Approximation of the critical buckling factor for composite panels

This article is concerned with the approximation of the critical buckling factor for thin composite plates. A new method to improve the approximation of this critical factor is applied based on its behavior with respect to lamination parameters and loading conditions. This method allows accurate approximation of the critical buckling factor for non-orthotropic laminates under complex combined loadings (including shear loading). The influence of the stacking sequence and loading conditions is extensively studied as well as properties of the critical buckling factor behavior (e.g concavity over tensor D or out-of-plane lamination parameters). Moreover, the critical buckling factor is numerically shown to be piecewise linear for orthotropic laminates under combined loading whenever shear remains low and it is also shown to be piecewise continuous in the general case. Based on the numerically observed behavior, a new scheme for the approximation is applied that separates each buckling mode and builds linear, polynomial or rational regressions for each mode. Results of this approach and applications to structural optimization are presented

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression

Predominant constitutive CFTR conductance in small airways

BACKGROUND: The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. METHODS: We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. RESULTS: In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25), but when gluconate replaced luminal Cl(-), the bionic Cl(- )diffusion potentials (-58 ± 3 mV; n = 25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl(- )permeability was at least 5 times greater than Na(+ )permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM)+IBMX (100 μM), ATP (100 μM), or adenosine (100 μM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM), GlyH-101* (5–50 μM), and CFTR(Inh)-172* (5 μM). RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. CONCLUSION: These results indicate that the small airway of the pig is characterized by a constitutively active Cl(- )conductance that is most likely due to CFTR

Maternal and neonatal factors related to prematurity

ABSTRACT OBJECTIVE To identify maternal and neonatal factors associated with prematurity in the municipality of Porto Alegre. METHOD This was a population-based case-control study. The cases were newborns under 37 weeks of gestation and the controls were newborns over 37 weeks. The data came from the records of 19,457 births in the city of Porto Alegre in the year 2012 from the Information System on Live Births of the Municipal Health Department. The analysis was carried outand adjusted by a Logistic Regression according to a hierarchical model. The variables studied were allocated into three hierarchy levels: sociodemographic variables; reproductive history; and gestational and birth factors. RESULTS There were 767 cases allocated and 1,534 controls in a design of a case for two controls (1:2) by simple randomization. In the final model, a statistically significant association was found for prematurity for the following variables: mother's age under 19 years old (OR=1.32; CI 95%: 1.02-1.71) or over 34 years old (OR=1.39; CI 95%: 1.12-1.72); inadequate maternal schooling for age (OR=2.11; CI 95%: 1.22-3.65); multiple pregnancies (OR=1.14; CI 95%: 1.01-1.29); C-section (OR=1.15; CI 95%: 1.03-1.29); birth weights under 2,500g (OR=4.04; CI 95%: 3.64-4.49); Apgar score at five minutes between zero and three (OR=1.47; CI 95%: 1.12-1.91); and inadequate prenatal care (OR=1.18; CI 95%: 1.02-1.36). CONCLUSION The present study showed the most immediate consequence of prematurity for newborns by evidencing its association with worse Apgar scores and low birth weight. The following factors were also shown as possible more distal determinants of prematurity: mother's age; inadequate maternal education; multiple gestation; inadequate prenatal care; and C-section

An Antiviral Response Directed by PKR Phosphorylation of the RNA Helicase A

The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the α subunit of the eukaryotic translation initiation factor 2 (eIF2α) to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA). Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR)–mediated type 1 human immunodeficiency virus (HIV-1) gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism

Drug Metabolism in Human Brain: High Levels of Cytochrome P4503A43 in Brain and Metabolism of Anti-Anxiety Drug Alprazolam to Its Active Metabolite

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more α-hydroxy alprazolam (α-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both α-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of α-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of α-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action