Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride

[EN] The synthesis of capped mesoporous silica nanoparticles (MSN) conjugated with an antibody (AB) as a gatekeeper has been carried out in order to obtain a delivery system able to release an entrapped cargo (dye) in the presence of a target molecule (antigen) to which the conjugated antibody binds selectively. In particular, MSN loaded with rhodamine B and functionalized on the external surface with a suitable derivative of N-(t-butyl)- 3-oxo-(5a,17b)-4-aza-androst-1-ene-17-carboxamide (finasteride) have been prepared (S1). The addition of polyclonal antibodies against finasteride induced capping of the pores due to the interaction with the anchored hapten-like finasteride derivative to give a MSN¿hapten¿AB nanoparticle S1-AB. It was found that the addition of capped material S1-AB to water solutions containing finasteride resulted in displacement of the antibody, pore uncapping and entrapped-dye release. The response of the gated material is highly selective, and only finasteride, among other steroids, was able to induce a significant uncapping process. Compared with finasteride, the finasteride metabolite was able to release 17% of the dye, whereas the exogen steroids testosterone, metenolone and 16-b-hydroxystanozolol only induced very little release of rhodamine B (lower than 10%) from aqueous suspensions containing sensing solid S1-AB. A detection limit as low as 20 ppb was found for the fluorimetric detection of finasteride. In order to evaluate a possible application of the material for label-free detection of finasteride, the capped material was isolated and stored to give final sensing solid S1-AB-i. It was found to display a similar behavior towards finasteride as to that shown by freshly prepared S1-AB; even after a period of two months, no significant loss of selectivity or sensitivity was noted. Moreover, to study the application for the detection of finasteride in biological samples, this ¿aged¿ material, S1-AB-i, was tested using commercially available blank urine as matrix. Samples containing 70 and 90% blank urine were spiked with a defined amount of finasteride, and the concentration was determined using capped S1-AB-i. Recovery ranges from 94% to 118% were reached.Financial support from the Spanish Government (project MAT2009-14564-C04-01) and the Generalitat Valenciana (Spain) (projects PROMETEO/2009/016 and PROMETEO/2010/008) is gratefully acknowledged. E. C. thanks the Minesterio de Ciencia e Innovacion (MICINN, Spain) for her fellowship.Climent Terol, E.; Martínez Mañez, R.; Maquieira Catala, Á.; Sancenón Galarza, F.; Marcos Martínez, MD.; Brun Sánchez, EM.; Soto Camino, J.... (2012). Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride. ChemistryOpen. 1:251-259. https://doi.org/10.1002/open.201100008S251259

Disk-based one-dimensional photonic crystal slabs for label-free immunosensing

[EN] One-dimensional photonic crystal slabs are periodic optical nanostructures that produce guided-mode resonance. They couple part of the incident light into the waveguide generating bandgaps in the transmittance spectrum, whose position is sensitive to refractive index variations on their surface. In this study, we present one-dimensional photonic crystal slab biosensors based on the internal nanogrooved structure of Blu-ray disks for label-free immunosensing. We demonstrated that this polycarbonate structure coated with a critical thickness of TiO2 generates guided-mode resonance. Its optical behavior was established comparing it with other compact disk structures. The results were theoretically calculated and experimentally demonstrated, all them being in agreement. The bioanalytical performance of these photonic crystals was experimentally demonstrated in a model assay to quantify IgGs as well as in two immunoassays to determine the biomarkers C-reactive protein and lactate dehydrogenase (detection limits of 0.1, 87, and 13 nM, respectively). The results are promising towards the development of new low-cost, portable, and label-free optical biosensors that join these photonic crystals with dedicated bioanalytical scanners based on compact disk drives.This research was supported by FEDER grants and the Spanish Ministry of Economy and Competitiveness projects (CTQ2013-45875-R and CTQ2016-75749-R).Sancho-Fornes, G.; Avella-Oliver, M.; Carrascosa Rubio, J.; Fernández-Sánchez, ME.; Brun, EM.; Maquieira Catala, Á. (2019). Disk-based one-dimensional photonic crystal slabs for label-free immunosensing. Biosensors and Bioelectronics. 126:315-323. https://doi.org/10.1016/j.bios.2018.11.005S31532312

Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

24 Pág.The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we reported on the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino-acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino-acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and was correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed, and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin-converting enzyme 2 (K18-hACE2) in mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the level of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine.This research was funded by Instituto de Salud Carlos III, Fondo COVID-19 de proyectos de investigación sobre SARS-CoV-2 y la enfermedad COVID-19 grant COV20/00901, and grant PID2021-128466OR-I00 funded by funded by MCIN/AEI/10.13039/501100011033 as part of Plan Estatal de Investigación Científica, Desarrollo e Innovación. This research work was also funded by the European Commission—NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global). All experiments using bioluminescent imaging approach were supported by NIH grant to WM. Research on SARS-CoV-2 in L.M-S laboratory was partially supported by the San Antonio Partnership for Precision Therapeutics, the San Antonio Medical Foundation, and the Texas Biomedical Research Institute Forum Foundation.Peer reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

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

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

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

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

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