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It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies.

Leukocyte infiltration plays an active role in controlling tumor development. In the early stages of carcinogenesis, T cells counteract tumor growth. However, in advanced stages, cancer cells and infiltrating stromal components interfere with the immune control and instruct immune cells to support, rather than counteract, tumor malignancy, via cell–cell contact or soluble mediators. In particular, metabolites are emerging as active players in driving immunosuppression. Here we demonstrate that in a prostate cancer model lactate released by glycolytic cancer-associated fibroblasts (CAFs) acts on CD4+T cells, shaping T-cell polarization. In particular, CAFs exposure (i) reduces the percentage of the antitumoral Th1 subset, inducing a lactate-dependent, SIRT1-mediated deacetylation/degradation of T-bet transcription factor; (ii) increases Tregcells, driving naive T cells polarization, through a lactate-based NF-kB activation and FoxP3 expression. In turn, this metabolic-based CAF-immunomodulated environment exerts a pro-invasive effect on prostate cancer cells, by activating a previously unexplored miR21/TLR8 axis that sustains cancer malignancy.

Built-up edge (BUE) has been noted as a major cause for surface finish deterioration in micromachining processes—even a trace formation of hardened and brittle structure on the tool edge alters the chip load, creates ad hoc and irregular material flow patterns, and results in deposits and smeared regions on the machined surface. To date, few investigations have addressed the formation and effects of BUE in micromachining. This paper is one of the first experimental investigations of the BUE effects on surface quality and its prediction in micromachining. Experiments were conducted on a Haas OM2 CNC milling system with air bearing spindle. The experiments consisted of micromilling 12mm long thin channels on 316L stainless steel plates (30mm×40mm×0.5mm) using uncoated tungsten carbide micromills (from Performance Micro Tools with flat end and Φ0.406mm diameter) at 16 different settings of carefully selected combination of cutting speed and chip load with minimum quantity lubrication (MQL). The surface morphology including BUE distribution, as well as BUE formation on tool surfaces were studied ex situvia optical and scanning electron microscopy. We introduce two metrics to quantify the severity of BUE, namely, BUE density and its distribution entropy. These metrics capture, respectively, the extent and dispersion of BUE on the surface. We also conducted empirical studies to assess the extent to which these quantifiers can determine the variation in surface finish (Sa). Results suggest that the BUE is the major determinant of surface finish besides the chip load effect in micromachining. Statistical Granger-causality tests suggest also that estimation of the BUE density can help with improving the accuracy (R2) of surface finish Saprediction from a negative value (poor fit) with conventional model to 0.4, i.e., 40% of Savariation in the micromachining experiments can be attributed to the BUE effect.

Background and objectives:Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and results:We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s−1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator‐stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions:Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

The aim of this study was to select virulent strains of microfungi against Leucoagaricus gongylophorus, a symbiotic fungus cultivated by leaf-cutting ants. The results from in vitroassays showed that microfungal strains had a variable and significant impact on the colony development of L. gongylophorus. Specifically, Trichoderma harzianum, Escovopsis weberiCBS 810.71 and E. weberiA088 were more effective, inhibiting the L. gongylophoruscolonies by 75, 68 and 67%, respectively (P< 0.05) after 15 days. Strain E. weberiA086 and Acremonium kiliensewere less effective: 43 and 26%, respectively (P< 0.05). In spite of the current negative perspective of a microbiological control approach for these ants, the present work discusses the possibility of using mycopathogenic fungi for the control of these insects, and points out the importance of encouraging more studies in this area.The aim of this study was to select virulent strains of microfungi against Leucoagaricus gongylophorus, a symbiotic fungus cultivated by leaf-cutting ants. The results from in vitroassays showed that microfungal strains had a variable and significant impact on the colony development of L. gongylophorus. Specifically, Trichoderma harzianum, Escovopsis weberiCBS 810.71 and E. weberiA088 were more effective, inhibiting the L. gongylophoruscolonies by 75, 68 and 67%, respectively (P< 0.05) after 15 days. Strain E. weberiA086 and Acremonium kiliensewere less effective: 43 and 26%, respectively (P< 0.05). In spite of the current negative perspective of a microbiological control approach for these ants, the present work discusses the possibility of using mycopathogenic fungi for the control of these insects, and points out the importance of encouraging more studies in this area.

Summary. Fungus-growing ants of the genus Mycetarotes are among the least studied in the tribe Attini. This report documents nest architecture and worker population numbers for 19 nests of M. parallelus and 5 nests of M. acutus, including the first such report for M. acutus. This new information is integrated with the scant biological information reported on Mycetarotes to date. The resulting picture of Mycetarotes life history, as well as the relative ease with which large numbers of nests can be collected and observed in the field, suggest that Mycetarotes (particularly M. parallelus) is an ideal model system for the study of coevolution of lower-attine ants and their cultivated fungi.

Ejaculated sperm cells from both bovine and swine animals depleted of the seminal fluid were used as vectors for transferring different plasmid DNAs into eggs during the fertilization process. PCR screening of about 2000 blastocysts showed that transformed embryos were obtained in both animal species with varying efficiencies, and that the rate of transformation depended on the plasmid used. The most efficient rate was obtained in both species with the pSV2CAT construct, yielding 22% positive blastocysts in bovine and 5.7% in swine respectively. Artificial insemination of ten sows with boar sperm cells that had been preincubated with pSV2CAT DNA produced 82 offspring. Southern blot analysis of the DNAs extracted from the animal tails showed that five animals were transgenic and contained sequences complementary to pSV2CAT DNA that appeared to be rearranged compared to the original plasmid. These results indicate that sperm-mediated DNA transfer protocols can be successfully adapted for the generation of genetically transformed livestock.

The restoration work of the frescoes in the Brancacci Chapel (Chiesa del Carmine, Firenze) offered us the opportunity of recording about one hundred reflectance spectra of selected areas on the frescoes before and after restoration. Our previous research was mainly devoted to pigment identification. In the present paper, color analysis is performed by computing chromaticity coordinates, purity, and dominant wavelength, starting from the reflectance spectra previously recorded. Afterwards, color difference between restored and not-restored fresco is evaluated and its distribution examined. The obtained results are then discussed in connection both to the causes which produced the color modification and to the possibility of performing electronic restoration on paintings.

This paper describes an extensive spectrophotometric study on several acid-base indicators immobilized, by means of a silylation process, on quartz powder and on controlled pore glass. The spectrophotometric properties of the immobilized indicators are at variance with those of the free indicators with respect to pH dependence and ranges. The different behavior of both types of indicators in the liquid and immobilized phases may be explained by both a modification in the electronic structure of the indicators and a distribution of the molecules on different sites. The differences among the spectrophotometric properties of the indicators, when these are immobilized on different solid supports, can be justified by taking into account the steric hindrance and the reactivity of the indicators. Particular attention was paid to the pH-sensitive bands and their position, keeping in mind that the investigated material could possibly be used as a transducer for pH fiber-optic sensors.

About one hundred significant spots (area = 0.5 cm2) that were homogeneously colored were selected on the frescoes “Resurrection of the son of Teofilo,” “Saint Peter in pulpit,” and “Saint Peter heals invalids by his shadow” in the Brancacci Chapel (Chiesa del Carmine, Florence). The reflectance spectra of these spots were recorded before and after restoration with the use of an external integrating sphere, which was connected through optical fibers to a UV/visible spectrophotometer, and the data were stored in a personal computer. Spectrophotometric investigations were also performed on small samples of frescoes, which were appropriately prepared, in a laboratory, with pure pigments. The results we obtained are discussed in the light of our main purposes: (1) to achieve nondestructive identification of pigments; (2) to help create time-unalterable color archives; (3) to establish a method for monitoring eventual color changes; and finally (4) to obtain useful information for the fields of art restoration and art history.

It is shown how the characteristic features of the angular overlap model allow a straightforward evaluation of the Jahn-Teller coupling constants. Moreover, differently from the crystal field or more general molecular orbital approaches, the expressions we have obtained contain a very limited number of parameters and have the advantage of the transferability from one chromophore MXqto another MXpof different symmetry. In the present communication an outline of the method is given and some applications to inorganic complexes and to biological molecules containing transition metal ions are presented.

Principal component analysis (PCA) of diffuse reflectance near-infrared (NIR) spectra has been used as a suitable methodology for discriminating areas involved in the sulfation process of calcareous stones. NIR spectra of standard mixtures containing CaSO4· 2H2O, CaSO3· 1/2H2O, and CaCO3were recorded. For all data sets submitted to PCA, a good discrimination between the two reaction products, i.e., CaSO3· 1/2H2O and CaSO4· 2H2O, in the alteration process was obtained. The actual availability of fiber-optic spectrum analyzers working in the NIR region suggests that the proposed procedure can be used as a safe and nondestructive method for monitoring alteration processes in calcareous works of art.

Abstract: The basic concept of this project is to identify and then use the changes which occur in the chemical and physical properties of traditional paint media both to indicate and integrate the effects of environmental conditions on paintings. To achieve this aim, test paint films are being prepared in accordance with traditional artists' recipes. Changes in material properties are monitored using a combination of non-invasive spectroscopy (Bacci), microsensors, thermoanalytical techniques (Odlyha), and microscale analytical mass spectrometry for molecular structure analysis (Boon). The test strips are calibrated by exposure to controlled environments (light, temperature, relative humidity and noxious gases) and alterations in their properties are quantified. This provides information on the nature and rate of change at the molecular level and a data base for evaluating the molecular monitoring strips after their exposure in the field. Field sites have been selected and include various locations in the Tate Gallery (UK), Sandham Chapel (Burghclere, UK), the Uffizi Gallery (It) and the Rijksmuseum (NL). Environmental conditions of some of these locations are being evaluated at present using the glass sensors described in project EV5VCT92 0144. Small piezoelectric quartz crystal humidity sensors will be installed to determine localised variations in relative humidity and temperature on [1] Stanley Spencer paintings in Sandham Chapel and [2] Giotto's “Madonna di Ognissanti” in the Uffizi Gallery. In addition novel coatings using picture varnishes are being applied to similar piezoelectric quartz crystal sensors to evaluate the effects of environmental impact on the chemistry of varnishes on paintings. Data are also being collected on the nature of chemical and physical changes in varnishes and paint media in actual paintings at the molecular level.

A new kind of oxygen sensitive transducer was realized. It is based on the reflectance change of bis(Histidinato)Cobalt(II), Co(His)2, solution immobilized on a Thin Layer Chromatographic plate (TLC plate). The treated TLC plate was coated with a 2-component silicone layer in order to ensure a wet microenvironment and to guarantee a mechanical protection for the sensitive layer. Experimental characterization of such a probe has been carried out in order to determine the response time as a function of the pH of the solution.

The membrane-potential changes of pig oocytes during maturation are described. Cumulus-enclosed oocytes have a resting potential of −41.81 ± 0.60 mV; the removal of cumulus cells caused this potential to drop to −30.95 ± 0.43 mV. Adding LH to the culture medium did not influence the potential of denuded oocytes but depolarized the potential of cumulus-enclosed oocytes to −32.90 ± 0.43 mV. FSH did not affect the membrane potential of denuded or cumulus-enclosed oocytes, but significantly reduced the amplitude of the depolarization induced by LH. The effect of gonadotropins on cultured granulosa cells was also investigated. Plated granulosa cells have a resting potential of −45.21 ± 0.72 mV, similar to that of cumulus-enclosed oocytes. As recorded in cumulus-enclosed oocytes, LH depolarized granulosa cell membrane potential (−30.33 ± 0.69 mV) and FSH reduced this effect. To evaluate if oocyte maturation in vivo is accompanied by membrane-potential depolarization, follicular growth and oocyte maturation were induced in 6 prepubertal gilts by using an eCG-hCG treatment. Twenty hours after the beginning of oocyte maturation in vivo (induced by hCG), the membrane potential of the oocyte was depolarized to −28.84 ± 1.01 mV, a value similar to that observed in vitro.These data indicate that both LH and FSH can influence the membrane potential of follicular somatic cells and, consequently, that of the oocyte. The electrical coupling between somatic cell and oocyte may represent a means by which the gonadotropin message is passed to the germinal cell by the somatic compartment.

The experimental and theoretical investigations performed at the Istituto di Ricerca sulle Onde Elettromagnetiche since 1970 on absorption and luminescence spectra of metal impurities in ionic crystals are reported. These systems represent a typical example where the Jahn-Teller effect plays an important role. On the basis of this effect an extensive interpretation of the relative complex phenomenology has been proposed. Experimental investigations, devoted to check theoretical models, are mainly concerned with the influence of external fields (electric, magnetic) on the optical properties of such materials.

The author is aware that the argument treated in this review article is so wide that it cannot be exhausted in a single paper and, perhaps, not even in a book. However, the principal purpose was to give a panoramic view as wide as possible of the problems concerning metallo-proteins and, furthermore, to show how knowledges from different fields (physics, chemistry, biology) can concur to the understanding of their properties.

Emission and decay kinetics properties of heavily doped CsI : Tl+are compared with those of a low concentration sample. New emission bands at 2.79, 2.37 and 2.10 eV are ascribed to Tl+dimers. Theoretical investigation of the coexistence of three nonequivalent excited state minima of Tl+in a body-centered cubic host is reported. Coexistence can be obtained for reasonable values of parameters in CsI : Tl+.

Some statements related to the Jahn-Teller effect are often misunderstood. Here it is stressed that there exist physical systems for which electronic degeneracy cannot be resolved by vibrational modes.

Leucocoprinus gongylophorus, the fungus cultured by the leaf-cutting antAtta sexdens rubropilosa, is able to degrade efficiently cellulose, microcrystaline cellulose, carboximethylcellulose, and cellobiose. Analysis of the degradation products indicate that the fungus produce extracellular ß-glucosidase, exo- and endo-glucanase. The importance of cellulose degradation to the association of fungus and ant is discussed.