Small polaron formation in many-particle states of the Hubbard-Holstein model: The one-dimensional case

We investigate polaron formation in a many-electron system in the presence of a local repulsion sufficiently strong to prevent local-bipolaron formation. Specifically, we consider a Hubbard-Holstein model of interacting electrons coupled to dispersionless phonons of frequency $\omega_0$. Numerically solving the model in a small one-dimensional cluster, we find that in the nearly adiabatic case $\omega_0 < t$, the necessary and sufficient condition for the polaronic regime to occur is that the energy gain in the atomic (i.e., extremely localized) regime ${\cal E}_{pol}$ overcomes the energy of the purely electronic system ${\cal E}_{el}$. In the antiadiabatic case, $\omega_0 > t$, polaron formation is instead driven by the condition of a large ionic displacement $g/\omega_0 >1$ ($g$ being the electron-phonon coupling). Dynamical properties of the model in the weak and moderately strong coupling regimes are also analyzed

A new specific neuronal modulatory effect of nicotine: the functional cross talk between nicotinic and glutamate receptors

We here have addressed the topic of the cross-talk between receptors. We provide evidence supporting the co-localization and the functional interaction between nicotinic acetylcholine receptors and some glutamatergic receptors. The recruitment of nicotinic acetylcholine receptors dynamically and negatively modulates the function of both N-methyl-D-aspartic acid (NMDA) and ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors throughout their selective internalization. This dynamic control by cholinergic nicotinic system of NMDA and ?-AMPA receptors is operative even at very low concentrations of nicotine. Nicotinic and glutamatergic receptors have been both implicated in important neurological and psychiatric disorders such as Alzheimer’s and Parkinson’s disease, schizophrenia, and anxiety. Thus, a more extensive and detailed knowledge of this new modulatory role of nicotine may eventually enable us to develop specific therapeutic interventions for these pathologies

PRINCIPAL COMPONENTS OF THE 180°-TURN WITH THE BALL KINEMATICS IN YOUTH SOCCER PLAYERS

The interpretation of parameters extracted from sophisticated sport-specific techniques is not always straightforward. This is the case of the 180° change of direction with the ball in soccer. The 180°-turn performance of ten Under-13, sub-elite soccer players was recorded by means of a motion capture system. Principal Component Analysis (PCA) was applied to a set of 21 anthropometrics and kinematic variables including center of mass related quantities and joints range of motion. The first three principal components, explaining 61% of the overall variance, were retained and discussed. PCA unveiled the relevant structure of the dataset, describing both movement speed and amplitude issues, and the relationship between body size and the change of direction ability

Start-up size: the role of external financing

Abstract We investigate the role of external financing in influencing firms&apos; start-up size. The econometric estimates run on a sample of Italian young firms operating in high-tech industries highlight that bank debt-financed firms are not larger than firms created only through founders&apos; personal savings, while firms that received external private equity financing have greater start-up size.

Comparing Machine and Deep Learning Methods for Large 3D Heritage Semantic Segmentation

In recent years semantic segmentation of 3D point clouds has been an argument that involves different fields of application. Cultural heritage scenarios have become the subject of this study mainly thanks to the development of photogrammetry and laser scanning techniques. Classification algorithms based on machine and deep learning methods allow to process huge amounts of data as 3D point clouds. In this context, the aim of this paper is to make a comparison between machine and deep learning methods for large 3D cultural heritage classification. Then, considering the best performances of both techniques, it proposes an architecture named DGCNN-Mod+3Dfeat that combines the positive aspects and advantages of these two methodologies for semantic segmentation of cultural heritage point clouds. To demonstrate the validity of our idea, several experiments from the ArCH benchmark are reported and commented

DAT atypical inhibitors as novel antipsychotic drugs

Despite its classification as a psychiatric disease, schizophrenia is both a behavioral and a biological disorder resulting in neurocognitive dysfunction. Social and economic costs of schizophrenia are extremely high compared to its incidence and prevalence, however, due to a heterogeneous pattern of brain pathology and symptoms and to an unknown etiology, developing an effective treatment has been really challenging. Among the many neurochemical hypothesis, the dysregulation of dopaminergic neurotransmission has been considered as a central dogma of schizophrenia over the last few decades. In fact, patients with this pathology exhibit increased dopamine (DA) synthesis and release in the striatum which seems to correlate with positive symptoms and moreover, most of the effective antipsychotic drugs (APDs) are D2-receptor antagonists. Unfortunately, chronic treatment with APDs is associated with the induction of extrapyramidal side effects (EPS). In order to identify new possible APDs with a novel mechanism of action and potentially less EPS we tested 3 different compounds generated from the structural modification of vanoxerine (or GBR12909), a known atypical inhibitor of the presynaptic DA transporter (DAT) with cocaine-like activity but cardiotoxic properties that have precluded its clinical use. Preliminary in vitro studies showed that DAhLIs (DAT atypical inhibitors) are able to bind to DAT and inhibit DA reuptake. Additionally, our in vivo results showed that DAhLI i) have putative central effects, ii), unlike vanoxerine, reduce novelty-induced locomotor activity, and iii) counteract cocaine stimulating effects, suggesting that DAhLI may potentiate DA reuptake via DAT. These compounds may provide a way to reduce DA extracellular levels and DA neurotransmission with a selective action on active DA synapses, thus with reduced EPS typical of D2 antagonists, representing a new promising class of presynaptic APDs

Constrained 1,4-dialkylpiperazines as monoamine transporters inhibitors for cocaine-related abuse

Cocaine abuse and addiction remain grave health and societal problems with nearly 11,000 overdose deaths in 2015. Despite the high prevalence of cocaine use, no FDA-approved therapeutic for treating cocaine addiction has been achieved. The primary target for cocaine is dopamine transporter (DAT) and the rewarding and reinforcing effects of cocaine are mediated predominantly by its inhibition, with a consequent ‘reverse agonist’ effect. Several DAT inhibitors have been proposed as potential drugs for cocaine abuse.[1-2] One of the most studied DAT inhibitors, GBR12909 (Ki DAT = 3.7 nM), is able to slightly increase DA level and to blunt the cocaine-induced elevation of extracellular DA in vivo without exerting the central exciting effects of cocaine and addiction. Unfortunately, the phase I clinical trials failed, due to its cardiotoxicity.[3-4] In a lead optimisation program focused to identify novel and safe GBR12909 analogues, nine constrained derivatives were design and synthesized in a ligand based approach. Maintaining unaltered the fluoro-phenyl and phenylpropylpiperazine moiety, the rigidification of the ethylene ether, by means of tetrahydrofuran, dioxolane, dioxane, oxathiolane and dithiolane ring, was investigated in a focused SAR study (Fig. 1). All the compounds were assayed for the determination of the binding affinity for DAT, NET and SERT. In particular, two dioxolane derivatives displayed a binding affinity comparable to that of GBR12909, with Ki of 21.2 and 13.9 nM for DAT, and a selectivity ratio SERT/DAT &gt; 30. Since the cyclization introduces one chiral centre, the two enantiomers of one racemic mixture were prepared following enantioselective synthetic procedures. The (R)- and (S)-forms showed a binding affinity comparable to the one determined for the racemate (Ki DAT of 16 and 46 nM, respectively), suggesting that the configuration of the stereocenters slightly affect the binding to the DAT transporter. For the most interesting derivatives, uptake inhibition assays were conducted in rat brain synaptosomes. It was observed that the potency trend parallel the affinity values

Microdispersions of ellagic acid and pomegranate extracts as new potential nutraceutical ingredients

The health properties attributed to several fruits (i.e. pomegranates, raspberries, strawberries, blackberry, chestnuts, walnuts, pecan), herbs (tea) and seeds (berries seeds) are attributed to an important group of natural polyphenols classified as hydrolysable tannins (HT) named Ellagitannins (ETs), that have shown in vitro multi-target biological properties relevant to the treatment of several human diseases. In vivo, ETs are rather not absorbed, and they are hydrolysed providing mainly Ellagic acid (EA). EA is endowed with the same biological properties of ETs and it could be considered as the responsible of their health benefits. Unfortunately, EA cannot be exploited for in vivo applications because of its poor water solubility (9.7 \u3bcg/mL) and accordingly low bioavailability. At first, aiming to increase EA solubility, an EA solid microdispersion (EA-md) was realized by employing only water and low methoxylated pectin, as a food compatible excipient, by applying spray drying technology. EA-md showed a 22% (w/w) Drug Loading (DL), a 30 times improved water solubility maintaining a remarkable radical scavenging activity [1]. It has been analytically characterised and used for in vivo pharmacological treatments in order to evaluate it as potential nutraceutical ingredient. Adult (3-6 months old) and old (20-22 old months) male mice were chronically administered EA-md dissolved in the drinking water (about 150 mg / Kg) for 14 days. During this period, animals were monitored for the spontaneous motor activity and for curiosity before, during and at the end of the EA-md treatment. Adult and old mice were then sacrificed for \u201cex vivo, in vitro\u201d analysis to test the efficiency of noradrenaline release from cortical nerve endings. It is known that noradrenaline exocytosis from cortical nerve endings is significantly impaired during ageing. We found that the chronic administration of EA-md did not alter the noradrenaline exocytosis from cortical nerve endings of adult mice, but significantly recovered the reduced noradrenaline overflow in aged mice. Further investigations are needed to explore the cellular cascade of events accounting for the beneficial effect. In a second step, pomegranate, as a natural source of EA, has been considered to similarly prepare and investigate an analogous formulation. Since pomegranate fruit is recognized as one of the most important sources of ETs, mainly localized in the by-products obtained after industrial juice squeezing, a method to convert the squeezing marcs into a potential nutraceutical ingredient has been explored. In particular, Pulsed Ultrasound-Assisted Extraction (PUAE), using just water as solvent, resulted to be suitable for extracting the water-soluble bioactive molecules (PEx), whose content in hydrolysable tannins, standardized in EA, has been determined. Furthermore, the already mentioned spray drying microdispersion has been employed to formulate and to stabilize it over time. This last formulation (PEx-md) will be subjected to the already mentioned pharmacological experiments in order to study its nutraceutical properties too. [1] S. Alfei, F. Turrini, S. Catena, P. Zunin, B. Parodi, G. Zuccari, A.M. Pittaluga, R. Boggia, New J. Chem, 43, 2438-2448 DOI: 10.1039/C8NJ05657

Blockade of stress-induced increase of glutamate release in the rat prefrontal/frontal cortex by agomelatine involves synergy between melatonergic and 5-HT2C receptor-dependent pathways

<p>Abstract</p> <p>Background</p> <p>Agomelatine is a melatonergic receptor agonist and a 5HT_2Creceptor antagonist that has shown antidepressant efficacy. In order to analyze separately the effect of the two receptorial components, rats were chronically treated with agomelatine, melatonin (endogenous melatonergic agonist), or S32006 (5-HT_2Cantagonist), and then subjected to acute footshock-stress.</p> <p>Results</p> <p>Only chronic agomelatine, but not melatonin or S32006, completely prevented the stress-induced increase of glutamate release in the rat prefrontal/frontal cortex.</p> <p>Conclusions</p> <p>These results suggest a potential synergy between melatonergic and serotonergic pathways in the action of agomelatine.</p