Transcriptomic analysis of autistic brain reveals convergent molecular pathology.

Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder

Ésteres alquílicos de ácidos grasos isomerizados como aditivos para el mejoramiento de las propiedades de flujo en frío del biodiesel

El biodiesel ha sido propuesto como el principal remplazo del diésel convencional, por lo cual su producción ha incrementado en los últimos años. El principal inconveniente técnico de este es que no presenta un comportamiento adecuado en ambientes fríos. Con el fin de mejorar las propiedades de flujo en frio del biodiesel, la síntesis de ésteres alquílicos de ácidos grasos ramificados mediante catálisis heterogénea ha demostrado buenos resultados mejorando las mismas sin afectar significativamente otras propiedades. Teniendo en cuenta que la reacción de isomerización usando catalizadores heterogéneos ácidos no se puede llevar a cabo sobre ácidos grasos saturados, se propuso la síntesis, caracterización y uso de una zeolita tipo ferrierita impregnada con platino como catalizador heterogéneo sobre ácidos grasos saturados e insaturados para llevar a cabo la reacción de hidroisomerización. El catalizador fue preparado partiendo de una zeolita comercial a través de tratamiento con ácido clorhídrico e intercambio iónico con nitrato de amonio, seguido de impregnación húmeda y reducción de cloruro de tetraaminplatino (II), el cual fue caracterizado por SEM, EDX, TEM, XRF, TPD-NH3, IR, y sortometría de nitrógeno. Debido a los tratamientos aplicados a la ferrierita, nueva mesoporosidad fue creada, facilitando el arribo y adsorción de los ácidos grasos a los sitios activos. La reacción de hidroisomerización fue llevada a cabo a 275 ºC, presión de 1.7 MPa por 6 h. Los productos de la reacción fueron caracterizados mediante RMN. Dichos productos fueron esterificados y sus propiedades de flujo en frio fueron evaluadas, mostrando que presentaban valores de punto de nube y punto de fluidez mejores que los ésteres alquílicos de los ácidos grasos no ramificados. El uso de ésteres isobutílicos de ácidos grasos ramificados como aditivos para el mejoramiento de las propiedades de flujo en frió mostro reducir en punto de nube y punto de fluidez del biodiesel de oleína de palma en 6 (10 a 4°C) y 4 ºC (7 a 3°C) respectivamente.Abstract. The biodiesel has been proposed as the main replacement of conventional diesel oil, whereby its production has increased in the last years. The main technical problem of this fuel is that doesn´t have an adequate behavior in cold environments. In order to enhance biodiesel cold flow properties, branching of the fatty acids through isomerization reaction over acid heterogeneous catalyst has shown good results improving these properties without affect significantly other properties. Taking into account that isomerization reaction cannot be done on saturated fatty acid, in this work has been proposed the synthesis, characterization and use of a ferrierite zeolite impregnated with platinum as heterogeneous acid catalyst for carry out the hydroisomerization reaction over saturated and unsaturated fatty acid alkyl esters. The catalyst was prepared through activation with chlorhydric acid and ammonium nitrate ionic exchange followed by wet impregnation of Tetraamminplatinum (II) chloride over a commercial ferrierite and characterized by SEM, EDX, TEM, XRF, TPD-NH3, infrared analysis, and nitrogen sorption measurements. Due to the treatments, which that were applied to ferrierite, new mesoporosity was created, facilitating the arrival and adsorption of the fatty acid alkyl esters to active sites Hydroisomerization reaction, was carried out to 285 ºC and 1.7 MPa by 6h. Reaction products were characterized through NMR analysis. They are esterified and their cold flow properties were evaluated, showed that they have better cold flow properties than non-branching fatty acid alkyl esters. The use of isobutyl esters as cold flow properties improvers reached decrease the cloud point and the pour point in 6 (10 a 4°C) and 4 ºC (7 a 3°C) of palm olein biodiesel respectively.Maestrí

Ciudad Informal: Procesos de conformación y transformación orgánica

Este documento se enfoca en la conformación y la cualificación del espacio urbano de la ciudad informal y explora sus lógicas particulares, valiéndose de tres aspectos fundamentales que la definen: No ser planificada, crecimiento a pequeñas dosis y autoconstrucción o autogestión. Con base en estos aspectos se puede asumir que el espacio de la ciudad informal es visible, no solamente en los barrios de periferia de la ciudad latinoamericana, sino también en asentamientos árabes, turcos, medievales y demás desarrollos urbanos históricos; estas condiciones se han encargado de llevar a la ciudad informal a través del tiempo a sus propios y únicos niveles de consolidación, hasta convertirse en un organismo mutable difícil de comprender desde la perspectiva “formal” y normativa de las ciudades tradicionales. El trabajo aborda la relación entre los fenómenos socio-culturales y los aspectos morfológicos que se desarrollan básicamente con la ayuda metodológica de Christopher Alexander y su lenguaje de patrones, y puestos a prueba en un sector del barrio Diana Turbay.Abstract. The present work focuses on the development and qualification of the urban space of the informal city and exposes its particular logics, using three fundamental aspects that define it: Not planned, growth by little doses, self-construction or self-management. Based on this aspects, it can assume the space of the informal city is identifiable not only in Latin America peripheral neighborhoods, but also in Arab, Turkish, Medieval settlements and other historical urban developments; these conditions have been responsible for bringing the informal city overtime to its own unique levels of consolidation, to become a mutable organism difficult to understand from the “formal” and normative perspective of traditional cities. This document aboard the relationship between socio-cultural phenomena and the morphological aspects that are basically developed with the methodological help of Christopher Alexander and his pattern language, and put to the test in a sector of neighborhood Diana Turbay.Maestrí

Compaction of mixtures of rigid and highly deformable particles: a micro-mechanical model

We analyze the isotropic compaction of mixtures composed of rigid and deformable incompressible particles by the non-smooth contact dynamics approach (NSCD). The deformable bodies are simulated using a hyper-elastic neo-Hookean constitutive law by means of classical finite elements. For mixtures that varied from totally rigid to totally deformable particles, we characterize the evolution of the packing fraction, the elastic modulus, and the connectivity as a function of the applied stresses when varying inter-particle coefficient of friction. We show first that the packing fraction increases and tends asymptotically to a maximum value $\phi_{max}$, which depends on both the mixture ratio and the inter-particle friction. The bulk modulus is also shown to increase with the packing fraction and to diverges as it approaches $\phi_{max}$. From the micro-mechanical expression of the granular stress tensor, we develop a model to describe the compaction behavior as a function of the applied pressure, the Young modulus of the deformable particles, and the mixture ratio. A bulk equation is also derived from the compaction equation. This model lays on the characterization of a single deformable particle under compression together with a power-law relation between connectivity and packing fraction. This compaction model, set by well-defined physical quantities, results in outstanding predictions from the jamming point up to very high densities and allows us to give a direct prediction of $\phi_{max}$ as a function of both the mixture ratio and the friction coefficient

Cultural, demographic, and other non-demographic factors associated with cancer genetic counseling patients appointment accompaniment preferences in the United States.

Although the presence of companion(s) in a genetic counseling session can positively influence session dynamics, research has found that some patients prefer to attend their appointments alone. To date, no studies have examined patient accompaniment preferences across different cultural groups in the context of genetic counseling. This quantitative study aimed to identify factors associated with individual preferences in accompaniment at cancer genetic counseling appointments in a sample (N = 130) of Hispanic/Latine (n = 29) and non-Hispanic/Latine White (n = 101) participants at a large academic medical institution. Variables examined included demographics, horizontal and vertical collectivism, and Hispanic and American acculturation. A link to an online questionnaire was emailed to patients who met four criteria: (1) identified as either Hispanic/Latine or non-Hispanic/Latine White; (2) had attended a cancer genetic counseling appointment at UCLA Health to discuss genetic testing options between October 2020 and December 2022; (3) were at least 18 years of age at the time of their appointment; and (4) indicated they were comfortable reading in Spanish or English; responses were anonymous. Logistic regression analyses identified four significant variables in the model associated with accompaniment preferences: individuals with at least one parent born outside of the US, those who attended their appointment in-person, and those with a higher horizontal collectivism score were less likely to want to attend their cancer genetic counseling appointment alone, while the converse was true among those with a higher American acculturation score. These findings highlight cultural and demographic factors that are associated with patient accompaniment preferences unrelated to ethnicity, indicating genetic counselors should not make assumptions regarding accompaniment preferences based solely on cultural or racial/ethnic background. Genetic counselors should incorporate this understanding when assessing patients accompaniment preferences

Micromechanical description of the compaction of soft pentagon assemblies

We analyze the isotropic compaction of assemblies composed of soft pentagons interacting through classical Coulomb friction via numerical simulations. The effect of the initial particle shape is discussed by comparing packings of pentagons with packings of soft circular particles. We characterize the evolution of the packing fraction, the elastic modulus, and the microstructure (particle rearrangement, connectivity, contact force and particle stress distributions) as a function of the applied stresses. Both systems behave similarly; the packing fraction increases and tends asymptotically to a maximum value $\phi_{max}$, where the bulk modulus diverges. At the microscopic scale we show that particle rearrangements occur even beyond the jammed state, the mean coordination increases as a square root of the packing fraction and, the force and stress distributions become more homogeneous as the packing fraction increases. Soft pentagons present larger particle rearrangements than circular ones, and such behavior decreases proportionally to the friction. Interestingly, the friction between particles also contributes to a better homogenization of the contact force network in both systems. From the expression of the granular stress tensor, we develop a model that describes the compaction behavior as a function of the applied pressure, the Young modulus and the initial shape of the particles. This model, settled on the joint evolution of the particle connectivity and the contact stress, provides outstanding predictions from the jamming point up to very high densities

Medications for opioid use disorder in traditional medicare beneficiaries: associations with age.

Rates of opioid use disorder (OUD) have increased in older adults (age ≥ 50). Medications for OUD (MOUD) treat OUD effectively; however, limited data exist on whether older adults with OUD are provided MOUD. Using 2016-2020 claims data from Medicare beneficiaries with a new episode of OUD, we calculated rates of MOUD initiation (first dispensing within 14 days of index event), engagement (dispensing of a second MOUD within 34 days of initiation), and retention (receiving MOUD consistently over 180 days). Among beneficiaries with qualifying index events (N = 40 336), 17%, 38%, and 45% were ages 20-49, 50-64, and ≥ 65, respectively. Five hundred and three beneficiaries with a qualifying index event (1.3%) initiated MOUD, 461 (1.1%) reached engagement, and 309 (0.8%) were retained. Multivariable logistic regressions showed older age was associated with reduced MOUD initiation (compared with those aged 20-49, adjusted odds ratios [aORs] were 0.79 [95% CI, 0.64-0.98] and 0.36 [95% CI, 0.25-0.51] for ages 50-64 and ≥65, respectively). Reduced MOUD initiation was associated with female sex (aOR = 0.74; 95% CI, 0.61-0.89) and increasing comorbidity score (aOR = 0.76 per 1-point increase; 95% CI, 0.72-0.80). These results suggest that in addition to general efforts to increase uptake of MOUD, age-specific strategies are needed

In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy.

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo. EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG. PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy. CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology