Cationic Carbosilane Dendritic Systems as Promising Anti-Amyloid Agents in Type 2 Diabetes

The most common denominator of many of the neurodegenerative diseases is badly folded protein accumulation, which results in the formation of insoluble protein deposits located in different parts of the organism, causing cell death and tissue degeneration. Dendritic systems have turned out to be a promising new therapeutic approach for the treatment of these diseases due to their ability to modulate the folding of these proteins. With this perspective, and focused on type 2 diabetes (T2D), characterized by the presence of deposits containing the amyloidogenic islet amyloid polypeptide (IAPP), we demonstrate how different topologies of cationic carbosilane dendrimers inhibit the formation of insoluble protein deposits in pancreatic islets isolated from transgenic Tg-hIAPP mice. Also, the results obtained by the modification of dendritic carbosilane wedges with the chemical chaperone 4-phenylbutyric acid (4-PBA) at the focal point confirmed their potential as anti-amyloid agents with a concentration efficiency in their therapeutic action five orders of magnitude lower than that observed for free 4-PBA. Computational studies, which determined the main interaction between IAPP and dendrimers at the atomic level, support the experimental work.Agencia Estatal de InvestigaciónComunidad de MadridJunta de Comunidades de Castilla-La ManchaMinisterio de Economía y Competitivida

Derechas, historia y memoria: Teoría y praxis de las dictaduras en el poder

Acción financiada por la Comunidad de Madrid a través del Convenio Plurianual con la Universidad Autónoma de Madrid en su línea de actuación estímulo a la investigación de jóvenes doctores, en el marco del V PRICIT (V Plan Regional de Investigación Científica e Innovación Tecnológica). Referencia SI1/PJI/2019-0025

The Caldera. No. 16

Cuando hablamos de paz, generalmente asociamos el vocablo con adjetivos, momentos, experiencias que nos produzcan un estado de relajación, de calma, de quietud; es decir, la zozobra, la inquietud e incluso, el debate, serían antónimos de paz: Este año nuestra querida Institución Educativa se ha propuesto marcar la pauta en este tema; por tal razón, se ha implementado, dentro de los diferentes espacios pedagógicos que disfrutan nuestros educandos, la “CÁTEDRA DE LA PAZ”, como una alternativa viable, que les permita a nuestros estudiantes, desde los primeros años de preescolar, hasta los últimos de bachillerato, lograr acercamientos a distintas situaciones cotidianas, que hacen parte de nuestra condición humana y permanente de seres comunicativos y sociales; por tanto, las aulas de clase, los distintos escenarios en los que nos movemos deben convertirse en espacios en los que se deben llegar a establecer acuerdos que nos permitan ambientes, de estudio, de trabajo, de recreación, aún más agradables y cordiales.Biografías: Steve Jobs, John Lennon; Por: Javier Felipe Molina Salazar e Isabella Polo García…04 II Concurso Intercolegiado de Oratoria “Literatura y paz” “El arte de leer”; Por: Mariana Alejandra Galvis M. …08 Deporte en el Instituto Caldas Instituto Caldas: Subcampeón Departamental de Baloncesto…10 El pequeño gran ajedrecista; Por: Sebastián Felipe Blanco…11 Escritores memorables, Kafka; Por: Daniel José Galvis Jaimes…12 Proyectos Pedagógicos (Preescolar); Por: Slendy Pinzón González…15 Talentos caldistas…16 Reloj Solar 2014…20 Expresiones caldistas…22 Galería de Imágenes…29When we speak of peace, we generally associate the word with adjectives, moments, experiences that produce us a state of relaxation, calm, and stillness; that is to say, anxiety, concern and even debate, would be antonyms for peace: This year our beloved Educational Institution has proposed to set the standard on this issue; For this reason, the "CHAIR OF PEACE" has been implemented within the different pedagogical spaces that our students enjoy, as a viable alternative that allows our students, from the first years of preschool, to the last years of high school, achieve approaches to different daily situations, which are part of our human and permanent condition of communicative and social beings; therefore, the classrooms, the different settings in which we move, must become spaces in which agreements must be reached that allow us environments, study, work, recreation, even more pleasant and cordial

The Caldera. No. 25 Special Edition 2022. 70 years

Especial: Instituto Caldas, 70 años de historia En las siguientes páginas, los estudiantes rinden homenaje a nuestra querida Institución, a través, especialmente, de la Palabra. Mi eterna gratitud a cada uno de ellos, jóvenes lectores, escritores, dibujantes pero, sobre todo, Caldistas de CORAZÓN: Laura Camila Herrera, Victoria Chacón Gil, María Paula Méndez, Steven Gómez Guerrero, Constanza Narváez Solano, Yatana Zea Arenas, Carolina Valencia Neira, Valery Samara Meza, Steffy Picón Carrillo y Gabriela Portilla Castellanos.Especial 70 años. Instituto Caldas 6 Reloj Solar 2021 43 IX Concurso de Lectura en Voz Alta 46 La Cuna de Excélsior 48 Equipo de Maestros 51 Perfiles Caldistas 54 Expresiones Caldistas 58 Día Caldista 98 Galería de Imágenes 103Special: Instituto Caldas, 70 years of history In the following pages, the students pay homage to our beloved Institution, especially through the Word. My eternal gratitude to each of them, young readers, writers, cartoonists but, above all, Caldistas of HEART: Laura Camila Herrera, Victoria Chacón Gil, María Paula Méndez, Steven Gómez Guerrero, Constanza Narváez Solano, Yatana Zea Arenas, Carolina Valencia Neira, Valery Samara Meza, Steffy Picón Carrillo and Gabriela Portilla Castellanos

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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

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 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

Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s}$ = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s}$ = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s} =$ 7 TeV, as well as with theoretical predictions