que los tests de dominio global. El objetivo final de este estudio es proporcionar un marco para el análisis del estatus de las lenguas minoritarias habladas por las comunidades de inmigrantes

Overstating the evidence - double counting in meta-analysis and related problems

Background: The problem of missing studies in meta-analysis has received much attention. Less attention has been paid to the more serious problem of double counting of evidence. Methods: Various problems in overstating the precision of results from meta-analyses are described and illustrated with examples, including papers from leading medical journals. These problems include, but are not limited to, simple double-counting of the same studies, double counting of some aspects of the studies, inappropriate imputation of results, and assigning spurious precision to individual studies. Results: Some suggestions are made as to how the quality and reliability of meta-analysis can be improved. It is proposed that the key to quality in meta-analysis lies in the results being transparent and checkable. Conclusions: Existing quality check lists for meta-analysis do little to encourage an appropriate attitude to combining evidence and to statistical analysis. Journals and other relevant organisations should encourage authors to make data available and make methods explicit. They should also act promptly to withdraw meta-analyses when mistakes are found

Linguistic theory and the analysis of minority languages: native, immigrant and heritage Spanish

In this paper we aim to contribute to the emerging field of heritage studies by investigating whether Spanish heritage speakers in Canada, namely the second or subsequent generation of Spanish speakers who grew up as English-Spanish bilinguals, differ from native Spanish speakers (those who have always lived in a Spanishspeaking country) and from immigrant Spanish speakers (those who immigrated to Canada as adults) with respect to their grammatical competence and to their processing strategies. Taking as a point of departure recent proposals from linguistic theory, we provide a description of Spanish restrictive relative clauses with so-called resumptive pronouns (Es una mujer que nunca LA vimos llorar) in order to determine whether and how our three groups of speakers differ in terms of the grammatical intuitions and processing resources they display when confronted with this type of constructions. We discuss to what extent language attrition, influence from English (in the case of both immigrant and heritage speakers), or incomplete acquisition (in the case of heritage speakers) may be behind the characteristics of the immigrant and the heritage speakers’ linguistic behaviour. We argue that sophisticated experimental tasks provide a better tool than global proficiency tests to compare these three groups of speakers. The ultimate aim of this study is to provide a framework for analyzing the status of the minority languages spoken by immigrant communities.Este artículo quiere contribuir al emergente campo de los estudios de la herencia (heritage), investigando si los hablantes de herencia de español en Canadá (los hablantes de español de segunda o posterior generación que crecieron como bilingües de inglés-español) se diferencian de los hablantes de español nativos (aquellos que han vivido siempre en un país de habla hispana) y de los inmigrantes hablantes de español (los que inmigraron a Canadá como adultos), con respecto a su capacidad gramatical y a sus estrategias de procedimiento. Tomando como punto de partida las propuestas más recientes de la teoría lingüística, presentamos una descripción de las cláusulas relativas restrictivas con pronombres de reasuntivos en español ('Es una mujer que nunca LA vimos llorar') con el fin de determinar las diferencias entre los tres grupos de hablantes en términos de intuiciones gramaticales y de recursos de procesamiento que utilizan al enfrentarse a este tipo de construcciones. Se discute en qué medida la erosión de la lengua, por influencia del inglés (en el caso de los hablantes inmigrantes y de herencia), o una adquisición incompleta (en el caso de los hablantes de herencia) pueden estar detrás del comportamiento lingüístico. Se discute también si las pruebas experimentales sofisticadas son mejores herramientas, para comparar los tres grupos de hablantes, que los tests de dominio global. El objetivo final de este estudio es proporcionar un marco para el análisis del estatus de las lenguas minoritarias habladas por las comunidades de inmigrantes

Ejaculation failure on the day of oocyte retrieval for IVF: Case report

Unexpected ejaculation failure on the day of oocyte retrieval for IVF occurs once or twice a year in our Reproductive Medicine Unit, where ∼500 oocyte retrievals are performed each year. Two clinical situations which occurred in 2001 are presented. In the first case, sperm were finally obtained by epididymal aspiration and resulted in the fertilization of five oocytes by ICSI. The transfer of two fresh embryos did not result in a pregnancy and the three supernumerary zygotes were cryopreserved. The male patient presented an anxio-depressive episode necessitating psychiatric hospitalization 1 week after the oocyte retrieval. In the second case, no sperm were obtained and the four oocytes were therefore lost. The couple went through a crisis in their relationship and tried another cycle of IVF 10 months later, after the preventive cryopreservation of a sperm sample. On the day of oocyte retrieval the patient was unable to produce a fresh sample but three zygotes were obtained through ICSI using the back-up cryopreserved sperm. Two embryos were transferred but no pregnancy ensued. The clinical decision-making processes for these two cases are described, as well as the measures employed to help prevent these unfortunate situation

Hybrid Local-Order Mechanism for Inversion Symmetry Breaking

Using classical Monte Carlo simulations, we study a simple statistical mechanical model of relevance to the emergence of polarisation from local displacements on the square and cubic lattices. Our model contains two key ingredients: a Kitaev-like orientation-dependent interaction between nearest neighbours, and a steric term that acts between next-nearest neighbours. Taken by themselves, each of these two ingredients is incapable of driving long-range symmetry breaking, despite the presence of a broad feature in the corresponding heat capacity functions. Instead each component results in a "hidden" transition on cooling to a manifold of degenerate states, the two manifolds are different in the sense that they reflect distinct types of local order. Remarkably, their intersection---\emph{i.e.} the ground state when both interaction terms are included in the Hamiltonian---supports a spontaneous polarisation. In this way, our study demonstrates how local ordering mechanisms might be combined to break global inversion symmetry in a manner conceptually similar to that operating in the "hybrid" improper ferroelectrics. We discuss the relevance of our analysis to the emergence of spontaneous polarisation in well-studied ferroelectrics such as BaTiO$_3$ and KNbO$_3$.Comment: 8 pages, 8 figure