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AbstractDairy goat’s lactation persistence forces farmers at limiting nutrient supply to reduce yield at dry-off. Omitting dry period could be a solution, but metabolic effects of this practice have never been tested. Eight Alpine (AL) and 12 Saanen (SA) goats approaching their second kidding blocked by breed and number of kids carried (single - SIN - or double - DOU) were allocated to one out of two groups (4 AL and 6 SA; 5 SIN and 5 DOU in each group). At −42 ± 7 days from kidding (DFK), they were either dried off (DR) or milked continuously until kidding (CL). Body condition score (BCS) was assessed, and blood samples were collected at −10, −3, 5, 12, and 29 DFK to determine metabolic profile. Milk yield and composition were assessed at −56, 7, 31, 62, and 97 DFK. Compared with DR, CL had higher plasma reactive oxygen metabolites and liver enzymes. Compared with DR counterparts, AL-CL had higher nonesterified fatty acids (NEFA) at −10, whereas SA-CL had lower NEFA at −3 DFK. CL goats had lower BCS, higher plasma beta-hydroxybutyrate (BHB) and urea before kidding, but higher glucose at −3 and 5, lower NEFA at 5 and 12, and higher BCS at 29 DFK. CL goats had lower haptoglobin and myeloperoxidase at −3 and 5 DFK, paired with higher albumin, cholesterol, and paraoxonase at 12 DFK. Omitting dry period mitigated the inflammatory condition around kidding in dairy goats, possibly accounting for an improved energy balance in early lactation, despite body reserve mobilisation prepartum was greater under continuous lactation.

We consider a dynamic principal‐agent problem, where the soleinstrument the principal has to incentivize the agent is the disclosure of information. The principal aims at maximizing the (discounted) number of times the agent chooses the principal's preferred action. We show that there exists an optimal policy, where the principal recommends its most preferred action and discloses information as a reward in the next period, until either this action becomes statically optimal for the agent or the agent perfectlylearns the state.

Heterogeneous Fenton-like reactions using O2as the sole oxidant are gaining interest for designing organic contaminant degradation in soils and groundwaters since they may provide alternatives to current processes involving strong oxidants. Indeed, several Fe(II)-bearing oxide and sulfide mineral phases have been proven to generate reactive species upon air oxidation. However, the mechanisms of these reactions and the identity of the reactive species produced upon oxygenation may deserve further research. Here, we show using electron paramagnetic resonance (EPR) spectroscopy combined with the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trap that air oxidation of pH 7 phosphate-buffered aqueous suspensions of magnetite (Fe3O4) or mackinawite (FeS) nanoparticles produces a reactive species that is distinct from the hydroxyl radical (•OH) and abstracts a hydrogen atom from ethanol. This reactive species grows dramatically with phosphate concentration, and ultrafiltration reveals that it occurs as both aqueous and surface species. Based on these evidence and from extant reports, we hypothesize that the nonhydroxyl reactive species produced is Fe(IV), whose formation is enhanced in the presence of phosphate ligands. Fe3O4magnetite (∼14 nm) generates about 30% more of this putative ferryl species than FeS mackinawite (∼9 nm), while FeS2(pyrite ∼12 nm + marcasite ∼4 nm) appears unreactive under these conditions.

An increasing number of critical functionalities integrated in embedded critical systems rely on deep learning (DL) technology. This article summarizes certain key aspects of DL’s intrinsic stochastic and training-data-dependent nature that are at odds with current domain-specific functional safety standards. We exemplify how redundancy and diversity of neural networks can help to reconcile DL technology and functional safety requirements.

AbstractThirty-six multiparous Holstein mid-lactating cows were housed in 6 pens (6 cows/pen) and allocated in two groups (3 pens/group), receiving a control total mixed ration (CTR), or the same diet supplemented with a feed additive (TRT). Between 15 and 35 days from enrolment (DFE) the dry matter intake (DMI) of each pen, and the individual milk yield (MY), rumination time (RT), the compositions of milk and rumen fluid and the metabolic profile of plasma were monitored regularly. At 35 DFE, cows started a 1-week wash-up period prior to the changeover. Data were analysed with a mixed model using repeated measures. Cows receiving the additive had higher DMI and MY (p < .01), a longer RT between 22 and 29 DFE (p < .05), a higher total VFA concentration and a lower pH in the rumen fluid (p < .01 and p = .04, respectively). At 15 DFE, TRT cows had a higher concentration of lactose in their milk, and lower concentrations of BHB, ceruloplasmin and haptoglobin, paired with higher concentrations of albumin, paraoxonase and aspartate aminotransferase in their plasma (p < .01). These outcomes suggest a positive effect of the additive on increasing DMI and MY, possibly reflecting that it had a combined action on the rumen and the liver.HighlightsThe additive increased feed intake, rumination time and milk yield.It improved rumen fermentations and liver activity, and mitigated ketogenesis and inflammatory conditions.Beneficial actions of the active components on rumen and liver functions could be hypothesised.

We consider general asset marketenvironments in which agents with quasilinear payoffs are endowed with objects and have demands for other agents' objects. We show that if all agents have a maximum demand of one object and are endowed with at most one object, the VCG transfer of each agent is equal to the largest net Walrasian priceof this agent. Consequently, the VCG deficit is equal to the sum of the largest net Walrasian prices over all agents. Generally, whenever Walrasian prices exist, the sum of the largest net Walrasian prices is a nonnegative lower bound for the deficit, implying that no dominant‐strategy mechanism runs a budget surplus while respecting agents' ex post individual rationality constraints.

Introduction: Real-world pharmacoutilization analysis of biological drugs in psoriatic arthritis (PsA) patients with the aim to evaluate biologic treatment patterns and pharmacoutilization among patients with PsA in Italy. Methods: A retrospective study was conducted using administrative databases of Italian Entities. PsA patients were included and diagnosed by hospitalization and/or an active exemption code. Two analyses were performed: a cross-sectional for treatment patterns in patients enrolled among 2017–2020, and a longitudinal study during 2015 to investigate the pharmacoutilization, in terms of persistence and monthly maintenance dosage of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Patients with or without b/tsDMARDs prescriptions before inclusion were defined as bioexperienced or naïve, respectively. An analysis on ixekizumab-treated patients (IXE patients) from the 2017-to study ending was performed. Results: PsA was diagnosed in 24,786 (2017), 27,221 (2018), 28,889 (2019), and 29,292 (2020) patients. Across 2017–2020, 31.1–40.5% of PsA patients were untreated with systemic medications, and 16.4–18.8% were under biological therapies. Among b/tsDMARD-treated patients, decreasing use of TNF-inhibitors (77.6–57.1%) and increasing IL-inhibitors (19.6–33.2%) was found across 2017–2020, respectively. Persistence to TNF-inhibitors and IL inhibitors as first-line ranged, respectively, 74.9–83.0% and 73.0–84.6%; specifically, 73.1–76.9% and 73.0–83.8% among bio-naïve, 83.3–90.0%, and 87.0% among bio-experienced. Among IXE-patients (N= 178), 55.6% were bio-naïve, while 21.9% previously used secukinumab, 12.9% adalimumab, 10.1% etanercept. During a 1-year follow-up, 6.8% of IXE patients switched therapy. Conclusions: This real-world study of PsA pharmacoutilization in Italy showed that more than one-third of patients were systemically untreated, and almost 20% were receiving biological medications. Among biological users, increasing use of IL-inhibitors and a decrease in TNF-inhibitors prescriptions over the years were found. A rather-high extent of persistency in treatment was observed. A focused analysis on IXE patients revealed over half of them to be bio-naïve, while around one-fourth were bio-experienced to IL inhibitors.

The price mechanism is fundamental to economics but difficult to reconcile with incentive compatibility and individual rationality. We introduce a double clock auction for a homogeneous good market with multidimensional private information and multiunit traders that is deficit‐free, ex post individually rational, constrained efficient, and makes sincere bidding a dominant strategy equilibrium. Under a weak dependence and an identifiability condition, our double clock auction is also asymptotically efficient. Asymptotic efficiency is achieved by estimating demand and supply using information from the bids of traders that have dropped out and following a tâtonnement process that adjusts the clock prices based on the estimates.

AbstractOur study investigates metabolic changes occurring at dry-off and the contribution of milk yield (MY) in such alterations. Thirteen Holsteins were dried off at 55 days from expected calving day (assumed as 0 days from dry-off, DFD) and divided in two groups according to their average daily MY in the last week of lactation, assuming a cut-off of 15 kg·d−1: low MY (7 cows) and high MY (6 cows). From −7 to 34 DFD dry matter intake (DMI) and rumination time were measured. Blood samples were collected at −7, 2, 7, 27 and 34 DFD to assess an haematological and metabolic profile and at −7, 7 and 34 DFD to test functions of circulating white blood cell (WBC) through ex vivochallenges. Data were included in a mixed model for repeated measures assuming MY at dry-off, time and their interaction as fixed effects. After dry-off, DMI was reduced and rumination time was increased in all the animals. High MY cows had greater DMI and rumination time than low MY cows. In blood, WBC counts decreased at 7 DFD and increased the production of pro-inflammatory cytokines at 7 and 34 DFD. Plasmatic concentrations of liver enzymes indicators, positive acute phase proteins (APPs); and nitrogen species increased after dry-off. Conversely, negative APPs and antioxidant species decreased. Those alterations were more marked in high MY animals. This study suggests that dry-off decreased liver function, triggered a systemic inflammation and depleted antioxidant systems, especially in the group of cows with high MY at dry-off.HighlightsInflammation, liver dysfunctions and altered redox balance has been detected after dry-off in all the animals.Cows with highest milk yield before halting of milk removal faced the most severe metabolic challenges.Such founding indicates the management of dry-off as a key point for dairy cows health.

The synthesis of enantiomerically pure benzoins by hydrogenation of readily available benzils has been long thwarted by their base-sensitivity. We show here that an iron(II) hydride complex catalyzes the asymmetric transfer hydrogenation of benzils from 2-propanol. When strictly base-free conditions are granted, excellent enantioselectivity is achieved even with o-substituted substrates, which are particularly challenging to prepare with other methods. Hence, under optimized reaction conditions, chiral benzoins were prepared in good yields (up to 83%) and excellent enantioselectivity (up to 98% ee) in short reaction times (30–75 min). Also, this work confirms that both enantiomers of the benzoin products can be accessed when a metal catalyst is used, which is a clear advantage over enzymatic methods.

Food fortification through the increase and/or modulation of bioactive compounds has become a major goal for preventing several diseases, including cancer. Here, strawberry lines of cv. Calypso transformed with a construct containing an anthocyanidin synthase (ANS) gene were produced to study the effects on anthocyanin biosynthesis, metabolism, and transcriptome. Three strawberry ANStransgenic lines (ANS L5, ANS L15, and ANS L18) were analyzed for phytochemical composition and total antioxidant capacity (TAC), and their fruit extracts were assessed for cytotoxic effects on hepatocellular carcinoma. ANS L18 fruits had the highest levels of total phenolics and flavonoids, while those of ANS L15 had the highest anthocyanin concentration; TAC positively correlated with total polyphenol content. Fruit transcriptome was also specifically affected in the polyphenol biosynthesis and in other related metabolic pathways. Fruit extracts of all lines exerted cytotoxic effects in a dose/time-dependent manner, increasing cellular apoptosis and free radical levels and impairing mitochondrial functionality.

Hybrid methods combining quantum chemistry and classical models are largely used to describe solvent effects in absorption and emission processes of solvated chromophores. Here we compare three different formulations of these hybrid approaches, using a continuum, an atomistic, or a mixed description of the solvent. In all cases mutual polarization effects between the quantum and the classical subsystems are taken into account. As a molecular probe, 3-hydroxyflavone has been selected due to its rich photophysics, which involves different tautomeric and anionic forms. We show that a clear assignment of the measured spectroscopic signals to each specific form can be achieved by combining the different solvation models into an integrated and cost-effective strategy. Previously proposed mechanisms for the excited-state proton transfer (ESIPT), specific solvent perturbation effects on ESIPT, and solvent-assisted anion formation are also validated in terms of short- and long-range solvation effects.

The orange carotenoid protein (OCP), which is essential in cyanobacterial photoprotection, is the first photoactive protein containing a carotenoid as an active chromophore. Static and time-resolved Fourier transform infrared (FTIR) difference spectroscopy under continuous illumination at different temperatures was applied to investigate its photoactivation mechanism. Here, we demonstrate that in the OCP, the photo-induced conformational change involves at least two different steps, both in the second timescale at 277 K. Each step involves partial reorganization of α-helix domains. At early illumination times, the disappearance of a nonsolvent-exposed α-helix (negative 1651 cm–1band) is observed. At longer times, a 1644 cm–1negative band starts to bleach, showing the disappearance of a solvent-exposed α-helix, either the N-terminal extension and/or the C-terminal tail. A kinetic analysis clearly shows that these two events are asynchronous. Minor modifications in the overall FTIR difference spectra confirm that the global protein conformational change consists of—at least—two asynchronous contributions. Comparison of spectra recorded in H2O and D2O suggests that internal water molecules may contribute to the photoactivation mechanism.

Hydride cis-β-[FeH(CNCEt3)(1)]BF4(5) (1is a chiral N2P2macrocycle) is the catalytically active species in the asymmetric transfer hydrogenation of ketones formed upon reaction of [Fe(CNCEt3)2(1)](BF4)2(3) with base. Stoichiometric reactions show that hydride 5is formed by H-elimination from the 2-propoxo complex [Fe(OiPr)(CNCEt3)(1)]BF4(8a) and inserts the C═O bond of acetophenone to give the diastereoisomeric alcoholato complexes [Fe(OCH(Me)Ph)(CNCEt3)(1)]BF4(10Rand 10S). Complexes 5, 8a, and 10were characterized by NMR spectroscopy, and their structures were calculated by DFT. The DFT study supports a bifunctional mechanism with the alkoxo complexes 8aand 10as resting species. The stereochemical model reproduces the high enantioselectivity with acetophenone, which results from the combination of the rigid macrocyclic scaffold with the bulky, yet conformationally flexible isonitrile.

AbstractThe increased resistance to disease observed after monensin treatment could reflect a reduction of inflammation and oxidative stress. We hypothesised that if monensin supplementation was given before calving, it would help in controlling inflammation, reduce the susceptibility to disease and increase the performance. Fourteen pregnant heifers (PR) and 24 multiparous cows (ML) were randomly assigned to a treated group (Mon) or a control group (Ctr). The Mon group received 32.4 g of monensin in a controlled-release capsule 21 days before calving (expected release rate, 335 mg/d for 95 days). Their health status, rumination activity, and plasma parameters were monitored from –28 to 56 days from calving. The milk yield (MY), milk composition, and cheese-making properties were also monitored. Rumen samples were collected at 30 days from calving to assess the volatile fatty acids composition and investigate immunological parameters. After calving, the Mon group had fewer clinical diseases, an increased rumination time, and a higher MY. Monensin reduced the infiltration of both T and B cells in rumen fluid. In ML, the Mon group had lower levels of β-hydroxybutyrate in the early postpartum period and a lower level of total reactive oxygen species. Of PR, the Mon group had a tendency for lower levels of nonesterified fatty acids, higher levels of ceruloplasmin after the first month of lactation, a tendency for lower levels of paraoxonase, higher levels of γ-glutamyl transferase and higher levels of total reactive oxygen species. Monensin treatment decreased the cheese-making properties in the milk of PR.HighlightsMonensin improved the performance of all the animals and decreased the disease incidence in all of them.Monensin heightened the inflammatory and oxidative stress status and reduced the cheese-making properties in pregnant heifers.Although different effects were seen in cows with different parity, dairy cows generally beneficed of monensin administration.

Introduction: Cardiac arrhythmias are challenging diseases in childhood. Most of them in pediatric subjects (90.2%) are atrioventricular reentrant tachycardias and atrioventricular nodal reentrant tachycardias. The standard 12-lead ECG is a highly accurate diagnostic tool but an invasive electrophysiological study is often required. The main concern about this kind of procedures is their invasive nature and the need of radiations, so antiarrhythmic agents are currently the first line therapy. However, they often show side effects and can be insufficient for the rate control. Materials and Methods: We performed a systematic research on Embase and PubMed. We found 563 articles and selected the most representative 50. Discussion: Management of cardiac arrhythmias could be very difficult in several scenarios, especially in children with body weight <15 kg and age <4 years. In general, pediatric subjects show a cumulative risk of malignancy greater than adults, having greater life expectancy. On this basis the guiding principle during radiation delivery in electrophysiological procedures is “as low as reasonably achievable” (acronym: ALARA). The development of 3-dimensional (3D) electroanatomical mapping systems allowed significant reduction of exposure. The most recently reported experiences demonstrate safety and feasibility of fluoroless ablation in the most common arrhythmias in children, even in challenging conditions. Conclusion: The first reasonable approach in cardiac arrhythmias involving younger patients seems to be pharmacological. However antiarrhythmic drugs pose problems both in terms of side effects and often have poor efficacy. Expertise in electrophysiological techniques is constantly increasing and the development of new technologies allow us to encourage the use of electroanatomical mapping systems in order to reduce the radiation exposure in children undergoing to catheter ablation, especially for accessory pathways.

In an article of 1967 Edge gave a description of some beautiful geometric properties of the Kummer surface complete intersection of three quadrics in . Working on it, Dye proved in 1982 and 1992 that all its osculating spaces have dimension less than the expected 5. Here we discuss these results, also in the light of some recent result about varieties with hypo-osculating behaviour.

Strawberry (Fragaria× ananassa) fruits are an excellent source of L-ascorbic acid (AsA), a powerful antioxidant for plants and humans. Identifying the genetic components underlying AsA accumulation is crucial for enhancing strawberry nutritional quality. Here, we unravel the genetic architecture of AsA accumulation using an F1population derived from parental lines ‘Candonga’ and ‘Senga Sengana’, adapted to distinct Southern and Northern European areas. To account for environmental effects, the F1and parental lines were grown and phenotyped in five locations across Europe (France, Germany, Italy, Poland and Spain). Fruit AsA content displayed normal distribution typical of quantitative traits and ranged five-fold, with significant differences among genotypes and environments. AsA content in each country and the average in all of them was used in combination with 6,974 markers for quantitative trait locus (QTL) analysis. Environmentally stable QTLs for AsA content were detected in linkage group (LG) 3A, LG 5A, LG 5B, LG 6B and LG 7C. Candidate genes were identified within stable QTL intervals and expression analysis in lines with contrasting AsA content suggested that GDP-L-Galactose Phosphorylase FaGGP(3A),and the chloroplast-located AsA transporter gene FaPHT4;4(7C)might be the underlying genetic factors for QTLs on LG 3A and 7C, respectively. We show that recessive alleles of FaGGP(3A)inherited from both parental lines increase fruit AsA content. Furthermore, expression of FaGGP(3A)was two-fold higher in lines with high AsA. Markers here identified represent a useful resource for efficient selection of new strawberry cultivars with increased AsA content.

Early monitoring of the failure of metabolic adaptation to calving, represents the most effective measure for allowing a prompt intervention on transition dairy cows. This prevents deleterious effects on animal performance, health and welfare which are driven by multiple disorders during the following lactation. Applying metabolic profiling could 1) provide a deeper view on the etiology of any pathological condition affecting transition cows, aimed at increasing the effectiveness and timely application of any treatment, and 2) provide detailed feedback on the management practices adopted in a farm during this challenging phase based on animal responses.

We compare properties of galaxies in loose groups with those in field environment by analyzing the Nearby Optical Galaxy (NOG) catalog of galaxy systems. We consider as group galaxies objects belonging to systems with at least five members identified by means of the “friends of friends method”, and, as field galaxies, all galaxies with no companions. We analyze both a magnitude-limited sample of 959 and 2035 galaxies (groups vs. field galaxies, respectively, $B<14$mag, and $2000

ABSTRACTGlobe artichoke (Cynara cardunculusL. var. scolymus) plants of a typical landrace (‘Montelupone A’) from the Marche region (Italy) and three commercial cultivars (‘Apollo’, ‘Romanesco C3’, ‘Exploter’) were compared as a detailed analysis of their productive, morphological, qualitative, and nutritional parameters was carried out to characterise their particularities and suitability for the fresh market or the processing industry. Cultivar ‘Apollo’ stands out for its qualitative and agronomic aspects, with ‘Romanesco C3’ showing high flower head yield, as the most important Romanesco cultivar that is widely cultivated in central Italy. ‘Exploter’ shows high productivity and qualitative characteristics. The lower phenol content of ‘Exploter’ indicates its suitability for processing as a fresh cut preparation. The ‘Montelupone A’ landrace is characterised by beneficial nutritional values that indicate its use for fresh consumption and as a source of antioxidant compounds. The ‘Apollo’ and ‘Romanesco C3’ commercial cultivars show higher processing yield due to flower head characteristics. In particular, ‘Apollo’ has an interesting profile according to its technological qualitative and nutritional value. ‘Exploter’ differs in its high yield and suitability for the fresh market. Analysis of the ‘Montelupone A’ landrace confirms its interesting qualitative and nutritional values.

We study morphology and luminosity segregation of galaxies in loose groups. We analyze the two catalogs of groups identified in the Nearby Optical Galaxy (NOG) sample, by means of hierarchical and percolation “friends-of-friends” methods (HG and PG catalogs, respectively). In the first part of our analysis we consider 387 and 436 groups of HG and PG and compare morphology- (luminosity-) weighted to unweighted group properties: velocity dispersion, mean pairwise distance, and mean groupcentric distance of member galaxies. The second part of our analysis is based on two ensemble systems, one for each catalog, built by suitably combining together galaxies of all groups (1584 and 1882 galaxies for HG and PG groups). We find that earlier-type (brighter) galaxies are more clustered and lie closer to the group centers, both in position and in velocity, than later-type (fainter) galaxies. Spatial segregations are stronger than kinematical segregations. These effects are generally detected at the $\mathrel{\hbox{\rlap{\hbox{\lower4pt\hbox{~}}}\hbox{$>$}}}$3-sigma level. Luminosity segregation is shown to be independent of morphology segregation. Our main conclusions are strengthened by the detection of segregation in both hierarchical and percolation catalogs. Our results agree with a continuum of segregation properties of galaxies in systems, from low-mass groups to massive clusters.

In IR difference spectroscopy of proteins and biological systems, as in many other biophysical techniques, experiments at different hydration levels, and after H/D or H216O/H218O exchange are particularly important, for band assignment and for mechanistic studies. Evaluate the kinetics, the effectiveness and the feasibility of an isopiestic approach for controlled hydration and isotopic exchange on bacterial photosynthetic reaction centers as a model for membrane proteins. Mid-Infrared and Near Infrared spectroscopy experiments at different times and kinetic data treatment. Equilibria for hydration/dehydration, and for isotopic exchange are rapid (hour time scale) and can easily be applied in normal conditions. The exact hydration state and the effectiveness of isotopic exchange can be precisely assessed through FTIR or NIR spectroscopies. Furthermore, effectiveness of isotopic exchange (especially for internal exchangeable residues or molecules) appears to be higher compared to traditional methods. The isopiestic method can be easily applied to obtain controlled hydration conditions and high rate of isotopic exchange. This approach can be in principle applied to any biophysical technique.

Models including an energy transfer from CDM to DE were widely considered in the literature, namely to allow DE a significant high-zdensity. Strongly Coupled cosmologies assume a much larger coupling between DE and CDM, together with an uncoupled warm DM component, the role of Cbeing mostly restricted to radiative eras. This allows us to preserve small scale fluctuations even if the warm particle is quite light, O(100 eV). Linear theory shows full agreement between these cosmologies and ΛCDM on supergalactic scales; e.g., CMB spectra are identical. Simultaneously, simulations show that they ease problems related to the properties of MW satellites and cores in dwarfs. While opening new perspectives on early black hole formation and possibly leading towards unificating DE and inflationary fields, the critical prediction of SC cosmologies is a sterile neutrino or gravitino of mass∼ 100 eV.

The previously reported silica-grafted iridium(iii) hydride complex [IrH(O–SBA-15)(POCOP)] (2), prepared by treating [IrH2(POCOP)] (1) (POCOP is 1,3-bis((di-tert-butylphosphino)oxy)benzene) with SBA-15 (mesoporous silica), hydrogenates liquid alkenes (1-decene, trans-5-decene, cyclohexene, styrene, and 4-phenyl-1-butene) at room temperature and under 1 atm H2. Internal alkenes react at a lower rate than the terminal ones. For the sake of comparison, the hydrogenation of the same substrates was studied with the homogeneous catalyst [IrH2(POCOP)] (1). The heterogeneous catalyst 2hydrogenates 1-decene, cyclohexene, and 4-phenyl-1-butene faster than 1, whereas the opposite is true for styrene and trans-5-decene, which suggests that different active species are involved in the heterogeneous and homogeneous reactions. Catalysis by a truly heterogeneous species is supported by a series of “hot filtration tests”. NMR spectroscopic studies showed that 2does not undergo degrafting upon longer exposure to alkenes compared to ethene under hydrogenation conditions.

Peridinin-Chlorophyll-a-Proteins (PCPs) are water-soluble light harvesting complexes from dinoflagellates. They have unique light-harvesting and energy transfer properties which have been studied in details in the last 15 years. This review aims to give an overview on all the main aspects of PCPs photophysics, with an emphasis on some aspects which have not been reviewed in details so far, such as vibrational spectroscopy studies, theoretical calculations, and magnetic resonance studies. A paragraph on the present development of PCPs towards technological applications is also included.

Transition metal (TM) ions can be covalently attached to a silica surface by means of a M–OSi bond (grafting) to give site-isolated complexes. Acting as a ligand in such grafted species, the surface influences the electronic nature and the coordination number of the TM ion, in contrast to anchored complexes, in which a linker separates the metal ion and the surface and hence reduces their interaction. This perspective reviews general grafting strategies on an oxide surface and focuses on the peculiarity of silica-grafted catalysts of late TMs, which have a higher tendency to undergo aggregation into metal nanoparticles under reducing conditions than early TMs. Soft ligands (hydride, phosphines) and/or π-acceptors (CO) promote aggregation. In particular, silica-grafted hydride complexes of late TM ions are not stable and tend to undergo reductive elimination of silanol. The coordination chemistry background of this behaviour is discussed, and possible strategies to avoid aggregation are suggested.

Obesity is an increasing epidemic worldwide; however, little is known about effects of obesity produced by high-fat diet (HFD) on the cerebral circulation. The purpose of this study was to examine the functional and temporal effects of a HFD on carotid and cerebral vascular function and to identify mechanisms that contribute to such functional alterations.

The hypothesis of a relationship between sarcoidosis and malignancy was firstly formulated in 1972 by Brincker. He documented an association of sarcoid reactions or sarcoidosis with 19 lymphomas and associated malignancies. Based on various epidemiological studies, for more than 20 years sarcoidosis has been considered as a condition at increased risk for cancer, particularly lymphoproliferative disorders. The existence of a sarcoidosis-lymphoma syndrome was therefore proposed, highlighting, as a potential mechanism, the uncontrolled lymphocyte proliferation and mitotic activity. A reduced ability to eliminate an antigen and chronic inflammation have been suggested as triggering events. Leading to a reduced tumor immune surveillance, a diminished myeloid dendritic cells (mDC) function, despite up-regulated co-stimulatory and maturation markers, was also raised as potential mechanism. However, some subsequent studies have questioned the presence of a close association between the two entities and have explained those previously published as the result of selection bias and misclassification. Recently, a Swedish population-based cohort study documented a significant overall excess incidence of cancer among sarcoidosis patients, especially those with multiple hospitalizations or admission in older age, emphasizing again a potential neoplastic risk. Therefore, currently, whether these patients have an increased risk of developing malignant lesions is still debated. Larger and unbiased studies are needed before drawing definite conclusions.

Background:MicroRNAs (miRNAs) are endogenous, non-coding, short, single-stranded RNAs and represent a new class of gene regulators. Recent evidence supports a role for miRNAs in cardiovascular pathophysiology and atherosclerosis development. We have previously demonstrated that miR-145 is widely expressed in human atherosclerotic lesions and its downregulation has been correlated with vascular smooth muscle cell dedifferentiation, a cardinal step in the development of atherosclerosis. However, no evidences are available at this time about modulation of miR-145 in the setting of hypertension. Thus, the aim of this study was to investigate the expression of miR-145 in complicated hypertension.Materials and methods:Atherosclerotic plaques were obtained from 22 patients undergoing carotid endarterectomy for high-grade internal carotid artery stenosis. Plaques were subdivided into hypertension (n 15) and control (n 7) groups according to the presence or absence of hypertension (as defined by blood pressure > 140/90 mmHg or current antihypertensive treatment). In study plaques, miR-145 values were evaluated using real-time PCR. The level of induction has been tested by using ΔΔ cycle threshold method.Results:We found that miR-145 was significantly more expressed in atherosclerotic plaques of hypertensive patients than in control plaques (1.201 ± 0.260 vs 0.483 ± 0.148 fold induction ± SE; p 0.026). Moreover, a post-hoc analysis showed that treatment with angiotensin receptor blockers may be associated with the maximum increase in miR-145 levels, although these data did not show any statistical significance probably due to the limited sample size.Conclusions:To the best of our knowledge, this study is the first demonstration that hypertension may upregulate miR-145 expression in human atherosclerotic plaques. Future investigations will be necessary to establish the molecular readout of miR-145 upregulation in atherosclerotic lesions in hypertension.

The diagnosis and control of hypertension depend on accurate measurement of blood pressure (BP). The literature on the accuracy of BP recording by health professionals is, however, limited, and no study directly interviewed patients in the hospital setting. This multicenter cross-sectional study aimed at evaluating the compliance to current recommendations on BP measurement by health professionals directly from patients and to investigate potential predictors of higher quality in BP recording.

Objectives:Recent evidence indicates that rosuvastatin 40 mg may exert a beneficial effect in both carotid and coronary atherosclerosis progression. In particular, 2-year rosuvastatin treatment reduced the progression of carotid intima-media thickness (cIMT) in patients with low cardiovascular risk. However, despite the fact that in clinical practice lower doses of rosuvastatin are usually administered at this time, there are no clear data about its effect on cIMT. Thus, the aim of this study was to evaluate the effect of rosuvastatin 10 mg/day on cIMT over a 2-year follow-up.Methods:Forty-five patients with hypercholesterolemia and asymptomatic carotid atherosclerosis on baseline carotid ultrasound investigation were treated with rosuvastatin 10 mg/day for 24 months. cIMT and lipid profile were assessed after 12 months and at the end of the study (24 months).Results:After 24 months, the treatment showed a 35.67% reduction in low-density lipoprotein cholesterol concentration (171 vs 110 mg/dl; p < 0.001), a 32.27% reduction in total cholesterol (251 vs 170 mg/dl; p < 0.001), a 19.67% increase in high-density lipoprotein cholesterol concentration (49 vs 61 mg/dl; p < 0.001), and a 10% reduction in triglycerides (120 vs 108 mg/dl; p < 0.01). Rosuvastatin treatment was associated with a 26.6% reduction in left cIMT (1.20 vs 0.90 mm; p < 0.001) and a 22.2% reduction in right cIMT (1.22 vs 0.95 mm; p < 0.001).Conclusion:Two-year treatment with rosuvastatin 10 mg/day in hypercholesterolemic adults with evidence of subclinical atherosclerosis establishes a significant reduction in cIMT and improves lipid and lipoprotein levels, with a good tolerability profile.

Atherosclerotic plaque rupture is considered the most important mechanism that underlies the onset of stroke, myocardial infarction, and sudden death. Several evidences demonstrated the pivotal role of inflammatory processes in plaque destabilization. MicroRNAs (miRNAs) are small endogenous RNAs and represent a new important class of gene regulators. Nevertheless, no data exist about the expression profile of miRNAs in atherosclerotic plaques. Thus, the aim of this study was to investigate the expression level of miRNAs in human plaques and to correlate it with clinical features of plaque destabilization.

Arachidonic acid metabolism plays a key role in atherothrombotic events affecting the coronary or cerebrovascular territory, as reflected by experimental studies based on biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. Two cyclooxygenase (COX)-isozymes exist, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and susceptibility to inhibition by drugs. Whereas the role of COX-1 expressed in platelets in acute coronary syndromes and ischemic stroke is definitely established through several large clinical studies with aspirin, the role of COX-2 activity in these settings is still unclear, because this enzyme was characterized only recently (1991) and its inhibitors (coxibs) only became available in 1998. In this review, we discuss the different expression profile of COX-2-related enzymes in the cells actively involved in atherothrombosis, the role of these enzymes as cause of plaque “instability”, and the clinical consequences of their inhibition. Recent studies suggest that variable expression of transmembrane and downstream receptors, as well as genetic mutations represent important determinants of the functional consequences of COX-2 expression and inhibition in different clinical settings.

The object of our study was to compare the effect of high-dose vs low-dose atorvastatin vs nonstatin-based treatment (cholestyramine plus sitosterol) on cell composition of carotid plaque.

Modern methodologies for the development of high-integrity real-time systems build on abstract representations or models instead of code artifacts. Since analysis techniques are applied to models, it is important that system properties asserted during the analysis and the assumptions made for the analysis to hold are preserved across implementation and execution. In this paper we contend that the extent of properties preservation we require cannot be warranted using exclusively the language constructs allowed by the Ravenscar Profile. Hence, in the light of the new Ada 2005 features, we propose the formalization of a new augmented profile, fit for the purpose and yet still adhering to the pristine Ravenscar rationale.

Abstract: Tomatoes are a very important part of the Mediterranean diet. The possibility of a much healthier tomato option represents a great opportunity for the population to enhance their daily diet. Folate is an important bioactive compound for human health and increasing folate content in tomatoes can contribute to reduce some of the problems associated with this deficiency. In this review, the new option of a biofortified tomato produced by the use of DNA recombinant technology will be discussed in terms of food safety of the new genetically modified product. The possibility to increase folate content has been recently demonstrated through two modifications: the first was based on the development of a synthetic form of engineered GTP cyclohydrolase I (GCHI) (based on mammalian synthesis), which was introduced in the plants to prevent the retroinhibition of the GCHI (folate precursor) in plants; the second was based on the pteridine-overproduction trait expressing the aminodeoxychorismate synthase (AtADCS) from Arabidopsis thaliana. Genetically modified tomatoes, able to accumulate an average of 25-fold more folate than controls, were produced. These fruits could provide the complete adult daily requirement in less than one standard serving. The modification also resulted in a 20 times higher accumulation of pteridines and PABA as compared with the wild-type control. The possible risks and benefits derived from the GM modification of the tomato, and the safety of the final product for consumers will be discussed.

Tomatoes are a very important part of the Mediterranean diet. The possibility of a much healthier tomato option represents a great opportunity for the population to enhance their daily diet. Folate is an important bioactive compound for human health and increasing folate content in tomatoes can contribute to reduce some of the problems associated with this deficiency. In this review, the new option of a biofortified tomato produced by the use of DNA recombinant technology will be discussed in terms of food safety of the new genetically modified product. The possibility to increase folate content has been recently demonstrated through two modifications: the first was based on the development of a synthetic form of engineered GTP cyclohydrolase I (GCHI) (based on mammalian synthesis), which was introduced in the plants to prevent the retroinhibition of the GCHI (folate precursor) in plants; the second was based on the pteridine-overproduction trait expressing the aminodeoxychorismate synthase (AtADCS) from Arabidopsis thaliana. Genetically modified tomatoes, able to accumulate an average of 25-fold more folate than controls, were produced. These fruits could provide the complete adult daily requirement in less than one standard serving. The modification also resulted in a 20 times higher accumulation of pteridines and PABA as compared with the wild-type control. The possible risks and benefits derived from the GM modification of the tomato, and the safety of the final product for consumers will be discussed.

The likeand unlikeisomers of phosphoramidite (P*) ligands are found to react differently with iridium(I), which is a key to explaining the apparently inconsistent results obtained by us and other research groups in a variety of catalytic reactions. Thus, the unlikediastereoisomer (aR,S,S)‐[IrCl(cod)(1 a)] (2 a; cod=1,5‐cyclooctadiene, 1 a=(aR,S,S)‐(1,1′‐binaphthalene)‐2,2′‐diyl bis(1‐phenylethyl)phosphoramidite) forms, upon chloride abstraction, the monosubstituted complex (aR,S,S)‐[Ir(cod)(1,2‐η‐1 a,κP)]+(3 a), which contains a chelating P* ligand that features an η2interaction between a dangling phenyl group and iridium. Under analogous conditions, the likeanalogue (aR,R,R)‐1 a′gives the disubstituted species (aR,R,R)‐[Ir(cod)(1 a′,κP)2]+(4 a′) with monodentate P* ligands. The structure of 3 awas assessed by a combination of X‐ray and NMR spectroscopic studies, which indicate that it is the configuration of the binaphthol moiety (and not that of the dangling benzyl N groups) that determines the configuration of the complex. The effect of the relative configuration of the P* ligand on its iridium(I) coordination chemistry is discussed in the context of our preliminary catalytic results and of apparently random results obtained by other groups in the iridium(I)‐catalyzed asymmetric allylic alkylation of allylic acetates and in rhodium(I)‐catalyzed asymmetric cycloaddition reactions. Further studies with the unlikeligand (aS,R,R)‐(1,1′‐binaphthalene)‐2,2′‐diyl bis{[1‐(1‐naphthalene‐1‐yl)ethyl]phosphoramidite} (1 b) showed a yet different coordination mode, that is, the η4‐arene–metal interaction in (aS,R,R)‐[Ir(cod)(1,2,3,4‐η‐1 b,κP)]+(3 b).

During the last few years, the nutritional value of fruit has been widely studied and requested by consumers, especially for the general health benefits it can provide. Some of these benefits can be ascribed to the antioxidant capacity of fruit. Both quality and antioxidant attributes are currently considered as good tools to describe the nutritional quality of fruit. In this study, offspring from inter and intra-specific strawberry cross combinations were studied with the aim of evaluating and identifying new genotypes that can show the best compromise between quality and nutritional characteristics. Parents and offspring populations were studied by analyzing fruit nutritional quality taking in account the following parameters: Total antioxidant capacity, total phenol and anthocyanin content. Eighty strawberry offspring, originating from 8 Fragaria spp. inter and intra-specific crosses, were screened to study the role of the genetic origin of the parents in segregating new genotypes with an improved nutritional quality of the fruit. Strawberry progenies having F. virginiana glauca as a common parent showed a significant enhancement of their fruit quality and nutritional features confirming the interest that wild species are useful in improving several characteristics in cultivated strawberries.

During the last few years, the nutritional value of fruit has been widely studied and requested by consumers, especially for the general health benefits it can provide. Some of these benefits can be ascribed to the antioxidant capacity of fruit. Both quality and antioxidant attributes are currently considered as good tools to describe the nutritional quality of fruit. In this study, offspring from inter and intra-specific strawberry cross combinations were studied with the aim of evaluating and identifying new genotypes that can show the best compromise between quality and nutritional characteristics. Parents and offspring populations were studied by analyzing fruit nutritional quality taking in account the following parameters: Total antioxidant capacity, total phenol and anthocyanin content. Eighty strawberry offspring, originating from 8 Fragaria spp. inter and intra-specific crosses, were screened to study the role of the genetic origin of the parents in segregating new genotypes with an improved nutritional quality of the fruit. Strawberry progenies having F. virginiana glauca as a common parent showed a significant enhancement of their fruit quality and nutritional features confirming the interest that wild species are useful in improving several characteristics in cultivated strawberries.

Cyclooxygenase (COX) is the key enzyme of the arachidonic acid metabolism and it plays a major role in development of both coronary and cerebrovascular disease. In this review, we will analyze the role of COX and prostaglandin synthases in plaque stability.

Leucine on silica constitutes an interesting system from the point of view of origins of life studies since leucine coadsorbed on SiO2together with glutamic acid can give rise to rather long linear polypeptides upon activation. It is also an ideal system to test methods of molecular characterization of biomolecules deposited on mineral surfaces since it combines a small-scale model of peptides and proteins, which are among the most important components of biodevices, with one of the most widely used inorganic materials. We have deposited l-leucine on a high surface fumed silica in the submonolayer range and characterized it by a multipronged approach including macroscopic information (thermogravimetry, X-ray diffraction), in situ spectroscopic methods (IR, multinuclear solid-state NMR including single-pulse and CP-MAS, 2-D HETCOR), and molecular modeling by density functional theory (DFT), including calculation of NMR parameters. Specific information can be obtained on the adsorption and interaction mechanism. Leucine is rather strongly adsorbed without any covalent bonds, through the formation of a specific lattice of H-bonds that often involve coadsorbed water molecules. Its state is indeed strongly dependent on the drying procedure: insufficient drying results in liquid-like surroundings for the leucine functional groups, while vacuum drying only retains a limited number of waters (of the order of 5 per leucine molecule). The most stable models have zwitterionic leucine interacting directly with surface silanols through their ammonium group, while the carboxylate interacts through bridging waters. Experimental NMR chemical shifts are satisfactorily predicted for these models, and leucine can be viewed as a probe for specific groups of surface sites known as silanol nests.

Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and matrix metalloproteinase dynamics], mechanical properties (vessel stiffness), and reactivity to pressure and vasoactive factors were measured in third-order mesenteric arteries in control Wistar and type 2 diabetic Goto-Kakizaki (GK) rats fed either a regular or high-fat diet. M/L ratios, total collagen, and myogenic tone were increased in diabetes. Addition of the high-fat diet altered collagen patterns (mature versus new collagen) in favor of matrix accumulation. Addition of a high-fat diet caused increased constriction to endothelin-1 (0.1-100 nM), showed impaired vasorelaxation to both acetylcholine (0.1 nM-1 microM) and sodium nitroprusside (0.1 nM-1 microM), and increased cardiovascular risk factors in diabetes. These results suggest that moderate elevations in blood glucose, as seen in our lean GK model of type 2 diabetes, promote resistance artery remodeling resulting in increased medial thickness, whereas addition of a high-fat diet contributes to diabetic vascular disease predominantly by impairing vascular reactivity in the time frame used for this study. Although differential in their vascular effects, both hyperglycemia and diet-induced dyslipidemia need to be targeted for effective prevention and treatment of diabetic vascular disease.

Ovarian primary carcinoid tumors of pure histological type can pose a significant diagnostic challenge in its separation from metastatic carcinoids from the gastrointestinal tract. Yet, their clinical management and prognosis are drastically different. At the molecular level, ovarian primary carcinoid tumors are thought to be of germ cell origin, frequently after the first meiotic division. We report a 21.5-cm ovarian insular carcinoid tumor in a 50-year-old woman who had no evidence of extraovarian tumor. The absence of teratomatous components and the presence of lymphovascular invasion prompted additional studies to rule out a metastatic tumor. The nature of this primary ovarian tumor was eventually confirmed by demonstration of its germ cell origin through DNA genotyping.

It wasnt until 1990, when the existence of two different cyclooxygenases was hypothesized, based on the evidence that steroids inhibited the increase in COX activity induced by bacterial lipopolysaccharides in macrophages, without any effects on the basal production of prostaglandins or leukotrienes. The first isoform, COX-1 is responsible for the production of “housekeeping” prostaglandins critical to the maintenance of normal renal function, gastric mucosal integrity, platelet aggregation, and the autocrine response to circulating hormones. COX-2 on the other hand is an inducible enzyme, upregulated 20-fold in macrophages, monocytes, synoviocytes, chondrocytes, fibroblasts, osteoblasts and endothelial cells by various inflammatory stimuli and cytochines. Classical findings shown that the therapeutics effects of NSAIDs are largely dependent on COX-2 inhibition, whereas some undesirable side effects are bound to COX- 1 blockade, such as gastrointestinal bleeding and renal failure. Therefore, agents that selectively inhibit COX-2 over COX-1 are desirable for the treatment of inflammation. However, since September 2004 reports of increased risk of thrombotic cardiovascular events had accumulated for coxibs, the COX-2 inhibitors. Our goal is to provide an overview of the relevant biology and pharmacology of this enzyme in atherosclerosis.