EEG Fractal Analysis Reflects Brain Impairment after Stroke

Stroke is the commonest cause of disability. Novel treatments require an improved understanding of the underlying mechanisms of recovery. Fractal approaches have demonstrated that a single metric can describe the complexity of seemingly random fluctuations of physiological signals. We hypothesize that fractal algorithms applied to electroencephalographic (EEG) signals may track brain impairment after stroke. Sixteen stroke survivors were studied in the hyperacute (<48 h) and in the acute phase (∼1 week after stroke), and 35 stroke survivors during the early subacute phase (from 8 days to 32 days and after ∼2 months after stroke): We compared resting-state EEG fractal changes using fractal measures (i.e., Higuchi Index, Tortuosity) with 11 healthy controls. Both Higuchi index and Tortuosity values were significantly lower after a stroke throughout the acute and early subacute stage compared to healthy subjects, reflecting a brain activity which is significantly less complex. These indices may be promising metrics to track behavioral changes in the very early stage after stroke. Our findings might contribute to the neurorehabilitation quest in identifying reliable biomarkers for a better tailoring of rehabilitation pathways.     

Sulphur content estimation of Venezuelan heavy oil by fast neutron and gamma transmission technique

A compact and modern equipment for implementing the fast neutron and γ-ray transmission technique (FNGT) has been developed in order to estimate the sulphur content of crude oil. FNGT is employed for non- destructive analysis of different kinds of samples. The compact system presented in this work represents an improvement of our previous experimental set-up [1, 2]. It makes use of a ²⁵²Cf source, an EJ-301 liquid scintillator detector (2″ × 2″) with excellent n/γ discrimination capabilities, and modern nuclear electronics based on fast digitizers. The fast neutron and gamma transmission technique was employed to study a system for on-line sulphur concentration measurement in Venezuelan heavy sour oil. The range of sulphur concentrations investigated is between 0.1 and 6.5 wt%. The equipment performances and limitations are compared with those predicted by a Monte Carlo model built in GEANT4 v10.01. The results show the possibility to implement a compact unit for on-line determination of sulphur concentration in crude oil.

     

Targeting Bacterial Membranes: NMR Spectroscopy Characterization of Substrate Recognition and Binding Requirements of D‐Arabinose‐5‐Phosphate Isomerase

Lipopolysaccharide (LPS) is an essential component of the outer membrane of Gram‐negative bacteria and consists of three elements: lipid A, the core oligosaccharide, and the O‐antigen. The inner‐core region is highly conserved and contains at least one residue of 3‐deoxy‐D ‐manno‐octulosonate (Kdo). Arabinose‐5‐phosphate isomerase (API) is an aldo–keto isomerase catalyzing the reversible isomerization of D ‐ribulose‐5‐phosphate (Ru5P) to D ‐arabinose‐5‐phosphate (A5P), the first step of Kdo biosynthesis. By exploiting saturation transfer difference (STD) NMR spectroscopy, the structural requirements necessary for API substrate recognition and binding were identified, with the aim of designing new API inhibitors. In addition, simple experimental conditions for the STD experiments to perform a fast, robust, and efficient screening of small libraries of potential API inhibitors, allowing the identification of new potential leads, were set up. Due to the essential role of API enzymes in LPS biosynthesis and Gram‐negative bacteria survival, by exploiting these data, a new generation of potent antibacterial drugs could be developed.     

The O-neophyl rearrangement of 1,1-diarylalkoxyl radicals. Experimental evidence for the formation of an intermediate 1-oxaspiro[2,5]octadienyl radical

A product study on the reactivity of a 1,1-diarylalkoxyl radical bearing 2,2-diphenylcyclopropyl groups in the para-positions has been carried out. The exclusive formation of a product deriving from cyclopropyl ring-opening has been observed, indicating that 1,1-diarylalkoxyl radicals exist in equilibrium with a bridged 1-oxaspiro[2,5]octadienyl radical. This represents the first experimental evidence in support of the stepwise nature of the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals.     

UV‐Dissipation Mechanisms in the Eumelanin Building Block DHICA

The UV‐dissipative mechanisms of the eumelanin building block 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA) and the 4,7‐dideutero derivative (DHICA‐d₂) in buffered H₂O or D₂O have been characterized by using ultrafast time‐resolved fluorescence spectroscopy. Excitation of the carboxylate anion form, the dominating state at neutral pH, leads to dual fluorescence. The band peaking at λ=378 nm is caused by emission from the excited initial geometry. The second band around λ=450 nm is owed to a complex formed between the mono‐anion and specific buffer components. In the absence of complex formation, the mono‐anion solely decays non‐radiatively or by emission with a lifetime of about 2.1 ns. Excitation of the neutral carboxylic acid state, which dominates at acidic pH, leads to a weak emission around λ=427 nm with a short lifetime of 240 ps. This emission originates from the zwitterionic state, formed upon excitation of the neutral state by sub‐ps excited‐state intramolecular proton transfer (ESIPT) between the carboxylic acid group and the indole nitrogen. Future studies will unravel whether this also occurs in larger building blocks and ESIPT is a built‐in photoprotective mechanism in epidermal eumelanin.     

Global QSAR models of skin sensitisers for regulatory purposes

Background

The new European Regulation on chemical safety, REACH, (Registration, Evaluation, Authorisation and Restriction of CHemical substances), is in the process of being implemented. Many chemicals used in industry require additional testing to comply with the REACH regulations. At the same time EU member states are attempting to reduce the number of animals used in experiments under the 3 Rs policy, (refining, reducing, and replacing the use of animals in laboratory procedures). Computational techniques such as QSAR have the potential to offer an alternative for generating REACH data. The FP6 project CAESAR was aimed at developing QSAR models for 5 key toxicological endpoints of which skin sensitisation was one.

Results

This paper reports the development of two global QSAR models using two different computational approaches, which contribute to the hybrid model freely available online.

Conclusions

The QSAR models for assessing skin sensitisation have been developed and tested under stringent quality criteria to fulfil the principles laid down by the OECD. The final models, accessible from CAESAR website, offer a robust and reliable method of assessing skin sensitisation for regulatory use.

     

Combined analysis by GC (RI), GC-MS and 13C NMR of the supercritical fluid extract of Abies alba twigs

Two samples (leaves and twigs) of Abies alba Miller from Corsica were extracted using supercritical CO2 and their chemical compositions were compared with those of the essential oils obtained from the same batch of plant material. In total 45 components were identified using combined analysis by GC (RI), GC-MS and 13C NMR. It was observed that the contents of monoterpenes (mainly represented by limonene, alpha-pinene and camphene) were significantly lower in the supercritical fluid extract (SFE) than in the essential oil (EO). Conversely, the proportions of sesquiterpenes were much higher in CO2 extracts than in essential oils (around 30% vs 4%). Cis-abienol, a diterpene alcohol, was identified only in SFE, and the proportions of this constituent (7.5% and 17.3%) were determined using quantitative 13C NMR since it was under estimated using the standard conditions of GC.     

Assessment of clinical data of nonlinear stochastic deconvolution versus block-circulant singular value decomposition for quantitative dynamic susceptibility contrast magnetic resonance imaging

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) allows the noninvasive assessment of brain hemodynamics alterations by quantifying, via deconvolution, the cerebral blood flow (CBF) and mean transit time (MTT). Singular value decomposition (SVD) and block-circulant SVD (cSVD) are the most widely adopted deconvolution method, although they bear some limitations, including unphysiological oscillations in the residue function and bias in the presence of delay and dispersion between the tissue and the arterial input function. A nonlinear stochastic regularization (NSR) has been proposed, which performs better than SVD and cSVD on simulated data both in the presence and absence of dispersion. Moreover, NSR allows to quantify the dispersion level. Here, cSVD and NSR are compared for the first time on a group of nine patients with severe atherosclerotic unilateral stenosis of internal carotid artery before and after carotid stenting to investigate the effect of arterial dispersion. According to region of interest-based analysis, NSR characterizes the pathologic tissue more accurately than cSVD, thus improving the quality of the information provided to physicians for diagnosis. In fact, in 7 (78%) of the 9 subjects, CBF and MTT maps provided by NSR allow to correctly identify the pathologic hemisphere to the physician. Moreover, by emphasizing the difference between pathologic and healthy tissues, NSR may be successfully used to monitor the subject's recovery after the treatment and/or surgery. NSR also generates dispersion level and non-dispersed CBF and MTT maps. The dispersion level provides information on CBF and MTT estimates reliability and may also be used as a clinical indicator of pathological tissue state complementary to CBF and MTT, thus increasing the clinical information provided by DSC-MRI analysis.     

Algebraic semantics and model completeness for Intuitionistic Public Announcement Logic

In the present paper, we start studying epistemic updates using the standard toolkit of duality theory. We focus on public announcements, which are the simplest epistemic actions, and hence on Public Announcement Logic (PAL) without the common knowledge operator. As is well known, the epistemic action of publicly announcing a given proposition is semantically represented as a transformation of the model encoding the current epistemic setup of the given agents; the given current model being replaced with its submodel relativized to the announced proposition. We dually characterize the associated submodel-injection map as a certain pseudo-quotient map between the complex algebras respectively associated with the given model and with its relativized submodel. As is well known, these complex algebras are complete atomic BAOs (Boolean algebras with operators). The dual characterization we provide naturally generalizes to much wider classes of algebras, which include, but are not limited to, arbitrary BAOs and arbitrary modal expansions of Heyting algebras (HAOs). Thanks to this construction, the benefits and the wider scope of applications given by a point-free, intuitionistic theory of epistemic updates are made available. As an application of this dual characterization, we axiomatize the intuitionistic analogue of PAL, which we refer to as IPAL, prove soundness and completeness of IPAL w.r.t. both algebraic and relational models, and show that the well known Muddy Children Puzzle can be formalized in IPAL.