Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

Quantum-state input-output relations for absorbing cavities

The quantized electromagnetic field inside and outside an absorbing high-$Q$ cavity is studied, with special emphasis on the absorption losses in the coupling mirror and their influence on the outgoing field. Generalized operator input-output relations are derived, which are used to calculate the Wigner function of the outgoing field. To illustrate the theory, the preparation of the outgoing field in a Schr\"{o}dinger cat-like state is discussed.Comment: 12 pages, 5 eps figure

A tutored discourse on microcontrollers, single board computers and their applications to monitor and control chemical reactions

This Tutored Discourse constitutes a preliminary exposure on how synthesis chemists can engage positively with inexpensive, low-power microcontrollers to aid control, monitoring and optimisation of chemical reactions.H2020-FETOPEN-2016-2017 programme of the European Commission (grant agreement number: 737266-ONE FLOW

First Digit Distribution of Hadron Full Width

A phenomenological law, called Benford's law, states that the occurrence of the first digit, i.e., $1,2,...,9$, of numbers from many real world sources is not uniformly distributed, but instead favors smaller ones according to a logarithmic distribution. We investigate, for the first time, the first digit distribution of the full widths of mesons and baryons in the well defined science domain of particle physics systematically, and find that they agree excellently with the Benford distribution. We also discuss several general properties of Benford's law, i.e., the law is scale-invariant, base-invariant, and power-invariant. This means that the lifetimes of hadrons follow also Benford's law.Comment: 8 latex pages, 4 figures, final version in journal publicatio

Initial monotherapy with eslicarbazepine acetate for the management of adult patients with focal epilepsy in clinical practice: a meta-analysis of observational studies

This study was funded by Laboratorios Bial, S.A. (Madrid, Spain).The authors thank Alejandro Pedromingo (Bio-estadistica. com, Madrid, Spain) for the statistical analysis, and Isabel San Andrés (Incimed, Madrid, Spain) for performing the literature search. Their participation has been funded by Laboratorios Bial, S.A. (Madrid, Spain).Aim of the study To assess the effectiveness, overall tolerability of eslicarbazepine acetate (ESL) as an initial or early monotherapy treatment of adult patients with focal epilepsy under real-world practice conditions. Materials and methods We focused on real-world longitudinal studies that included or separately reported the results of at least one of the efficacy outcomes of interest. A DerSimonian-Laird random effects model was used with the presentation of the 95% confidence intervals of the estimate Results 5 studies met our selection criteria and were included in the quantitative synthesis. All studies were observational and uncontrolled studies, and all but one were retrospective studies. The pooled proportion of patients who were seizure-free for the entire study period was 64.6% (95% CI, 45.7 to 79.8) at month 6 and 56.6% (95% CI, 50.2 to 62.8) at month 12. Pooled retention rates were 95.0% (95% CI, 90.3 to 97.5) at 6 months and 83.6% (95% CI, 73.9 to 90.1) at 12 months. The pooled proportion of patients who reported at least one adverse event was 27.2% (95% CI, 21.7 to 33.6), and the pooled proportion of patients who discontinued ESL due to adverse events was 8.9% (95% CI 6.2 to 12.6). Conclusions Our results suggest that initial or early monotherapy with ESL is effective and well-tolerated for the management of adult patients with focal epilepsy in clinical practice, with results that are at least similar to those reported in the pivotal randomized clinical trial of ESL monotherapy. No new safety signals with ESL have been identified in this systematic review.Bial Grou

Rapid, selective and stable HaloTag-Lb ADH immobilization directly from crude cell extract for the continuous biocatalytic production of chiral alcohols and epoxides

A strategy for biocatalyst immobilization in flow directly from the crude cell extract is described.EPSRC (Award Nos. EP/K009494/1 and EP/K039520/1), the German Federal Ministry of Education and Research (BMBF) within the project “Molecular Interaction Engineering” (funding code 031A095)

Developmental refinement of cortical systems for speech and voice processing

Development typically leads to optimized and adaptive neural mechanisms for the processing of voice and speech. In this fMRI study we investigated how this adaptive processing reaches its mature efficiency by examining the effects of task, age and phonological skills on cortical responses to voice and speech in children (8-9years), adolescents (14-15years) and adults. Participants listened to vowels (/a/, /i/, /u/) spoken by different speakers (boy, girl, man) and performed delayed-match-to-sample tasks on vowel and speaker identity. Across age groups, similar behavioral accuracy and comparable sound evoked auditory cortical fMRI responses were observed. Analysis of task-related modulations indicated a developmental enhancement of responses in the (right) superior temporal cortex during the processing of speaker information. This effect was most evident through an analysis based on individually determined voice sensitive regions. Analysis of age effects indicated that the recruitment of regions in the temporal-parietal cortex and posterior cingulate/cingulate gyrus decreased with development. Beyond age-related changes, the strength of speech-evoked activity in left posterior and right middle superior temporal regions significantly scaled with individual differences in phonological skills. Together, these findings suggest a prolonged development of the cortical functional network for speech and voice processing. This development includes a progressive refinement of the neural mechanisms for the selection and analysis of auditory information relevant to the ongoing behavioral task