Frequency response analysis under faults in weak power systems

The renewable energy sources (RESs) projects are solutions with environmental benefits that are changing the traditional power system operation and concept. Transient stability analysis has opened new research trends to guarantee a secure operation high penetration. Problems such as frequency fluctuations, decoupling between generator angular speed, network frequency fluctuation and kinetic energy storing absence are the main non-conventional RESs penetration in power systems. This paper analyzes short-circuit influence on frequency response, focusing on weak distribution networks and isolated, to demonstrate relevance in frequency stability. A study case considered a generation outage and a load input to analyze frequency response. The paper compares frequency response during a generation outage with a short-circuit occurrence. In addition, modular value and angle generator terminal voltage affectation by electric arc and network ratio R⁄X, failure type influence in power delivered behavior, considering fault location, arc resistance and load. The arc resistance is defined as an added resistance that appears during failure and influences voltage modulus and angle value results showing that intermittent non-conventional RES participation can lead to frequency fluctuations. Results showed that arc resistance, type of failure, location and loadability determine the influence of frequency response factors in weak power systems.

Site response analysis of liquefiable soil employing continuous wavelet transform

Propagation of the earthquake motion towards the ground surface alters both the acceleration and frequency content of the motion. Acceleration time record and Fourier amplitude spectrum of the motion reveal changes in the acceleration and frequency content. However, Fourier amplitude spectrum fails to give frequency-time variation. Wavelet transform overcomes this difficulty. In the present study, site response analysis of a liquefiable soil domain has been investigated employing wavelet transform. Three earthquake motions with distinct predominant frequencies are considered. It is revealed that the moment soil undergoes initial liquefaction, it causes a spike in the acceleration time history. Frequency of the spikes is found to be greater than the predominant frequency of the acceleration-time history recorded at the ground surface from the analysis. Interestingly, the spikes belong to the sharp tips of the shear stress-shear strain curve. Immediately after the spike, acceleration deamplification is observed. Post-liquefaction deamplification (filtering) of the frequency components is also observed.

Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case–control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46–2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69–4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33–1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1–2 years after commencing the drug (OR, 2.66; 95% CI, 1.97–3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09–1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30–2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

Identification of an Orally Bioavailable, Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor

Modulation of the endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiological processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines tricyclic chemotype with a high conformational similarity in comparison to the existing leads. These compounds are structurally unique, confirming their chemotype novelty. In our continuing search for new chemotypes as selective CB2 regulatory molecules, following SAR approaches, a total of 17 selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs were synthesized and tested for their ability to bind to the CB1 and CB2 receptor orthosteric sites. A competitive [3H]CP-55,940 binding screen revealed five compounds that exhibited >60% displacement at 10 μM concentration. Further concentration-response analysis revealed two compounds, 4k and 4q, as potent and selective CB2 ligands with sub-micromolar activities (Ki = 146 nM and 137 nM, respectively). In order to support the potential efficacy and safety of the analogs, the oral and intravenous pharmacokinetic properties of compound 4k were sought. Compound 4k was orally bioavailable, reaching maximum brain concentrations of 602 ± 162 ng/g (p.o.) with an elimination half-life of 22.9 ± 3.73 h. Whether administered via the oral or intravenous route, the elimination half-lives ranged between 9.3 and 16.7 h in the liver and kidneys. These compounds represent novel chemotypes, which can be further optimized for improved affinity and selectivity toward the CB2 receptor.