An Overview,Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon-Like Peptide-1 Receptor

Due to uncomfortable injection regimens of peptidic agonists of glucagon-like peptide-1 receptor (GLP-1R), orally available nonpeptide positive allosteric modulators (PAMs) of GLP-1Rs are foreseen as the possible future mainstream therapy for type 2 diabetes. Herein, current GLP-1R PAMs are reviewed. Based on the effectiveness and in silico predicted physicochemical properties, pharmacokinetics, and toxicity, possible candidates for further development as oral drugs were selected. The suggestion is that GLP-1R PAMs might be used orally alone or in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors, which could offer an optimal treatment option next to metformin monotherapy in type 2 diabetes mellitus, or in a wider spectrum of indications. Quercetin acts as a GLP-1R PAM and DPP-4 inhibitor, and therefore, might be considered as a pioneering agent with a dual mechanism of action, in terms of GLP-1R positive allosteric modulation and DPP-4 inhibition for potentiating GLP-1 dependent effects.     

Stressed Skin Design Versus Braced Frame Design Through Efficient Numerical Modelling

International Journal of Steel Structures - Steel frame structures are traditionally designed with bracings that stabilize the main bearing structure. Another approach is to apply the...     

Implication of PSA uncertainties on risk-informed decision making

Nuclear power plants risk-informed policy is introduced in order to improve safety decision making and regulatory efficiency. The corresponding regulatory guides define the acceptable risk measures and their changes resulting from the modifications in the licensed design of the nuclear power plant. The risk measures used in the acceptance guidelines are the core damage frequency and large early release frequency.The risk measures and their corresponding changes are assessed by the Probabilistic Safety Assessment. The uncertainties of Probabilistic Safety Assessment should be appropriately addressed in the context of the decision making, considering their implication on the obtained results. The Probabilistic Safety Assessment uncertainties include epistemic uncertainties resulting from parameter, model, and completeness uncertainties.The paper presents the obtained results from the uncertainty analysis of the Probabilistic Safety Assessment of the reference nuclear power plant and their implication on risk-informed decision making. The paper focuses particularly on parameter and model uncertainties. The analysed modification is extension of the test interval of the emergency diesel generators. The core damage frequency is the used risk measure in the analysis.The need for the appropriate consideration of the uncertainties in the Probabilistic Safety Assessment in order to adequately support the risk-informed decision making is identified. The deficiency of usage of percentile measures is identified and acknowledged. The need for the adaptation of the risk-informed decision-making principles considering new nuclear power plants is recognized.     

Genetic algorithm optimisation of the maintenance scheduling of generating units in a power system

A new method for optimisation of the maintenance scheduling of generating units in a power system is developed. Maintenance is scheduled to minimise the risk through minimisation of the yearly value of the loss of load expectation (LOLE) taken as a measure of the power system reliability. The proposed method uses genetic algorithm to obtain the best solution resulting in a minimal value of the annual LOLE value for the power system in the analysed period. The operational constraints for generating units are included in the method. The proposed algorithm was tested on a Macedonian power system and the obtained results were compared with the results received from the approximate methodology. The results show the improved reliability of a power system with the maintenance schedule obtained by the new method compared to the results from the approximate methodology.     

The effect of contingency analysis on the nodal prices in the day-ahead market

We look at the effect of modeling branch-outage contingencies on locational marginal prices. To model contingencies in the day-ahead auction, we formulate a two-stage stochastic program. Rather than follow the current practice of including a list of possible contingencies that must be satisfied, we incorporate a larger set of contingencies in the model and allow contingencies to result in load reductions/outages at a cost. The model can be used and interpreted in two ways. One is to look at the tradeoff between reliability and outage costs. Another is to consider the load losses resulting from a contingency to be consumer offers of load reductions in response to line outages as part of the day-ahead auction. In analyzing the model structure, we find that the prices in the model closer in definition to those currently used in the day-ahead auction do not maximize expected surplus because the day-ahead auction produces prices that assume shortages will never occur. This raises issues with the design of auctions with important stochastic elements in the market. We present results for a 68-node grid with 86 branches (lines and transformers) to illustrate how prices and expected values change as the costs of outages are varied.     

Application of the fault tree analysis for assessment of power system reliability

A new method for power system reliability analysis using the fault tree analysis approach is developed. The method is based on fault trees generated for each load point of the power system. The fault trees are related to disruption of energy delivery from generators to the specific load points. Quantitative evaluation of the fault trees, which represents a standpoint for assessment of reliability of power delivery, enables identification of the most important elements in the power system. The algorithm of the computer code, which facilitates the application of the method, has been applied to the IEEE test system. The power system reliability was assessed and the main contributors to power system reliability have been identified, both qualitatively and quantitatively.     

Technostress aus einer neurobiologischen Perspektive

Despite the positive impact of information and communication technology (ICT) on an individual, organizational, and societal level (e.g., increased access to information, as well as enhanced performance and productivity), both scientific research and anecdotal evidence indicate that human-machine interaction, both in a private and organizational context, may lead to notable stress perceptions in users. This type of stress is referred to as technostress. A review of the literature shows that most studies used questionnaires to investigate the nature, antecedents, and consequences of technostress. Despite the value of the vast amount of questionnaire-based technostress research, we draw upon a different conceptual perspective, namely neurobiology. Specifically, we report on a laboratory experiment in which we investigated the effects of system breakdown on changes in users?? levels of cortisol, which is a major stress hormone in humans. The results of our study show that cortisol levels increase significantly as a consequence of system breakdown in a human-computer interaction task. In demonstrating this effect, our study has major implications for ICT research, development, management, and health policy. We confirm the value of a category of research heretofore largely neglected in ICT-related disciplines (particularly in business and information systems engineering, BISE, as well as information systems research, ISR), and argue that future research investigating human-machine interactions should consider the neurobiological perspective as a valuable complement to traditional concepts.     

Interplay between nematic ordering and thermomechanical response in a side-chain liquid single crystal elastomer containing pendant azomesogen units

Photoactive materials based on azobenzene derivatives exhibit interesting properties related to the reversible photo-isomerisation between the trans and cis isomers of the azo-compound. In this work we report the preparation and physical-chemical characterization of Liquid Single Crystal Elastomers (LSCEs) containing azobenzene derivative side-chain mesogens as co-monomer. The interplay between the orientational ordering and mechanical response in the nematic phase is investigated by thermomechanical measurements as well as by deuteron NMR spectroscopy. We demonstrate that local nematic order can be reliably probed in azo-LSCEs using low molar mass deuterated cyanobiphenyl nematogen in low concentrations. No phase separation of the dopant is observed. The nematoelastic coupling eav(T)∝Sav(T) between the effective sample deformation and average nematic order parameter is present over a wide temperature range even in the systems with relatively large heterogeneity of the nematic order and misaligned nematic domains.     

Aerodynamic characteristics of two slipstreaming race cars

Journal of Mechanical Science and Technology - A computational model was developed to study aerodynamic forces acting on two closed-wheel race cars in the slipstreaming (drafting) arrangement,...     

Chemometric-Assisted Optimization of RP-HPLC Method for Determination of Some Bioflavonoids in Brassica oleracea Species and Their Antioxidative Activity

In the present work, the rapid RP-HPLC method with UV (DAD) detection for simultaneous quantification of bioflavonoids: quercetin, apigenin, catechin, epicatechin, kaempferol, and luteolin in Brassica oleracea species samples (cauliflower, broccoli, and Brussels sprouts) was developed with the aid of LC-Simulator (ACD Labs® suite) software. A series of extracts obtained with different extraction method were evaluated for antioxidant activity. The optimal conditions for separation and quantification were established after nine scouting runs entered to LC-Simulator software. The optimized separation was achieved on Hypersil GOLD aQ column with isocratic elution and mobile phase composition A:2 % acetic acid in water and B:acetonitrile in 91:9 (v/v %) ratio. The R _s values were in the range from 2.6 to 8.00, indicating good selectivity of the method. The obtained results generally show good agreement with published data. Low detection limits (0.02–0.055 μg/mL) were obtained with acceptable recoveries (90–109 %). Total time of analysis was less than 11 min; therefore, the proposed method represents significant improvement over existing methods. Extracts from Brassica vegetables, obtained using different extraction procedures, were studied for their radical scavenging effects. Scavenging of DPPH showed different kinetics at the beginning of the assay period and after 15 min from the initialization of reaction. Different kinetics suggested the presence of polymerized and/or less active antioxidants with different scavenging mechanisms for particular polyphenolic compounds.