Kinetic and mechanistic studies of Pd-catalyzed amination of aryl halides

The Pd-catalyzed amination of aryl halides (Buchwald-Hartwig amination) has become a versatile and widely used technology to synthesize and produce aromatic amines relevant in pharmaceutical and agrochemical industries. The aim of the work presented in this thesis is to achieve a better mechanistic understanding of this reaction. The methodologies used were not traditional and focused on kinetic studies, carried out using in-situ tools, mainly reaction calorimetry. Reactions using different amines have been considered: the kinetic behaviour of a straight-chain primary amine (n-hexylamine) was found to be very different from the kinetics of benzophenone hydrazone. This difference was rationalised by considering the mechanism and by proposing a change in the rate-limiting step. Spectroscopic studies, aimed at determining the catalyst resting state, supported our proposals. We subsequently started studies on the competitive system of two amines and one aryl halide. We found that, surprisingly, the less reactive amine, when in competition, reacted first. This intriguing behaviour was rationalised by considering the Curtin- Hammett principle and by recognizing that in this case selectivity was controlled by relative stability of intermediates, not relative reactivity. This was termed “monopolizing” regime, in contrast to the “major-minor” regime in which the minor but more reactive intermediate produces the major product. Subsequent studies revealed that the benzophenone hydrazone product also binds to the Pd/BINAP catalyst, and, during the hexylamine reaction, inhibits the rate and induces a change in the rate limiting step and catalyst resting state. Reactions using benzophenone imine were then studied. The competitive system of benzophenone imine and benzophenone hydrazone provided an example of a system showing a change from the “monopolizing regime” to the “major-minor” regime. These concepts can be generalized and applied to explain selectivity in other competitive catalytic systems

Can the outside-in half-tunnel technique reduce femoral tunnel widening in anterior cruciate ligament reconstruction? A CT study

There are different techniques for drilling the femoral tunnel in the anterior cruciate ligament reconstruction (ACLR), but their influence in the bone tunnel enlargement in unknown. The purpose of this study was to compare two different surgical techniques for evaluating femoral tunnel enlargement in ACLR. The hypothesis was that tunnel placement using the outside-in technique leads to less tunnel enlargement compared to the transtibial technique. METHODS: Forty-four patients treated for ACLR between March 2013 and March 2014 were prospectively enrolled in this study. According to the surgical technique, subjects were assigned to Group A (Out-in) or Group B (Transtibial). All patients underwent CT examination in order to evaluate the femoral tunnel enlargement at four different levels. Moreover, all patients were evaluated with the Lachman test and pivot shift test, and the KT1000 arthrometer was used to measure the anterior laxity of the knee. A subjective evaluation was performed using the 2000 International Knee Documentation Committee Subjective Knee score, Lysholm knee score and Tegner activity scale. All patients were assessed after 24 months of follow-up. RESULTS: At the final follow-up, there were statistically significant differences (p 0.05). CONCLUSIONS: In ACLR with a suspension system, the outside-in technique leads to less enlargement of the femoral tunnel lower than the transtibial technique. KEYWORDS: Anterior cruciate ligament reconstruction; CT imaging; Drilling technique; Femoral tunnel enlargement PMID: 28389757 DOI: 10.1007/s00590-017-1950-8 Share on FacebookShare on TwitterShare on Google+ LinkOut - more resource

Relationship between habitat, densities and metabolic profile in brown hares (Lepus europaeus Pallas)

Some habitat traits and haematic parameters were studied to understand the relationships between the hare densities, habitat characteristics and physiological and nutritional condition of the animals. A total of 33 protected areas, reserved for wild game reproduction, located in the Province of Florence (Central Italy), were monitored during a 2-year period. In each protected area the hares were submitted to census. The habitat features of the protected areas were studied and the following parameters were categorised: altitude; cleared-land/total-land ratio; main exposure; main ground composition; water availability; main slope; anthropogenic presence; predator presence; wooded borders; presence of trees and shrubs; surveillance against hunting; demographic predator control; kind of cultivation; unharvested crops for game. After the census the hares were captured for translocation outside in "free" hunting areas. During capture the hares were put in darkened, wooden capture-boxes and remained inside for a variable period of time (10min to 3h). A sample of 3 to 7 hares, captured per year and per each protected area, were removed from the boxes (physically restrained, with covered eyes) for blood sample collection, sex, age and live weight determination. The following analyses were performed on frozen plasma samples: ALanine aminoTransferase (ALT), ASpartate aminoTransferase (AST), glucose, cholesterol, Blood Urea Nitrogen (BUN), Ca, P, Mg, Na, K, and Cl concentrations. The relationship between hare density and habitat characteristics was analysed by single regressions analysis. Then the habitat characteristics were subjected to multivariate analysis in relationship to hare body condition. The haematic parameters were analysed by least square means considering habitat traits, animal density, age and sex, as main categorical factors, interaction sex*age, and "pregnant and non-reproducing" nested within sex. Results showed that the highest density and best body conditions can be found in highlands, open fields with low tree presence and wooded borders, medium mixture soils, scarce predator presence and limited anthropogenic presence and with abundant water availability and shrubbiness. The study of the absolute values of metabolic profile, indicator of the physiological and nutritional condition of the reared animals, did not show any nutritional winter deficiency in wild hares and, as census data, should be repeated for several years since, probably, only their variations can be used as indicators of preliminary problems

Electron Collision Cross Sections in Tetrafluoropropene HFO1234ze(E) for Gas Mixtures in Resistive Plate Chambers

In recent years, there has been growing interest in tetrafluoropropene HFO1234ze(E) (C$_{3}$H$_{2}$F$_{4}$) for Resistive Plate Chambers (RPCs). This novel gas is considered a promising alternative to the standard mixtures currently used in RPCs, thanks to its low global warming potential. The knowledge of electron collision cross sections in C$_{3}$H$_{2}$F$_{4}$ enables reliable predictions of electron transport coefficients and reaction rates in C$_{3}$H$_{2}$F$_{4}$-based gas mixtures. This allows for optimizing the C$_{3}$H$_{2}$F$_{4}$-based gas mixtures to achieve the desired performance in RPCs. From measurements of electron transport coefficients and reaction rates, a complete set of scattering cross sections for electrons in C$_{3}$H$_{2}$F$_{4}$ has been derived. Validation of the electron collision cross sections is achieved through systematic comparisons of electron swarm parameters with experimental data in both pure C$_{3}$H$_{2}$F$_{4}$ and C$_{3}$H$_{2}$F$_{4}$/CO$_{2}$ gas mixtures. Given the influence of electron attachment in C$_{3}$H$_{2}$F$_{4}$ by the gas density, this work also includes precise calculations of the critical electric field strength in such mixtures. This set of cross sections has been further utilized to compute the effective ionization Townsend coefficient in gas mixtures containing C$_{3}$H$_{2}$F$_{4}$, potentially applicable for RPCs.Comment: Added section "Tetrafluoropropene-based Gas Mixtures for Resistive Plate Chambers

Anonymity and Confidentiality in Secure Distributed Simulation

Research on data confidentiality, integrity and availability is gaining momentum in the ICT community, due to the intrinsically insecure nature of the Internet. While many distributed systems and services are now based on secure communication protocols to avoid eavesdropping and protect confidentiality, the techniques usually employed in distributed simulations do not consider these issues at all. This is probably due to the fact that many real-world simulators rely on monolithic, offline approaches and therefore the issues above do not apply. However, the complexity of the systems to be simulated, and the rise of distributed and cloud based simulation, now impose the adoption of secure simulation architectures. This paper presents a solution to ensure both anonymity and confidentiality in distributed simulations. A performance evaluation based on an anonymized distributed simulator is used for quantifying the performance penalty for being anonymous. The obtained results show that this is a viable solution.Comment: Proceedings of the IEEE/ACM International Symposium on Distributed Simulation and Real Time Applications (DS-RT 2018

Relationship between Anti-European Brown Hare Syndrome Serological Titers and Brown Hare (Lepus europaeus Pallas) Densities

Thirty-three protected wild game reproduction areas, located in the province of Florence (Central Italy), were monitored for habitat characteristics and hare census over a period of 2 years. A total of 172 hares was captured, checked for sex, and age, and blood samples were taken. Serum samples were analyzed by competitive ELISA test for detection and titration of anti-European brown hare syndrome virus (EBHSV) antibodies. Results showed that EBHSV seropositive hares from areas with high and medium population densities had higher antibody titers than those coming from low-density areas and that adults showed lower values than young animals. Anti-EBHSV antibody levels were inversely related to the distances between protected areas and private hunting areas while a high density of protected areas was not associated with any similarity in the values or prevalence of EBHSV

Home range e utilizzo del territorio in pernici rose (Alectoris rufa rufa L.) nate in allevamento e allo stato selvatico

RIASSUNTO In Italia sono state ricostituite numerose piccole popolazioni di pernici rosse (Alectoris rufa L.) in areali dove la specie era estinta. Allo stato attuale, poiché la dimensione delle popolazioni ricostituite non raggiunge la dimensione minima necessaria per preservare la specie da una nuova estinzione, devono essere programmati interventi di sostentamento con rilascio di animali di altra provenienza. Al fine di utilizzare pernici nate in allevamento è quindi indispensabile effettuare una ricerca per valutare la capacità di integrazione, la sopravvivenza, l’uso dell’habitat e gli home-range di tali animali liberati in aree occupate da neopopolazioni selvatiche. All’interno di una Zona di Ripopolamento e Cattura (Petroio-Vinci-Firenze) dove è presente una popolazione stimata di 60 pernici selvatiche sono state immesse 350 pernici allevate nel mese di agosto. In gennaio sono state quindi catturate 6 pernici allevate e 21 pernici selvatiche. 6 soggetti per tesi (allevate o selvatiche) sono stati quindi radiocollarati e localizzati bisettimanalmente fino a luglio 2006. La mortalità osservata degli animali radiocollarati è risultata identica (50% =3 soggetti per ciascuna tesi) fra i soggetti selvatici ed i pochi soggetti allevati ricatturati che avevano superato l’inverno (mortalità stimata post-rilascio = 95,1%). I soggetti allevati sopravvissuti all’inverno sono stati in grado di integrarsi in brigate miste con quelli selvatici ed anche gli animali allevati sono stati in grado di riprodursi: delle 3 nidiate osservate, 1 apparteneva alla tesi selvatiche e 2 a quella allevate. L’habitat più frequentato dalle pernici è risultato il vigneto non lavorato, mentre l’aumento significativo della distanza dai punti di alimentazione artificiale sussidiari durante la cova ha fornito l’indicazione gestionale di aumentare e disperdere maggiormente le mangiatoie in primavera per compensare la dispersione delle coppie legata alla territorialità naturale. La distanza dalle abitazioni e gli home-range non sono risultati infine differire fra pernici selvatiche e allevate. SUMMARY In Italy several small populations of red-legged partridges (Alectoris rufa L.) has been reconstituted in areas where the species was extinguished. In these areas release of different animals must be programmed, since the dimension of the reconstituted populations does not catch up the minimal dimension required to guard the species from a new extinction. We have thought therefore indispensable to carry out a research in order to estimate the integration ability of the released raised-partridges with the wild population, the survival rates, the use of the habitat and the home-ranges of both populations. In a protected area of Central Italy (Petroio-Vinci-Florence), where an estimated population of 60 wild partridges is estimated, 350 raised partridges were released during the August month. In January 6 raised partridges and 21 wild partridges has been captured by traps. 6 subjects for each thesis (raised or wild) have been therefore equipped with radio necklaces and localised biweekly until July 2006. No difference in mortality rates (50% = 3 birds each) was observed between wild or raised partridges that had survived to the winter (estimated mortality after release = 95.1%). Raised partridges, that survive after their release in the wild, were able to integrate themselves in mixed brigades with the wild partridges. Also the raised partridges were able to breed (of the 3 observed broods of the radiotagged birds 2 belonged to the raised and 1 to the wild). Vineyards with interlined grass were the habitat most frequented (more than 25% of the localizations). The distance from the subsidiary artificial feeding points significantly increased during broods showing the necessity to increase the number and dispersion of the supplementary feeders in spring, to help the animals from an alimentary point of view. The distance from the houses and home ranges surfaces did not differ between wild and raised partridges

Anomalous vascularization in a Wnt medulloblastoma: A case report

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. To date only few cases of medulloblastoma with hemorrhages have been reported in the literature. Although some studies speculate on the pathogenesis of this anomalous increased vascularization in medulloblastoma, the specific mechanism is still far from clearly understood. A correlation between molecular medulloblastoma subgroups and hemorrhagic features has not been reported, although recent preliminary studies described that WNT-subtype tumors display increased vascularization and hemorrhaging. CASE PRESENTATION: Herein, we describe a child with a Wnt-medulloblastoma presenting as cerebellar-vermian hemorrhagic lesion. Brain magnetic resonance imaging (MRI) showed the presence of a midline posterior fossa mass with a cystic hemorrhagic component. The differential diagnosis based on imaging included cavernous hemangioma, arteriovenous malformation and traumatic lesion. At surgery, the tumor appeared richly vascularized as documented by the preoperative angiography. CONCLUSIONS: The case we present showed that Wnt medulloblastoma may be associated with anomalous vascularization. Further studies are needed to elucidate if there is a link between the hypervascularization and the Wnt/β-catenin signaling activation and if this abnormal vasculature might influence drug penetration contributing to good prognosis of this medulloblastoma subgroup

The Multifaceted Origin of Taurine Cattle Reflected by the Mitochondrial Genome

A Neolithic domestication of taurine cattle in the Fertile Crescent from local aurochsen (Bos primigenius) is generally accepted, but a genetic contribution from European aurochsen has been proposed. Here we performed a survey of a large number of taurine cattle mitochondrial DNA (mtDNA) control regions from numerous European breeds confirming the overall clustering within haplogroups (T1, T2 and T3) of Near Eastern ancestry, but also identifying eight mtDNAs (1.3%) that did not fit in haplogroup T. Sequencing of the entire mitochondrial genome showed that four mtDNAs formed a novel branch (haplogroup R) which, after the deep bifurcation that gave rise to the taurine and zebuine lineages, constitutes the earliest known split in the mtDNA phylogeny of B. primigenius. The remaining four mtDNAs were members of the recently discovered haplogroup Q. Phylogeographic data indicate that R mtDNAs were derived from female European aurochsen, possibly in the Italian Peninsula, and sporadically included in domestic herds. In contrast, the available data suggest that Q mtDNAs and T subclades were involved in the same Neolithic event of domestication in the Near East. Thus, the existence of novel (and rare) taurine haplogroups highlights a multifaceted genetic legacy from distinct B. primigenius populations. Taking into account that the maternally transmitted mtDNA tends to underestimate the extent of gene flow from European aurochsen, the detection of the R mtDNAs in autochthonous breeds, some of which are endangered, identifies an unexpected reservoir of genetic variation that should be carefully preserved