Chemical modification of different compounds with nitrogen-containing heterocycles

Heterocyclic compounds have an extremely important practical application, since many heterocycles are the basis of the most valuable medicinal substances, both natural (vitamins, enzymes, alkaloids, etc.) and synthetic biologically active compounds. The work mainly considers the most relevant directions for various purposes drugs search by modifying known bioactive natural, organoelement and framework compounds with 1,2-azole, oxazole, oxadiazole, thiazole, triazole, pyridine, pyrimidine heterocycles over the past 10 years. Chemical modification makes it possible to increase the water solubility of the compounds, which is important when choosing the pathways for the most rational drug introduction into the body, to reduce the toxicity of the corresponding substances, to increase the breadth of the therapeutic action, and also to give new valuable medicinal properties, thus significantly expanding their application in medicine and agriculture.

Current Perspectives on the Role of TNF in Hematopoiesis Using Mice With Humanization of TNF/LT System

TNF is a multifunctional cytokine with its key functions attributed to inflammation, secondary lymphoid tissue organogenesis and immune regulation. However, it is also a physiological regulator of hematopoiesis and is involved in development and homeostatic maintenance of various organs and tissues. Somewhat unexpectedly, the most important practical application of TNF biology in medicine is anti-TNF therapy in several autoimmune diseases. With increased number of patients undergoing treatment with TNF inhibitors and concerns regarding possible adverse effects of systemic cytokine blockade, the interest in using humanized mouse models to study the efficacy and safety of TNF-targeting biologics in vivo is justified. This Perspective discusses the main functions of TNF and its two receptors, TNFR1 and TNFR2, in steady state, as well as in emergency hematopoiesis. It also provides a comparative overview of existing mouse lines with humanization of TNF/TNFR system. These genetically engineered mice allow us to study TNF signaling cascades in the hematopoietic compartment in the context of various experimental disease models and for evaluating the effects of various human TNF inhibitors on hematopoiesis and other physiological processes.

Estradiol Priming Potentiates the Kisspeptin-Induced Release of LH in Ovariectomized Cows

The present study examined whether priming with estradiol benzoate (EB) for 12 h increased both the peak and duration of LH release in response to kisspeptin (KISS1, KP) in cows. In a Latin square design, ovariectomized Nelore cows (n = 8) received: Control, i.m. 4 mL of 0.9% saline; KP, i.m. 4 mg murine KISS1-10; EBKP, i.m. 4 mg KISS1-10 + i.m. 2 mg EB simultaneously; EB12KP, i.m. 4 mg KISS1-10 + i.m. 2 mg EB 12 h before KISS1-10. Concentrations of LH were determined in blood samples obtained at time 0 (treatment), 20, 40, 60, 90, 120, 150, 180, 210 and 270 min. Concentrations of LH were analyzed by Proc GLIMMIX for repeated measures. In case of significance, the adjusted Tukey test was used to test for differences among treatments. GraphPad 8.0 PRISM® was used to determine the area under the LH-response curve (AUC) after injection of KISS1-10. Plasma LH remained relatively constant throughout sampling after treatment with saline. The peak in LH after injection of KISS1-10 occurred at 20 min in Groups KP and EBKP and at 40 min in Group EB12KP. The peak LH response (∆LH, ng/mL) was greater (p < 0.01) in Group EB12KP (5.6 ± 0.9) than in Groups KP (2.4 ± 0.9) and EBKP (3.5 ± 0.9), which did not differ. AUC (LH ng/mL*min) was greater (p = 0.02) in Group EB12KP (439 ± 73) than in Groups KP (176 ± 73) and EBKP (241 ± 73), with the latter two groups not differing. The findings indicated that 12 h priming with EB increased both the peak and duration of the LH response to treatment with KISS1. The incorporation of EB priming and KISS1 could improve the efficiency of estrus synchronization with fixed-time AI in cows. This would have an important practical application in assisted breeding in beef and dairy cattle.

“Exact” and Approximate Methods for Bayesian Inference: Stochastic Volatility Case Study

We conduct a case study in which we empirically illustrate the performance of different classes of Bayesian inference methods to estimate stochastic volatility models. In particular, we consider how different particle filtering methods affect the variance of the estimated likelihood. We review and compare particle Markov Chain Monte Carlo (MCMC), RMHMC, fixed-form variational Bayes, and integrated nested Laplace approximation to estimate the posterior distribution of the parameters. Additionally, we conduct the review from the point of view of whether these methods are (1) easily adaptable to different model specifications; (2) adaptable to higher dimensions of the model in a straightforward way; (3) feasible in the multivariate case. We show that when using the stochastic volatility model for methods comparison, various data-generating processes have to be considered to make a fair assessment of the methods. Finally, we present a challenging specification of the multivariate stochastic volatility model, which is rarely used to illustrate the methods but constitutes an important practical application.

A novel Siamese Attention Network for visual object tracking of autonomous vehicles

In the environment perception stage of autonomous driving, vehicles need to track its surrounding objects quickly and accurately to avoid dangerous behaviors. Therefore, visual object tracking has important practical application value in autonomous driving system. However, the performance of most hierarchical convolutional feature trackers are limited by ignoring the complex environment of autonomous driving. In this paper, a novel Siamese Attention Network to explore the rich spatial and channel information of objects was proposed. Because of the lack of important information between the channel and the spatial position, the tracking performance is reduced by the challenges of illumination change and deformation. The spatial attention block and channel attention block focus on the importance of different spatial positions and channels, respectively. The effective fusion of the two makes our tracker achieve the state-of-the art performance of 0.300 in the EAO criterion of 2017, which exceeds the baseline by 5.7%.

Análisis de la situación en la pista de los jugadores en el saque y su relación con la dirección, el lado de la pista y el resultado del punto en pádel de alto nivel (Analysis of the situation on the court of the players in the serve and its relationship

El objetivo de este estudio fue conocer la influencia de la situación en la pista de los jugadores al saque y su relación con la dirección, el lado de la pista y el resultado del punto en pádel de alto nivel. La muestra incluyó un total de 1071 puntos correspondientes a nueve partidos donde participaron 36 jugadores masculinos de 1º Categoría Nacional. Se analizaron variables relacionadas con la táctica utilizada en el saque (tradicional o australiana), la dirección del saque (pared lateral o “T”), el lado de la pista (derecho o izquierdo) y el resultado del punto (gana o pierde la pareja al saque). Los resultados mostraron que los jugadores sacan entre un 75% y un 85% de las ocasiones a la pared lateral en el lado de izquierdo de la pista. En el lado derecho, se incrementa el porcentaje de saques a la “T”, especialmente utilizando una situación en la pista australiana. A nivel general, los jugadores ganan un porcentaje mayor de puntos al saque cuando utilizan la táctica tradicional frente a la australiana. Sin embargo, estas diferencias no fueron significativas cuando los jugadores sacaron a la “T” o a la pared lateral, desde ambos lados de la pista. Finalmente, el porcentaje de puntos ganados al saque disminuyó a medida que avanzó el partido de pádel, especialmente con táctica australiana del segundo al tercer set. Estos datos tienen una importante aplicación práctica en el diseño de ejercicios de pádel basados en las demandas técnico-tácticas específicas de la competición. Abstract. The aim of this study was to know the influence of the players’ serve tactical position and its relationship with the direction, the side of the court and the point outcome in elite padel. The sample included a total of 1071 points corresponding to nine matches with 36 male players of 1st National Category. Variables related to the serve tactic position (conventional or Australian), serve direction (side wall or "T"), court side (right or left) and point outcome (serve pair win or lose) were analyzed. The results showed that padel players serve between 75% and 85% of the times to the side wall on the left side of the court (advantages side). On the right side, the percentage of serves to the "T" is increased, especially using an Australian tactical position. Furthermore, serving pair win a higher percentage points when they use traditional tactic. However, these differences are not significant when the players serve to the "T" or the side wall, from both sides of the court. Finally, the percentage of points won by serving pair decreases as the padel match progresses, especially with Australian tactic from the second to the third set. These data have an important practical application in the design of padel exercises based on the specific technical-tactical competition demands.

A Survey of Network Representation Learning Methods for Link Prediction in Biological Network

Background: Networks are powerful resources for describing complex systems. Link prediction is an important issue in network analysis and has important practical application value. Network representation learning has proven to be useful for network analysis, especially for link prediction tasks. Objective: To review the application of network representation learning on link prediction in a biological network, we summarize recent methods for link prediction in a biological network and discuss the application and significance of network representation learning in link prediction task. Method & Results: We first introduce the widely used link prediction algorithms, then briefly introduce the development of network representation learning methods, focusing on a few widely used methods, and their application in biological network link prediction. Existing studies demonstrate that using network representation learning to predict links in biological networks can achieve better performance. In the end, some possible future directions have been discussed.

The risk of Xylella fastidiosa outbreaks will decrease in the Mediterranean olive-producing regions

The bacterium Xylella fastidiosa (Xf) is a worldwide distributed invasive insect-borne plant pathogen, which causes lethal diseases to many economically-important crops including olives, citrus, almonds and grapes as well as numerous forest, ornamental, and uncultivated plants. The Mediterranean basin is the top supplier of olive oil with 93% of the world production and is consequently highly concerned about the recent invasion of Xf in Europe. Recently, bioeconomic models estimated putative losses induced by the spread of Xf across the European olive-producing area ranging from 1.9 to 5.2 billion euros over 50 years; however, such models did not take into account the insect vectors, which constitute a key driver of Xf spread. In the present study, we used bioclimatic species distribution models to predict the current and future climate suitability of the Mediterranean area for the main efficient or putative transmitters of Xf to olive (i.e. Philaenus spumarius, Neophilaenus campestris and Aphrophora alni). An important part of the total extent of the Mediterranean olive-producing area, mainly situated in southern Spain, Turkey and Greece, is predicted as currently poorly suitable for these vector species. Moreover, models forecast that nearly the totality of the Mediterranean olive-producing regions will likely become climatically little suitable for these vectors by 2050 due to climate change. In Europe, Xf outbreaks have occurred so far only in localities predicted as climatically suitable for these main vector species (e.g. the Apulia region of Italy) while the areas predicted as poorly suitable are still apparently Xf-free, which suggests that climate tolerances of vectors might play a main role in shaping Xf outbreaks patterns. This pattern highlights the crucial necessity of accounting for vectors when assessing risk of Xf outbreaks, and when considering vector-borne diseases in general. The risk maps presented here will have important practical application for the optimization of current and future strategies to control Xf in the Mediterranean region.

Does the neighbourhood matter for neighbourhood satisfaction? A meta-analysis

Urbanists are keenly interested in individuals’ satisfaction with their neighbourhoods, and especially in the determinants of satisfaction. To the extent that we all want to be satisfied with our neighbourhoods, this work has an important practical application, providing guidance to planners, developers, local leaders and others on how to build satisfying neighbourhoods. However, do neighbourhoods matter for neighbourhood satisfaction? This study answers that question using a meta-analysis to pool 126 estimates from 27 studies of the association between neighbourhoods and neighbourhood satisfaction. I find that neighbourhoods do matter for neighbourhood satisfaction, but that their direct effect is weak. I consider several possible explanations for this finding, and discuss the practical significance of calling into question whether changes to a neighbourhood’s built or social environment can meaningfully improve residents’ neighbourhood satisfaction.

Role of the oral microbiota in the development of Alzheimer’s disease

Dementia and, in particular, Alzheimer’s disease (AD), affects millions of people around the world and its prevalence is steadily rising annually. Some risk factors for AD, such as age, cannot be modified, while others could possibly be corrected. In recent years, many studies are tackling the problem of the oral and gut microbiota as a provoking factor for AD and other neurodegenerative diseases, but their relationship and specific pathophysiological mechanisms remain understudied. The microbiota of the oral cavity can be of particular importance due to the specificity of microorganisms and their localization, as well as the possibility of provoking neuroinflammation, which requires further study. This review covers the specific features of the oral microbiota, current views on the pathophysiological role of the oral microbiota in the development of AD, as well as the beneficial role of probiotics. The study of this issue can have an important practical application both for the early diagnosis of AD, and for its further treatment.