An orthogonal biocatalytic approach for the safe generation and use of HCN in a multistep continuous preparation of chiral O-acetylcyanohydrins

An enantioselective preparation of O-acetylcyanohydrins has been accomplished by a three-step telescoped continuous process. The modular components enabled accurate control of two sequential biotransformations, safe handling of an in situ generated hazardous gas, and in-line stabilization of products. This method proved to be advantageous over the batch protocols in terms of reaction time (40 vs 345 min) and ease of operation, opening up access to reactions which have often been neglected due to safety concerns.We gratefully acknowledge the Deutsche Forschungsgemeinschaft (DFG) within the research training group GRK 1166 “Biocatalysis in non-conventional media (BioNoCo)”, and the EPSRC (Award Nos. EP/K009494/1 and EP/K039520/1)This is the final version of the article. It first appeared from Georg Thieme Verlag KG via http://dx.doi.org/10.1055/s-0035-156064

Loop Groups and Discrete KdV Equations

A study is presented of fully discretized lattice equations associated with the KdV hierarchy. Loop group methods give a systematic way of constructing discretizations of the equations in the hierarchy. The lattice KdV system of Nijhoff et al. arises from the lowest order discretization of the trivial, lowest order equation in the hierarchy, b_t=b_x. Two new discretizations are also given, the lowest order discretization of the first nontrivial equation in the hierarchy, and a "second order" discretization of b_t=b_x. The former, which is given the name "full lattice KdV" has the (potential) KdV equation as a standard continuum limit. For each discretization a Backlund transformation is given and soliton content analyzed. The full lattice KdV system has, like KdV itself, solitons of all speeds, whereas both other discretizations studied have a limited range of speeds, being discretizations of an equation with solutions only of a fixed speed.Comment: LaTeX, 23 pages, 1 figur

The PT-symmetric brachistochrone problem, Lorentz boosts and non-unitary operator equivalence classes

The PT-symmetric (PTS) quantum brachistochrone problem is reanalyzed as quantum system consisting of a non-Hermitian PTS component and a purely Hermitian component simultaneously. Interpreting this specific setup as subsystem of a larger Hermitian system, we find non-unitary operator equivalence classes (conjugacy classes) as natural ingredient which contain at least one Dirac-Hermitian representative. With the help of a geometric analysis the compatibility of the vanishing passage time solution of a PTS brachistochrone with the Anandan-Aharonov lower bound for passage times of Hermitian brachistochrones is demonstrated.Comment: 12 pages, 2 figures, strongly extended versio

Willmore Surfaces of Constant Moebius Curvature

We study Willmore surfaces of constant Moebius curvature $K$ in $S^4$. It is proved that such a surface in $S^3$ must be part of a minimal surface in $R^3$ or the Clifford torus. Another result in this paper is that an isotropic surface (hence also Willmore) in $S^4$ of constant $K$ could only be part of a complex curve in $C^2\cong R^4$ or the Veronese 2-sphere in $S^4$. It is conjectured that they are the only examples possible. The main ingredients of the proofs are over-determined systems and isoparametric functions.Comment: 16 pages. Mistakes occured in the proof to the main theorem (Thm 3.6) has been correcte

Does the Constitution Provide More Ballot Access Protection for Presidential Elections Than for U.S. House Elections?

Both the U.S. Constitution and The Federalist Papers suggest that voters ought to have more freedom to vote for the candidate of their choice for the U.S. House of Representatives than they do for the President or the U.S. Senate. Yet, strangely, for the last thirty-three years, the U.S. Supreme Court and lower courts have ruled that the Constitution gives voters more freedom to vote for the candidate of their choice in presidential elections than in congressional elections. Also, state legislatures, which have been writing ballot access laws since 1888, have passed laws that make it easier for minor-party and independent candidates to get on the ballot for President than for the U.S. House. As a result, voters in virtually every state invariably have far more choices on their general election ballots for the President than they do for the House. This Article argues that the right of a voter to vote for someone other than a Democrat or a Republican for the House is just as important as a voter’s right to do so for President, and that courts should grant more ballot access protection to minor-party and independent candidates for the House

Neuronal calcium sensor-1 binds to regulated secretory organelles and functions in basal and stimulated exocytosis in PC12 cells

Neuronal calcium sensor-1 (NCS-1) and its non-mammalian homologue, frequenin, have been implicated in a spectrum of cellular processes, including regulation of stimulated exocytosis of synaptic vesicles and secretory granules (SGs) in neurons and neuroendocrine cells and regulation of phosphatidylinositol 4-kinase beta activity in yeast. However, apart from these intriguing putative functions, NCS-1 and frequenin are relatively poorly understood. Here, the distribution, dynamics and function of NCS-1 were studied using PC12 cells that stably express NCS-1-EYFP (NCS-1 fused to enhanced yellow fluorescent protein) or that stably overexpress NCS-1. Fluorescence and electron microscopies show that NCS-1-EYFP is absent from SGs but is present on small clear organelles, some of which are just below the plasma membrane. Total internal reflection fluorescence microscopy shows that NCS-1-EYFP is associated with synaptic-like microvesicles (SLMVs) in growth cones. Overexpression studies show that NCS-1 enhances exocytosis of synaptotagmin-labeled regulated secretory organelles (RSOs) under basal conditions and during stimulation by UTP. Significantly, these studies implicate NCS-1 in the enhancement of both basal and stimulated phosphoinositide-dependent exocytosis of RSOs in PC12 cells, and they show that NCS-1 is distributed strategically to interact with putative targets on the plasma membrane and on SLMVs. These studies also reveal that SLMVs undergo both fast directed motion and highly hindered diffusive motion in growth cones, suggesting that cytoskeletal constituents can both facilitate and hinder SLMV motion. These results also reveal interesting similarities and differences between transport organelles in differentiated neuroendocrine cells and neurons

Cre-Dependent Expression of Multiple Transgenes in Isolated Neurons of the Adult Forebrain

Background: Transgenic mice with mosaic, Golgi-staining-like expression of enhanced green fluorescent protein (EGFP) have been very useful in studying the dynamics of neuronal structure and function. In order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. However, it has been difficult to obtain reproducible expression in the same subset of neurons for direct comparison of neurons expressing different functional proteins. Principal Findings: Here we describe a Cre-transgenic line that allows reproducible expression of transgenic proteins of choice in a small number of neurons of the adult cortex, hippocampus, striatum, olfactory bulb, subiculum, hypothalamus, superior colliculus and amygdala. We show that using these Cre-transgenic mice, multiple Cre-dependent transgenes can be expressed together in the same isolated neurons. We also describe a Cre-dependent transgenic line expressing a membrane associated EGFP (EGFP-F). Crossed with the Cre-transgenic line, EGFP-F expression starts in the adolescent forebrain, is present in dendrites, dendritic protrusions, axons and boutons and is strong enough for acute or chronic in vivo imaging. Significance: This triple transgenic approach will aid the morphological and functional characterization of neurons in various Cre-dependent transgenic mice

Angiogenesis Markers Quantification in Breast Cancer and Their Correlation with Clinicopathological Prognostic Variables

Tumoural angiogenesis is essential for the growth and spread of breast cancer cells. Therefore the aim of this study was to assess the diagnostic performance of angiogenesis markers in tumours and there reflecting levels in serum of breast cancer patients. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. We observed that breast cancer tumours exhibited high levels of PDGF-BB, bFGF and VEGF, and extremely high levels of TIMP-1 and Ang-2, whereas in serum we found significantly higher levels of Ang-2, PDGF-BB, bFGF, ICAM-1 and VEGF in patients with breast cancer compared to the benign breast diseases patients. Moreover, some of these angiogenesis markers evaluated in tumour and serum of breast cancer patients exhibited association with standard clinical parameters, ER status as well as MVD of tumours. Angiogenesis markers play important roles in tumour growth, invasion and metastasis. Our results suggest that analysis of angiogenesis markers in tumour and serum of breast cancer patients using multiplex protein assay can improve diagnosis and prognosis in this diseases

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Introduction: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. Methods: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. Results: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. Discussion: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD