359 research outputs found
TulipaProfileFitting.jl: A Julia package for fitting renewable energy time series profiles
This paper introduces the TulipaProfileFitting.jl package, a tool developed
in Julia for generating renewable energy profiles that fit a specified capacity
factor. It addresses the limitations of naive methods in adjusting existing
profiles to match improved technology efficiency, particularly in scenarios
lacking detailed weather data or technology specifications. By formulating the
problem mathematically, the package provides a computationally efficient
solution for creating realistic renewable energy profiles based on existing
data. It ensures that the adjusted profiles realistically reflect the
improvements in technology efficiency, making it an essential tool for energy
modellers in analyzing -neutral energy systems
Critical Dialog: Response to Rachel M. Gillum’s Review of The Politics of the Headscarf in the United States
A Critical Dialog between the reviewer, Rachel M. Gillum, of The Politics of the Headscarf in the United States and the authors, Bozena C. Welborne, Aubrey L. Westfall, Özge Çelik Russell, and Sarah A. Tobin. Ithaca: Cornell University Press, 2018. 264p
AMPK Is the Crucial Target for the CDK4/6 Inhibitors Mediated Therapeutic Responses in PANC-1 and MIA PaCa-2 Pancreatic Cancer Cell Lines
The survival rate of pancreatic ductal adenocarcinoma (PDAC) patients is short, and PDAC is a cancer type that ranks fourth in the statistics regarding death due to cancer. Mutation in the KRAS gene, which plays a role in pancreatic cancer development, activates the PI3K/AKT/mTOR signaling pathway. The activity of the AMPK as a cellular energy sensor is one of the fundamental mechanisms that can induce effective therapeutic responses against CDK4/6 inhibitors via adjusting the cellular and tumor microenvironment stress management. The phosphorylation of AMPKα at the different phosphorylation residues such as Thr172 and Ser 377 causes metabolic differentiation in the cells following CDK4/6 inhibitor treatment in accordance with an increased cell cycle arrest and senescence under the control of different cellular players. In this study, we examined the competencies of the CDK4/6 inhibitors LY2835219 and PD-0332991 on the mechanism of cell survival and death based on AMPK signaling. Both CDK4/6 inhibitors LY2835219 and PD-0332991 modulated different molecular players on the PI3K/AKT/mTOR and AMPK signaling axis in different ways to reduce cell survival in a cell type dependent manner. These drugs are potential inducers of apoptosis and senescence that can alter the therapeutic efficacy cells
Complex health interventions in complex systems: improving the process and methods for evidence-informed health decisions
Methods for managing miscarriage:a network meta-analysis
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:The objectives of this review are:• to estimate the relative effectiveness and safety profiles for methods of management of miscarriage;• to provide a ranking of the available methods according to their effectiveness and safety profile
Reduced Efficacy of d-Amphetamine and 3,4-Methylenedioxymethamphetamine in Inducing Hyperactivity in Mice Lacking the Postsynaptic Scaffolding Protein SHANK1
Genetic defects in the three SH3 and multiple ankyrin repeat domains (SHANK) genes (SHANK1, SHANK2, and SHANK3) are associated with multiple major neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BPD). Psychostimulant-induced hyperactivity is a commonly applied paradigm to assess behavioral phenotypes related to BPD and considered to be the gold standard for modeling mania-like elevated drive in mouse models. Therefore, the goal of our present study was to test whether Shank1 plays a role in the behavioral effects of psychostimulants and whether this is associated with genotype-dependent neurochemical alterations. To this aim, male and female null mutant Shank1-/- mice were treated with d-amphetamine (AMPH; 2.5 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, commonly known as ecstasy; 20 mg/kg), and psychostimulant-induced hyperactivity was compared to heterozygous Shank1+/- and wildtype Shank1+/+ littermate controls. Results show that Shank1-/- mice display reduced psychostimulant-induced hyperactivity, although psychostimulants robustly stimulated locomotor activity in littermate controls. Shank1 deletion effects emerged throughout development, were particularly prominent in adulthood, and seen in response to both psychostimulants, i.e., AMPH and MDMA. Specifically, while AMPH-induced hyperactivity was reduced but still detectable in Shank1-/- mice, MDMA-induced hyperactivity was robustly blocked and completely absent in Shank1-/- mice. Reduced efficacy of psychostimulants to stimulate hyperactivity in Shank1-/- mice might be associated with alterations in the neurochemical architecture in prefrontal cortex, nucleus accumbens, and hypothalamus. Our observation that psychostimulant-induced hyperactivity is reduced rather than enhanced in Shank1-/- mice clearly speaks against a behavioral phenotype with relevance to BPD. Lack of BPD-like phenotype is consistent with currently available human data linking mutations in SHANK2 and SHANK3 but not SHANK1 to BPD
Over restrictive elimination of foods in children with foodallergy
Background. Previous studies demonstrated critical deficits in diagnosis and management of childhood foodallergy (FA), and recent developments in FA research support adopting a proactive approach in FA management.Our objective was to describe FA knowledge and management patterns of pediatricians.Method. We applied a 24-item survey to 170 general pediatricians, pediatric allergists and pediatricgastroenterologists practicing in Turkey.Results. Some IgE-mediated symptoms of FA such as cough, urticaria, wheezing and anaphylaxis were falselyrecognized as symptoms of non-IgE-mediated FA by 30%, 29%, 25% and 19% of the participants, respectively.By contrast, 50% of the participants falsely recognized bloody stool, a finding of IgE-mediated FA. Mostfrequently and least frequently used diagnostic tools were specific IgE (30.5%) and oral food challenge test(1.7%), respectively. Maternal diet restrictions and infant diet restrictions were advised by 82% and 82%,respectively. Percentages of physicians eliminating only 1 food were 21%, 19%; 2 foods were 15%, 11%; 3 foodswere 7%, 8%; 4-5 foods were 8%, 11%; 5 to 10 foods were 21%, 26%; and >10 foods were 28%, 25% from thematernal and infant diet, respectively. Cow’s milk, cheese, butter, yoghurt, baked milk products and hen’s eggwere the most commonly restricted items.Conclusion. Overall, FA knowledge of pediatricians was fair. Pediatricians utilize an overly restrictive approachwhen advising diet eliminations in FA. Recent developments favor a more proactive approach to induce immunetolerance and need to be encouraged in pediatric clinical practice. Future educational efforts should focus onemphasizing the deleterious effects of injudicious and extensive eliminations
Interaction of the Psychiatric Risk Gene Cacna1c With Post-weaning Social Isolation or Environmental Enrichment Does Not Affect Brain Mitochondrial Bioenergetics in Rats
The pathophysiology of neuropsychiatric disorders involves complex interactions between genetic and environmental risk factors. Confirmed by several genome-wide association studies, Cacna1c represents one of the most robustly replicated psychiatric risk genes. Besides genetic predispositions, environmental stress such as childhood maltreatment also contributes to enhanced disease vulnerability. Both, Cacna1c gene variants and stressful life events are associated with morphological alterations in the prefrontal cortex and the hippocampus. Emerging evidence suggests impaired mitochondrial bioenergetics as a possible underlying mechanism of these regional brain abnormalities. In the present study, we simulated the interaction of psychiatric disease-relevant genetic and environmental factors in rodents to investigate their potential effect on brain mitochondrial function using a constitutive heterozygous Cacna1c rat model in combination with a four-week exposure to either post-weaning social isolation, standard housing, or social and physical environmental enrichment. Mitochondria were isolated from the prefrontal cortex and the hippocampus to evaluate their bioenergetics, membrane potential, reactive oxygen species production, and respiratory chain complex protein levels. None of these parameters were considerably affected in this particular gene-environment setting. These negative results were very robust in all tested conditions demonstrating that Cacna1c depletion did not significantly translate into altered bioenergetic characteristics. Thus, further investigations are required to determine the disease-related effects on brain mitochondria
Influence of the gut microbiome on IgE and non-IgE-mediated food allergies
Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) -- MAY 26-30, 2018 -- Munich, GERMANYWOS: 000441690400204Background: The prevalence of food allergy (FA) in children has been increasing in last decade. Recent studies show changes in gut microbiome with FA. However, whether gut microbiome may differ between IgE and non‐IgE‐mediated FA is not defined. The aim of this study is to examine the intestinal microbiome composition in infants with IgE and non‐IgE‐mediated FA and healthy infants. Method: Infants younger than 1‐year‐old, breastfed and diagnosed with FA by a physician were included in the study. DNA was isolated from stool samples of infants with non‐IgE‐mediated FA (n = 25) and IgE‐mediated FA (n = 11) and healthy infants (n = 7). Whole genome shotgun sequencing was applied to identify the composition of microbial DNA (an average depth of 3.1 ± 0.8 million paired end reads and 0.9 ± 0.2 gigabase pairs). Results: There were compositional differences among 3 different groups. Shannon index was significantly higher in IgE‐mediated FA compared to non‐IgE‐mediated FA group (Kruskal‐Wallis test, P = 0.034). Even though β‐diversity was similar, the Sparse Partial Least Square Discriminant Analysis (sPLS‐DA) demonstrated that there were taxa‐level differences among three groups. In species level, Veillonella parvula was in a significantly higher density in healthy infants compared to IgE and non‐IgE‐mediated FA groups. Rahnella aquatilis and Lactobacillus salivarius were significantly lower and Treponema succinifaciens significantly higher in IgE‐mediated FA group compared to other groups. Additionally, Prevotella sp. oral taxon 299 was significantly lower in non‐IgE‐mediated FA group compared to others. Prevotella sp oral taxon 299 was related to mucus in stool whereas urticaria related species were Olsenall uli, Bactreoides thetaiotaomicron, Klebsiella variiocola, Rahnella aquatilis, Treponema succinfaciens, Ethanoligenens harbinenese. Conclusion: Analysis of microbiome differences in FA patients may aid in the understanding of the disease process. The present data suggest that there are compositional variations mostly in species‐ level among infants with FA and healthy ones. Our results suggest that the gut microbiome has a stronger relationship to IgE‐mediated than non‐IgE‐mediated FA. Further functional analysis of the microbiome may help better understand the changes seen in the gut microbiome in FAs and improve our knowledge in the disease etiopathology.European Academy of Allergy and Clinical Immunolog
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