Nonlinear observers for burning zone temperatures and torque estimation of the rotary cement kiln.

Due to consistent expansion in the infrastructure and housing sectors worldwide have given a new way for the rapid growth of global cement market. Increased global demand for the cement production makes the attractive research topic which can lead to the quality and overall efficiency of the product. Measurement of the temperature in the burning zone is vital to maintain product quality and kiln efficiency in the cement industry. Often the BZT is un-measurable due to internal kiln conditions, dusty environment, extreme heat, harshness for example and this leads to kiln not being driven as efficient as possible. Multi-physics tools are core to modern engineering, and smart manufacturing, but have not been extensively utilized in this low-cost industry, hence proposed approach is to find a reduced ordered model (ROM) of the thermodynamics of the kiln using data centric approach along with Multiphysics tool

Relationships between odd- and branched-chain fatty acid profiles in milk and calculated enteric methane proportion for lactating dairy cattle

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Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Intensive diabetes control has been associated with increased mortality in type 2 diabetes (T2DM); this has been suggested to be due to increased hypoglycemia. We measured hypoglycemia-induced changes in endothelial parameters, oxidative stress markers and inflammation at baseline and after a 24-hour period in type 2 diabetic (T2DM) subjects versus age-matched controls. Case-control study: 10 T2DM and 8 control subjects. Blood glucose was reduced from 5 (90 mg/dl) to hypoglycemic levels of 2.8 mmol/L (50 mg/dl) for 1 hour by incremental hyperinsulinemic clamps using baseline and 24 hour samples. Measures of endothelial parameters, oxidative stress and inflammation at baseline and at 24-hours post hypoglycemia were performed: proteomic (Somalogic) analysis for inflammatory markers complemented by C-reactive protein (hsCRP) measurement, and proteomic markers and urinary isoprostanes for oxidative measures, together with endothelial function. Between baseline and 24 -hours after hypoglycemia, 15 of 140 inflammatory proteins differed in T2DM whilst only 1 of 140 differed in controls; all returned to baseline at 24-hours. However, elevated hsCRP levels were seen at 24-hours in T2DM (2.4 mg/L (1.2–5.4) vs. 3.9 mg/L (1.8–6.1), Baseline vs 24-hours, P < 0.05). In patients with T2DM, between baseline and 24-hour after hypoglycemia, only one of 15 oxidative stress proteins differed and this was not seen in controls. An increase (P = 0.016) from baseline (73.4 ng/mL) to 24 hours after hypoglycemia (91.7 ng/mL) was seen for urinary isoprostanes. Hypoglycemia resulted in inflammatory and oxidative stress markers being elevated in T2DM subjects but not controls 24-hours after the event

Author Correction: Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects (Scientific Reports, (2020), 10, 1, (4750), 10.1038/s41598-020-61531-z)

© 2020, The Author(s). The original version of this Article contained a typographical error in the spelling of the author Johannes Graumann, which was incorrectly given as Johannes Grauman. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file

Transcriptional drug repositioning and cheminformatics approach for differentiation therapy of leukaemia cells.

Differentiation therapy is attracting increasing interest in cancer as it can be more specific than conventional chemotherapy approaches, and it has offered new treatment options for some cancer types, such as treating acute promyelocytic leukaemia (APL) by retinoic acid. However, there is a pressing need to identify additional molecules which act in this way, both in leukaemia and other cancer types. In this work, we hence developed a novel transcriptional drug repositioning approach, based on both bioinformatics and cheminformatics components, that enables selecting such compounds in a more informed manner. We have validated the approach for leukaemia cells, and retrospectively retinoic acid was successfully identified using our method. Prospectively, the anti-parasitic compound fenbendazole was tested in leukaemia cells, and we were able to show that it can induce the differentiation of leukaemia cells to granulocytes in low concentrations of 0.1 μM and within as short a time period as 3 days. This work hence provides a systematic and validated approach for identifying small molecules for differentiation therapy in cancer

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Prediction of ruminal volatile fatty acid proportions of lactating dairy cows based on milk odd- and branched-chain fatty acid profiles: new models, better predictions

The volatile fatty acids (VFA) produced in the rumen and the proportions in which they are produced are important determinants of a ruminant's metabolism, but their monitoring requires rumen-fistulated animals, which is not feasible under practical conditions or in experimental setups at herd level. An alternative approach was suggested earlier, consisting of predicting the VFA proportions from measured odd- and branched-chain fatty acid concentrations in the milk with a linear model. Here, we have improved this strategy through the development and application of 2 new model structures: the quadratic model, containing quadratic terms and interactions, and the rational model, consisting of a ratio of linear expressions. Both were found to improve prediction accuracy significantly compared with the linear model. Although the quadratic model achieved the best prediction accuracy, the rational model has the interesting property that it takes the dependence of the 3 predicted VFA into account and guarantees that the 3 proportions add up to 1. Adding a study effect to correct for a possible study bias in the multi-study data improved prediction substantially for all 3 methods. Our results demonstrate the potential of using milk odd- and branched-chain fatty acid concentrations to predict rumen VFA proportions

A graphical approach for rationalization of bi-enzymatic reactions based on a kinetic model

A model and a graphical method have been developed to describe and visualize the interaction between two enzymes with a redox mediator. In this bi-enzymatic process, the enzyme cellobiose dehydrogenase (CDH; EC 1.1.99.18) oxidizes lactose at the C-1 position of the reducing sugar moiety to lactobionolactone, which spontaneously hydrolyzes to lactobionic acid. 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) is used as electron acceptor and is continuously regenerated by laccase (EC 1.10.3.2). Oxygen is the terminal electron acceptor and is fully reduced to water by laccase, a copper containing oxidase. Oxygen is added to the system by means of bubble-free oxygenation. The general aim is to assist in understanding the process and to provide a tool for rational design of similar biocatalytic processes leading to intensification and/or a more efficient use of the biocatalysts and redox mediator. This can be accomplished by describing the reaction system with differential equations and integrating them over a desired time interval. Hence, the simulation of reactions of much greater complexity can be attained in comparison with addressing a Michaelis–Menten, steady-state approach. We focused on elaborating a methodology to determine the influence of the limiting rate of cellobiose dehydrogenase and laccase and the initial ABTS concentration on the productivity for a given oxygen mass transfer coefficient. This way, the use of the enzymes and the redox mediator ABTS can be rationalized. Using the model, the productivity of the process is investigated by simultaneous solution of the rate equations for varying enzyme quantities and redox mediator concentrations, solved with the aid of a numerical solution. The isocharts developed in this work, provide a novel and easy-to-use graphical tool to determine optimal process conditions. The used methodology can be extended for similar and other enzymatic conversions with cofactor regeneration. The accuracy of the model has been assessed and is in good agreement with experimental data