Physicochemical and Mechanical Properties of Non-Isocyanate Polyhydroxyurethanes (NIPHUs) from Epoxidized Soybean Oil: Candidates for Wound Dressing Applications.

Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from petrochemical sources and the application of eco-friendly synthesis processes is crucial for the development of biomaterials. Therefore, polyhydroxyurethanes have been utilized, as their synthesis route allows for the carbonation of vegetable oils with carbon dioxide and the substitution of isocyanates known for their high toxicity, carcinogenicity, and petrochemical origin. In this study, polyhydroxyurethanes were obtained from carbonated soybean oil in combination with two diamines, one that is aliphatic (1,4-butadiamine (putrescine)) and another that is cycloaliphatic (1,3-cyclohexanobis(methylamine)). Four polyhydroxyurethanes were obtained, showing stability in hydrolytic and oxidative media, thermal stability above 200 °C, tensile strength between 0.9 and 1.1 MPa, an elongation at break between 81 and 222%, a water absorption rate up 102%, and contact angles between 63.70 and 101.39. New formulations of bio-based NIPHUs can be developed with the inclusion of a cycloaliphatic diamine (CHM) for the improvement of mechanical properties, which represents a more sustainable process for obtaining NIPHUs with the physicochemical, mechanical, and thermal properties required for the preparation of wound dressings.

Incorporation of Chitosan in Polyurethanes Based on Modified Castor Oil for Cardiovascular Applications.

The increased demand for vascular grafts for the treatment of cardiovascular diseases has led to the search for novel biomaterials that can achieve the properties of the tissue. According to this, the investigation of polyurethanes has been a promising approach to overcome the present limitations. However, some biological properties remain to be overcome, such as thrombogenicity and hemocompatibility, among others. This paper aims to synthesize polyurethanes based on castor oil and castor oil transesterified with triethanolamine (TEA) and pentaerythritol (PE) and with the incorporation of 1% chitosan. Analysis of the wettability, enzymatic degradation, mechanical properties (tensile strength and elongation at break), and thermal stability was performed. Along with the evaluation of the cytotoxicity against mouse fibroblast (L929) and human dermal fibroblast (HDFa) cells, the hemolysis rate and platelet adhesion were determined. The castor-oil-based polyurethanes with and without 1% chitosan posed hydrophobic surfaces and water absorptions of less than 2% and enzymatic degradation below 0.5%. Also, they were thermally stable until 300 °C, with tensile strength like cardiovascular tissues. The synthesized castor oil/chitosan polyurethanes are non-cytotoxic (cell viabilities above 80%) to L929 and HDFa cells and non-thrombogenic and non-hemolytic (less than 2%); therefore, they are suitable for cardiovascular applications.

Imaging of common hip pathologies in runners.

Running is an increasingly popular sport and form of exercise. Because of the importance of the hip in the biomechanics involved with running, forming the primary connection between the axial and appendicular skeleton of the lower extremities, accurate diagnosis and reporting of hip pathology are vital for appropriate management. This review provides an overview of the most common hip pathologies and injuries encountered in runners. Radiologic studies, primarily conventional radiography and magnetic resonance imaging (MRI) provide useful diagnostic information and should be used in combination with clinical findings to help guide therapeutic management.

Assessment of the Anti-Thrombogenic Activity of Polyurethane Starch Composites.

The increasing morbidity and mortality of patients due to post-surgery complications of coronary artery bypass grafts (CABPG) are related to blood-material interactions. Thus, the characterization of the thrombogenicity of the biomaterial for cardiovascular devices is of particular interest. This research evaluated the anti-thrombogenic activity of polyurethanes-starch composites. We previously synthesized polyurethane matrices that were obtained from polycaprolactone diol (PCL), polyethylene glycol (PEG), pentaerythritol (PE), and isophorone diisocyanate (IPDI). In addition, potato starch (AL-N) and zwitterionic starch (AL-Z) were added as fillers. The anti-thrombogenic property was characterized by the clot formation time, platelet adhesion, protein absorption, TAT complex levels, and hemolysis. Additionally, we evaluated the cell viability of the endothelial and smooth muscle cells. Statically significant differences among the polyurethane matrices (P1, P2, and P3) were found for protein absorption and the blood clotting time without fillers. The polyurethanes composites with AL-Z presented an improvement in the anti-thrombogenic property. On the other hand, the composites with AL-Z reduced the viability of the endothelial cells and did not significantly affect the AoSCM (except for P1, which increased). These results classify these biomaterials as inert; therefore, they can be used for cardiovascular applications.

Draft Genome Sequence of Streptomyces sp. Strain RKCA744, Isolated from the Arauca River, Colombia.

Streptomyces sp. strain RKCA744 was isolated from sediment collected from the Arauca River, Colombia.

Influence of Starch on the Structure-Properties Relationship in Polyethylene Glycol/Polycaprolactone Diol Polyurethanes.

Improvements in the antithrombogenicity activity of biomaterials for cardiovascular applications are necessary to meet the demand for vascular grafts in the world. Zwitterionic compounds tend to be used due to their anti-fouling properties, which reduce platelet adhesions and protein absorptions. Therefore, in this research, potato starch (AL-N) and zwitterionic starch (AL-Z) (obtained by Williamson etherification) were included as fillers in polyurethane (PU) matrices from polycaprolactone diol (PCL), polyethylene glycol (PEG), pentaerythritol (PE) and isophorone diisocyanate (IPDI) in order to study their effect in terms of their physicochemical, mechanical and thermal properties. We conducted our evaluation using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), contact angle analysis, swelling behavior, thermogravimetric analysis (TGA), tensile/strain analysis, scanning electron microscopy equipped with energy dispersive X-ray spectroscopy (SEM-EDS), dynamic mechanic analysis (DMA), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The results showed that AL-N and AL-Z modified these properties, where AL-N improved tensile strength, and AL-Z increased the hydrophilicity of polyurethanes matrices; additionally, AL-N had interactions with the soft segments, and AL-Z had interactions with the hard segments. Finally, both fillers reduced the degree of crystallinity and did not affect the thermal stability of polyurethanes.

Spontaneous Condensation of RNA into Nanoring and Globular Structures.

The effect of polyvalent cations, like spermine, on the condensation of DNA into very well-defined toroidal shapes has been well studied and understood. A great effort has been made to obtain similar condensed structures from RNA molecules, but so far, it has been elusive. In this work, we show that single-stranded RNA (ssRNA) molecules can easily be condensed into nanoring and globular structures on a mica surface, where each nanoring structure is formed mostly by a single RNA molecule. The condensation occurs in a concentration range of different cations, from monovalent to trivalent, but at a higher concentration, globular structures appear. RNA nanoring structures were observed on mica surfaces by atomic force microscopy (AFM). The samples were observed in tapping mode and were prepared by drop evaporation of a solution of RNA in the presence of one type of the different cations used. As far as we know, this is the first time that nanorings or any other well-defined condensed RNA structures have been reported in the presence of simple salts. The RNA nanoring formation can be understood by an energy competition between the hydrogen bonding forming hairpin stems-weakened by the salts-and the hairpin loops. This result may have an important biological relevance since it has been proposed that RNA is the oldest genome-coding molecule, and the formation of these structures could have given it stability against degradation in primeval times. Even more, the nanoring structures could have the potential to be used as biosensors and functionalized nanodevices.

Imaging Review of Subscapularis Tendon and Rotator Interval Pathology.

As the largest rotator cuff muscle, the subscapularis plays a major role in stabilizing the glenohumeral joint, in conjunction with surrounding rotator cuff structures. Injury to the subscapularis tendon can be isolated, but more commonly is seen in conjunction with supraspinatus tendon pathology. Injury can be associated with biceps pulley instability, superior labral anterior-posterior (SLAP) tears, humeral head subluxation, and anterosuperior and coracoid impingements. The involvement of the rotator interval can lead to what is called "the hidden lesion," due to its difficulty to diagnose during arthroscopy. Understanding the anatomical relations of the subscapularis tendon with the rest of the rotator cuff and rotator interval, as well as common patterns of injury that involve the subscapularis tendon, can aid in proper diagnosis of these injuries leading to prompt surgical repair. This review describes the anatomy of the subscapularis muscle and tendon, and the magnetic resonance imaging (MRI) patterns of subscapularis tendon injury.

Vitamin A does not influence mRNA expression of hormone hepcidin but other biomarkers of iron homeostasis in young male Wistar rats.

The effects of an adequate supply of vitamin A and iron, in comparison with diets low or absent in vitamin A and low in iron, on the mRNA expression of some biomarkers of iron homeostasis as hepcidin (Hamp), transferrin receptor-1 (Tfrc), iron regulatory protein-2 (Ireb2) and ferritin (Fth1) in rats were investigated. 35 male Wistar rats were randomly divided into 5 dietary groups: control, sufficient in iron and insufficient in vitamin A (FesvAi), sufficient in iron and depleted in vitamin A (FesvAd), insufficient in iron and sufficient in vitamin A (FeivAs) and insufficient in both iron and vitamin A (FeivAi). After 6 weeks rats showed no significant effects of variations in vitamin A on the expression of Hamp relative to the control group (FesvAi: 1.37-fold; FesvAd: 1.22-fold); however, iron deficiency showed significant reduction on it relative to the control group (FeivAs: 71.4-fold, P = 0.0004; FeivAi: 16.1-fold, P = 0.0008). Vitamin A deficiency (FesvAd) affects expression of Fth1 independent of low dietary iron in spleen (0.29-fold, P = 0.002) and duodenum (5.15-fold, P = 0.02). Variations of dietary iron and vitamin A showed significant effects relative to the control group for expression of Tfrc in spleen (FesvAd: 0.18-fold, P = 0.01; FeivAs: 0.24-fold, P < 0.0001; FeivAi: 0.42-fold, P = 0.014), Ireb2 in spleen (FeivAs: 3.7-fold, P < 0.0001; FeivAi: 2.9-fold, P < 0.0001) and Ireb2 in duodenum (FeivAs: 2.68-fold, P = 0.012; FeivAi: 2.60-fold, P = 0.014). These results show that vitamin A and iron must be supplied together to regulate some of the main biomarkers of iron metabolism as a strategy to reduce prevalence of iron deficiency anemia.

Inter-Reader Consistency and Exclusionary Findings During Radiographic Screening for Phase 3 Trials of Tanezumab in Patients With Osteoarthritis.

Objective: Describe the radiograph-based screening program and frequencies of ineligibility in 3 large, international, randomized, double-blind, phase 3 studies of subcutaneous tanezumab in patients with osteoarthritis (OA). Design: Standardized bilateral shoulder, hip, and knee screening radiographs were obtained by trained imaging technologists and centrally read by 1 of 5 musculoskeletal radiology experts trained using a program-specific imaging atlas. Inter-reader consistency was tracked with test cases blindly inserted into the reader queue. Readers attended quarterly calibration meetings. Protocol-specified radiographic exclusion criteria included rapidly progressive OA (RPOA) or risk factors for RPOA (including severe malalignment of the knee, subchondral insufficiency fracture, atrophic OA, and osteonecrosis). Patients reporting disproportionate pain to radiographic evidence of OA in the hip or knee (without other pathology) were ineligible under a nonradiographic exclusion criterion. Results: At >480 international sites, 23,079 patients entered screening and 13,797 were radiographically assessed. Across 6 sets of quarterly testing, pairwise central reader agreement on radiographic eligibility was 72-87% (kappa: 0.41-0.71) and on radiographic OA grading 77-84% (kappa: 0.68-0.75). Among the 5,773/13,797 (41.8%) patients who met exclusionary criteria, 27% had disproportionate pain to radiographic findings (~10% of knee/hip radiographs). RPOA or risk factors for RPOA were each identified in <5% of patients (usually 1 joint) and <3% of knee/hip/shoulders. Conclusions: The phase 3 tanezumab screening program demonstrated the utility of radiographs to screen patients entering NGF inhibitor trials. A high degree of reader concordance was achieved. RPOA and risk factors for RPOA were not commonly observed. NCT02697773, NCT02709486, NCT02528188.

Classic and emergent indicators for the assessment of human iron status.

Iron deficiency is the leading cause of anemia, a significant global public health problem. Different methods exist for assessing iron nutritional status, including laboratory tests that focus on storage, transportation, and iron functional compartment parameters. Classical markers such as bone marrow, serum iron, ferritin, hemoglobin, erythrocyte parameters, transferrin, transferrin receptors, and zinc protoporphyrin are discussed in this review. Additional parameters calculated from these indicators, including transferrin saturation, ferritin index and Thomas plot, and some emergent parameters such as hepcidin, erythroferrone, and low hemoglobin density are also discussed. There is no a single indicator for assessing iron nutritional status. Therefore, the use of more than one indicator may be the best practice to obtain the correct diagnosis, also considering the influence of inflammation/infection on many of these indicators. The constant validation of the current parameters, the improvement of assessment methods, and the identification of new indicators will be the key to refine the assessment of iron nutritional status and the right choice of treatment for its improvement.

Expression of early angiogenesis indicators in mature versus immature teeth.

BACKGROUND: Proper oxygen balance in the dental pulp is essential for cell metabolism. Angiogenesis in the pulp is a constant process during the life of the tooth. Hypoxia indicators in a tissue, such as HIF-1α, as well as vascular destabilization markers, such as ANG2 and its receptor TIE2, are necessary for angiogenesis. Therefore the purpose of this study is to evaluate the expression of HIF-1α, ANG1, ANG2 and TIE2 in dental pulp as early angiogenesis indicators in teeth with complete and incomplete root development. METHODS: Forty human dental pulps were obtained from freshly extracted third molars divided into two groups: incomplete (n = 20) and complete (n = 20) root development. Dental pulps were stored at - 80 °C, defrosted in an ice bath and re-frozen with their respective thaws to disintegrate the tissue. Three sonication cycles were performed until the tissues were homogenized, then thaw were centrifuged and the supernatant was collected for the detection of the markers to be studied. The samples were processed for the ELISA test using the ELISA-sandwich principle. Student t and Mann-Whitney U tests were performed to determine statistically significant differences between groups. RESULTS: In the complete root development, HIF-1α, ANG1, ANG2 and TIE2 expressions were significantly higher than their expression in the incomplete root development group. CONCLUSIONS: The angiogenic process seems to be a physiological process in the dental pulp. Angiogenic activity is higher in teeth with mature than immature apex teeth.

Graphene-Capped Liquid Thin Films for Electrochemical Operando X-ray Spectroscopy and Scanning Electron Microscopy.

Electrochemistry is a promising building block for the global transition to a sustainable energy market. Particularly the electroreduction of CO2 and the electrolysis of water might be strategic elements for chemical energy conversion. The reactions of interest are inner-sphere reactions, which occur on the surface of the electrode, and the biased interface between the electrode surface and the electrolyte is of central importance to the reactivity of an electrode. However, a potential-dependent observation of this buried interface is challenging, which slows the development of catalyst materials. Here we describe a sample architecture using a graphene blanket that allows surface sensitive studies of biased electrochemical interfaces. At the examples of near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) and environmental scanning electron microscopy (ESEM), we show that the combination of a graphene blanket and a permeable membrane leads to the formation of a liquid thin film between them. This liquid thin film is stable against a water partial pressure below 1 mbar. These properties of the sample assembly extend the study of solid-liquid interfaces to highly surface sensitive techniques, such as electron spectroscopy/microscopy. In fact, photoelectrons with an effective attenuation length of only 10 Å can be detected, which is close to the absolute minimum possible in aqueous solutions. The in-situ cells and the sample preparation necessary to employ our method are comparatively simple. Transferring this approach to other surface sensitive measurement techniques should therefore be straightforward. We see our approach as a starting point for more studies on electrochemical interfaces and surface processes under applied potential. Such studies would be of high value for the rational design of electrocatalysts.

Influence of Polyol/Crosslinker Blend Composition on Phase Separation and Thermo-Mechanical Properties of Polyurethane Thin Films.

Polyurethanes (PUs) from Polyethylene glycol (PEG) and polycaprolactone diol (PCL) and a crosslinker, Pentaerythritol (PE), were synthetized with isophorone diisocyanate (IPDI). In this study, we investigated the effect of polyol and crosslinker composition on phase separation and thermo-mechanical properties. The properties were studied through dynamic mechanical analysis, X-ray scattering, atomic force microscopy (AFM), and thermogravimetric analysis (TGA). The results showed changes in PUs properties, microphase structure, and separation due to the composition of polyol/crosslinker blend. So, the largest concentration of PE produced multimodal loss factor patterns, indicating segment segregation while PUs with a PEG/PCL = 1 displayed a monomodal loss factor pattern, indicating a homogeneously distributed microphase separation. Additionally, the increase of the PEG concentration enhanced the damping capacity. On the other hand, agglomeration and thread-like structures of hard segments (HS) were observed through AFM. Finally, the thermal behavior of PUs was affected by chemical composition. Lower concentration of PE reduced the crosslinking; hence, the temperature with the maximum degradation rate.

Influence of Dietary Vitamin A and Iron Deficiency on Hematologic Parameters and Body Weight of Young Male Wistar Rats.

Micronutrient deficiency is one of the most prominent public health concerns; in particular, vitamin A and iron are determinants of appropriate development, and vitamin A influences iron homeostasis and metabolism. Here we compared the effects of diets that were sufficient and insufficient in vitamin A and iron on the hematologic parameters and body weight of rats. Male Wistar rats were randomly divided into 5 dietary groups (n = 7 per group): adequate in iron and vitamin A (control); adequate in iron but low in vitamin A (FesvAi); adequate in iron but lacking vitamin A (FesvAd); low in iron but adequate in vitamin A (FeivAs); and low in both iron and vitamin A (FeivAi). After 6 wk, rats showed significant differences in serum iron relative to the control diet (control, 256 ± 44 µg/dL; FesvAi, 220± 16 µg/dL; FesvAd, 181 ± 15 µg/dL; FeivAs, 131 ± 44 µg/dL; FeivAi, 75 ± 19 µg/dL). Rats on iron-deficient diets showed reduced Hgb values relative to the control diet (control, 15.9 ± 0.7 g/dL; FeivAs, 13.2 ± 1.6 g/dL; FeivAi, 12.9 ± 1.0 g/dL), MCV (control: 57 ± 10 fL; FeivAs, 48 ± 10 fL; FeivAi, 44 ± 3 fL), and Hct (control, 53% ± 2%; FeivAs, 44% ± 5%; FeivAi, 42% ± 8%). All of the experimental dietary groups showed significant differences in reticulocyte count when compared with the control group (control, 2.7% ± 2.2%; FesvAd, 0.6% ± 0.2%; FesvAi, 0.3% ± 0.1%; FeivAs, 1.2% ± 0.2%; FeivAi, 0.6% ± 0.5%). The mean difference in body weight for the experimental groups, relative to the control group, was 30 ± 10 g. These results suggested that, in young male Wistar rats, both iron and vitamin A are essential to cause increases in body weight and various hematologic parameters.

Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought?

Osteoarthritis (OA) of the hip and knee is among the most common joint disorders. Intra-articular corticosteroid (IACS) injections are frequently performed to treat OA and other joint-related pain syndromes; however, there is conflicting evidence on their potential benefit. There is a lack of prospective and large retrospective studies evaluating potential joint findings, including increased risk for accelerated OA progression or adverse joint events, after treatment with IACS injection. Four main adverse joint findings have been structurally observed in patients after IACS injections: accelerated OA progression, subchondral insufficiency fracture, complications of osteonecrosis, and rapid joint destruction, including bone loss. Physicians, including radiologists, should be familiar with imaging findings and patient characteristics that may help them identify potential joints at risk for such events. The purpose of this report is to review the existing literature, describe observed adverse joint events after IACS injections, and provide an outlook on how this may affect clinical practice. Additional research endeavors are urgently needed to better understand and identify risk factors prior to intervention and to detect adverse joint events after injection as early as possible to prevent or minimize complications.

Influence of side chain isomerism on the rigidity of poly(3-alkylthiophenes) in solutions revealed by neutron scattering.

Using small-angle neutron scattering, we conducted a detailed conformational study of poly(3-alkylthiophene) solutions in deuterated dichlorobenzene. The focus was placed on addressing the influence of the spatial arrangement of side chain constituents on backbone conformation. We demonstrate that by introducing a branch point in the side chain, side chain steric interactions may promote torsional motion between backbone units, resulting in greater chain flexibility. Our findings highlight the key role of topological isomerism in determining the chain rigidity and throw new light on the debate about the effective approaches for optimizing the electronic properties of conducting polymers via side chain engineering.

Candidate Polyurethanes Based on Castor Oil (Ricinus communis), with Polycaprolactone Diol and Chitosan Additions, for Use in Biomedical Applications.

Polyurethanes are widely used in the development of medical devices due to their biocompatibility, degradability, non-toxicity and chemical versatility. Polyurethanes were obtained from polyols derived from castor oil, and isophorone diisocyanate, with the incorporation of polycaprolactone-diol (15% w/w) and chitosan (3% w/w). The objective of this research was to evaluate the effect of the type of polyol and the incorporation of polycaprolactone-diol and chitosan on the mechanical and biological properties of the polyurethanes to identify the optimal ones for applications such as wound dressings or tissue engineering. Polyurethanes were characterized by stress-strain, contact angle by sessile drop method, thermogravimetric analysis, differential scanning calorimetry, water uptake and in vitro degradation by enzymatic processes. In vitro biological properties were evaluated by a 24 h cytotoxicity test using the colorimetric assay MTT and the LIVE/DEAD kit with cell line L-929 (mouse embryonic fibroblasts). In vitro evaluation of the possible inflammatory effect of polyurethane-based materials was evaluated by means of the expression of anti-inflammatory and proinflammatory cytokines expressed in a cellular model such as THP-1 cells by means of the MILLIPLEX® MAP kit. The modification of polyols derived from castor oil increases the mechanical properties of interest for a wide range of applications. The polyurethanes evaluated did not generate a cytotoxic effect on the evaluated cell line. The assessed polyurethanes are suggested as possible candidate biomaterials for wound dressings due to their improved mechanical properties and biocompatibility.

Local elasticity in nonlinear rheology of interacting colloidal glasses revealed by neutron scattering and rheometry.

The flow of colloidal suspensions is ubiquitous in nature and industry. Colloidal suspensions exhibit a wide range of rheological behavior, which should be closely related to the microscopic structure of the systems. With in situ small-angle neutron scattering complemented by rheological measurements, we investigated the deformation behavior of a charge-stabilized colloidal glass at particle level undergoing steady shear. A short-lived, localized elastic response at particle level, termed as the transient elasticity zone (TEZ), was identified from the neutron spectra. The existence of the TEZ, which could be promoted by the electrostatic interparticle potential, is a signature of deformation heterogeneity: the body of fluids under shear behaves like an elastic solid within the spatial range of the TEZ but like fluid outside the TEZ. The size of the TEZ shrinks as the shear rate increases in the shear thinning region, which shows that the shear thinning is accompanied by a diminishing deformation heterogeneity. More interestingly, the TEZ is found to be the structural unit that provides the resistance to the imposed shear, as evidenced by the quantitative agreement between the local elastic stress sustained by the TEZ and the macroscopic stress from rheological measurements at low and moderate shear rates. Our findings provide an understanding on the nonlinear rheology of interacting colloidal glasses from a micro-mechanical view.

Surface Response Methodology-Based Mixture Design to Study the Influence of Polyol Blend Composition on Polyurethanes' Properties.

Polyurethanes are materials with a strong structure-property relationship. The goal of this research was to study the effect of a polyol blend composition of polyurethanes on its properties using a mixture design and setting mathematic models for each property. Water absorption, hydrolytic degradation, contact angle, tensile strength hardness and modulus were studied. Additionally, thermal stability was studied by thermogravimetric analysis. Area under the curve was used to evaluate the effect of polyol blend composition on thermal stability and kinetics of water absorption and hydrolytic degradation. Least squares were used to calculate the regression coefficients. Models for the properties were significant, and lack of fit was not (p < 0.05). Fit statistics suggest both good fitting and prediction. Water absorption, hydrolytic degradation and contact angle were mediated by the hydrophilic nature of the polyols. Tensile strength, modulus and hardness could be regulated by the PE content and the characteristics of polyols. Regression of DTG curves from thermal analysis showed improvement of thermal stability with the increase of PCL and PE. An ANOVA test of the model terms demonstrated that three component influences on bulk properties like water absorption, hydrolytic degradation, hardness, tensile strength and modulus. The PEG*PCL interaction influences on the contact angle, which is a surface property. Mixture design application allowed for an understanding of the structure-property relationship through mathematic models.