1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine and its derivatives

The synthesis of the parent ring system and some of the derivatives of 1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine are described.     

The role of left and right hemispheres in the comprehension of idiomatic language: an electrical neuroimaging study

Background  

The specific role of the two cerebral hemispheres in processing idiomatic language is highly debated. While some studies show the involvement of the left inferior frontal gyrus (LIFG), other data support the crucial role of right-hemispheric regions, and particularly of the middle/superior temporal area. Time-course and neural bases of literal vs. idiomatic language processing were compared. Fifteen volunteers silently read 360 idiomatic and literal Italian sentences and decided whether they were semantically related or unrelated to a following target word, while their EEGs were recorded from 128 electrodes. Word length, abstractness and frequency of use, sentence comprehensibility, familiarity and cloze probability were matched across classes.     

'On-the-fly' hydrogen/deuterium exchange liquid chromatography/mass spectrometry using a dual-sprayer atmospheric pressure ionisation source

In-source 'on-the-fly' hydrogen/deuterium (H/D) exchange liquid chromatography mass spectrometry (LC/MS) has been investigated. The work was performed using a dual-sprayer source. The analyte was introduced through an electrospray ionisation sprayer and D2O was introduced through an atmospheric pressure chemical ionisation sprayer. To achieve H/D exchange sufficient to determine the number of exchangeable H atoms of a compound, a saturated 'steady-state' D2O atmosphere had to be created in the ion source by having a 2:1 or higher D2O-to-analyte flow rate ratio. Under these conditions H/D exchange levels of 32-90% were achieved. In most cases the H/D exchange was sufficient to measure the number of exchangeable H atoms in some antiulcerative and anthelmintic pharmaceuticals. The concept of in-source 'on-the-fly' H/D exchange by introducing the deuterating agent via a second sprayer has been shown. It allows the integrity of the chromatographic separation to be kept, since the H/D exchange takes place post-separation.     

In Silico Identification of Tripeptides as Lead Compounds for the Design of KOR Ligands

The kappa opioid receptor (KOR) represents an attractive target for the development of drugs as potential antidepressants, anxiolytics and analgesics. A robust computational approach may guarantee a reduction in costs in the initial stages of drug discovery, novelty and accurate results. In this work, a virtual screening workflow of a library consisting of ~6 million molecules was set up, with the aim to find potential lead compounds that could manifest activity on the KOR. This in silico study provides a significant contribution in the identification of compounds capable of interacting with a specific molecular target. The main computational techniques adopted in this experimental work include: (i) virtual screening; (ii) drug design and leads optimization; (iii) molecular dynamics. The best hits are tripeptides prepared via solution phase peptide synthesis. These were tested in vivo, revealing a good antinociceptive effect after subcutaneous administration. However, further work is due to delineate their full pharmacological profile, in order to verify the features predicted by the in silico outcomes.     

FDR,an easier way to NNLO calculations: a two-loop case study

In this paper we illustrate the simplifications produced by FDR in NNLO computations. We show with an explicit example that—due to its four-dimensionality—FDR does not require an order-by-order renormalization and that, unlike the one-loop case, FDR and dimensional regularization generate intermediate two-loop results which are no longer linked by a simple subtraction of the ultraviolet (UV) poles in $\epsilon $ . Our case study is the two-loop amplitude for $H \rightarrow \gamma \gamma $ , mediated by an infinitely heavy top loop, in the presence of gluonic corrections. We use this to elucidate how gauge invariance is preserved with no need of introducing counterterms in the Lagrangian. In addition, we discuss a possible four-dimensional approach to the infrared problem compatible with the FDR treatment of the UV infinities.     

A reliable approach to the solution of Navier–Stokes equations

In this paper we will demonstrate an affective approach of solving Navier–Stokes equations by using a very reliable transformation method known as the Cole–Hopf transformation, which reduces the problem from nonlinear into a linear differential equation which, in turn, can be solved effectively.     

Weighted intriguing sets of finite generalised quadrangles

We construct and analyse interesting integer valued functions on the points of a generalised quadrangle which lie in the orthogonal complement of a principal eigenspace of the collinearity relation. These functions generalise the intriguing sets introduced by Bamberg et al. (Combinatorica 29(1):1?C17, 2009), and they provide the extra machinery to give new proofs of old results and to establish new insight into the existence of certain configurations of generalised quadrangles. In particular, we give a geometric characterisation of Payne??s tight sets, we give a new proof of Thas?? result that an m-ovoid of a generalised quadrangle of order (s,s ²) is a hemisystem, and we give a bound on the values of m for which it is possible for an m-ovoid of the four dimensional Hermitian variety to exist.