Dirhodium Complexes as Possible Dual-Binding Photodynamic Therapy Agents

2012 Denman Undergraduate Research Forum Winner. Third Place. Mathematical and Physical SciencesA new type of dirhodium paddlewheel complexes were synthesized that contain ligands with extended π-systems. These ligands are expected to increase the affinity of these complexes for DNA because they are known to intercalate between the DNA bases in related systems. In addition, the new complexes possess equatorial acetonitrile ligands that exchange for water molecules upon photolysis, which produces an activated form of the complex that is able to bind covalently to DNA. These features lead to dual-binding through covalent binding to DNA upon irradiation and intercalation of the extended π-system ligand between the DNA bases. Currently, there are no reports of photoactivated dual-binding agents. These complexes possess features desired of photodynamic therapy agents, primarily because they are inactive in the dark, and readily bind to DNA when irradiated. The dirhodium bis-amidate complexes cis-H,H-[Rh2(HNOCCH3)2(bpy)(CH3CN)4][BF4]2 (bpy = 2,2´-bipyridine) and cis-H,H-[Rh2(HNOCCH3)2(dpq)(CH3CN)4][BF4]2 (dpq = dipyrido[3,2-f:2',3'-h]-quinoxaline) were successfully synthesized from cis-H,H-[Rh2(HNOCCH3)2(CH3CN)6][BF4]2 with the corresponding bidentate ligand. The bpy complex was prepared in 7 days, and because it cannot intercalate between the DNA bases, it is used as a control for no intercalation, but it was shown to bind covalently to DNA upon irradiation. The dpq complex was synthesized successfully in 1 day. Studies of this complex are underway and its intercalation ability has not yet been proven. The synthesis of related complexes with other bidentate ligands is ongoing. The preparation of complexes possessing acetate bridging ligands instead of amidates were attempted from the reaction of cis-[Rh2(CH3COO)2(CH3CN)6]2+ and bpy. Cis-[Rh2(CH3COO)2(bpy)(CH3CN)4]2+ was not successfully synthesized, but it is still of interest, since its precursor cis-[Rh2(CH3COO)2(CH3CN)6]2+ binds to DNA upon irradiation and it is inactive under dark conditions.No embarg

Impact of the COVID-19 pandemic on tuberculosis management in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacte; TuberculosiCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacto; TuberculosisCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impact; TuberculosisBackground The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. Methods Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. Results A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 ( P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 ( P = 0.001). Conclusions The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.MLA was supported by a postdoctoral grant “Rio Hortega” and ASM was supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from the Instituto de Salud Carlos III through the Spanish Ministry of economy and competitiveness

Transdisciplinary studies in socio-ecosystems: Theoretical considerations and its application in Latin American contexts

Debido a limitaciones para abordar la complejidad de la relación sociedad-naturaleza, los esfuerzos para solucionar los problemas ambientales han sido en general infructuosos. Aquí proponemos que el enfoque holístico de “socio-ecosistema” por parte de la academia, podría contribuir a disminuir estas limitaciones desde la adopción de cuatro cambios: i) ontológico, que presenta el concepto de “socio-ecosistemas”; ii) epistemológico, que propone a la transdisciplina como la forma de entenderlos, iii) metodológico, que sugiere intervenir en ellos de forma participativa y adaptativa y, iv) cambios institucionales que facilitarían la adopción de esta propuesta. Este planteamiento se complementa con la descripción de una experiencia transdiciplinaria en la cuenca del río San Juan Zitácuaro, México, en el contexto de un curso internacional de manejo de socio-ecosistemas.Given the difficulties to approach the complex relationship bettween society and nature, efforts to solve environmental problems have generally been unsuccessful. Here we suggest that a hollistic “socio-ecosystem” approach by the sciencies could help diminish these difficulties by embracing four kinds of changes: i) ontological, which introduces the concept of “socio-ecosystem”; ii) epistemological, which proposes transdiscipline as the way to understand them, iii) metholodogical, which suggests that in intervention in them must be participatory and adaptive, iv) institutional changes that would facilitate the adoption of this approach. This is then followed by a description of a transdisciplinary work experience in the Zitácuaro river basin, in Mexico, in the context of an international course on socio-ecosystem management.Fil: Ortega Uribe, Tamara. Universidad de Chile; ChileFil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Villarroel Torrez, Daniel. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piaz, Agustín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica ; ArgentinaFil: Vallejos, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Saenz Ceja, Jesús Eduardo. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Gallego, Federico. Universidad de la República. Facultad de Ciencias; UruguayFil: Franquesa Soler, Monserrat. Instituto de Ecología; MéxicoFil: Calzada Peña, Leonardo. Universidad Nacional Autónoma de México; MéxicoFil: Espinosa Mellado, Noelia. Universidad de la Armada; MéxicoFil: Fiestas Flores, Jerico. Instituto de Estudios Peruanos; PerúFil: Gill Mairhofer, Luis R.. Ministerio de la Defensa Pública; ParaguayFil: González Espino, Zarahí. Instituto Superior de Tecnologías y Ciencias Aplicadas. Facultad de Medio Ambiente. Departamento de Meteorología; CubaFil: Luna Salguero, Betsabé Montserrat. Sociedad de Historia Natural Niparajá; MéxicoFil: Martinez Peralta, Claudia María. Comisión de Ecología y Desarrollo Sustentable del Estado de Sonora. Dirección General de Conservación; MéxicoFil: Ochoa, Olivia. Universidad Nacional Autónoma de México; MéxicoFil: Pérez Volkow,Lucía. No especifica;Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Sánchez Rose, Isabelle. Universidad Central de Venezuela; VenezuelaFil: Weeks, Madeline. University of Cambridge; Reino UnidoFil: Ávila García, Daniela. Universidad Nacional Autónoma de México; MéxicoFil: García Reyes, Isabel Bueno. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Carmona, Alejandra. Universidad Austral de Chile. Instituto de Economía Agraria; ChileFil: Castro Videla, Fernando Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan; ArgentinaFil: Ferrer Gonzalez, César Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Frank Buss, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: López Carapia, Gabriela. Universidad Nacional Autónoma de México; MéxicoFil: Núñez Cruz, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Taboada Hermoza, Rossi. Universidad Nacional Mayor de San Marcos; PerúFil: Benet, Daniel. Alternare A. C.; MéxicoFil: Venegas, Ysmael. Alternare A. C.; MéxicoFil: Balvanera, Patricia. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Mwampamba, Tuyeni H.. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Lazos Chavero, Elena. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Noellemeyer, Elke Johanna. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maass, Manuel. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; Méxic

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere’s Disease

Meniere’s disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627); p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD

KM3NeT broadcast optical data transport system

The optical data transport system of the KM3NeT neutrino telescope at the bottom of the Mediterranean Sea will provide more than 6000 optical modules in the detector arrays with a point-to-point optical connection to the control stations onshore. The ARCA and ORCA detectors of KM3NeT are being installed at a depth of about 3500 m and 2500 m, respectively and their distance to the control stations is about 100 kilometers and 40 kilometers. In particular, the two detectors are optimised for the detection of cosmic neutrinos with energies above about 1 TeV (ARCA) and for the detection of atmospheric neutrinos with energies in the range 1 GeV-1 TeV (ORCA). The expected maximum data rate is 200 Mbps per optical module. The implemented optical data transport system matches the layouts of the networks of electro-optical cables and junction boxes in the deep sea. For efficient use of the fibres in the system the technology of Dense Wavelength Division Multiplexing is applied. The performance of the optical system in terms of measured bit error rates, optical budget are presented. The next steps in the implementation of the system are also discussed

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

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe