An Exact Solution for Static Scalar Fields Coupled to Gravity in (2+1)(2+1)-Dimensions

We obtain an exact solution for the Einstein's equations with cosmological constant coupled to a scalar, static particle in static, "spherically" symmetric background in 2+1 dimensions.Comment: 9 pages. Replaced by a revised versio

An Extensively Humanized Mouse Model to Predict Pathways of Drug Disposition and Drug/Drug Interactions, and to Facilitate Design of Clinical Trials

Species differences in drug metabolism and disposition can confound the extrapolation of in vivo pharmacokinetic data to man, and also profoundly compromise drug efficacy studies due to differences in pharmacokinetics, in metabolites produced (which are often pharmacologically active) and in differential activation of the transcription factors CAR and PXR which regulate the expression of enzymes such as P450s and drug transporters. These differences have gained additional importance as a consequence of the use of genetically modified mouse models for drug efficacy testing and also patient-derived xenografts to predict individual patient responses to anti-cancer drugs. A number of humanised mouse models for cytochrome P450s, CAR and PXR have been reported. However, the utility of these models has been compromised as a consequence of the redundancy of P450 reactions across gene families where the remaining murine P450s can metabolise the compounds being tested. To remove this confounding factor and create a mouse model which more closely reflects human pathways of drug disposition we have substituted 33 murine P450s from the major gene families involved in drug disposition, together with Car and Pxr, for human CAR, PXR, CYP1A1, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP3A7. We have also created a mouse line where 34 P450s have been deleted from the mouse genome. We demonstrate using model compounds and anti-cancer drugs how these mouse lines can be applied to predict drug-drug interactions in patients and discuss their potential application in the more informed design of clinical trials and the personalised treatment of cancer

Ranolazine exhibits anti-inflammatory and antioxidant activities in H9c2 cardiomyocytes

OBJECTIVE: The aim of this study was to evaluate the effectiveness of ranola-zine on hypoxia-inducible factor-1 alpha (HIF-1 alpha) and oxidative stress in H9c2 cardiomyocyte cells.MATERIALS AND METHODS: We have as-sessed the effects of increasing concentrations of methotrexate (MTX) and ranolazine on prolif-eration of H9c2 rat cardiomyocyte cells by MTT assay. Malondialdehyde (MDA) protein oxidation [advanced oxidation protein products (AOPPs)], lipid hydroperoxide (LOOH) and xanthine oxidase (XO) activity as oxidative stress markers and HIF-1 alpha levels increased and total thiol (T-SH), cata-lase (CAT) activity and total antioxidant capacity (TAC) antioxidant capacity markers decreased in MTX-treated cells compared to control cells.RESULTS: Oxidative stress markers decreased, and antioxidant capacity markers increased in cells treated with ranolazine alone compared to control cells. For all parameters, we showed that the levels of oxidant, antioxidant markers and HIF-1 alpha in cells treated with MTX and ranolazine together reached the level of the control group, and ranolazine re-versed the oxidative damage caused by MTX.CONCLUSIONS: The cell viability increased the levels of oxidant and prooxidant markers and decreased the levels of antioxidant markers de-creased in H9c2 cardiomyocytes induced by oxi-dative stress. These results suggest that ranola-zine may protect the cardiomyocytes from MTX-in-duced oxidative damage. The effects of ranolazine could result from its antioxidant properties

Constraining Bosonic Supersymmetry from Higgs results and 8 TeV ATLAS multi-jets plus missing energy data

The collider phenomenology of models with Universal Extra Dimensions (UED) is surprisingly similar to that of supersymmetric (SUSY) scenarios. For each level-1 bosonic (fermionic) Kaluza-Klein (KK) state, there is a fermionic (bosonic) analog in SUSY and thus UED scenarios are often known as bosonic supersymmetry. The minimal version of UED (mUED) gives rise to a quasi-degenerate particle spectrum at each KK-level and thus, can not explain the enhanced Higgs to diphoton decay rate hinted by the ATLAS collaboration of the Large Hadron Collider (LHC) experiment. However, in the non-minimal version of the UED (nmUED) model, the enhanced Higgs to diphoton decay rate can be easily explained via the suitable choice of boundary localized kinetic (BLK) terms for higher dimensional fermions and gauge bosons. BLK terms remove the degeneracy in the KK mass spectrum and thus, pair production of level-1 quarks and gluons at the LHC gives rise to hard jets, leptons and large missing energy in the final state. These final states are studied in details by the ATLAS and CMS collaborations in the context of SUSY scenarios. We find that the absence of any significant deviation of the data from the Standard Model (SM) prediction puts a lower bound of about 2.1 TeV on equal mass excited quarks and gluons.Comment: 19 page

The first Italian validation of the Nurse-NursCollaboration Scale

Background and aim of the work: Collaboration between colleagues is an essential element of clinical nursing care because it helps to ensure patient safety. This study aimed to evaluate the psychometric properties of the Italian version of the Nurse-Nurse Collaboration Scale (NNCS). The secondary goal of this study was to assess the degree of collaboration between nurses in Italy. Methods: First, the cultural adaptation of the NNCS tool was performed. The face and content validity of the tool were assessed through the involvement of nursing experts. To test construct validity, a cross-sectional web-based study was conducted on a sample of 362 clinical nurses. Results: The Italian version of the NNCS was composed of 23 items distributed across the original five domains. Ten items were removed from the original instrument because they showed several cross-loadings on more than one factor. The five-dimensional model showed an adequate model goodness of fit (RMSEA=0.075, CFI=0.883, SRMR=0.072). The NNCS dimension with the highest average score was Professionalism (M=3.10 ± 0.45), while Conflict Management (M=2.14 ± 0.47) exhibited the lowest score. Conclusions: The Italian version of the NNCS is a valid and reliable tool. More effort should be made to ensure the proper management of conflicts in healthcare environments

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Energy optimization of a light projection system for buildings that virtually restores artworks

Published March 2022: Erratum regarding missing Declaration of Competing Interest statements in previously published articles - Part 1 (Digital Applications in Archaeology and Cultural Heritage, Volume 24, March 2022, Pages e00209). DOI: https://doi.org/10.1016/j.daach.2021.e00209; Erratum incluido en el documentoThe need to achieve energy efficiency standards in the lighting systems of buildings makes it necessary to optimize all aspects of them. Here, the development of a light projection system that achieves this goal by studyingand modifying the spectral output, compared to conventional illumination, is described. A lighting system thatestimates the reflectance characteristics of artwork and emits optimized lighting can reduce light absorption. Adamage-minimizing point-by-point light projection system is developed using an optimization algorithm, toimprove the appearance of the surfaces of artworks whose color has faded. In this case, a simulation of an aged oilpainting was made by manipulating the original photograph, which was printed and to which the proposedsystem was applied. The results show that, when the aged printed image is illuminated with the optimized lightsource, it appears indistinguishable from the non-aged oil painting.This research was supported by project RTI2018-097633-A-I00 from the Spanish Ministry funding "Proyectos I + D Retos de Investigación" entitled Photonic restoration applied to cultural heritage: application to Dali's picture "Dos Figuras

A New Heterobinuclear FeIIICuII Complex with a Single Terminal FeIII–O(phenolate) Bond. Relevance to Purple Acid Phosphatases and Nucleases

A novel heterobinuclear mixed valence complex [Fe^IIICu^II(BPBPMP)(OAc)_2]ClO_4, 1, with the unsymmetrical N_5O_2 donor ligand 2-bis[{(2-pyridylmethyl)aminomethyl}-6-{(2-hydroxybenzyl)(2-pyridylmethyl)} aminomethyl]-4-methylphenol (H_2BPBPMP) has been synthesized and characterized. A combination of data from mass spectrometry, potentiometric titrations, X-ray absorption and electron paramagnetic resonance spectroscopy, as well as kinetics measurements indicates that in ethanol/water solutions an [Fe^III-(nu)OH-Cu^IIOH_2]+ species is generated which is the likely catalyst for 2,4-bis(dinitrophenyl)phosphate and DNA hydrolysis. Insofar as the data are consistent with the presence of an Fe_III-bound hydroxide acting as a nucleophile during catalysis, 1 presents a suitable mimic for the hydrolytic enzyme purple acid phosphatase. Notably, 1 is significantly more reactive than its isostructural homologues with different metal composition (Fe^IIIM^II, where M^II is Zn^II, Mn^II, Ni^II,or Fe^II). Of particular interest is the observation that cleavage of double-stranded plasmid DNA occurs even at very low concentrations of 1 (2.5 nuM), under physiological conditions (optimum pH of 7.0), with a rate enhancement of 2.7 x 10^7 over the uncatalyzed reaction. Thus, 1 is one of the most effective model complexes to date, mimicking the function of nucleases

Energy optimization of a light projection system for buildings that virtually restores artworks

The need to achieve energy efficiency standards in the lighting systems of buildings makes it necessary to optimize all aspects of them. Here, the development of a light projection system that achieves this goal by studying and modifying the spectral output, compared to conventional illumination, is described. A lighting system that estimates the reflectance characteristics of artwork and emits optimized lighting can reduce light absorption. A damage-minimizing point-by-point light projection system is developed using an optimization algorithm, to improve the appearance of the surfaces of artworks whose color has faded. In this case, a simulation of an aged oil painting was made by manipulating the original photograph, which was printed and to which the proposed system was applied. The results show that, when the aged printed image is illuminated with the optimized light source, it appears indistinguishable from the non-aged oil painting