Isolation, spectroscopic characterization, X-ray, theoretical studies as well as in vitro cytotoxicity of Samarcandin

Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a = 10.8204 (5) Å, b = 12.9894 (7) Å, c = 15.2467 (9) Å, V = 2142.9 (2) Å3, space group P212121 and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose-dependent manner with IC50 = 11 μM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G∗∗ standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found. © 2016 Elsevier Inc. All rights reserved

Anisotropy in the dielectric spectrum of hydration water and its relation to water dynamics

Proteins, molecules, and macromolecular assemblies in water are surrounded by a nanometer-sized hydration layer with properties very different from bulk water. Here, we use classical molecular dynamics simulations to study the dielectric response of hydration water next to hydrophobic and hydrophilic planar surfaces. We find the interfacial dielectricabsorption of water to be strongly anisotropic: compared to bulk water, which shows a broad dielectricabsorption maximum around 15 GHz in the imaginary part of the dielectric function, the absorption for electric fields parallel to the surface is of similar strength and shows a slight redshift, while for perpendicular electric fields it is strongly attenuated and blueshifted. This anisotropy is generic for hydrophobic and hydrophilic surfaces. From our spatially resolved dielectric functions and a modified Maxwell-Garnett theory that accounts for anisotropic hydration layers around spherical particles, the dielectricabsorption of solutions of organic molecules and micelles is derived to exhibit the experimentally known attenuation in combination with a redshift. These two features are traced back to the subtle interplay of interfacial depolarization effects and the dielectricanisotropy in the hydration layer. By a detailed analysis of the individual water molecule dynamics the perpendicular blueshift is shown not to be linked to accelerated water reorientation, but rather to dielectric boundary effects. Carefully conducted angularly resolved experiments at planar aqueous interfaces will be able to resolve this dielectricanisotropy and thus to confirm the subtle connection between spectralabsorption features and the molecular water dynamics in hydration layers

Computed Tomography With Intravenous Contrast Alone: The Role of Intra‐abdominal Fat on the Ability to Visualize the Normal Appendix in Children

Background Computed tomography ( CT ) with enteric contrast is frequently used to evaluate children with suspected appendicitis. The use of CT with intravenous ( IV ) contrast alone ( CT IV ) may be sufficient, however, particularly in patients with adequate intra‐abdominal fat ( IAF ). Objectives The authors aimed 1) to determine the ability of radiologists to visualize the normal (nondiseased) appendix with CT IV in children and to assess whether IAF adequacy affects this ability and 2) to assess the association between IAF adequacy and patient characteristics. Methods This was a retrospective 16‐center study using a preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV scan and measured weights and for whom appendectomy history was known from medical record review were included. The sample was chosen based on age to yield a sample with and without adequate IAF . Radiologists at each center reread their site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was categorized as “adequate” if there was any amount of fat completely surrounding the cecum and “inadequate” if otherwise. Results A total of 280 patients were included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no history of prior appendectomy; therefore, each patient had a presumed normal appendix. A total of 102 patients (36.4%) had adequate IAF . The proportion of normal appendices visualized with CT IV was 72.9% (95% confidence interval [ CI ] = 67.2% to 78.0%); the proportions were 89% (95% CI  = 81.5% to 94.5%) and 63% (95% CI  = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for difference of proportions = 16% to 36%). Greater weight and older age were strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a stronger predictor, particularly in females. Although statistically associated, there was noted overlap in the weights and ages of those with and without adequate IAF . Conclusions Protocols using CT with IV contrast alone to visualize the appendix can reasonably include weight, age, or both as considerations for determining when this approach is appropriate. However, although IAF will more frequently be adequate in older, heavier patients, highly accurate prediction of IAF adequacy appears challenging solely based on age and weight. Resumen Tomografía Computarizada Únicamente con Contraste Intravenoso: El Papel de la Grasa Intrabadominal en la Capacidad para Visualizar el Apéndice Normal en los Niños Introduction La tomografía computarizada ( TC ) con contraste entérico es usada frecuentemente para evaluar a los niños con sospecha de apendicitis. El uso de la TC únicamente con contraste intravenoso ( TC IV ) puede ser suficiente, especialmente en pacientes con adecuada grasa intrabdominal ( GIA ). Objetivos 1) Determinar la capacidad de los radiólogos para visualizar el apéndice normal (sin enfermedad) con TC IV en niños, y valorar si la cantidad de GIA afecta a esta capacidad; y 2) valorar la asociación entre la idoneidad de la GIA y las características del paciente. Metodología Estudio retrospectivo de 16 hospitales que utilizó una base de datos prexistente de TC abdominales. Se incluyó a los niños entre 3 y 18 años que tenían una TC IV , una medida del peso e historia de apendectomía conocida por la revisión de la historia clínica. La muestra se eligió en base a la edad con el fin de conseguir una muestra con y sin GIA adecuada. Los radiólogos de cada centro releyeron las TC IV de sus centros para valorar la visualización del apéndice y la adecuación de la GIA . La GIA se clasificó como “adecuada” si había cualquier cantidad de grasa completamente alrededor del ciego e “inadecuada” si era de otra manera. Resultados Se incluyeron 280 pacientes, con una media de edad de 10,6 años (rango 3,1 a 17,9 años). Ninguno tenía historia previa de apendectomía; por lo tanto todos los pacientes tuvieron un apéndice presumiblemente normal. Ciento dos pacientes (36,4%) tuvieron GIA adecuada. El porcentaje de apéndices normales visualizados con TC IV fue de 72,9% ( IC 95% = 67,2% a 78,0%); la proporción fue 89% ( IC 95% = 81,5% a 94,5%), y 63% ( IC 95% = 56,0% a 70,6%) en aquéllos con y sin GIA adecuada ( IC 95% para la diferencia de proporciones = 16% a 36%). El mayor peso y la mayor edad se asociaron fuertemente con la adecuación de la GIA (p < 0,001), y el peso resultó ser el mayor factor predictivo, especialmente en mujeres. Aunque se asoció estadísticamente, se vio un solapamiento en los pesos y edades de aquéllos con y sin GIA adecuada. Conclusiones Los protocolos que usan la TC IV para visualizar el apéndice pueden razonablemente incluir el peso, la edad, o ambas como consideraciones para determinar cuándo esta aproximación es apropiada. Sin embargo, aunque la cantidad de GIA será frecuentemente más apropiada en los pacientes más mayores y de mayor peso, la predicción certera de adecuación de GIA es altamente desafiante si se basa sólo en la edad y el peso.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99695/1/acem12185.pd

Evaluation of haptoglobin phenotypes in acute myocardial infarction (AMI) and their association with some risk factors

Acute myocardial infarction (AMI) is one of the most common cardiovascular complications with a complex pathogenesis where inflammatory markers are involved in disease etiology. The aim of this study was to investigate haptoglobin phenotypes and their association with some risk factors in patients with a history of AMI. 120 patients who were referred to the emergency department of Amir Al Momenin hospital of Zahedan city, Zahedan-Iran were recruited in a cross-sectional case control study. 120 normal individuals were also chosen as controls for this study. Serum was isolated from routine bloods taken for diagnostic tests and used to determine haptoglobin phenotype distribution by electrophoresis. Phenotype differences as percent of phenotype frequency in patient and control groups were analysed using the χ2 test and SPSS software. A high frequency of serum Hp2-2 haptoglobin phenotype in patients and healthy control were found (62.5% and 58.3% respectively). A meaningful statistical correlation between high frequency of Hp2-2 haptoglobin phenotype and AMI was not found (p value = 0.484). Whereas high frequency of Hp1-1 and HP2-2 phenotypes was associated with hyperlipidemia and hypertension respectively (p value = 0.01 and 0.04). Our results showed that there was a high frequency of Hp2-2 haptoglobin phenotype in patients as well as healthy controls in the population studies. High frequencies of Hp1-1and Hp2-2 phenotypes were associated with AMI in patients with hyperlipidemia and hypertension respectively. Thus these phenotypes in AMI patients may modulate the inflammatory response in combination with hyperlipidemia and hypertension

Efficient nanoscale photonic devices and monolithic electronic-photonic subsystems in sub-100 nm SOI CMOS

We demonstrate efficient photonic devices that rely on sub-100nm features in unmodified 45nm SOI CMOS, including photonic crystals, array-antenna grating couplers, and modulators. We then show monolithically integrated electronicphotonic systems comprising millions of transistors and thousands of photonic devices, including a complete chip-to-chip photonic link

Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.</p

Predicting and elucidating the etiology of fatty liver disease : A machine learning modeling and validation study in the IMI DIRECT cohorts

Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Methods and findings We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n= 795) or at high risk of developing the disease (n= 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (= 5%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86;p = 5%) rather than a continuous one. Conclusions In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see:) and made it available to the community.Peer reviewe

Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials

Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods: In this genome-wide analysis we included adults (aged ≥18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings: 4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G→A (Gly168Ser) in the GLP1R (0·08% [95% CI 0·04–0·12] or 0·9 mmol/mol lower reduction in HbA1c per serine, p=6·0 × 10−5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6·7 × 10−8), largely driven by rs140226575G→A (Thr370Met; 0·25% [SE 0·06] or 2·7 mmol/mol [SE 0·7] greater HbA1c reduction per methionine, p=5·2 × 10−6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6–11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation: This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists. Funding: Innovative Medicines Initiative and the Wellcome Trus

An overview of energy planning in Iran and transition pathways towards sustainable electricity supply sector

Despite a substantial potential of renewable energy sources, the current energy supply system in Iran relies almost entirely on fossil fuel resources. It has imposed significant financial burden on the country and has led to considerable GHG emissions. Moreover, the country is confronting several challenges for harnessing alternative clean energy sources and promoting rational energy policies over the recent decades. To probe the root cause of these problems, this paper first provides an overview on the previous energy planning attempts in Iran. It shows that adequate commitment to a long-term energy planning could have meaningfully prevented these serious challenges. However, the previous studies have had some limitations in terms of employing appropriate planning tools, comprehensive evaluations, and scenarios definition and ranking. This paper thus proposes a power planning framework to assess the sustainability of future electricity scenarios for the period 2015–2050. MESSAGE, a systems engineering optimization model, is employed to evaluate the potential impacts of transitioning to a low-carbon electricity supply system. Using a combined AHP-TOPSIS method, the scenarios are then ranked based on 18 different techno-economic, environmental, and social dimensions of sustainability. The results indicate that scenario Cl_32, in which the share of non-hydro clean energy for electricity generation reaches 32%, is ranked best