Esterification of free fatty acid from simulated waste cooking oil using ionic liquid as catalyst

Ionic liquid is a catalyst which is homogeneous (liquid phase) catalyst. Ionic liquid has been recognize as a potential catalyst in esterification of free fatty acid from waste cooking oil which contain high amount of free fatty acid due to the triglyceride hydrolysis during frying due to its properties which is adjustable by adjusting its combination of cation and anion. It also recognize as a substitution of sulphuric acid in biodiesel synthesis. In this project, different combination of cation and anion has been tested by four types of ionic liquid which involve the uses of pyridinium, 1-methyl-3 butylimidazolium (BMIM), 1 -ethyl-3 -methylimidazole (EMIM) as cation and the uses salicylate, sulphate, as an anion. The four types of catalyst can be considered as novel catalyst since no other researchers tried this combination of cation and anion. All this catalyst is characterize first using IR, CHNS and HNMIR spectrometer. Then the catalytic performance test is done for all the catalyst in the esterification reaction of free fatty acid in simulated waste cooking oil. As the result of the catalytic performance only BMIM SCL showed the conversion with only 30% conversion

The use of in vitro unbound drug fraction and permeability in predicting central nervous system drug penetration

The permeation of drugs across the blood-brain barrier (BBB) is a prerequisite for central nervous system (CNS) drug penetration. The BBB, possessing efflux transporters and tight junctions, limits drug penetration to the brain. Consequently, the discovery of novel drugs to treat CNS diseases remains problematic and is lagging behind other therapeutic areas. In vitro assays have progressed understanding of the factors that govern brain penetration. Central nervous system drug penetration is now thought to be modulated by three main processes, namely BBB permeability, active transport at the BBB and drug binding in blood and brain tissue. A more integrated approach to CNS drug discovery programmes is emerging which encompasses these processes in order to examine the rate and extent of drug brain penetration across species and improve predictions in human.A primary porcine in vitro BBB model was developed and characterised for the prediction of CNS drug permeability in vivo. Characterisation confirmed that the model exhibited physiologically realistic cell architecture, the formation of tight junction protein complexes, transcellular electrical resistance consistently >2000 Ω.cm2, functional expression the P-gp efflux transporter and ?-glutamyl transpeptidase and alkaline phosphatase activities.Transport of 12 centrally acting test drugs was investigated across four in vitro BBB models in order make comparisons between models and to generate in vitro permeability and efflux measurements. Blood-brain barrier permeability and active efflux processes are two major influences on the rate of drug penetration across the BBB. Species differences in fublood and fubrain, two prime influences on the extent of drug penetration, were investigated using equilibrium dialysis. Fraction unbound in brain was shown to be comparable across species suggesting that species differences in brain penetration could be due to variation in fublood for drugs that cross the BBB by passive diffusion, and/or species differences in transporter characteristics for drugs that are subject to active transport processes at the BBB. An in-house hybrid-PBPK rat CNS model was used to predict calculated rat Kp,uu using in vitro permeability, efflux, fublood and fubrain parameters generated during this work. The predicted Kp,uu generated using the rat CNS hybrid-PBPK model were within 3-fold of calculated Kp,uu. The rat CNS hybrid-PBPK model has potential use, as a tool for drug discovery scientists to aid the prediction of the extent of drug penetration in the early stages of drug discovery.This work has demonstrated that in vitro permeability and unbound drug fraction can be used to predict CNS drug penetration.EThOS - Electronic Theses Online ServiceGlaxoSmithKlineBBSRCGBUnited Kingdo

Combination of Statistical Shape Modeling and Statistical Parametric Mapping to Quantify Cartilage Contact Mechanics in Hip Dysplasia

Finite element models can predict subject-specific chondrolabral stresses and help to elucidate the effect of under-coverage and incongruency of the hip joint in patients with dysplasia. However, complex stress patterns are difficult to generalize and evaluate statistically. With an established correspondence across shapes from statistical shape modeling (SSM), statistical parametric mapping (SPM) allows for evaluation of local variability while preserving model subject-specificity. Herein, we evaluated the combined application of SSM and SPM to compare cartilage contact stress between control subjects and patients with dysplasia. Previously published hip joint contact stresses were mapped onto chondrolabral surface meshes and incorporated into an SSM. Principal component analysis (PCA) quantified shape variation. Contact stress values from heel-strike of stair ascent (AH), stair descent (DH), and level walking (WH) and mid-stance of level walking (WM) were evaluated. Using SPM, regions of significant contact stress variation were identified based on test statistics from general linear statistical models and corrected for multiple comparisons using Gaussian random fields. Shape differences of the femoral and acetabular cartilage with labrum were captured by two and one PCA mode, respectively. Contact stress differences were observed in anterosuperior regions of the femoral cartilage for AH and DH and of the acetabular cartilage for DH and WM (Figure 1). The SPM identified regions of varied contact stresses were small and likely would have been diluted through averaging or region-splitting using traditional analysis methods. The combined application of SSM and SPM provides a method to generalize and statistically-compare subject-specific mechanics and joint morphology

Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia

Abstract Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I–associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. Therefore, these posttranslationally modified neoantigens provide logical targets for cancer immunotherapy. Cancer Immunol Res; 5(5); 376–84. ©2017 AACR.</jats:p

Drug Transport at the Brain and Endothelial Dysfunction in Preeclampsia: Implications and Perspectives

Transport of drugs across biological barriers has been a subject of study for decades. The discovery and characterization of proteins that confer the barrier properties of endothelia and epithelia, including tight junction proteins and membrane transporters belonging to the ATP-binding cassette (ABC) and Solute Carrier (SLC) families, represented a significant step forward into understanding the mechanisms that govern drug disposition. Subsequently, numerous studies, including both pre-clinical approaches and clinical investigations, have been carried out to determine the influence of physiological and pathological states on drug disposition. Importantly, there has been increasing interest in gaining a better understanding of drug disposition during pregnancy, since epidemiological and clinical studies have demonstrated that the use of medications by pregnant women is significant and this condition embodies a series of significant anatomical and physiological modifications, particularly at excretory organs and barrier sites (e.g., placenta, breast) expressing transporter proteins which influence pharmacokinetics. Currently, most of the research in this field has focused on the expression profiling of transporter proteins in trophoblasts and endothelial cells of the placenta, regulation of drug-resistance mechanisms in disease states and pharmacokinetic studies. However, little attention has been placed on the influence that the cerebrovascular dysfunction present in pregnancy-related disorders, such as preeclampsia, might exert on drug disposition in the mother’s brain. This issue is particularly important since recent findings have demonstrated that preeclamptic women suffer from long-term alterations in the integrity of the blood-brain barrier (BBB). In this review we aim to analyze the available evidence regarding the influence of pregnancy on the expression of transporters and TJ proteins in brain endothelial cells, as well the mechanisms that govern the pathophysiological alterations in the BBB of women who experience preeclampsia. Future research efforts should be focused not only on achieving a better understanding of the influence of preeclampsia-associated endothelial dysfunction on drug disposition, but also in optimizing the pharmacological treatments of women suffering pregnancy-related disorders, its comorbidities and to develop new therapies aiming to restore the integrity of the BBB

Precisely tracking childhood death

Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12-15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality

Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)

BACKGROUND: Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). METHODS AND RESULTS: Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000-2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and >0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000-2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) μmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO. CONCLUSIONS: In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults

The Massive Progenitor of the Possible Type II-Linear Supernova 2009hd in Messier 66

We present observations of SN2009hd in the nearby galaxy M66. This SN is one of the closest to us in recent years but heavily obscured by dust, rendering it unusually faint in the optical, given its proximity. We find that the observed properties of SN2009hd support its classification as a possible Type II-L SN, a relatively rare subclass of CC-SNe. High-precision relative astrometry has been employed to attempt to identify a SN progenitor candidate, based on a pixel-by-pixel comparison between HST F555W and F814W images of the SN site prior to explosion and at late times. A progenitor candidate is identified in the F814W images only; this object is undetected in F555W. Significant uncertainty exists in the astrometry, such that we cannot definitively identify this object as the SN progenitor. Via insertion of artificial stars into the pre-SN HST images, we are able to constrain the progenitor's properties to those of a possible supergiant, with M(F555W)0>-7.6 mag and (V-I) 0>0.99 mag. The magnitude and color limits are consistent with a luminous RSG; however, they also allow for the possibility that the star could have been more yellow than red. From a comparison with theoretical massive-star evolutionary tracks, which include rotation and pulsationally enhanced mass loss, we can place a conservative upper limit on the initial mass for the progenitor of <20 M_sun. If the actual mass of the progenitor is near the upper range allowed by our derived mass limit, then it would be consistent with that for the identified progenitors of the SNII-L 2009kr and the high-luminosity SNII-P 2008cn. The progenitors of these three SNe may possibly bridge the gap between lower-mass RSG that explode as SNeII-P and LBV, or more extreme RSG, from which the more exotic SNeII-n may arise. Very late-time imaging of the SN2009hd site may provide us with more clues regarding the true nature of its progenitor.Comment: 19 pages, 9 figures, 3 tables, accepted for publication in Ap