Pronounced reduction of postprandial glucagon by lixisenatide:a meta-analysis of randomized clinical trials

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. Methods: Six randomized, placebo-controlled studies of lixisenatide 20μg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. Results: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9mmol/l, p<0.001) and glucose excursion (LS mean difference vs. placebo: -4.5mmol/l, p<0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0ng/l, p<0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p<0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. Conclusions: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. © 2014 John Wiley and Sons Ltd.

Reduction of nonlinear intrachannel effects by channel asymmetry in transmission lines with strong bit overlapping

We have examined the statistics of simulated bit-error rates in optical transmission systems with strong patterning effects and have found strong correlation between the probability of marks in a pseudorandom pattern and the error-free transmission distance. We discuss how a reduced density of marks can be achieved by preencoding optical data.

Fluorescent probe for detection of bacteria:conformational trigger upon bacterial reduction of an azo bridge

Using biomimetic chemical reduction or Clostridium perfringens cell extract containing azoreductase, the dimer-fluorescent probe 2,4-O-bisdansyl-6,7- diazabicyclooct-6-ene, which possesses a conformationally constrained cis-azo bridge, is reduced to the tetra-equatorial 2,4-O-bisdansyl-cyclohexyl-3,5- bisammonium salt which exhibits fluorescence indicative of a dansyl monomer. © 2012 The Royal Society of Chemistry.

Dimension Reduction of the Explanatory Variables in Multiple Linear Regression

2002 Mathematics Subject Classification: 62J05, 62G35.

Investigation of skewing effects on the vibration reduction of three-phase switched reluctance motors

Switched reluctance motors (SRMs) are gaining in popularity because of their robustness, low cost, and excellent high-speed characteristics. However, they are known to cause vibration and noise primarily due to the radial pulsating force resulting from their double-saliency structure. This paper investigates the effect of skewing the stator and/or rotor on the vibration reduction of the three-phase SRMs by developing four 12/8-pole SRMs, including a conventional SRM, a skewed rotor-SRM (SR-SRM), a skewed stator-SRM (SS-SRM), and a skewed stator and rotor-SRM (SSR-SRM). The radial force distributed on the stator yoke under different skewing angles is extensively studied by the finite-element method and experimental tests on the four prototypes. The inductance and torque characteristics of the four motors are also compared, and a control strategy by modulating the turn-ON and turn-OFF angles for the SR-SRM and the SS-SRM are also presented. Furthermore, experimental results validate the numerical models and the effectiveness of the skewing in reducing the motor vibration. Test results also suggest that skewing the stator is more effective than skewing the rotor in the SRMs.

CO2 emissions reduction of Chinese light manufacturing industries:a novel RAM-based global Malmquist-Luenberger productivity index

Climate change has become one of the most challenging issues facing the world. Chinese government has realized the importance of energy conservation and prevention of the climate changes for sustainable development of China's economy and set targets for CO2 emissions reduction in China. In China industry contributes 84.2% of the total CO2 emissions, especially manufacturing industries. Data envelopment analysis (DEA) and Malmquist productivity (MP) index are the widely used mathematical techniques to address the relative efficiency and productivity of a group of homogenous decision making units, e.g. industries or countries. However, in many real applications, especially those related to energy efficiency, there are often undesirable outputs, e.g. the pollutions, waste and CO2 emissions, which are produced inevitably with desirable outputs in the production. This paper introduces a novel Malmquist-Luenberger productivity (MLP) index based on directional distance function (DDF) to address the issue of productivity evolution of DMUs in the presence of undesirable outputs. The new RAM (Range-adjusted measure)-based global MLP index has been applied to evaluate CO2 emissions reduction in Chinese light manufacturing industries. Recommendations for policy makers have been discussed.

Consistent reduction of postprandial glucagon and insulin by lixisenatide in the GetGoal clinical trial programme

Background and aims: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in subjects with type 2 diabetes mellitus. We evaluated 2-hour glucose, glucagon and insulin changes following a standardized mixed-meal tolerance test before and after 24 weeks of treatment with the once-daily prandial GLP-1 receptor agonist lixisenatide (approved for a therapeutic dose of 20 μg once daily) in six randomized, placebo-controlled studies within the lixisenatide Phase III GetGoal programme. In the studies, the mixed-meal test was conducted before and after: (1) lixisenatide treatment in patients insufficiently controlled despite diet and exercise (GetGoal-Mono), (2) lixisenatide treatment in combination with oral antidiabetic drugs (OADs) (GetGoal-M and GetGoal-S), or (3) lixisenatide treatment in combination with basal insulin ± OAD (GetGoal-Duo 1, GetGoal-L and GetGoal-L-Asia).Materials and methods: A meta-analysis was performed (lixisenatide n=1124 vs placebo n=707) combining ANCOVA least squares (LS) mean values using an inverse variance weighted analysis. Results: Lixisenatide significantly reduced 2-hour postprandial glucose from baseline (LS mean difference vs placebo: -4.9 mmol/L, p<0.0001, Figure) and glucose excursions (LS mean difference vs placebo: -4.5 mmol/L, p<0.0001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs placebo: -19.0 ng/L, p<0.0001) and insulin (LS mean difference vs placebo: -64.8 pmol/L, p<0.0001), although the glucagon/insulin ratio was increased (LS mean difference vs placebo: 0.15, p=0.02) compared with placebo. Conclusion: The results show that lixisenatide potently reduces the glucose excursion after meal ingestion in subjects with type 2 diabetes, in association with marked reductions in glucagon and insulin levels. It is suggested that diminished glucagon secretion and slower gastric emptying contribute to reduced hepatic glucose production and delayed glucose absorption, enabling postprandial glycaemia to be controlled with less demand on beta-cell insulin secretion. Clinical Trial Registration Number: NCT00688701; NCT00712673; NCT00713830; NCT00975286; NCT00715624; NCT00866658 Supported by: Sanofi

Perforated exit regions for the reduction of micro-pressure waves from tunnels

The authors are grateful to the following bodies that provided financial support for the project: (i) China Scholarship Council (20117 00029), (ii) National Natural Science Foundation of China (Grant no. U1334201) and (iii) UK Engineering and Physical Sciences Research Council (Grant no. EP/G069441/1).

Perforated exit regions for the reduction of micro-pressure waves from tunnels

The authors are grateful to the following bodies that provided financial support for the project: (i) China Scholarship Council (20117 00029), (ii) National Natural Science Foundation of China (Grant no. U1334201) and (iii) UK Engineering and Physical Sciences Research Council (Grant no. EP/G069441/1).

The Influence of Creative Tourism on Sustainable Development of Tourism and Reduction of Seasonality – Case Study of Óbidos

Tourism remains one of the most fast growing and important industries in the world. It is hard to underestimate the importance and the spectrum of the benefits that tourism provides. On the other hand, nowadays, the increasing growth of tourism poses a range of challenges and problems that need to be solved. These challenges resonate in the emergence of the so called 'alternative' or sustainable forms of tourism, which deem to be an antidote against the harms the traditional forms of tourism cause to the environment and local communities. These new forms of tourism, among which is creative tourism, are reinforced by the new breed of tourists, who are no longer satisfied with the static offer of tourism but rather prefer the dynamic one. The present research shows on the case of Óbidos the potential of creative tourism to meet these new needs of modern tourists while also solving number of problems that many destinations face, namely seasonality in tourism, as well as how creative tourism contributes to the sustainable development of tourism.

Reduction of salt in yeasted wheat bread: impact on bread quality and solutions using sourdough fermented by functional lactic acid bacteria strains

The dietary intake of sodium chloride has increased considerably over the last few decades due to changes in the human diet. This higher intake has been linked to a number of diseases including hypertension and other cardiovascular diseases. Numerous international health agencies, as well as the food industry, have now recommended a salt intake level of 5-6 g daily, approximately half of the average current daily intake level. Cereal products, and in particular bread, are a major source of salt in the Western diet. Therefore, any reduction in the level of salt in bread could have a major impact on global health. However, salt is a critical ingredient in bread production, and its reduction can have a deleterious effect on the production process as well as on the final bread quality characteristics such as shelf-life, bread volume and sensory characteristics, all deviating from the bakers’ and consumers’ expectations. This work addresses the feasibility of NaCl reduction in wheat bread focusing on options to compensate NaCl with the use of functional sourdoughs. Three strains were used for the application of low-salt bread; L. amylovorus DSM19280, W. cibaria MG1 and L. reuteri FF2hh2. The multifunctional strain L. reuteri FF2hh2 was tested the first time and its application could be demonstrated successfully. The functionalities were based on the production of exopolysaccharides as well as the production of antifungal compounds. While the exopolysaccharides, mainly high molecular dextrans, positively influenced mainly bread loaf volume, crumb structure and staling rate, the strains producing antifungal compounds prolonged the microbial shelf life significantly and compensated the lack of salt. The impact on the sensory characteristics of bread were evaluated by descriptive sensory evaluation. The increase in surface area as well as the presence of organic acids impacted significantly on the flavour profile of the sourdough bread samples. The flavour attribute “salt” could be enhanced by sourdough addition and increased the salty perception. Furthermore, a trained sensory panel evaluated for the first time the impact of yeast activity, based on different salt and yeast concentrations, on the volatile aroma profile of bread crumb samples. The analytical measurements using high resolution gas chromatography and proton-transfer-reaction mass spectrometry (PTR-MS) resulted in significantly different results based on different yeast activities. Nevertheless, the extent of the result could not be recognised by the sensory panel analysing the odour profile of the bread crumb samples. Hence, the consumer cannot recognised low-salt bread by its odour. The use of sourdough is a natural option to overcome the broad range of technological issues caused by salt reduction and also a more popular alternative compared to existing chemical salt replacers.

The effect of a reduction of nitrogen and phosphorus to eutrophic and mesotrophic conditions towards silver nanoparticle (AgNP) on freshwater green algae species

We investigated the sensitivity of algae towards silver nanoparticles with OECD test medium and lower nutrient concentrations under standard test conditions to improve comparability and to exclude any other confounding factor aside nutrient levels. Two unicellular freshwater microalgae Desmodesmus subspicatus and Raphidocelis subcapitata were chosen due to their status as standard test organisms for the algae growth inhibition test and the response to changes in nutrient supply was compared. The original medium was used as the reference (standard). For the other four media, the amount of either nitrogen or phosphorus in the medium was lowered from half (50%) to one-fourth (25 %) of that of the OECD guideline, resulting in the following media: 50% N, 25% N, 50% P and 25% P medium. As test substance, the OECD reference material NM-300K was used. For this reason, the characterization of AgNP was done using DLS and Absorption spectra (UV/vis). Actual silver concentrations and ionic silver concentrations were measured at the highest test concentration used (100 µg Ag L-1) in R. subcapitata treatments only to reduce the number of samples. All tests were run according to the OECD guideline 201 with sterilized 50 mL cell culture flask. Each medium was tested using the test conditions for culturing with 3 replicates. Test concentrations for both algae species were 0, 25, 50 and 100 µg Ag L-1 for OECD, 50% P and 25% P while for both N reductions, the silver concentrations were 0, 10, 25 and 100 µg Ag L-1. Samples for determining the algal density were taken at every 24 h.

Correlation between the photocatalysed oxidation of methylene blue in solution and the reduction of resazurin in a photocatalyst activity indicator ink (Rz Paii)

Understanding catalytic reactions over zeolites: A density functional theory study of selective catalytic reduction of NOX by NH3 over Cu-SAPO-34

Metal exchanged CHA-type (SAPO-34 and SSZ-13) zeolites are promising catalysts for selective catalytic reduction (SCR) of NOx by NH3. However, the understanding of the process at the molecular level is still limited, which hinders the identification of its mechanism and the design of more efficient zeolite catalysts. In this work, modelling the reaction over Cu-SAPO-34, a periodic density functional theory (DFT) study of NH3-SCR was performed using hybrid functional with the consideration of van der Waals (vdW) interactions. A mechanism with a low N–N coupling barrier is proposed to account for the activation of NO. The redox cycle of Cu2+ and Cu+, which is crucial for the SCR process, is identified with detailed analyses. Besides, the decomposition of NH2NO is shown to readily occur on the Brønsted acid site by a hydrogen push-pull mechanism, confirming the collective efforts of Brønsted acid and Lewis acid (Cu2+) sites. The special electronic and structural properties of Cu-SAPO-34 are demonstrated to play an essential role the reaction, which may have a general implication on the understanding of zeolite catalysis.