The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene hydrochloride were studied. The apparent ionization constants (p
K
a
*) ...of raloxifene were determined potentiometrically in methanol–water mixtures (45%-55% w/w), and the p
K
a
values (p
K
a1
= 7.21 ± 0.02, p
K
a2
= 7.86 ± 0.02, p
K
a3
= 9.97 ± 0.04) defining ionization in aqueous media were obtained by extrapolating the p
K
a
* values to 0% of methanol. The obtained p
K
a
values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of
β
-CD, HP-
β
-CD and polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10
–3
M HP–
β-
CD which was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of 10
–3
M
β
-CD.
Graphical abstract
Purpose
Given the great potential of macrophages in the processes of tissue repair and regeneration, the aim of our study was to examine the contribution that macrophages will have in osteogenic ...process when combined and implanted with blood clot (BC) and mineral bone substitute (MBS) in mice subcutaneous implantation model.
Methods
Three types of implants were constructed and implanted subcutaneously into BALB/c mice: (1) RMBM implants (made of resident tissue macrophages, BC and MBS), (2) BM implants (made of BC and MBS), and (3) M implants (made of MBS only) where the last two served as control implants. One, two, four and eight weeks after implantation implants were explanted, and histochemical, immunohistochemical, and histomorphometric analyses were performed.
Results
Increased vascularization, particularly pronounced two and four weeks after implantation and pronounced tissue infiltration in eight week term in RMBM implants compared with both other types, likewise the presence of osteoblast-like cells, osteoid-like structures, and more prominent osteopontin and osteocalcin immunoexpression in RMBM implants indicated more pronounced osteogenic process within them.
Conclusion
Our results suggest that macrophages deserve to be considered as a cell component when constructing implants in bone regenerative medicine strategies to improve bone fracture healing process.
Summary Organic food market in Serbia is characterized by underdeveloped supply and limited demand. Demand of organically produced food has certain specifics. Paper analyzes research results of ...domestic and foreign authors aiming to identify key characteristics and to carry out a systematization of the factors that determine demand and consumption of organic products in Serbian and foreign markets. The aim of the research is to develop demographic profile of organic consumers, and to provide a picture of “typical” organic consumer. Most authors agree that there is a positive correlation between the level of education and consumption of organic products. Studies conducted in Serbia suggest that concern for health is one of the most important factors of buying organic products, while foreign customers, in addition, are also motivated by environmental and animal welfare attributes, and with desire to consume “local” food. In both groups of consumers sensory characteristics of the product were recognized as the key factors for the consumption of organic products. Price is one of the relevant factors that limit the purchase of these products. Significant attention was paid to marketing channels. Since domestic organic producers are underdeveloped and unadjusted to customers’ requirements, getting familiar with the basic characteristics of buyers of organic food is the starting point for development of adequate marketing concept for growers, processors and retail of this group of products.
•Interpretation of drug-human serum albumin interaction is performed.•The retention mechanism on human serum albumin column is described.•Appropriate parameters corresponding to plasma protein ...affinity were selected.•Significant molecular characteristics have been analysed.•A method for predicting drug-protein plasma affinity has been developed.
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The drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumin using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase. The 33 compounds that have a wide structural and therapeutic diversity were analyzed by performing a large number of experiments. The interaction mechanism was interpreted based on: i) retention characteristics of structurally related compounds, ii) retention modeling, iii) quantitative structure retention relationship (QSRR), and iv) molecular docking. Small structural differences of related compounds (e.g., reflected in different lipophilicity and polarity) have been found to affect their different binding to human serum albumin. It was found that drug retention in HSA column can be successfully described by using the quadratic function. The isocratic (logk(14%)) and extrapolated (b0(LSS)) retention factors showed the highest correlation (r > 0.76) with the constant that defines the binding affinity for human serum albumin (ACD/I-Lab). Therefore, selected chromatographic parameters can demonstrate reliable applicability for rapid screening of drug-plasma protein binding in drug discovery. In QSRR study, the resulting SVM/logk(14%) and MLR/b0(LSS) models display high internal and external predictive power. The constitutional properties (double bonds, aromatic rings, benzyl, allyl, -amino and -sulfur containing functional groups) supported by the charged parts of surface area had a significant impact on human serum albumin-binding affinity, which was also confirmed with molecular docking study. The high structural diversity of the data set provides wide applicability of tested chromatographic conditions and constructed models for defining the pharmacokinetic profile and possible structural modifications that can increase plasma protein binding of newly synthesized, pharmaceutically important compounds.
•Data potential utilized for the characterization of pedestrian movements.•Data-driven spatio-temporal discretization framework.•Robustness with respect to the simulation noise and to the sampling ...frequency.•Flexible and general methodological framework.
We propose a novel approach to pedestrian flow characterization. The definitions of density, flow and velocity existing in the literature are extended through a data-driven spatio-temporal discretization framework. The framework is based on three-dimensional Voronoi diagrams. Synthetic data is used to empirically investigate the performance of the approach and to illustrate its advantages. Our approach outperforms the considered approaches from the literature in terms of the robustness with respect to the simulation noise and with respect to the sampling frequency. Additionally, the proposed approach is by design (i) independent from an arbitrarily chosen discretization; (ii) appropriate for the multidirectional composition of pedestrian traffic; (iii) able to reflect the heterogeneity of the pedestrian population; and (iv) applicable to pedestrian trajectories described either analytically or as a sample of points.
•Probabilistic modeling approach to characterize speed–density relationship of pedestrian traffic.•Data-driven approach which is motivated by the empirically observed heterogeneity.•Model estimation ...and validation based on two case studies (data from a real scene and from controlled experiments).•Results show satisfactory predictive capabilities of the model and its superiority compared to the deterministic approaches from the literature.
We propose a probabilistic modeling approach to represent the speed–density relationship of pedestrian traffic. The approach is data-driven, and it is motivated by the presence of high scatter in the raw data that we have analyzed. We show the validity of the proposed approach, and its superiority compared to deterministic approaches from the literature using a dataset collected from a real scene and another from a controlled experiment.
•A macroscopic loading model for congested, multi-directional pedestrian flow is proposed.•Multi-directional flow is decomposed into a set of interacting pedestrian streams.•The interaction between ...streams is modeled by an anisotropic fundamental diagram.•A calibration on two real case studies using maximum likelihood estimation is performed.•The explicit modeling of anisotropy is shown to significantly improve the model performance.
A macroscopic loading model for multi-directional, time-varying and congested pedestrian flows is proposed. Walkable space is represented by a network of streams that are each associated with an area in which they interact. To describe this interaction, a stream-based pedestrian fundamental diagram is used that relates density and walking speed in multi-directional flow. The proposed model is applied to two different case studies. The explicit modeling of anisotropy in walking speed is shown to significantly improve the ability of the model to reproduce empirically observed walking time distributions. Moreover, the obtained model parametrization is in excellent agreement with the literature.
The paper deals with the daughter-father avoidant attachment. The purpose of the study is to identify the characteristics, relationships and behaviour of fathers that are perceived by the daughters ...as the key ones for the formation of avoidant attachment with fathers. Bearing this in mind, the study focuses on youth who have a combination of two patterns, secure attachment to the mother and avoidant attachment to the father. The research was designed as a mixed-method study. In the first phase, 233 young people aged 15 to 35 (73.1% women) were included and the Experience in Close Relationships Scale was administered. From this sample, we then selected the participants (N=49, 73.6% women, Mage=20.9) who had a combination of secure attachment to the mother and avoidant attachment to the father. The final sample in the second, qualitative phase of the research consisted of nine girls who accepted to be interviewed. The data were collected through a semi-structured interview based on the AAI and analysed through Interpretative Phenomenological Analysis. The results point to three identified topics common to experiences of all nine participants. The topics relate to the consequences of fathers' physical absence during the period of growing up of their daughters, the consequences of the lack of two-way communication within the father-daughter interaction, as well as to the daughters' feeling that the father is a person in whose presence they cannot act freely and naturally in the way they can act in the presence of the mother, to whom they are securely attached. Research findings are discussed in the context of specific fathers' parenting characteristics, significant for the attachment development.
We introduce a probabilistic modeling approach for pedestrian speed-density relationship. It is motivated by a high scatter in real data that precludes the use of traditional equilibrium ...relationships. To characterize the observed pattern, we relax the homogeneity assumption of equilibrium relations and propose a multiclass model. In addition to the general modeling framework, we also present some concrete model specifications. Real data are utilized to test the performance of the approach. The approach is able to reveal fundamental properties causing the heterogeneity in population and describe their impact on pedestrian movement. We also show the advantages of the proposed approach compared with approaches from the literature. The proposed model is flexible, and it provides richer information than traditional models.
The e-companion is available at
https://doi.org/10.1287/trsc.2018.0849
.
The subject of this study is the analysis of foreign trade and competitiveness of raspberries from Serbia and selected major producers and exporters (Poland and Ukraine), as well as from neighboring ...countries where raspberries play an increasingly important role in production and export (Bosnia and Herzegovina and Bulgaria), in the period 2010- 2021. The aim of the paper is to examine the competitive position of raspberries from Serbia and selected countries on global market and to give insight into changes between countries regarding competitiveness of raspberries. The results show that Serbia and Poland are leaders in the global market of frozen raspberries. Frozen raspberries from Serbia, Ukraine and Bulgaria are quality competitive, while Polish raspberries are competitive in price. The decrease in competitiveness of the leading countries on global market of frozen raspberries is noticeable, while the greatest increase in competitiveness was achieved in Ukraine.
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