Computer simulation of the phase diagram for a fluid confined in a fractal and disordered porous material

We present a grand canonical Monte Carlo simulation study of the phase diagram of a Lennard-Jones fluid adsorbed in a fractal and highly porous aerogel. The gel environment is generated from an off-lattice diffusion limited cluster-cluster aggregation process. Simulations have been performed with the multicanonical ensemble sampling technique. The biased sampling function has been obtained by histogram reweighting calculations. Comparing the confined and the bulk system liquid-vapor coexistence curves we observe a decrease of both the critical temperature and density in qualitative agreement with experiments and other Monte Carlo studies on Lennard-Jones fluids confined in random matrices of spheres. At variance with these numerical studies we do not observe upon confinement a peak on the liquid side of the coexistence curve associated with a liquid-liquid phase coexistence. In our case only a shouldering of the coexistence curve appears upon confinement. This shoulder can be associated with high density fluctuations in the liquid phase. The coexisting vapor and liquid phases in our system show a high degree of spatial disorder and inhomogeneity.Comment: 8 pages, 8 figures, to be published in Phys. Rev.

Harvesting the Promise of AOPs: An assessment and recommendations

The Adverse Outcome Pathway (AOP) concept is a knowledge assembly and communication tool to facilitate the transparent translation of mechanistic information into outcomes meaningful to the regulatory assessment of chemicals. The AOP framework and associated knowledgebases (KBs) have received significant attention and use in the regulatory toxicology community. However, it is increasingly apparent that the potential stakeholder community for the AOP concept and AOP KBs is broader than scientists and regulators directly involved in chemical safety assessment. In this paper we identify and describe those stakeholders who currently—or in the future—could benefit from the application of the AOP framework and knowledge to specific problems. We also summarize the challenges faced in implementing pathway-based approaches such as the AOP framework in biological sciences, and provide a series of recommendations to meet critical needs to ensure further progression of the framework as a useful, sustainable and dependable tool supporting assessments of both human health and the environment. Although the AOP concept has the potential to significantly impact the organization and interpretation of biological information in a variety of disciplines/applications, this promise can only be fully realized through the active engagement of, and input from multiple stakeholders, requiring multi-pronged substantive long-term planning and strategies

Liquid-liquid coexistence in the phase diagram of a fluid confined in fractal porous materials

Multicanonical ensemble sampling simulations have been performed to calculate the phase diagram of a Lennard-Jones fluid embedded in a fractal random matrix generated through diffusion limited cluster aggregation. The study of the system at increasing size and constant porosity shows that the results are independent from the matrix realization but not from the size effects. A gas-liquid transition shifted with respect to bulk is found. On growing the size of the system on the high density side of the gas-liquid coexistence curve it appears a second coexistence region between two liquid phases. These two phases are characterized by a different behaviour of the local density inside the interconnected porous structure at the same temperature and chemical potential.Comment: 5 pages, 4 figures. To be published in Europhys. Letter

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

The conditioning of medical gases with hot water humidifiers

During invasive mechanical ventilation due to the dryness of medical gases is necessary to provide an adequate level of conditioning. The hot water humidifiers (HWH) heat the water, thus allowing the water vapor to heat and humidify the medical gases. In the common HWH there is a contact between the medical gases and the sterile water, thus increasing the risk of patient’s colonization and infection. Recently to avoid the condensation in the inspiratory limb of the ventilator circuit, new heated ventilator circuits have been developed. In this in vitro study we evaluated the efficiency (absolute/relative humidity) of three HWH: (1) a common HWH without a heated ventilator circuit (MR 730, Fisher&Paykel, New Zeland), (2) the same HWH with a heated ventilator circuit (Mallinckrodt Dar, Italy) and (3) a new HWH (DAR HC 2000, Mallinkckrodt Dar, Italy) with a heated ventilator circuit in which the water vapor reaches the medical gases through a gorotex membrane, avoiding any direct contact between the water and gases. At a temperature of 35°C and 37°C the HWH and heated tube were evaluated. The absolute humidity (AH) and relative humidity (RH) were measured by a psychometric method. The minute ventilation, tidal volume respiratory rate and oxygen fraction were: 5.8 ± 0.1 l/min, 740 ± 258 ml, 7.5 ± 2.6 bpm and 100%, respectively. Ventilator P2 Use of a bougie during percutaneous tracheostom

MR Imaging Findings in 2 Cases of Late Infantile GM1 Gangliosidosis

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Abordaje del sobrepeso y la obesidad de niños preescolares en la clínica pediátrica

INTRODUCTION: childhood obesity is a serious public health problem. Prevalence in Argentina inchildren under 5 years of age for being overweight is 10% and obesity is 3.6%. It is recommended tocalculate the Body Mass Index (BMI) for all children over 2 years of age during the pediatric control.Acquisition from an early age of healthy eating habits and lifestyles are insufficiently considered aspectsin pediatric training. OBJECTIVE: know how pediatricians approach overweight and obesity in preschool children.MATERIAL AND METHODS: Analytical, observational, cross-sectional study. Population is a specialistin pediatrics who provides outpatient care for children from 2 to 5 years old and works at the Hospital deNiños de la Santísima Trinidad and / or at the Reina Fabiola University Clinic in Córdoba. All professionalsanswered a questionnaire to participate.RESULTS: The results were analyzed based on 155 responses. Regarding the calculation of BMI, 51%calculate it in all children from 2 to 5 years old, inclusive. 76% of those surveyed answered that they citebody mass index control. 42% said that parents were upset at some point when they raised their children'sproblem. 17% reported having completed a course on obesity and overweight.CONCLUSIONS: More than half of those surveyed reported calculating the BMI in all patients from 2 to5 years of age. There is an association between having taken a course on overweight and obesity and feelingcapable of addressing the issue. More than half of the participants refer to an appointment for a re-evaluationof the BMI. The barriers they recognize are that parents or patients are not receptive to advice on healthyeating and physical activity, socioeconomic factors, and a lack of local / community resources to addressthese issues.INTRODUCCIÓN: obesidad infantil es un problema de salud pública grave. La prevalencia en Argentinaen menores de 5 años para sobrepeso es de 10% y obesidad del 3,6%. Se recomienda calcular el Índice demasa corporal (IMC) a todo niño mayor de 2 años durante el control pediátrico. Adquisición desde edadestempranas de hábitos alimentarios y estilo de vida saludables son aspectos insuficientemente consideradosen la formación pediátrica.OBJETIVO: conocer cómo abordan los pediatras el sobrepeso y obesidad en niños preescolares.MATERIAL Y MÉTODO: Estudio analítico, observacional, transversal. Población médicos especialistasen pediatría que realice atención ambulatoria de niños de 2 a 5 años y trabaja en el Hospital de Niños de laSantísima Trinidad y/o en la Clínica Universitaria Reina Fabiola de Córdoba. Todos los profesionalesrespondieron un cuestionario para participar.RESULTADOS: Los resultados se analizaron en base a 155 respuestas. Respecto al cálculo del IMC, el51% lo calcula en todos los niños de 2 a 5 años, inclusive. El 76% de los encuestados respondieron quecitan para control del índice de masa corporal. El 42% refirió que en alguna oportunidad los padres semolestaron frente al planteo del problema de sus hijos. El 17% refirió haber completado un curso enobesidad y sobrepeso.CONCLUSIONES: Más de la mitad de los encuestados refiere calcular el IMC en todos los pacientes de 2a 5 años. Existe asociación entre haber realizado un curso en sobrepeso y obesidad y sentirse capacitadopara abordar el tema. Mas de la mitad de los participantes refiere citar para reevaluación del IMC. Lasbarreras que reconocen son que los padres o pacientes no son receptivos de consejos sobre alimentaciónsaludable y actividad física, factores socioeconómicos y escasez de recursos locales/comunitarios paraabordar estos temas

Interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in human epithelial cancer cells

Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpressed in cancer. This study reveals that the expression of cell surface MUC1 is a critical enhancer of EGF-induced EGFR activation in human breast and colon cancer cells. Both the MUC1 extracellular and intracellular domains are involved in EGFR activation but the predominant influence comes from its extracellular domain. Binding of galectin-3 to the MUC1 extracellular domain induces MUC1 cell surface polarization and increases MUC1–EGFR association. This leads to a rapid increase of EGFR homo-/hetero-dimerization and subsequently increased, and also prolonged, EGFR activation and signalling. This effect requires both the galectin-3 C-terminal carbohydrate recognition domain and its N-terminal ligand multi-merization domain. Thus, interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in epithelial cancer cells. As MUC1 and galectin-3 are both commonly overexpressed in most types of epithelial cancers, their interaction and impact on EGFR activation likely makes important contribution to EGFR-associated tumorigenesis and cancer progression and may also influence the effectiveness of EGFR-targeted cancer therapy

Immunohistochemical Distribution of Serotonin Transporter (SERT) in the Optic Lobe of the Honeybee, Apis mellifera

Visual information is processed in the optic lobes, which consist of three retinotopic neuropils. These are the lamina, the medulla and the lobula. Biogenic amines play a crucial role in the control of insect responsiveness, and serotonin is clearly related to aggressiveness in invertebrates. Previous studies suggest that serotonin modulates aggression-related behaviours, possibly via alterations in optic lobe activity. The aim of this investigation was to immunohistochemically localize the distribution of serotonin transporter (SERT) in the optic lobe of moderate, docile and aggressive worker honeybees. SERT-immunoreactive fibres showed a wide distribution in the lamina, medulla and lobula; interestingly, the highest percentage of SERT immunoreactivity was observed across all the visual neuropils of the docile group. Although future research is needed to determine the relationship between the distribution of serotonin fibres in the honeybee brain and aggressive behaviours, our immunohistochemical study provides an anatomical basis supporting the role of serotonin in aggressive behaviour in the honeybee

Optical–SZE scaling relations for DES optically selected clusters within the SPT-SZ survey

We study the Sunyaev–Zel'dovich effect (SZE) signature in South Pole Telescope (SPT) data for an ensemble of 719 optically identified galaxy clusters selected from 124.6 deg² of the Dark Energy Survey (DES) science verification data, detecting a clear stacked SZE signal down to richness λ ∼ 20. The SZE signature is measured using matched-filtered maps of the 2500 deg2 SPT-SZ survey at the positions of the DES clusters, and the degeneracy between SZE observable and matched-filter size is broken by adopting as priors SZE and optical mass–observable relations that are either calibrated using SPT-selected clusters or through the Arnaud et al. (A10) X-ray analysis. We measure the SPT signal-to-noise ζ–λ relation and two integrated Compton-yY500–λ relations for the DES-selected clusters and compare these to model expectations that account for the SZE–optical centre offset distribution. For clusters with λ > 80, the two SPT-calibrated scaling relations are consistent with the measurements, while for the A10-calibrated relation the measured SZE signal is smaller by a factor of 0.61 ± 0.12 compared to the prediction. For clusters at 20 < λ < 80, the measured SZE signal is smaller by a factor of ∼0.20–0.80 (between 2.3σ and 10σ significance) compared to the prediction, with the SPT-calibrated scaling relations and larger λ clusters showing generally better agreement. We quantify the required corrections to achieve consistency, showing that there is a richness-dependent bias that can be explained by some combination of (1) contamination of the observables and (2) biases in the estimated halo masses. We also discuss particular physical effects associated with these biases, such as contamination of λ from line-of-sight projections or of the SZE observables from point sources, larger offsets in the SZE-optical centring or larger intrinsic scatter in the λ–mass relation at lower richnesses