Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif−/− Mouse Uterus

This study addresses the regulation of the interleukin 1 (IL1) system in the murine uterine luminal epithelium (LE) and stroma by leukemia inhibitory factor (LIF). Using RT-PCR we compared expression of Il1a, Il1b, Il1rn, Il1r1, and Il1r2 during the pre- and peri-implantation periods of pregnancy in wild-type (WT) and LIF-null LE and stroma. In WT LE, Il1a transcripts were down-regulated on Day 4 of pregnancy (D4), with renewed expression by the evening of D4 (D4 pm). In Lif−/− LE there was a gradual decrease in expression on D2, and expression became undetectable by D6. Il1b and Il1r1 expression were similar in WT and null mice, but Il1rn expression was almost completely lost during the peri-implantation period in Lif−/− LE. In the stroma, Il1a was sharply down-regulated on D4 and reappeared on D4 pm but was only expressed from D3 to D5 in the null mice. Stromal Il1r1 and Il1r2 were also misregulated. Il1rn showed constitutive expression in null stroma in contrast to the loss of expression on D4 in the WT mouse. In Lif-deficient mice, immunostaining indicated a reduction of endometrial IL1A at the time of implantation and of IL1B in stroma. LE-stromal coculture revealed that LIF stimulated the apical secretion of both IL1A and PTGES2 by LE cells without affecting basal secretion of IL1A and with only a small effect on basal PTGES2 secretion. We conclude that Il1a and Il1rn in LE and Il1a, Il1rn, and Il1r1 in stroma are regulated by LIF, which stimulates apical secretion of IL1A by LE

User interaction and uptake challenges to successfully deploying Semantic Web technologies

The Semantic Web community could benefit greatly from 'eating its own dog food' in order to better understand the challenges and opportunities of a Semantic Web from the user perspective. In this paper we describe the deployment of Semantic Web applications and services at the 3rd European Semantic Web Conference (ESWC2006), before presenting results of an evaluation into how these technologies were experienced by delegates. Based on themes identified in the evaluation we highlight seven user interaction and uptake challenges raised by the conference experience, and discuss how these may generalize to the widespread deployment of Semantic Web technologies

A Comparison of Anthropometric Measures for Classification of Metabolic Syndrome and Cardiometabolic Risk Factors, NHANES 2007-2010

BACKGROUND: Type 2 diabetes and cardiovascular disease (CVD) are among the leading causes of death in the United States. The Metabolic Syndrome, which comprises a cluster of cardiometabolic risk factors, puts individuals at increased risk for these diseases. It is therefore important that people with Metabolic Syndrome, at high risk for CVD and type 2 diabetes, are identified and treated. Since it may not often be practical to obtain the laboratory measures necessary for diagnosing the Metabolic Syndrome, simple anthropometric measures are a useful way of quickly identifying individuals at increased risk for the Metabolic Syndrome. OBJECTIVE: The purpose of this thesis is to evaluate the utility of three of the most commonly used anthropometric measures – Body Mass Index (BMI), Waist Circumference (WC), and Waist-to-Height Ratio (WC) – for classifying individuals with and without the Metabolic Syndrome and its component risk factors in the United States. Using Receiver Operating Characteristic (ROC) curve analysis and Area Under the Curve (AUC) statistics, this thesis will assess the utility of each body measurement and compare it to BMI. METHODS: A large, multi-ethnic, nationally representative sample from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 was used for this analysis. The study sample was restricted to adults aged 20-65 with complete information on height, weight, waist circumference, blood pressure, HDL cholesterol, fasting glucose, and triglycerides (n=3,769). In order to compare the utility of different anthropometric measures for classification, weighted ROC curves were constructed for each anthropometric measure-outcome combination and AUC statistics were compared. AUC statistics were calculated by approximating the definite integral of the ROC curves with the trapezoidal rule. Variances for AUC statistics and differences in AUC statistics were estimated with jackknife repeated replication. Analyses were completed for the entire sample and separately for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. RESULTS: For the entire sample, WC (AUC=0.752) did a better job than BMI (AUC=0.728) at classifying individuals with and without the Metabolic Syndrome (p CONCLUSION: Waist circumference should be considered, especially over BMI, for risk stratification in clinical settings and research. Further research should attempt to identify optimum waist circumference cut points for use in the US population

Letter to the Editor: a response to Horne and Lucey (2017)

No abstract available

Small heat-shock proteins: important players in regulating cellular proteostasis

Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of post-translational modifications in sHsp chaperone function, particularly in the context of disease.SM was supported by a Royal Society Dorothy Hodgkin Fellowship, HE is supported by an Australian Research Council Future Fellowship (FT110100586) and JC is supported by a National Health and Medical Research Council Project Grant (#1068087)

Characterisation of waxy gas-condensates by high temperature capillary gas chromatography and oxidative degradation

High molecular weight (HMW) hydrocarbons (defined herein as C35+ compounds) are difficult to characterise by conventional analytical methods. Very few studies have reported precise and reproducible quantification of such compounds in fossil fuels. Nonetheless, such components have important effects on the physical and biological fate of fossil fuels in the geosphere. For example, the phase behaviour of waxy gas condensates is significantly affected by the varying proportions of HMW compounds. Similarly HMW compounds are amongst the most resistant petroleum components to biodegradation. The current study reports the development of reproducible quantitative high temperature capillary gas chromatography (HTCGC) methods for studying both these aspects of the chemistry of HMW hydrocarbons. In addition those hydrocarbons which remain unresolved when analysed by gas chromatography (so called unresolved complex mixtures UCMs) are also studied. UCMs may account for a large portion of the hydrocarbons in many fossil fuels yet very little is known about their composition. Knowledge of these compounds may be important in enhancing the prediction of phase behaviour. Oxidative degradation and GC-MS is used to elucidate the types of structures present within the UCM. The concentrations of C3S4h. ydrocarbons in two unusually waxy gas condensates from high temperature wells in the North Sea were determined by HTCGC. The whole C, 5+ fraction comprised about 20% of the total hydrocarbons and consisted of compounds with carbon numbers extending up to and beyond Coo. By paying particular attention to sample dissolution and injection, good reproducibility and precision were obtained. For example, for authentic n-C, to n-C60 alkanes a relative standard deviation of under 5% for manual injection, linear response factors (1.01 Cm to 0.99 C6), and a linear calibration for 5 ng to 25 ng on-column were found. Limits of detection are reported for the first time for HMW n-alkanes. The limits were found to be as low as 0.8 ng for Cto to 1.87 ng for C60. Tristearin is proposed as a suitable HTCGC internal standard for quantification since the FID response factor (1.1) was close to that of the HMW n-alkanes and response was linear. Importantly, when co-injected with the two waxy North Sea condensates, tristearin was adequately separated from the closest eluting alkanes, n-C59 and n-C60 under normal operating conditions. Qualitative characterisation of the HMW compounds in the waxy gas condensates and in synthetic wax blends (polywax 1000) using HTCGC-EI MS and HTCGC-CI MS produced molecular ions or pseudo molecular ions for n-alkanes up to n- C6o. The spectra of some HMW compounds contained fragment ions characteristic of branched compounds but detailed characterisation was very limited. This study has also shown, for the first time, the significance of the unresolved complex mixture in gas condensatesU. CM hydrocarbonsa ccountedf or over 20% of the total hydrocarbons in a waxy North sea condensateT. he condensatew as first distilled and the distillate UCMs isolated. Thesew ere found to be between 64 to 97 % unresolved after molecular sieving (5A) and urea adduction. The UCMs were oxidised using CrO3/AcOHw hich produced5 -12% C02, and 55-83% dichloromethane-solublep roducts. Thus 65-94% of the original UCMs were accounted for as oxidation products. The remainder were thought to be water soluble acids which could not be determined in the presence of the AcOH reagent. Of the recovered oxidised products, 27- 81 % were resolved and these comprised mainly n-monocarboxylic acids (19-48 %). The average chain length was found to be C12 indicating the average length of alkyl groups. Branched acids, ketones, ketoacids, ndicarboxylic acids, branched dicarboxylic acids, lactones, isoprenoid acids, alkylcyclohexane carboxylic acids and toluic acids accounted for the majority of the remaining resolved products. The distillate UCMs all showed variations in amountso f productsb ut not in composition. Retro-structurala nalysis suggestedth at the UCM in the gasc ondensatew as mainly aliphatic and branched.T he numbero f isomerso f simple brancheda lkaneso ver the UCM molecular weight range (determined by cryoscopy) was calculated to be over 15000. Overall, oxidation provided structural information for about half of the UCM. HTCGC was also used to measure the biodegradability of HMW alkanes in a waxy Indonesian oil. Traditional alkane isolation techniques (TLC and CC) discriminated against HMW compounds above C40 whereas adsorption onto alumina in a warm cyclohexane slurry provided an aliphatic fraction still rich in HMW compounds and suitable as a biodegradation substrate. A waxy Indonesian oil was subjected to 136 day biodegradation by Pseudomonas fluorescens. Extraction efficiencies of over 90 % (RSD <5 %) were obtained for n-alkanes up to C6o using continuous liquid-liquid extraction. Over 80 % of the oil aliphatic fraction was degraded within 14 days. After 136 days only 14% of the original aliphatic fraction remained, yet surprisingly no decreases in the concentrations of compounds above C45 were observed. However, the use of a rapid screening biodegradation method proved conclusively that Pseudomonasfluorescens was capable of utilising n-alkanes up to C60 once the bacteria had acclimated to the HMW alkanes. This is the first report of bacterial utilisation of an n-alkane as large as C.

Reification: A Process to Configure Java Realtime Processors

Real-time systems require stringent requirements both on the processor and the software application. The primary concern is speed and the predictability of execution times. In all real-time applications the developer must identify and calculate the worst case execution times (WCET) of their software. In almost all cases the processor design complexity impacts the analysis when calculating the WCET. Design features which impact this analysis include cache and instruction pipelining. With both cache and pipelining the time taken for a particular instruction can vary depending on cache and pipeline contents. When calculating the WCET the developer must ignore the speed advantages from these enhancements and use the normal instruction timings. This investigation is about a Java processor targeted to run within an FPGA environment (Java soft chip) supporting Java real-time applications. The investigation focuses on a simple processor design that allows simple analysis of WCET. The processor design has no cache and no instruction pipeline enhancements yet achieves higher performance than existing designs with these enhancements. The investigation centers on a process that translates Java byte codes and folds these translated codes into a modified Harvard Micro Controller (HMC). The modifications include better alignment with the application code and take advantage of the FPGA’s parallel capability. A prototyped ontology is used where the top level categories defined by Sowa are expanded to support the process. The proposed HMC and process are used to produce investigation results. Performance testing using the Sobel edge detection algorithm is used to compare the results with the only Java processor claiming real-time abilities

Panpsychism And Mind-Dust

It is only recently that panpsychism has emerged as a viable position in philosophy of mind and metaphysics. As such, the exploration and defense of it is not yet on par with some competing views. The current project is a step towards a remedy to this unfortunate state of affairs. It concerns one of the most important objections to the view, which I label the \u27mind-dust\u27 objection in homage to William James. It is essentially the conceptual difficulty of how proto-experiential being at the micro-level is supposed to \u27sum\u27 in a way that forms the consciousness with which we are intimately aware. I argue that the objection is more forceful than some suppose, and attempt to explicate a way around it. A possible route to circumvent the problem, I explain, is to develop a suggestion made by Grover Maxwell almost forty years ago. The insight is to conceive of proto-experiences not as particles or bits but as fields of influence. The end result is a position that looks in many ways similar to the epistemic neutral monism of Bertrand Russell, but is also a novel version of panpsychism. The suggestion is simply this: it might be the case that we should think of the world as inherently and ontologically qualitative in nature. I call this resultant position panqualiaism and hope that it represents a step forward