IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog, MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ (a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and miRNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins (p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity. These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epitheliaThis work was funded by project PI17/00578, from the “Instituto de Salud Carlos III” (Ministry of Science, Innovation and Universities) and co-funded by the European Regional Development Fund, and approved by the Ethics Committee of our Institution. It has been founded also by projects CB16/12/00228, PI16/00161, RD16/0011/0011, RD12/0019/0023 and SAF2017–84248-PS

Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

Peer reviewe

Search for new phenomena in final states with two opposite-charge, same-flavor leptons, jets, and missing transverse momentum in pp collisions at √s=13 TeV

Search results are presented for physics beyond the standard model in final states with two opposite-charge, same-flavor leptons, jets, and missing transverse momentum. The data sample corresponds to an integrated luminosity of 35.9 fb−1 of proton-proton collisions at s√=13 TeV collected with the CMS detector at the LHC in 2016. The analysis uses the invariant mass of the lepton pair, searching for a kinematic edge or a resonant-like excess compatible with the Z boson mass. The search for a kinematic edge targets production of particles sensitive to the strong force, while the resonance search targets both strongly and electroweakly produced new physics. The observed yields are consistent with the expectations from the standard model, and the results are interpreted in the context of simplified models of supersymmetry. In a gauge mediated supersymmetry breaking (GMSB) model of gluino pair production with decay chains including Z bosons, gluino masses up to 1500–1770 GeV are excluded at the 95% confidence level depending on the lightest neutralino mass. In a model of electroweak chargino-neutralino production, chargino masses as high as 610 GeV are excluded when the lightest neutralino is massless. In GMSB models of electroweak neutralino-neutralino production, neutralino masses up to 500-650 GeV are excluded depending on the decay mode assumed. Finally, in a model with bottom squark pair production and decay chains resulting in a kinematic edge in the dilepton invariant mass distribution, bottom squark masses up to 980–1200 GeV are excluded depending on the mass of the next-to-lightest neutralino

Search for electroweak production of charginos and neutralinos in multilepton final states in proton-proton collisions at root s=13 TeV

Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of protonproton collision data collected at p s = 13TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb1. The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simpli ed models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180GeV and 1150 GeV are excluded at 95% CL. These results signi cantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations.Sponsoring Consortium for Open Access Publishing in Particle Physic

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Chemical Composition and Anthelmintic Activity of the Peruvian Endemic Species Chuquiraga weberbaueri “Amaro” on Sheep Fasciolosis

Chuquiraga weberbaueri “amaro” (Asteraceae) is a plant species popularly used for the treatment of animal fasciolosis in Peru. However, biological and chemical studies of this species remain scarce. Hence, the objective of the present study was to evaluate the anthelmintic effect of the hydroethanolic and aqueous extracts of C. weberbaueri leaves on Fasciola hepatica, through a controlled and a therapeutic efficacy test in artificially infected sheep. In addition, the chemical composition of the extracts was evaluated using phytochemical screening and analysis by UHPLC-MS/MS. Among the evaluated extracts, the aqueous extract proved to be the most efficient and of low toxicity against F. hepatica, inhibiting about 70% of its oviposition, using a 100 mg/kg dose. The chemical study showed that the major constituents were phenolic derivatives, such as chlorogenic acid and ethyl caffeate, with the notable presence of flavonoids, saponins, and lactones. Therefore, it was possible to observe the antihelmintic effect of the C. weberbaueri on the F. hepatica, which suggests the use of this plant extract as a potential alternative in the sheep fasciolosis treatment.Trabajo financiado por fondos concursables de Canon Minero de la Universidad Nacional de Cajamarca, aprobado con Resolución de Consejo Universitario N° 2871, [Número de contrato 2871-2018-UNC

Pseudorapidity and transverse momentum dependence of flow harmonics in pPb and PbPb collisions

A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.Measurements of azimuthal angular correlations are presented for high-multiplicity pPb collisions at root s(NN) = 5.02 TeV and peripheral PbPb collisions at root s(NN) = 2.76 TeV. The data used in this work were collected with the Compact Muon Solenoid (CMS) detector at the European Organization for Nuclear Research (CERN) Large Hadron Collider (LHC). Fourier coefficients as functions of transverse momentum and pseudorapidity are studied using the scalar product method; four-, six-, and eight-particle cumulants; and the Lee-Yang zero technique. The influence of event plane decorrelation is evaluated using the scalar product method and found to account for most of the observed pseudorapidity dependence.Peer reviewe