Kinetics and spectral properties of electron and <SUP>&#8226;</SUP>OH adducts of dimethylpyridines: a pulse radiolysis study

The reactions of e-aq, &#8226;OH&#8226;-, O&#8226;- and SO&#8226;-4 with 2,4-, 2,6- and 3,5-dimethylpyridines have been investigated in aqueous solution by pulse radiolysis with optical detection. Both e-aq and &#8226;OH radicals have high reactivity toward these compounds with k = 4-8&#215;109 dm3 mol-1 s-1. The rates of O&#8226; and SO&#8226;-4 reactions (1-3 &#215; 109 dm3 mol-1 s-1 were lower compared to the rate observed with the &#8226;OH radical. The transient absorption spectra obtained in the reaction of e-aq with three isomers exhibited a weak broad band around 340-410 nm. The absorption maxima of the intermediates formed in the &#8226;OH and SO&#8226;-4 reactions were centred around 320-330 nm (&#949;= 2450- 3500 dm3 mol-1 cm-1/ with an additional broad peak in the range 460-520 nm which are attributed to the corresponding &#8226;OH adducts. The spectra in the O&#8226;- reaction have absorption maxima between 300 and 320 nm and it reacts both by addition and H-abstraction from the CH3 group. A reaction mechanism consistent with the observed results is proposed

Population balances combined with computational fluid dynamics : a modeling approach for dispersive mixing in a high pressure homogenizer

High pressure homogenization is at the heart of many emulsification processes in the food, personal care and pharmaceutical industry. The droplet size distribution is an important property for product quality and is aimed to be controlled in the process. Therefore a population balance model was built in order to predict the droplet size distribution subject to various hydrodynamic conditions found in a high pressure homogenizer. The hydrodynamics were simulated using Computational Fluid Dynamics and the turbulence was modeled with a RANS k–e model. The high energy zone in the high pressure homogenizer was divided into four compartments. The compartments had to be small enough to secure nearly homogeneous turbulent dissipation rates but large enough to hold a population of droplets. A population balance equation describing breakage and coalescence of oil droplets in turbulent flow was solved for every compartment. One set of parameters was found which could describe the development of the droplet size distribution in the high pressure homogenizer with varying pressure drop. An improvement of 65% was found compared to the same model containing just one compartment. The compartment approach may provide an alternative to direct coupling of CFD and population balances

Improving Power Delivery of Grid-Connected Induction Machine Based Wind Generators under Dynamic Conditions Using Feedforward Linear Neural Networks

In the conventional grid-connected Wind Energy Conversion System (WECS), the generator side inverter is typically controlled via Field Oriented Control (FOC), while Voltage Oriented Control (VOC) controls the grid side inverter. However, robust operation cannot be guaranteed during sudden changes in wind speeds and weak grid connections. This paper presents a novel method to improve the overall dynamic performance of on-grid induction machine-based wind generators. An online mechanical parameter estimation technique is devised using Recursive Least Squares (RLS) to compute the machine inertia and friction coefficient iteratively. An adaptive feedforward neural (AFN) controller is also proposed in the synchronous reference frame, which is constructed using the estimated parameters and the system's inverse. The output of the neural controller is added to the output of the speed PI controller in the outer loop of the FOC to enhance the speed response of the wind generator. A similar approach is taken to improve the classical VOC structure for the grid-side inverter. In this case, the RLS estimates the equivalent Thevenin's grid impedance in real-time. As for the adaptive action, two identical neural networks are integrated with the inner loop direct and quadrature axis current PI controllers. Under nominal operating conditions, it is observed that the PI+AFN provides a faster settling time for the generator's speed and torque response. Upon being subjected to variations in the wind speed, the PI+AFN outperforms the classical PI controller and attains a lower integral-time error. In addition, the proposed PI+AFN controller has a better ability to maintain the grid-side inverter stability during stochastic variations in grid impedance. One significant advantage of the proposed control approach is that no data for training or validation is required since the neural network weights are directly the output of the RLS estimator. Hardware verification for the improved FOC for wind generators using the adaptive controller is also made using the DSPACE 1007 AUTOBOX platform

Low Prevalence of Ocular Chlamydia trachomatis Infection and Active Trachoma in the Western Division of Fiji.

BACKGROUND: Trachoma is the leading infectious cause of blindness and is caused by ocular infection with the bacterium Chlamydia trachomatis (Ct). While the majority of the global disease burden is found in sub-Saharan Africa, the Western Pacific Region has been identified as trachoma endemic. Population surveys carried out throughout Fiji have shown an abundance of both clinically active trachoma and trachomatous trichiasis in all divisions. This finding is at odds with the clinical experience of local healthcare workers who do not consider trachoma to be highly prevalent. We aimed to determine whether conjunctival infection with Ct could be detected in one administrative division of Fiji. METHODS: A population-based survey of 2306 individuals was conducted using the Global Trachoma Mapping Project methodology. Population prevalence of active trachoma in children and trichiasis in adults was estimated using the World Health Organization simplified grading system. Conjunctival swabs were collected from 1009 children aged 1-9 years. DNA from swabs was tested for the presence of the Ct plasmid and human endogenous control. RESULTS: The prevalence of active trachoma in 1-9 year olds was 3.4%. The age-adjusted prevalence was 2.8% (95% CI: 1.4-4.3%). The unadjusted prevalence of ocular Ct infection in 1-9 year-olds was 1.9% (19/1009), and the age-adjusted infection prevalence was 2.3% (95% CI: 0.4-2.5%). The median DNA load was 41 Ct plasmid copies per swab (min 20, first quartile 32, mean 6665, third quartile 161, max 86354). There was no association between current infection and follicular trachoma. No cases of trachomatous trichiasis were identified. DISCUSSION: The Western Division of Fiji has a low prevalence of clinical trachoma. Ocular Ct infections were observed, but they were predominantly low load infections and were not correlated with clinical signs. Our study data suggest that trachoma does not meet the WHO definition of a public health problem in this Division of Fiji, but the inconsistency with previous studies warrants further investigation

Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology

Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process

Annulment of Oil Licences in Nigeria’s Upstream Petroleum Sector: A Legal Critique of the Costs and Benefits

Owing to various reasons, tenable and untenable, successive governments in Nigeria have annulled licenses duly granted to identifiable upstream petroleum operators. With due sense of circumspect, when irregularities manifest in the process and the grant of substantive licences, such does not vest in the government an unfettered right to annul the licence. There are evidences of such occurrence in spite of established procedures regulating annulments, commonly referred to as revocation or cancellation. This paper is a critique of the annulment of oil licenses and the associated contractualregulatory dimensions. The validity of the Federal Government’s actions also comes to the fore, particularly in the light of renewed drive to attract investments into the upstream sector. Thus, as some benefits are accruable to the players, it is also important to appraise the consequential costs attributable to undue annulment of oil licenses. The paper adopts a descriptive analytical method of available facts, expounds requisite statutory provisions and utilizes judicial precedents to highlight the context of the study. It is imperative that the Federal Government adheres to established procedures on oil license annulment, as a contrary posture will amount to several negative outcomes

Discordance in glycemic categories and regression to normality at baseline in 10,000 people in a Type 2 diabetes prevention trial

The world diabetes population quadrupled between 1980 and 2014 to 422 million and the enormous impact of Type 2 diabetes is recognised by the recent creation of national Type 2 diabetes prevention programmes. There is uncertainty about how to correctly risk stratify people for entry into prevention programmes, how combinations of multiple ‘at high risk’ glycemic categories predict outcome, and how the large recently defined ‘at risk’ population based on an elevated glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973 people at highest risk of diabetes in our population, and screened 10,000 of these with paired fasting plasma glucose and HbA1c for randomisation into a very large Type 2 diabetes prevention trial. Baseline discordance rate between highest risk categories was 45.6 %, and 21.3 - 37.0 % of highest risk glycaemic categories regressed to normality between paired baseline measurements (median 40 days apart). Accurate risk stratification using both fasting plasma glucose and HbA1c data, the use of paired baseline data, and awareness of diagnostic imprecision at diagnostic thresholds would avoid substantial overestimation of the true risk of Type 2 diabetes and the potential benefits (or otherwise) of intervention, in high risk subjects entering prevention trials and programmes

The risk factors potentially influencing hospital admission in people with diabetes, following SARS-CoV-2 infection : a population-level analysis

Introduction: Since early 2020 the whole world has been challenged by the SARS-CoV-2 virus and the associated global pandemic (Covid-19). People with diabetes are particularly at high risk of becoming seriously unwell after contracting this virus. Methods: This population-based study included people living in the Greater Manchester conurbation who had a recorded diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and subsequent Covid-19 infection. Each individual with T1DM (n = 862) or T2DM (n = 13,225) was matched with three Covid-19-infected non-diabetes controls. Results: For individuals with T1DM, hospital admission rate in the first 28 days after a positive Covid-19 test was 10% vs 4.7% in age/gender-matched controls [relative risk (RR) 2.1]. For individuals with T2DM, hospital admission rate after a positive Covid-19 test was 16.3% vs 11.6% in age/gender-matched controls (RR 1.4). The average Townsend score was higher in T2DM (1.8) vs matched controls (0.4), with a higher proportion of people with T2DM observed in the top two quintiles of greatest disadvantage (p < 0.001). For Covid-19-infected individuals with T1DM, factors influencing admission likelihood included age, body mass index (BMI), hypertension, HbA1c, low HDL-cholesterol, lower estimated glomerular filtration rate (eGFR), chronic obstructive pulmonary disease (COPD) and being of African/mixed ethnicity. In Covid-19-infected individuals with T2DM, factors related to a higher admission rate included age, Townsend index, comorbidity with COPD/asthma and severe mental illness (SMI), lower eGFR. Metformin prescription lowered the likelihood. For multivariate analysis in combined individuals with T2DM/controls, factors relating to higher likelihood of admission were having T2DM/age/male gender/diagnosed COPD/diagnosed hypertension/social deprivation (higher Townsend index) and non-white ethnicity (all groups). Conclusion: In a UK population we have confirmed a significantly higher likelihood of admission in people with diabetes following Covid-19 infection. A number of factors mediate that increased likelihood of hospital admission. For T2DM, the majority of factors related to increased admission rate are common to the general population but more prevalent in T2DM. There was a protective effect of metformin in people with T2DM

Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms

Background:Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.Methods:Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.Results:Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.Conclusions:Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actionsThis work was supported by national funding from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/ BIO-5289), and a unrestricted grant from by Merck/MS