Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of chrysanthenyl esters from the essential oil of Anthemis maritima L. investigated by GC/RI, GC-MS (EI and CI) and 13C-NMR spectroscopy: chemical composition and variability.

INTRODUCTION Anthemis maritima L. (Asteraceae) is a wild plant growing in Corsica and Sardinia. No previous studies of the chemical composition of A. maritima essential oil have been found. The oil contains two series of cis- and trans-chrysanthenyl esters for which the MS data are not present in available libraries and the 13C-NMR data are not reported in the literature. The determination of these compounds is a challenging problem since some of these esters are present in low concentrations and they exhibit very similar EI-MS. OBJECTIVE To develop comprehensive strategies involving integrated techniques including CC, GC/RI, GC-MS (EI and CI), 1H- and 13C-NMR and hemi-synthesis for the identification of both series of chrysanthenyl esters in A. maritima oils. METHODOLOGY Seventeen oil samples were prepared by hydrodistillation. A fine analysis of a pool of Corsican oils was conducted after repeated CC. A selected Sardinian oil was used as source of product for the hemi-synthesis of chrysanthenyl esters. The identification of these compounds was based on joint information from GC-MS (EI and CI), 13C-NMR and hemi-synthesis. RESULTS Integrated analysis of Corsican and Sardinian oils allowed the identification of 124 components accounting for 83.3-91.6% of the total oil. With the aid of principal component analysis, oil samples could be divided in two groups. Among 16 chrysanthenyl esters identified, 12 were laboratory-synthesised and their 13C-NMR data are reported for the first time. CONCLUSIONS The study illustrates the contribution of integrated techniques for the characterisation of unusual essential oils.
Increased mean platelet volume in patients with acute coronary syndromes.

CONTEXT Despite remarkable progress, the diagnosis of acute coronary syndromes (ACS) is still challenging. OBJECTIVE The mean platelet volume (MPV), a simple and reliable indicator of platelet size that correlates with platelet activation, might be an emerging cardiovascular risk marker and potentially helpful in stratifying cardiovascular risk. DESIGN We analyzed MPV values in 2304 adult patients who were consecutively admitted during a 1-year period to the emergency department of the University Hospital of Verona for chest pain suggestive of ACS. In all patients, a baseline blood sample was collected for routine hematologic testing, whereas cardiac troponin T measurements were collected both at baseline and after 4, 6, and 12 hours. RESULTS A total of 456 patients (19.8% of total) had ACS. These patients, all having cardiac troponin T levels of 0.03 ng/mL or greater in addition to ischemic electrocardiographic changes, had higher MPV values than non-ACS patients with normal cardiac troponin T levels (median, 8.0 fL [5th to 95th percentiles, 6.7-10.0 fL] versus median, 7.4 fL [5th to 95th percentiles, 6.5-9.5 fL]; P < .001). The diagnostic accuracy of MPV, calculated as the area under the curve by the receiver operating characteristic analysis, was 0.661 (P < .001). At the 9.0-fL cutoff, the negative and positive predictive values of MPV were 83% and 43%, respectively. CONCLUSIONS Because MPV is a simple and inexpensive laboratory measurement, it might be considered a useful rule-out test along with other conventional cardiac biomarkers for the risk stratification of ACS patients admitted to the emergency departments.
Renal Sodium Excretion and the Peritubular Capillary Physical Factors in Essential Hypertension

SUMMARY Peritubular capillary hydrostatic and oncotic forces and their relationship to the renal excretion of sodium (UNaV) were examined in 19 patients with moderate and uncomplicated essential hypertension (HT) and compared with data from 20 normotensire subjects (NT). Observations were made in hydropenia (C) and during sustained isotonlc saline volume expansion (E; 3% increase in body weight). The intrarenal renous pressure (IRVP) was used as an index of peritubular capillary hydrostatic pressure, and the efferent arteriolar colloid osmotic pressure (COP,n) was estimated from the arterial COP and the filtration fraction. C values (mean ± SEM) in HT (and NT) were: arterial pressure (MAP) 110 ± 3 mm Hg (85 ± 1, p< 0.001); glomerular filtration rate (GFR) 122 ± 4 ml/min/1.73 m* (128 ± 3, p> 0.05); renal blood flow (RBF) 1172 ± 38 ml/min/1.73 m1 (1298 ± 48, p< 0.05); IRVP 25.0 ± 1.0 mm Hg (24.8 ± 0.8, p> 0.05); COP.tt 33.0 ± 0.7 mm Hg (31.9 ± 0.6, p> 0.05); and UN.V 140 ± 13 $mole/min (161 ± 12, p> 0.05). During E, the increase of UH.V in HT was more than double that of NT (p< 0.001) while IRVP did not change in either group (p> 0.05) and COP.fr fell by 26% (p< 0.001) in both groups. GFR and RBF increased by 18% (p< 0.001) and 19% (p< 0.001) respectively, in HT, but did not change in NT. MAP remained unchanged in both groups. The results indicate that the peritubular capillary physical factors are normal in established essential hypertension, and that these forces are not involved in the exaggerated natriuretic response to volume expansion in essential hypertension.
Statistical Model Checking Of Multi-Agent Systems

This paper proposes an original approach to modelling and simulation of multi-agent systems which is based on statistical model checking (SMC). The approach is prototyped in the context of the popular UPPAAL SMC toolbox. Usefulness and validation of the approach are checked by applying it to a known complex and adaptive model of the Iterated Prisoner’s Dilemma (IPD) game, by studying the emergence of cooperation in the presence of different social interaction structures.
Diagnosing Customer Value: Integrating the Value Process and Relationship Marketing

The concept of value and, more specifically, customer value is of increasing interest to both academics and practitioners. This paper undertakes a substantial review of past and current literature on value and categorizes this considerable body of research into nine streams of literature. Building on the emerging relationship marketing paradigm, it then proposes a framework for relationship value management. Nine core streams of value literature are identified and discussed: consumer values and consumer value; the augmented product concept; customer satisfaction and service quality; the value chain; creating and delivering superior customer value; the customer's value to the firm; customer-perceived value; customer value and shareholder value; and relationship value. To date, the core focus of most of this literature has been on the nature of value from the perspective of the organization and its customers – the customer–supplier relationship. However, it is argued that the emergence of the relationship marketing paradigm has emphasized the role of other stakeholders in building relationships. An existing multiple stakeholder model of relationship marketing, the six markets model, is introduced and is integrated with key concepts from the value literature to produce a conceptual framework for relationship value management.
Earlier onset of Alzheimer disease symptoms in latino individuals compared with anglo individuals.

BACKGROUND Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in this population with those found in Anglo (white non-Latino) patients. OBJECTIVE To compare the age at AD symptom onset in Latino and Anglo individuals. DESIGN Cross-sectional assessment using standardized methods to collect and compare age at AD symptom onset, demographic variables, and medical variables. SETTING Five National Institute on Aging-sponsored Alzheimer's Disease Centers with experience evaluating Spanish-speaking individuals. PATIENTS We evaluated 119 Latino and 55 Anglo patients who had a diagnosis of AD. MAIN OUTCOME MEASURE Age at symptom onset. RESULTS After adjusting for center, sex, and years of education, Latino patients had a mean age at symptom onset 6.8 years earlier (95% confidence interval, 3.5-10.3 years earlier) than Anglo patients. CONCLUSIONS An earlier age at symptom onset suggests that US mainland Latino individuals may experience an increased burden of AD compared with Anglo individuals. The basis for the younger age at symptom onset remains obscure.
Menaquinone as pool quinone in a purple bacterium

Purple bacteria have thus far been considered to operate light-driven cyclic electron transfer chains containing ubiquinone (UQ) as liposoluble electron and proton carrier. We show that in the purple γ-proteobacterium Halorhodospira halophila, menaquinone-8 (MK-8) is the dominant quinone component and that it operates in the QB-site of the photosynthetic reaction center (RC). The redox potentials of the photooxidized pigment in the RC and of the Rieske center of the bc1 complex are significantly lower (Em = +270 mV and +110 mV, respectively) than those determined in other purple bacteria but resemble those determined for species containing MK as pool quinone. These results demonstrate that the photosynthetic cycle in H. halophila is based on MK and not on UQ. This finding together with the unusual organization of genes coding for the bc1 complex in H. halophila suggests a specific scenario for the evolutionary transition of bioenergetic chains from the low-potential menaquinones to higher-potential UQ in the proteobacterial phylum, most probably induced by rising levels of dioxygen 2.5 billion years ago. This transition appears to necessarily proceed through bioenergetic ambivalence of the respective organisms, that is, to work both on MK- and on UQ-pools. The establishment of the corresponding low- and high-potential chains was accompanied by duplication and redox optimization of the bc1 complex or at least of its crucial subunit oxidizing quinols from the pool, the Rieske protein. Evolutionary driving forces rationalizing the empirically observed redox tuning of the chain to the quinone pool are discussed.
Fasudil, a Rho-kinase inhibitor, reverses L-NAME exacerbated severe nephrosclerosis in spontaneously hypertensive rats

Background In this study, we tested the hypothesis that long-term Rho-kinase inhibition would reverse nitro-L-arginine methyl ester-exacerbated nephrosclerosis in spontaneously hypertensive rats and attempted to elucidate the mechanism involved. Methods Five groups (each n = 8) were studied: untreated spontaneously hypertensive rats; nitro-L-arginine methyl ester (50 mg/l in drinking water, for 3 weeks)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester with fasudil (10 mg/kg/day)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester for 3 weeks followed by fasudil for 3 weeks-treated spontaneously hypertensive rats (same doses), and nitro-L-arginine methyl ester for 3 weeks followed by untreated for 3 weeks. We examined renal function, blood pressure, histological features, oxidative stress markers, and mRNA expression in the renal cortex. Results Nitro-L-arginine methyl ester-treated spontaneously hypertensive rats had higher blood pressure, proteinuria, and serum creatinine and lower creatinine clearance, urinary NO3/NO2 ratio, and urinary cGMP excretion compared with control spontaneously hypertensive rats (all Ps < 0.05). Nitro-L-arginine methyl ester-treated spontaneously hypertensive rats also had increased free radical metabolites and abnormal morphological findings with increased nicotinamide adenine dinucleotide phosphate oxidase activity, phosphorylation of myosin phosphatase targeting subunit-1, and mRNA expression of RhoA, RhoB, RhoC, collagen I and III, transforming growth factor-β, nicotinamide adenine dinucleotide phosphate subunit, endothelial nitric oxide synthase, plasminogen activator inhibitor, and intercellular adhesion molecule-1 in the renal cortex compared with control spontaneously hypertensive rats. Long-term co-treatment with fasudil slightly improved these indices, but most of them were not statistically significant. Late fasudil treatment significantly improved kidney function, morphological changes, and alterations of mRNA expression in the renal cortex, although late untreated controls did not show any improvement. Conclusion These results suggest that Rho-kinase inhibition partly reverses hypertensive glomerulosclerosis. The renoprotective effect of the Rho-kinase inhibitor may have multiple mechanisms including inhibition of extracellular matrix production, oxidative stress, adhesion molecule production, and antifibrinolysis.
Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals.

OBJECTIVE The role of transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) as early indicators of cisplatin-induced ototoxicity in three different rodent species--the guinea pig. the albino rat, and the fat sand rat (Psammomys obesus)--was investigated. In addition, an attempt was made to determine which of the three rodent species is most susceptible to cisplatin-induced ototoxicity as measured by auditory brainstem responses (ABR), BACKGROUND: There have been numerous clinical and experimental reports on cisplatin-induced ototoxicity, but to the authors' best knowledge, there has been no comparative report on the short-term effects of cisplatin on OAE measured with commercially available equipment between different rodent species. METHODS Cisplatin was systemically administered as a single high dose (12 mg/kg intraperitoneally) to all three species, and the ototoxic effects were measured before and 3 days after the injection of cisplatin in the same animals, using ABR, TEOAE, and DPOAE. RESULTS The ABR thresholds were significantly elevated in the guinea pigs and the albino rats but not in the sand rats. Significant depression of TEOAE energy and DPOAE amplitude occurred only in the guinea pigs. The depression of the DPOAE was greater than that of the TEOAE. The guinea pigs showed the greatest degree of ototoxicity (depression of ABR and OAE). CONCLUSIONS Among the three rodent species, the guinea pig has the potential to be used as a sensitive animal model in studies of cisplatin ototoxicity. The study also showed that the recordings of TEOAE and DPOAE, in addition to ABR, are sensitive techniques for the assessment of cisplatin-induced ototoxicity.
Physiology and Pathophysiology of Iron Cardiomyopathy in Thalassemia

Abstract: Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. Magnetic resonance imaging (MRI) is ideally suited for monitoring thalassemia patients because it can detect cardiac and liver iron burdens as well as accurately measure left ventricular dimensions and function. However, patients with thalassemia have unique physiology that alters their normative data. In this article, we review the physiology and pathophysiology of thalassemic heart disease as well as the use of MRI to monitor it. Despite regular transfusions, thalassemia major patients have larger ventricular volumes, higher cardiac outputs, and lower total vascular resistances than published data for healthy control subjects; these hemodynamic findings are consistent with chronic anemia. Cardiac iron overload increases the relative risk of further dilation, arrhythmias, and decreased systolic function. However, many patients are asymptomatic despite heavy cardiac burdens. We explore possible mechanisms behind cardiac iron‐function relationships and relate these mechanisms to clinical observations.
Proline‐rich acidic protein 1 (PRAP1) is a novel interacting partner of MAD1 and has a suppressive role in mitotic checkpoint signalling in hepatocellular carcinoma

Loss of mitotic checkpoint of cells contributes to chromosomal instability and leads to carcinogenesis. Mitotic arrest deficient 1 (MAD1) is a key component in mitotic checkpoint signalling. In this study, we identified a novel MAD1 interacting partner, proline‐rich acidic protein 1 (PRAP1), using yeast‐two hybrid screening, and investigated its role in mitotic checkpoint signalling in hepatocellular carcinoma (HCC). We demonstrated the physical interaction of PRAP1 with MAD1 and of PRAP1 with MAD1 isoform MAD1β, using a co‐immunoprecipitation assay. Moreover, stable expression of PRAP1 in mitotic checkpoint‐competent HCC cells, BEL‐7402 and SMMC‐7721, induced impairment of the mitotic checkpoint (p < 0.01), formation of chromosome bridges (p < 0.01) and aberrant chromosome numbers (p < 0.001). Interestingly, ectopic expression PRAP1 in HCC cells led to significant under‐expression of MAD1. In human HCC tumours, 40.4% (23/57) of HCCs showed under‐expression of PRAP1 protein as compared with their corresponding non‐tumorous livers; up‐regulation of MAD1 protein was significantly associated with down‐regulation of PRAP1 (p = 0.030). Our data revealed that PRAP1 is a protein interacting partner of MAD1 and that PRAP1 is able to down‐regulate MAD1 and suppress mitotic checkpoint signalling in HCC. Published by John Wiley & Sons, Ltd. www.pathsoc. org.uk
Winding Inductances of an Interior Permanent Magnet (IPM) Machine With Fractional Slot Concentrated Winding

This paper investigates inductance characteristics of a novel 14 pole/18 slot, fractional-slot concentrated-winding (FSCW) IPM machine. The variations of the self and mutual inductances were calculated analytically and also obtained from the finite element model. These results were compared with experimentally measured values of the self and mutual inductances of the prototype machine. Study of the inductance characteristics reveals that both self and mutual inductances vary with rotor positions nonsinusoidally. Presence of harmonics in the magnetomotive force (MMF) is responsible for this nonsinusoidal variation of inductances. The conventional distributed winding machine does not have these harmonics. This paper analyses the contribution of these harmonics in the Ld and Lq parameters in a dq-model of the prototype FSCW machine constructed. The self and mutual inductances were represented by a Fourier series in the inductance matrix of the machine for dq-transformation. It was seen that the difference between d- and q-axis inductance is mainly contributed by the harmonic terms of the mutual inductance.
The Impact of Profit Taxation on Capitalized Investment with Options to Delay and Divest

In entrepreneurial decisions making uncertain future profits often are a main characteristics of real investment opportunities. If investors can react to uncertainty the degree of irreversibility and timing flexibility inherent in the available project should be integrated into the decision calculus. In this paper we investigate the interdependencies of effects from profit taxation and real options. We model an investment decision including an option to invest and an option to abandon. We show that increasing the tax rate can lead to paradoxical tax effects, i.e. may foster an investor's willingness to invest into a capitalized investment. Instead, if we abstract from the possibility to abandon the investment object such paradoxical effect cannot be identified. Determining the after-tax value of the option to enter the investment project with and without an abandonment option we receive a critical cash flow cutoff level. We find that the value of the option to abandon depends on the tax rate and the amount of periodical cash flows. The option value can be increasing or decreasing in the tax rate. We find scenarios with paradoxical tax effects and show that the observed paradoxical effects are due to the presence of the real abandonment option itself. This finding contributes to the stream of literature that explains potential sources of paradoxical tax effects. The generated decision rules are helpful for investors facing risky investment opportunities and for discussing the economic impact of tax reforms. Furthermore, we highlight the overwhelming importance of integrating taxes in typically applied valuation approaches.
UK Debt in Comparative Perspective: The Pernicious Legacy of Financial Sector Debt

Research Highlights and Abstract This article provides a comprehensive comparative analysis of UK debt. makes a contribution to the debate on the Anglo-liberal growth model and its consequences for the recovery of the UK economy. The UK has the highest private debt among the G7 states plus Spain. Both financial services and household debt are high. Financial services debt is much the more consequential of the two sectors. It was a central component of the growth model of the UK prior to 2008 and its legacy is making the UK's recovery from recession extremely difficult. Financial sector debt also had an impact on the UK's rising borrowing requirement from 2007. However, it was not the direct cause of the rise in the UK's budget deficit, which was in large part a product of the Brown government's approach to its political difficulties as growth came to an end. Despite the UK's high budget deficit in comparative terms, the UK has enjoyed considerable fiscal autonomy the past few years. However, this autonomy could yet be threatened by the ongoing consequences of financial sector debt.
Strongly proper forcing and some problems of Foreman

We answer several questions of Foreman, most of which are closely related to Mitchell’s notion of strongly proper forcing. We prove that presaturation of a normal ideal implies projective antichain catching, providing a solution to a problem of Foreman about ideal projections that is more comprehensive and simpler than the earlier solution obtained by Cox and Zeman. We answer an older question of Foreman about the relationship between generic hugeness and generic almost hugeness. Finally, we answer two technical questions of Foreman related to his Duality Theorem.
Met Kinase Inhibitor E7050 Reverses Three Different Mechanisms of Hepatocyte Growth Factor–Induced Tyrosine Kinase Inhibitor Resistance in EGFR Mutant Lung Cancer

Purpose: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKI) in EGFR mutant lung cancer cells by activating Met and the downstream phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, continuous exposure to HGF accelerates the emergence of EGFR-TKI–resistant clones. We assayed whether a new Met kinase inhibitor, E7050, which is currently being evaluated in clinical trials, could overcome these three mechanisms of resistance to EGFR-TKIs. Experimental Design: The effects of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant-selective (WZ4002) EGFR-TKIs were determined using the EGFR mutant human lung cancer cell lines PC-9 and HCC827 with an exon 19 deletion and H1975 with an T790M secondary mutation. PC-9 cells were mixed with HGF-producing fibroblasts, MRC-5 cells, and subcutaneously inoculated into severe combined immunodeficient mice, and the therapeutic effects of E7050 plus gefitinib were assayed. Results: E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. Conclusions: A new Met kinase inhibitor, E7050, reverses the three HGF-induced mechanisms of gefitinib resistance, suggesting that E7050 may overcome HGF-induced resistance to gefitinib and next-generation EGFR-TKIs. Clin Cancer Res; 18(6); 1663–71. ©2012 AACR.