Porosity defects are still a challenging issue in the fusion welding of molybdenum and its alloys due to the pre-existing interior defects associated with the powder metallurgy process. Fiber laser welding of end plug and cladding tube made of nanostructured high-strength molybdenum (NS-Mo) alloy was performed in this work with an emphasis on the role of welding heat input. The distribution and morphology of porosity defects in the welded joints were examined by computed tomography (CT) and scanning electron microscopy (SEM). Preliminary results showed that laser welding of NS-Mo under low heat input significantly reduced the porosity defects in the fusion zone. The results of computed tomography (CT) showed that when the welding heat input decreased from 3600 J/cm  to 250 J/cm , the porosity ratio of the NS-Mo joints declined from 10.7% to 2.1%. Notable porosity defects under high heat input were related to the instability of the keyhole, expansion and the merging of bubbles in the molten pool, among which the instability of the keyhole played the dominant role. The porous defects at low heat input were generated as bubbles released from the powder metallurgy base metal (BM) did not have enough time to overflow and escape. Due to its high fusion point, excellent mechanical properties and low neutron absorption cross-section ,2,3, nanWelding methods for Mo alloys include brazing ,12, elecAn et al.  investigIn this work, fiber laser welding of end plug and cladding tube made of NS-Mo alloys was carried out with an emphasis on the role of welding heat input. The NS-Mo alloy cladding tubes and end plugs for nuclear applications are prepared by powder metallurgy and hot rolling. The morphologies of welded seams, and porosity defects of the joints between NS-Mo alloy cladding tubes and end plugs prepared using laser welding under quite different heat inputs (i.e. 3600 J/cm and 250 J/cm) were investigated and compared.2O3 particles dispersed in the substrate. Micro pores are an inevitable problem for powder metallurgy material, as shown in The experimental material NS-Mo consists of a Mo metal substrate with 0.5 wt% nano-sized La3, and 30 mL of H2O. Next, the cross-sectional morphologies of the welded joints were observed using a Nikon Eclipse MA200 optical microscope . The porosity morphologies were observed by using an FESEM-SU6600 scanning electron microscope .After welding, the porosity defects in the welded seams were detected using a Y.CT Modular-YXLON industrial computed tomography (CT) system. The CT results were analyzed using the Mimics Medical software. Then, metallographic specimens of the welded joints were prepared using a standard metallographic method and etched with an etchant consisting of 10 mL of HF, 10 mL of HNOWelding tests were carried out according to the parameters listed in For convenience of discussing, the circumference of the welded seam is demonstrated in 2 and 1.76 mm2, respectively. As the welding speed of Joint 2 was much lower than that of Joint 1, the length of the molten pool of Joint 2 would be much larger than that of Joint 1. Therefore, the volume of the molten pool of Joint 2 would be much larger than that of Joint 1, leading to more liquid metal surrounding the keyhole and poor stability of the keyhole in the laser welding process of Joint 2. Moreover, the shape and the dynamic behavior of the keyhole are highly dependent on the welding speed during laser welding. Under low heat input and high welding speed, the inclination angle of the front keyhole wall increased significantly. In this case, the laser beam reflected more times on the upper part of the keyhole surface and went through a longer path before reaching the lower part of the keyhole, which was favorable for keeping the upper part of the keyhole open and avoiding excessive concentration of laser energy at the bottom of the keyhole, as shown in The cross-section areas of FZ in Joints 1 and 2  were aboIn P and V refer to the total volume of pores in a weld seam and the total volume of the corresponding weld seam zone, respectively. Then, it was calculated that WP of Joint 1 and Joint 2 were 2.1% and 10.7%, respectively.Results of the Computed Tomography (CT) test indicated that welding heat input had significant impact on the number and the size of the porosity defects in fusion welding joints of NS-Mo. Results of the SEM test also indicated that the welding heat input had significant impact on the shape of the porous defects in the joints of NS-Mo. As shown in Several studies on EBW of powder metallurgy Mo alloy demonstrated that micropores could significantly aggravate the porosity defects of the welded joint ,36. High1, ρ2, g, R and η refer to the floating speed of bubbles, the density  of Mo molten metal, the density of gas in bubbles, gravitational acceleration , the radius of bubbles, and the viscosity  of the molten Mo alloy, respectively [Analyzing the behavior of bubble overflow from the molten pool exerts significance on developing effective measures of reducing or eliminating porous defects. In practice, among current measures for controlling porous defects in the fusion welding process, the majority of measures are expected to inhibit porous defects by promoting the escape of bubbles from the molten pool. The sizes of the bubbles and the molten pool are two important factors influencing the time required for the overflow of bubbles from the molten pool. In general, the larger the size of bubbles, the larger is the buoyancy of the bubbles in the molten pool, so the speed of flotation of the bubbles increases and therefore the time required for the bubbles to escape from the molten pool declines. The larger the depth of the molten pool, the longer is the time required for bubbles at the bottom of molten pool to escape. A longer length of molten pool is advantageous for the bubbles to escape from the molten pool. Additionally, the bubbles in the interior of the molten pool require a shorter time to float and overflow from the molten pool, while those in the mushy zone around the solid/liquid interface need a longer time to float and escape from the molten pool owing to being hindered . The floectively . Accordi1 and R2 denote the radii of bubbles before and after volume expansion, while P1 and P2  represent the pressures before and after the volume expansion of bubbles in the base metal, respectively. Moreover, T1 and T2 separately refer to ambient temperature (298 K) and the temperature of the molten pool . It was assumed that the gas pressure and diameter of micropores in the BMs were 10 MPa and 10 μm, respectively. Therefore, according to Equation (3), it can be deduced that a large-size bubble with a diameter of about 99 μm would be formed after expansion of the high-pressure bubbles.It can be speculated from According to the results shown in (1)Laser welding of an NS-Mo alloy under a low heat input resulted in less spatters, and a smooth weld surface. In contrast, a large amount of spatter was observed for samples prepared with a high heat input.(2)When the welding heat input decreased from 3600 J/cm to 250 J/cm, the porosity ratio of the NS-Mo joints declined from 10.7% to 2.1%.(3)Notable irregularly-shaped porosities formed under a high welding heat input were mainly related to the instability of the keyhole, while the spherical defects formed at a low welding heat input were due to the fact that bubbles released from the powder metallurgy BM did not have enough time to escape.Fiber laser welding tests of the end plug and cladding tube made of powder metallurgy NS-Mo alloy were carried out and the welding heat inputs were taken as 250 J/cm and 3600 J/cm, respectively. The effects of the welding heat input on porosity defects in the fiber laser welding of powder metallurgy NS-Mo alloy was discussed. The main conclusions were as follows:As a recommendation, the authors would like to suggest employing low heat input combined with high welding speed in the fiber laser welding of molybdenum alloy, and suggest strict control of compactness and purity of the powder metallurgy base metal to be welded.


Plant cell walls are layered nanostructures that exhibit gradients of stiffness and tensile stress across their layers. The gradients are crucial for the regulation of cell wall growth and plant morphogenesis. in situ. This waviness is a manifestation of buckling that results from the heterogeneity of the elastic strain across the wall. In this study, this heterogeneity was confirmed by the spontaneous bending of isolated wall fragments that were initially flat. We combined the empirical data on the formation of waviness in growing cell walls with computations of the buckled wall shapes. We chose cylindrical-shaped organs with a high degree of longitudinal tissue stress because in such organs the surface deformation that accompanies the removal of the stress is strongly anisotropic and leads to the formation of waviness in which wrinkles on the inner wall surface are always transverse to the organ axis. The computations showed that the strain heterogeneity results from individual or overlaid gradients of pre-stress and stiffness across the wall. The computed wall shapes depend on the assumed wall thickness and mechanical gradients. Thus, a quantitative analysis of the wall waviness that forms after stress removal can be used to assess the mechanical heterogeneity of the cell wall.The relatively thick primary walls of epidermal and collenchyma cells often form waviness on the surface that faces the protoplast when they are released from the tensile in-plane stress that operates  Although tissue isolation does not affect turgor-driven stress, this stress can be removed by plasmolysis. The tensile in-plane stress in cell walls is necessary for growth, the irreversible deformation of the cell wall : the cell walls are like the walls of a pressurized vessel. An additional source of stress in cell walls are tissue stresses, sometimes referred to as tissue tension. Their origin, either from differential growth or from non-uniform structural and mechanical properties, is still under debate . Neverthell wall , and is ell wall . Therefoell wall .It has been shown that the removal of tensile stress (both tissue and turgor-driven) from the relatively thick primary cell walls leads to the formation of waviness of the wall layers that face the protoplast in the epidermis and collenchyma of growing plant organs such as coleoptiles or hypocotyls . The posin situ; the innermost layer, being the youngest one, is the least stressed, while in the deeper layers the stress increases with the distance from the youngest layer. However, these authors provided only limited support for their postulate. First, they did not verify the existence of elastic strain heterogeneity of the wall layers. Second, they did not consider the effect that heterogeneity in wall stiffness may have on buckling. Moreover, the calculations that they presented in support of their postulate involved simplified equations to describe the buckling of a structure composed of a thin, stiff film attached to a thick substrate of a much lower stiffness , etiolated hypocotyls of sunflower (Helianthus annuus cv. ‘Lech’), and etiolated coleoptiles of barley (Hordeum vulgare cv. ‘Stratus’). The dandelion plants were collected from pastures near Bielsko-Biała, southern Poland. The sunflower and barley plants were grown in a chamber. Sunflower achenes and barley caryopses were surface sterilized by immersion in 1% sodium hypochlorite for 20 min and then rinsed in tap water. After germinating on wet blotting paper for 24 h, the diaspores were transferred to plastic containers filled with moist vermiculite and grown in darkness at room temperature (23 °C). The sunflower hypocotyls were collected after 5 d when they were ~60–70 mm long; barley coleoptiles 40 mm long were collected after 4 d.The experiments were performed on the elongating peduncles of blooming inflorescences of dandelion , which contained at least one layer of cortical cells in addition to the epidermis, were immersed in a solution of 300 mM mannitol or 170 mM NaCl for 15–20 min, which caused incipient plasmolysis (to remove the turgor-driven stress). A microscope (Nikon Eclipse 80i) equipped with a Nomarski interference contrast system was used to examine the samples.4 for 2 h, rinsed in water, and dehydrated in a graded ethanol series. After dehydration, the samples were embedded in Epon resin. Ultrathin longitudinal–radial sections , 90 nm thick, were mounted on copper grids (200 mesh), double-stained with uranyl acetate and lead citrate, and examined by TEM (Hitachi H500).For transmission electron microscopy (TEM), epidermal strips with a circumferential length of ~4 mm and a width of 2 mm were peeled in the circumferential direction from the same hypocotyl, coleoptile, or peduncle regions as the strips that were used for Nomarski microscopy. A solution of 300 mM mannitol in 50 mM phosphate buffer (pH 7) was applied for 15 min to plasmolyse the samples. The samples were then immersed in fixative solution  for 3 h, buffered in 300 mM mannitol in 50 mM phosphate buffer (pH 7) post-fixed with 1% OsODeformation of an outer periclinal cell wall, which occurs due to the removal of stress by the isolation of a wall fragment, was examined in the etiolated hypocotyls of 4–5-d-old sunflower seedlings. First, a 3 mm thick disc  was excised from a hypocotyl ~10 mm below the cotyledons and immersed in one of three media: deionized water (hypotonic solution); 119 mM NaCl ; or 170 mM NaCl (hypertonic solution). A strip was peeled from the disc immersed in the solution, in the circumferential direction. The strip, containing the epidermis and a single layer of the underlying parenchyma, was placed on a glass slide (with the epidermis facing the glass), one of its ends was immobilized using forceps, and the parenchyma together with the inner periclinal walls of some of the epidermal cells were removed with a razor blade. The epidermal fragment, including the exposed outer periclinal walls, was cut into longitudinal sections  using a razor blade. The sections were observed in a drop of the respective solution under a microscope (Nikon Eclipse 80i) in the longitudinal–radial plane, that is, the same plane as the ultrathin sections.A) were assessed as the means of 4–20 measurements . From each micrograph, the wavelength (λ) and amplitude (urements . The tothttps://imagej.nih.gov/ij/). These data were used to calculate the turgor-driven stress in the wall plane.For the sunflower epidermis, various cellular parameters  were addin situ and from strips isolated and plasmolysed in 170 mM NaCl solution for 10–15 min. Casts obtained by filling the moulds with epoxy resin were sputter-coated and observed under a scanning electron microscope . Two images were obtained for each examined replica as a stereopair, tilted by 10º with respect to each other.For the sunflower hypocotyls and barley coleoptiles, changes in the shape of the epidermal surface due to the removal of stress were examined using the sequential replica method . Two repDeformation due to stress removal was assessed for 11 sunflower epidermal strips, 15 barley strips, and 27 dandelion strips. To assess the strain in the longitudinal direction, the apical and basal edges of the epidermal portion that was to be peeled were labelled with dots 4.8–5.2 mm apart, using a waterproof marker, and photographed under a stereoscopic microscope (Nikon SMZ288). Next, the strip was peeled, plasmolysed as described above, and photographed again. To assess the strain in the transverse direction, two dots were marked along the organ circumference at a close distance (0.5–0.7 mm) in order to avoid measurement bias due to surface curvature . The relative strain (shrinkage) in a given direction was computed as Lk was the distance between the dots in situ and Lp was the distance after the stress removal.where The epidermal cell surface was reconstructed using the stereoscopic reconstruction protocol based on the stereopairs of SEM images . A netwoAll of the codes were written in Matlab . Statistical analysis, image processing, and artwork preparation were performed using Matlab, Adobe Design Premium CS4  or CorelDRAW X6 (Corel Corp.).in situ  as 3.7 MPa and in the transverse direction (σtT) as 5.2 MPa  and the minimum in the transverse direction (σT≈5 MPa). The examined epidermal or collenchyma cells of the dandelion and barley plants studied were elongated, similar to the epidermal cells of sunflower, and are also under tensile longitudinal tissue stress in situ , while in barley, the change in the maximal cell curvature was less pronounced , where A is the amplitude, x and y are coordinates in the XY system, where the X and Y axes are, respectively, in the directions L and W in The shape of the wavy wall surface resembled a cosine curve. Thus, we assumed that the mathematical function describing the waviness is velength , and x aL shown in W in A gradient of the elastic strain . The straight wall portion was represented by plate 3. The outward gradient of the shrinkage of the wall layers after stress removal (i.e. layer shrinkage increasing with the distance from the protoplast) was represented by differences in the elastic strain of plates, that is, their shrinkage in the longitudinal direction . Third, when analysing the deformation of the elastic medium we ignored shear. This assumption did not affect the general trend but led to underestimation of the energy of the medium deformation  an outward pre-stress (σ) gradient (σ1 < σ2 < σ3); (ii) an inward modulus (E) gradient (E1 > E2 > E3), or (iii) two opposite gradients overlaid (σ1 < σ2 < σ3) and the modulus (E1 < E2 < E3). In order to represent these four gradient combinations, we assigned various moduli and pre-stress values to each plate  that would occur when the stress was removed and selected the cases with the outward strain gradient (ε1 < ε2 < ε3) for further consideration.Heterogeneity in the elastic strain of layered structures can result from a gradient of the Young’s modulus or the opposite gradient of pre-stress , the latoverlaid . Additioch plate . With th1,2,3), we then computed the lengths of plates 1 and 2 after stress removal. Then, assuming λ and knowing the lengths of all of the plates, we used a numerical method to compute the amplitudes of buckling plates 1 and 2 , searching for the length of the cosine function, which described the plate shape, that would fit the plate length. It should be noted that the lengths of the buckling plates were fixed and thus the amplitudes for various wavelengths differed. Second, for each set of λ, A1, and A2, we considered two energy components, one that was required to bend the plate (bending energy) and the other that was required to increase the distance between the plates .Next, for each assumed set of the plate modulus and the pre-stress, we searched for the shapes of plates 1 and 2 that required the minimum energy necessary for deformation to occur due to the formation of waviness , Fig. S2L in In order to compute the bending energy component, we considered portions of a plate equal to one-quarter of the wavelength . Becauseh1-2 and h2-3 in Ew) and the increase in volume , higher values of which correspond to more flattened waviness  or 0.04 (steep outward gradient). The modulus ratio, E1/E3, changed from 0.2 to 1 with decreasing steepness of the outward modulus gradient, and from 1 to 4 with increasing steepness of the inward gradient  increased non-linearly with the difference between the shrinkage of plates 3 and 1, in situ was manifested by high amplitudes of the wavy wall layers after stress removal.The steepness of the strain gradient modulated the waviness by affecting the amplitude of the buckled plates—the amplitude of plate 1 . Lower amplitudes : the thicker the plates, the bigger the wavelength (Ew); for a lower Ew the wavelength decreased , which attained higher values for a similar waviness of these plates . The lowest A2/A1, that is, the most different shapes of plates 1 and 2, was for the aligned gradients of the pre-stress and the modulus (green in A2/A1 is expected) was the effect of the boundary conditions of the plate shrinkage. The highest A2/A1 was generated by the least steep inward modulus gradient (black in E1/E3 close to 1). When the steepness of this gradient increased (higher E1/E3), A2/A1 gradually converged with the A2/A1 that had been generated by the overlaid opposite gradients of the modulus and pre-stress (red in A2/A1 is an emerging property of the mechanical heterogeneity of a cell wall that results from the interplay between the pre-stress and modulus gradients and the boundary conditions of the plate shrinkage.Ideally, the analysis of waviness of a cell wall should help to identify the mechanical gradient that existed in the wall prior to buckling. Indeed, the effect that the gradient combination had on the shape of the plates was differentiated by the ratio of the amplitudes of buckled plates 2 and 1 (e plates . As longe plates  or overlgreen in . This cos red in . Thus, tin situ by analysing changes in the amplitude across the cell wall layers. The amplitude of the layer that was located at one-quarter of the thickness of the wavy wall portion divided by the maximal amplitude corresponded to A2/A1. Thus, in the cell walls examined (We next attempted to infer which mechanical gradients were in the wall examined , B with examined .Cell wall stress, especially its anisotropy, affects the arrangement of the cortical microtubules and thus contributes to the well-documented growth regulation feedback . The outHere, we demonstrate that in the growing cell walls of both dicots and grasses, which differ profoundly in the composition of their wall matrix , wavinesOur computations imply that waviness similar to that of the growing cell wall is generated by the outward pre-stress gradient, alone or overlaid by outward or inward stiffness gradients. The outward gradients of pre-stress and stiffness are expected in growing walls, but the occurrence of the inward stiffness gradient, in which the youngest wall layers are the stiffest, is disputable. The wall stiffness depends on a strain stiffening effect that may occur during wall deformation . In the Cucumis sativus hypocotyl (Buckling occurs when the threshold of compressive force is surpassed. The cell wall layers most likely shrink to some extent under compression before buckling. This explains why the extent of layer shrinkage that was assessed from the TEM micrographs was lower than the longitudinal shrinkage of the epidermal strips in all of the examined tissues. However, because the compression threshold of the primary cell wall layers is unknown, in our computations we assumed that the plates buckle as soon as the compression occurs. Nevertheless, the heterogeneity of the compression threshold across the wall likely influences the formation of wall waviness and may explain why the relatively thick inner portions of the examined walls, which comprised numerous wall layers, formed waviness of similar amplitudes. In a growing cell, new wall layers are not expected to be under tension because of the mode in which the new wall material, especially the cellulose microfibrils, is deposited. Rather, the tensile in-plane stress and the related elastic strain increase with the age of a layer up to a certain maximal value—that is, the further the layer is from the protoplast, the more it is stretched. The reason why numerous inner wall layers form similar waviness despite the expected stress gradient may be that they differ in their compression threshold, and therefore prior to buckling the inner layers shrink more under compression than the slightly older ones. In composite materials or nanostructures such as cell walls . In partin situ. The strain heterogeneity of the cell walls results from the outward gradient of pre-stress, which is likely accompanied by the Young’s modulus gradient in the same direction. Such a heterogeneous pre-stress may have significant implications for our understanding of the involvement of cell wall mechanics in regulating growth.In conclusion, our experiments and computations prove the existence of an elastic strain gradient across the wall layers, with the youngest layers being the least stretched. This gradient is likely related to the deposition history of the wall layers and their modification after deposition. We show that a quantitative analysis of the wall waviness that arises after stress removal can be used to assess the mechanical heterogeneity of a wall JXB online.Supplementary data are available at Protocol S1. Estimation of turgor-driven in-plane wall stress.Protocol S2 Specification of parameters used to compute the energy.Protocol S3. Protocols used to compute the minimum energy configurations of plates.Protocol S4. Comparison of models of buckling structures and computation protocol dedicated to cell walls.Table S1. Wavelengths of buckled surfaces computed with the same assumptions using the computation protocol dedicated to cell walls and models on buckling of the layered structure.Fig. S1. Changes in cell curvature of the outer periclinal cell walls of epidermis of barley coleoptile due to stress removal.Fig. S2. Estimation of plate deformation during buckling.Fig. S3. Minimum energy configurations of plate 1 computed for different mechanical parameters.Fig. S4. Response of buckled plate shapes to plate mechanicsSupplementary Protocols and TableClick here for additional data file.Supplementary FiguresClick here for additional data file.


A set of 312 molecules have been used to build the model for the CB1 receptor, and a set of 187 molecules for the CB2 receptor. All of the molecules were recovered from the literature among those possessing measured Ki values, and Forge was used as software. The present model shows high and robust predictive potential, confirmed by the quality of the statistical analysis, and an adequate descriptive capability. A visual understanding of the hydrophobic, electrostatic, and shaping features highlighting the principal interactions for the CB1 and CB2 ligands was achieved with the construction of 3D maps. The predictive capabilities of the model were then used for a scaffold-hopping study of two selected compounds, with the generation of a library of new compounds with high affinity for the two receptors. Herein, we report two new 3D-QSAR models that comprehend a large number of chemically different CB1 and CB2 ligands and well account for the individual ligand affinities. These features will facilitate the recognition of new potent and selective molecules for CB1 and CB2 receptors.Two 3D quantitative structure–activity relationships (3D-QSAR) models for predicting Cannabinoid receptor 1 and 2 (CB In. In1 rec of 0.72 . An adeq1 and CB2 receptors. The model overviews show the areas where the QSAR model indicates that the molecular fields have a strong impact on ligand–receptor affinity. The larger the points (depicted as octahedrons), the stronger the correlation between the fields is (electrostatic and steric) in that position. The higher affinity related to the electrostatic potential is depicted in red for the positive values and in blue for the negative ones. For the steric bulk, the green area leads to higher receptor affinity, whereas the violet area leads to lower affinity.The 3D visualizations of the QSAR models are shown in 1 and CB2 receptor, respectively. The model map is superimposed to the two most selective CB1 and CB2 receptor ligands, AM-1220 and XLR-12, respectively. The different colors on the maps derived from the AA calculations highlight electrostatic, hydrophobic, and shape features of the different set of compounds. A more positive electrostatic field increases the receptor-affinity in the red region, whereas in the blue area, a more negative electrostatic field increases the affinity. The green and the violet areas account for the steric and bulk/hydrophobic interactions. In the green area, a steric/bulk interaction improves the binding affinity; in the violet area, a steric/bulk interaction decreases the affinity. The two selected molecules (AM-1220 and XLR-12) can be dissected in three different regions: (i) the substituent at the N1 position of the heterocyclic nucleus; (ii) the substituent at the 3-position of the heterocyclic nucleus; (iii) the central core. Such molecular features are typically described nowadays to distinguish most of the novel and emerging synthetic cannabinoids [1 or CB2 affinity/selectivity. Regarding the substitution of the N1 position, both models describe a wide favorable hydrophobic interaction area and in both models a negative electrostatic area is located at the end of the alkyl chain, suggesting that the introduction of electronegative atoms increases the affinity for both CB receptors. The occupancy of this area is fundamental for the affinity in both receptors; indeed, ligands that do not bear any substituent in this area result in low potency . On the other hand, this molecular portion appears to be linked with selectivity towards the CB1 receptor. A positive electrostatic region surrounds the initial part of that area, and a favorable interaction seems to be relevant for the selectivity toward the CB1 receptor . The same positive electrostatic area in the CB2 model doesn’t have any relevant interaction with potent and/or selective compounds for that receptor. For both models, there is not a strong SAR in the central core region, but a small favorable shape/hydrophobic region (green) is located near the positions 5 and 6 of the indole ring for the CB2 receptor, which means that small substituents in this region may increase the selectivity. The 2-position of the heterocyclic nucleus is located near an area in which the hydrophobic interactions are unfavorable. This area is larger for the CB1 model. Thus, in this case, the introduction of a small substituent may be better tolerated by the CB2 receptor. In the 3-position of the heterocyclic nucleus, the two models clearly describe different scenarios. For the CB1 receptor, the substituent in this branch is located within an unfavorable hydrophobic region; for the CB2 receptor, the situation is the opposite. This means that bulkier and hydrophobic substituents will raise the selectivity for the CB2 receptor and small/hydrophilic substituent will raise the selectivity toward the CB1 receptor. Furthermore, the same region in the CB2 model is contoured by a bigger negative electrostatic area, which means that the adding of an electronegative atom should increase the CB2 affinity. Also, it is interesting to note the different distribution of the 3D maps, among the two models, in the areas around the oxygen of the carbonyl group. In the CB1 model the oxygen is located near an area in which positive electrostatic coefficients will raise the affinity; this means that the oxygen atom in that position bears an unfavorable electrostatic contribution to the resultant ligand-receptor affinity. Conversely, the same oxygen in the CB2 model is located in an area where the negative electrostatic coefficient raises the potency; in fact, a relevant favorable electrostatic contribution is described by the model for the oxygen atom of the carbonyl group. Therefore, despite the carbonyl group present in most compounds designed as a CB1 ligand, the selection of a different connecting group might be exploited to improve the affinity for the CB1 receptor.To reveal the key features of the studied set of compounds against the targeted cannabinoid receptors, activity-atlas (AA) was used to perform a structure–activity relationship (SAR) study. AA is a visualization software implemented in Forge that is able to summarize structure–activity data into 3D maps in a qualitative manner through a Bayesian statistics approach. 1/CB2 predicted pKi, are reported in 1 and the CB2 receptors. All the nine groups of the virtually evaluated compounds resulted in a series of molecules more potent than their precursors. The most interesting results for the CB1 receptor were achieved from the molecules belonging to the series 3  of 154.5 compared to an index of 18.8 for the original AM-1220 ligand . The increase in selectivity has been achieved with a simple substitution of the group in 3-position to the central core. Further work around this area may provide additional molecular features to further increase selectivity for the CB1 receptor using scaffolds that have not been used yet. Interestingly, none of the compounds derived from the scaffold-hopping of XLR-12 . Considering that the most selective molecule for CB2 receptor in our dataset has a selectivity index of 0.019, we can consider our results promising, and we can conclude that maintaining the central core unchanged, a large increase in the selectivity can be achieved by an appropriate substitution of the substituent at the N1 and at the 3-position of the heterocyclic nucleus.On the other hand, in the case of the molecules virtually evaluated for the CB 4 and 6 . The two1 receptor ligands, and of the 187 CB2 receptor ligands were selected from the literature that reports the experimental Ki values, primarily involving assays where isolated CB1 and/or CB2 receptors were incubated with a predetermined fixed concentration of radiolabeled cannabinoid  [Ki (pKi = −logKi). Collected pKi values fall into a range 5.00–10.03 and 5.00–9.92 for the CB1 and CB2 receptors, respectively.The chemical structures of the 312 CB 55,490) ,43,56,57The structures of the studied molecules were built using Marvin Sketch  . The 2D Ki values, were imported into the chemistry software Forge . Out of the 312 ligands for the CB1 receptor, 250 molecules (80%) were randomly selected as a training set. The remaining 62 compounds (20%) were used as test set for the model quality evaluation. For the CB2 receptor, we used the same procedure: selecting 150 ligands (80%) as training set and 37 compounds (20%) as test set [All the 3D molecules, with their experimentally measured ptest set . The fietest set . Five hu1 and CB2 receptors , and were the largest group of NPS [Two 3D-QSAR models for CBp of NPS ), and anp of NPS ,73, the


To study and evaluate the adhesion between recycled concrete aggregate and asphalt, the contact angles (CAs) between droplet (water and ethanol) and recycled concrete aggregate (RCA), natural aggregates, and solid bitumen  were tested via the sessile drop method with an optical microscope. The surface free energy was then calculated. The CAs between hot asphalt and RCA and natural aggregates were tested via the hanging slice method. The adhesive energy between asphalt and RCA and natural aggregates were calculated based on the test results of the surface free energy and CAs. Then, the influence of RCA on the water stability and fatigue performance of the asphalt mixture was analyzed by testing the water stability and fatigue properties of hot mix asphalts containing RCA (HMA-RCA) with different aggregates and RCA dosages. The surface energy of the various aggregates and the CAs between aggregates and asphalts were sorted as follows: Granite > RCA > serpentinite > limestone. The surface energy and CA of RCA were very close to that of serpentinite. The adhesive energy between various aggregates and asphalt were sorted as follows: Limestone > serpentinite > RCA > granite. The adhesive energy between RCA and asphalt was also very close to that of serpentinite. The residual Marshall stability, tensile strength ratio, and fatigue performance of the HMA-RCAs were gradually reduced along with the increasing RCA dosage. This effect may be attributed to the fact that the adhesive energy between the RCA and the asphalt was less than that of water and that the asphalt was easily stripped from the RCA surface. Excessive RCA content in the aggregate can lead to excessive porosity of the HMA-RCA. The CAs and adhesive energy between RCA and asphalt showed significant effects on the water stability and fatigue performance of HMA-RCA. Given the constant development of human production activities, the contradiction between the supply and demand of high-quality gravels that are used in pavements becomes increasingly prominent, and the price of such products continues to increase. In addition, the construction and demolition of buildings, as well as the construction and renovation of cement concrete or asphalt concrete pavement, produce up to 600 million tons of solid wastes each year, thereby leading to a series of environmental and social problems. Therefore, recycling solid waste not only alleviates the shortage of natural aggregates, but also solves the problem of processing construction waste . RecyclexCaO·SiO2·yH2O), ettringite (3CaO·Al2O3·CaSO4·32H2O), single-sulfur type of calcium sulfoaluminate (3CaO·Al2O3·CaSO4·12H2O), and Ca(OH)2. These components have a certain activity that can lead to feeble chemical reactions with acid asphalt. The adhesion between RCA and asphalt is affected by chemical reactions. Moreover, the surface of RCA is rougher than that of natural gravels because of many micro cracks and voids. Therefore, the adhesion between RCA and asphalt demonstrates a unique behavior that complicates the relationship between the road performance of hot mix asphalt containing RCA (HMA-RCA) and the dosage of RCA. Moreover, the road performance of HMA-RCA cannot satisfy the required technical specifications. Therefore, revealing the micro-mechanism and influencing factors of the adhesion between RCA and asphalt serves as a theoretical basis for optimizing the design of HMA-RCA. The properties of asphalt mixture are closely related to the performance and adhesion between aggregate and asphalt. Loss of adhesion is caused by the breaking of adhesive bonds between the aggregate surface and the asphalt binder primarily because of the coupled action of water and load. Therefore, loss of adhesion leads to several distresses in the asphalt pavement, such as water damage and fatigue damage. Previous studies ,6 have sThe recycling of recycled aggregates in asphalt mixtures has attracted research attention in recent years. Existing studies mainly focus on the road performance of HMA-RCAs, including their Marshall and volume indices, water stability, permanent deformation, and fatigue performance. At the same time, some studies have evaluated the performance of HMA-RCAs from a microscopic perspective ,8. NumerMany studies have shown that the asphalt content of HMA-RCAs is higher than that of natural gravels due to a large amount of asphalt absorbed by the pores and micro cracks of RCAs, and it increases along with the increasing of RCA dosage ,10,11,12Water stability is caused by the stripping of asphalt from the aggregate surface because of the coupled actions of water and load. The water stability of HMA-RCA varies with RCA content, and the law behind such variation is very complicated. Some studies show that RCA can improve the water stability of HMA-RCA and that the water stability of HMA-RCA increases along with increasing RCA dosage ,20,21,22In terms of resistance to permanent deformation and modulus, some studies suggest that HMA-RCA is more capable of resisting permanent deformation, meeting specification requirements ,26,27,28The fatigue properties of HMA-RCA are identical to those of traditional HMA ,20,25, aFew studies have investigated the micro structure of RCA and the adhesion properties between RCA and asphalt. Hou et al.  studied In other words, the adhesive mechanism and its influencing factors must be determined to improve the road performance of HMA-RCA. In this study, the contact angles (CAs) among droplets (water and ethanol), RCA, several natural aggregates, and solid bitumen -modified asphalt) were tested using the sessile drop method. The surface free energy was then calculated. The CAs among hot asphalt, RCA, and natural aggregates were tested using the hanging slice method. The adhesive energy among the asphalt, RCA, and natural aggregates were calculated based on the test results of the surface free energy and CAs. HMA-RCAs with RCA dosages of 0%, 30%, 60%, and 100% were designed, and the water stability and fatigue performance of these HMA-RCAs were tested. The effects of the adhesive on the water stability and fatigue performance were then analyzed.The 70# matrix asphalt and SBS modified asphalt were used in experiments, and the technique performances were tested and shown in Waste cement concrete was directly collected from a bridge demolishing spot and then crushed and sorted to obtain RCA. The performance of RCAs was tested and shown in Water and ethyl alcohol were used in the CAs tests with aggregates and solid asphalts, and the parameters are shown in Four HMAs were designed to investigate the water stability of the mixture. The aggregate used in the asphalt mixture was RCA and limestone, and the content of RCA in the aggregate was 0%, 30%, 60%, and 100%, respectively, which were marked as M1, M2, M3, and M4. To determine the optimal asphalt content of the above HMAs, the bulk relative density, Marshall stability and flow value, air voids, voids in mineral aggregate, and voids filled with asphalt were measured according to the Chinese Specification of JTG F40-2004  . The resThe CA is an important index that indicates the wetting ability of a liquid to solid. On the junction of the three phases of gas, liquid, and solid, the tangent lines of the interface between gas and liquid and those of the interface between solid and liquid can be obtained. The CA refers to the angle between two tangent lines through the liquid internal part. The smaller the CA is, the greater the wetting ability of the liquid to solid is. The CA between the asphalt and aggregate indirectly reflects the adhesion in the asphalt mixture, which is a basic parameter for calculating the adhesive energy.This study used an optical CA measuring device that included a host computer, dosage controlling unit, an injecting unit, and a specific analysis software. The device is shown in An aggregate is usually a particulate and lacks a flat surface, which greatly influences the measurement of surface energy parameters. To improve the accuracy, stones with the same materials as those of the aggregates were polished using a metallographic polishing machine. Different types of the aggregate test pieces are shown in To calculate the adhesive energy between asphalt and aggregates, the CA between asphalt and aggregates must be determined. However, given the high viscosity properties, asphalt cannot be dropped to a solid surface even in a hot-melt state. Moreover, that the hot-melt asphalt will form a smooth surface on the solid surface cannot be ensured because of the favorable ductility of asphalt and the easy formation of long tar silk. Therefore, the CA cannot be easily measured using the CA measurement device. aγ), with the CA between the hot-melt asphalt and stone (θ) and the force value (N), satisfies Equation (1) as follows:aγ is the surface energy of the hot-melt asphalt, 10−3 J/m2.θ is the CA between the hot-melt asphalt and aggregate, °;N is the force value, N;m is the weight of the stone plate, g; andb and c are the length and width of aggregate, respectively, cm.The hanging slice method was selected to measure the CA between hot-melt asphalt and aggregate. The testing principle is described as follows. Before the stone or aggregate touches the surface of hot-melt asphalt, the asphalt surface can be regarded as a horizontal plane. When the stone touches the asphalt surface, the hot-melt asphalt rises along with the stone to a certain distance because of the effect of surface energy and then forms a new asphalt surface, as shown in sγ, slγ, and lγ are the surface free energies of the solid, solid-liquid interface, and liquid, respectively, N; and θ is the CA between the solid-liquid interface, °.Young equation  can be uThe adhesive energy in the adhesion process is equal to the variation of the Gibbs free energy per unit surface area, which can be calculated as follows. We can use the variation of the Gibbs free energy per unit surface area to describe the adhesive energy between the aggregate and the asphalt during the adhesion process. The formula is as follows:The adhesive energy can be calculated as follows according to Equations (2) and (3):ldγ and lpγ are the dispersion and polarity components  of the surface free energy of liquid, respectively; sdγ and spγ are the dispersion and polarity components  of the surface free energy of solid, respectively.The adhesive energy between asphalt and aggregate can be thought to be composed of two parts, namely, the dispersion component and polar component when combining van der Waals force theory and Lewis theory on acid and alkali, as well as by ignoring the small force between the molecules:According to Equations (4) and (5), the adhesive energy can be calculated as follows:0, was tested after being immersed in a 60 °C water bath for 30 min to 40 min, whereas the stability of the second group, MS1, was tested after being immersed in a 60 °C water bath for 48 h. The immersion RMS was then calculated using Equation (7). The evaluation method is similar to that specified in ASTM D 1559 :RMS is the residual Marshall stability, %;1 is the stability after 48 h immersion, kN; andMS0 is the stability after 30 min immersion, kN.MSResidual Marshall stability (RMS) is among the indices used to evaluate the water stability of an asphalt mixture. A large RMS value indicates the favorable water stability of asphalt mixtures. For each mixture type, eight specimens measuring Φ 101.6 mm × 63.5 mm were fabricated with 75 times of two-face compaction. These specimens were divided into two groups. The stability of the first group, MSTSR is the tensile strength ratio, %;0 is the tensile strength without freeze-thaw circles, MPa; andITS1 is the tensile strength under freeze-thaw circles, MPa.ITSTSR is another index for evaluating the water stability of asphalt mixture. A large TSR value indicates the favorable water stability of asphalt mixtures. For each mixture type, eight specimens measuring Φ 101.6 mm × 63.5 mm were fabricated with 50 times of two-face compaction. The specimens of group 1 were saturated under a 730 mm Hg vacuum condition for 15 min, placed in sealed plastic bags containing 10 mL water, placed in a refrigerator with a constant temperature of −18 °C for 16 h, taken out of the plastic bags, and immersed in a 60 °C water bath for 24 h. The specimens of both groups 1 and 2 were then tested to obtain their tensile strength after being immersed in a 25 °C water bath for 2 h. TSR was calculated with Equation (8). Although this testing method is similar to that specified in AASHTO T 283-03 , the experiment parameters were slightly different:According to the Chinese Specification of JTG E20-2011  , graniteThe CAs among the aggregates, solid asphalts, water, and ethanol were tested using a CA measurement device. (1)The polar components comprise the main part of the surface energy of various aggregates and are much greater than the dispersion components. The surface energy of aggregates is sorted as follows: Granite > RCA > serpentine > limestone.(2)The surface energy of the modified asphalt is greater than that of the matrix asphalt.According to the parameters of the surface energy of water and ethanol  and the (1)A small CA indicates the good wettability of asphalt to aggregate. The CA between various aggregates and the same melt-asphalt is sorted as follows: Granite > RCA > serpentine > limestone. The surface energy and CA of RCA and serpentinite are very similar to each other.(2)The CA between the SBS-modified asphalt and the aggregate is greater than that of the matrix asphalt because decreasing the light oil content in modified asphalt decreases its infiltration property, thereby increasing the CA of modified asphalt.It can be seen from the CA test that the CAs between different aggregates and water or asphalt were different. This may be due to the different chemical composition of the different aggregates. Related studies have shown that the CA between asphalt and aggregate has a close relationship with the content of elements, such as Si, Al, Ca, and Mg, on the aggregate surface, and the composition of the chemical composition determines the acidity and basicity of the aggregate to a certain extent, thereby affecting the chemical reaction with the asphalt.2 content, an alkaline aggregate, the surface is easily infiltrated by asphalt, and its CA is lower with asphalt, while granite is the opposite, the SiO2 is high and an acidic aggregate, so the same acidic asphalt is difficult to infiltrate. Although RCA has a complex chemical composition, the RCA surface contains a small amount of cement hydration products, including CSH, ettringite, monosulfide-type sulphoaluminate, and Ca(OH)2. These components have a certain activity and can cause weak chemical reactions with acidic asphalt. Therefore the CA between RCA and asphalt is between limestone and granite.Limestone has a high content of Ca and Mg, a low SiO(1)A great adhesive energy indicates the excellent adhesion between aggregate and asphalt. When the same asphalt is used, the adhesive energy of different aggregates is sorted as follows: Limestone > serpentine > RCA > granite. The adhesion between RCA and asphalt is similar to that of serpentinite.(2)The adhesive energy between modified asphalt and aggregate is greater than that of matrix asphalt because the SBS-modified asphalt has a high surface free energy.According to the parameters of the surface energy of asphalt  and the The adhesive energy between RCA and asphalt is less than that of serpentine according to the results of CA and adhesive energy. Therefore, the water stability of HMA-RCAs are worse than those of the traditional mixture. The adhesion of aggregate and asphalt, and the aggregate strength characteristics and the porosity of asphalt mixture are the main factors affecting the fatigue performance of asphalt mixture. It can be concluded from It can be seen from the test results that although the CA and adhesion energy of RCA are very similar to the CA and adhesion energy of serpentine, when the RCA content in the aggregate increased, the fatigue life of the test pieces were significantly reduced, and when the RCA content was 100%, the fatigue life of the test pieces were the lowest. This is because, in addition to adhesion, the strength characteristics of the aggregate and the void ratio of the asphalt mixture also affect the fatigue performance. From the test results of the aggregate crushing values in The polar component was the major part of the surface energy of aggregates and was much greater than the dispersion component. The surface energy of aggregates was sorted as follows: Granite > RCA > serpentine > limestone.The CA between various aggregates and the same melt-asphalt was sorted as follows: Granite > RCA > serpentine > limestone. The CA of RCA and serpentinite were very close, and activation can reduce the CA and improve wettability. When the same asphalt was used, the adhesive energy of different aggregates was sorted as follows: Limestone > serpentine > RCA > granite. The adhesion between RCA and asphalt was the same as that of serpentinite.The RMS and TSR of HMA-RCAs decrease gradually as the RCA content increases because the adhesive energy between RCA and asphalt was less than that of water. The water stability of HMA-RCAs was closely related to the CA and adhesive energy between RCA and asphalt. A small CA and great adhesive energy indicated good water stability.The variation law of the fatigue performance of HMA-RCAs along with RCA content was determined by the interaction of the adhesion and porosity effects. Although the CA and adhesion energy between RAC and asphalt was similar to that of serpentine, the porosity of asphalt concrete increases with the increase of RCA. Therefore, when the aggregate contains more RCA, the fatigue performance of the HMA-RCA will decrease.


Overcoming the disadvantages of low transmission and broad peak bandwidth of previously reported plasmonic color filters, a high-efficiency multispectral plasmonic color filter is theoretically proposed with two cascaded ultrathin metallic nanogratings separated by two heterogeneous dielectric layers, and its optical properties are theoretically investigated using the finite-difference time-domain method. The transmission spectrum presents three near-unity peak bands accompanied with three near-null dip bands adjacent around them. Both transmission efficiencies of above 90% and ultranarrow peak bandwidth of 20 nm are achieved in the visible regime. The peak band positions can be flexibly tailored by varying the structural parameters. The filter selects the visible color with high signal noise ratio at the peak bands. The outstanding spectral properties of this filter indicate significant improvement for the high-accuracy color filtering and multispectral imaging applications. The simulated near-field electromagnetic distributions suggest that the excitation of the hybrid antisymmetric surface plasmon polariton (SPP) leaky mode and metal-insulator-metal waveguide modes are responsible for the peak transmission bands, while the formation of the hybrid SPP bound modes confined on the bottom nanograting makes the dip transmission bands, all of which are the consequence of the plasmonic hybridization between the two neighboring metallic nanogratings. A plasmy 200 nm . A hexagy 200 nm . Throughficiency . Nonetheficiency ,22,23. HIn this paper, we theoretically propose and demonstrate a multispectral plasmonic color filter with near-perfect peak transmission efficiency and ultranarrow bandwidth by utilizing the two-dimensional finite-difference time-domain (FDTD) method. The designed structure includes two ultrathin metallic nanogratings cascaded with two heterogeneous dielectric layers, an air/vacuum layer, and a silicon dioxide dielectric layer, which results in three near-unity enhanced peak transmission bands and three near-null suppressed dip transmission bands in the visible and near-infrared regime. Especially, the peak bandwidths in the visible regime can be as narrow as 20 nm. Deep insights into the physical mechanisms of the observations are obtained from the calculations of the electromagnetic (EM) field distributions. By varying the geometric parameters, the proposed multispectral plasmonic color filter can accurately separate the visible light into many color channels based on the ultranarrow peak transmission bandwidth, which allow its spectral resolution imaging and sensing analysis to further surpass the human eye’s capability, and pave a noninvasive way for material identification, target location, quality monitoring, safety diagnosis, astronomy and space surveillance, and particularly for the acquisition of optical high-resolution spectral information ,25,26.ta and a silicon dioxide (SiO2) layer of thickness td, wherein the bottom nanograting is adhered under the SiO2 dielectric layer and the upper one is suspended atop the air layer (separation), resulting in asymmetric dielectric environments for both sides. The whole structure is free-standing and embedded in air. The two nanogratings have the same period of Λ and slit width of w, but with different thicknesses of tb and tu, respectively. The gap between two cascaded nanogratings can be considered as a series of horizontal MIM waveguides. The dielectric permittivity of SiO2 is dieε = 2.25. The relative permittivity of silver is described by the Drude model: ε∞ = 3.7, ωp = 1.3673 × 1016 rad/s and γ = 2.7325 × 1013 rad/s are extracted from the experimental data [The configuration of the proposed plasmonic multilayer structure is schematically illustrated in tal data . The FDTtu and tb, period Λ and the air separation ta are investigated. The new hybrid SPP modes formed at different wavelengths are demonstrated by the calculated spatial distribution of the EM fields.Under the irradiation of a TM polarized plane wave (with electric field perpendicular to the nanograting slit), SPP modes can be excited on the upper and bottom nanogratings, respectively . Due to tu is shown in tb = 30 nm, and other geometric parameters are given by Λ = 500 nm, w = 150 nm, and td = ta = 50 nm. Obviously, the transmission spectra present two ultranarrow peak transmission bands in the visible regime, which are respectively marked by P1 and P2. On their two lateral sides, there are three near-null dip transmission bands that are denoted by D1, D2, and D3. Notably, the dip bands of D1 and D2 in the visible regime possess the same full-width at half-maximum (FWHM) at the scale of tens of nanometers as that of the peak bands P1 and P2, while the dip band D3 in the near infrared region has an FWHM of hundreds of nanometers. Besides, there is a nonresonant peak transmission band, P3, with a FWHM of hundreds of nanometers located in the red side of D3. Here, “nonresonant” means that the wavelength of the peak band P3, which is about 3.5 times larger than the size of the periodic cell, does not satisfy the SPP waveguide resonance conditions. As tu increases, the wavelength of the peak band P1 always remains unchanged at around 495 nm, as shown in tu = 100 nm (as shown by the inset picture); for the peak band P2, the wavelength position displays a nonlinear redshift with the increase of tu, and its transmission efficiency varies in a nonmonotonic way and reaches 93% at tu = 100 nm with a FWHM of 40 nm; the peak band P3 with the broad FWHM linearly shifts toward the larger wavelength with increasing tu, but its transmission efficiency has no obvious fluctuate and remains above 90%. As tu increases, the wavelengths of the dip bands D2 and D3 display redshift and the FWHM of D2 obviously becomes broader; the transmission efficiency of three dip bands D1, D2, and D3, respectively, are suppressed to 0.2%, 0.3%, and 0.2% at tu = 100 nm, and remain at nearly zero with the increase of tu; both the position of the dip band D1 and the bandwidths of the dip bands D1 and D3 have no obvious change. It is supposed that the dip transmission behaviors have adjustments relative to the redshift of the peak bands with the increase of tu.The calculated transmission spectra of the multispectral plasmonic color filter with respect to the wavelengths and the upper nanogratings thicknesses tb at tu = 100 nm is shown in 1 and P2. These results indicate that the multispectral plasmonic color filter can perform not only improve the transmission behaviors at the peak bands, but also has nearly zero suppression behaviors at the dip bands, once the upper and bottom grating thicknesses are decreased comparable to its skin depth . Most importantly, the ultranarrow FWHM of peak and dip bands in the visible regime allow the accurate filtering of the light’s color, which is very important for the development of practical devices based on multi- and hyper-spectral imaging and sensing.In addition, the evolution of the calculated transmission spectra with varying bottom nanograting thicknesses tu = 100 nm and tb = 30 nm are displayed in 2 layer, and the bottom metallic nanograting. y (color map) and electric displacement (arrow map) distributions within two periodic cells of the multispectral plasmonic color filter at the peak band P1 of λ = 495 nm. It is clearly observed that magnetic fields are localized not only within the MIM waveguide layer, but also on the incident and transmission interfaces of the filter, with 2nd order standing-wave patterns along the x-direction, which are characterized by two field antinodes with the opposite phase formed in one periodic cell. However, there is no obvious SPP cavity mode formed in the vertical slit. Note that in the vertical direction, Hy fields within the MIM waveguide layer are in the opposite phase to that on the transmission and incident interfaces, which are subjected to double phase shifting of π vertically across the incident interface to the transmission side. It means that a new hybrid antisymmetric SPP leaky mode is formed due to the hybridization between SPP waves excited on the upper and bottom nanogratings, which is responsible for the peak transmission band. The electric displacements denoted by the black arrows demonstrate that two electric dipoles are respectively induced on the input and output slit portions of the multispectral plasmonic color filter, which play dominant roles in the peak band transmission [1. Since this SPP leaky mode associated with the peak band P1 matches the resonant condition on the transmission interface along the x-direction, its corresponding wavelength can be evaluated by:In order to explore the physical origin of the peak transmission bands presented in smission ,17. Upon2 of λ = 610 nm are displayed in 1, the Hy field is mainly concentrated within the horizontal MIM waveguide layer and form a 2nd order waveguide modes along the x-direction within one periodic cell, which is evidenced by the opposite phase of the two modes. In the vertical direction, Hy fields in the slits of the upper and bottom nanogratings couple together across the air and dielectric layers to generate a 1st order Fabry–Perot cavity SPP resonance mode, which possesses two mirrors of finite reflection at the end of the slit. In this case, Hy fields simultaneously participate in the horizontal waveguide mode and vertical cavity mode. The coupling effect between the MIM waveguide mode and cavity mode makes the peak band P2. On the top and bottom metallic nanogratings, two dipoles are respectively generated, as shown by the electric displacements, and dedicated to transferring light through the multispectral plasmonic color filter. The transmission spectrum profile of the multispectral plasmonic color filter is predominantly modulated by the cross-shaped cavities consisting of the horizontal waveguides and the vertical slits. The larger upper and bottom nanograting thickness increases the vertical length of the cross-shaped cavity, resulting in a linear redshift of the peak transmission band P2, which accords with the results in y field is located at the center of the nanograting ridge with a state of resonance. Based on the cross-shaped cavity, the wavelength of the peak transmission band P2 can be quantificationally estimated from the expression:The plots of the corresponding EM field distribution at the peak band PLeff denotes the effective cavity length and it is a function of the MIM waveguide and the thickness of the upper and bottom nanogratings. Therefore, it makes sense for the nonlinear dependence of the wavelength of the peak band P2 on the upper and bottom nanograting thickness of tu and tb shown in Here, hickness ,30. Leff3 of λ = 1745 nm, the EM field plots are presented in y field is mostly concentrated inside the layer of the MIM waveguide and forms a nonresonant 1st order waveguide mode along the horizontal direction due to the wavelength much larger than twice of the unit cell period. The intense antinode of the waveguide mode is concentrated on the center of the metallic ridges of the MIM layer, while there is no obvious cavity mode in the vertical slit. The nonresonant peak transmission band is a result of the lager-scale redshift of the 1st order resonant peak band under the modulation of the dip transmission band D3 at 1130 nm. Similarly, the formation of the electric dipoles on the input and output of the multispectral plasmonic color filter boosts the light transmission process.Under the incidence of the plane wave at the peak wavelength P1, D2, and D3, respectively. For the dip transmission band D1 at λ = 465 nm, the Hy field is mainly concentrated on the bottom nanograting, where 1st order SPP resonance is formed on the incident interface while the 4th order one is formed on the transmission interface in one periodic cell. Meanwhile, the phases of the Hy field on the two bottom nanograting surfaces are completely opposite, indicating the excitation of a complicated hybrid antisymmetric SPP bound mode wave on the bottom nanograting. Such a short-range mode eventually suppresses the light transmission through the upper nanograting, resulting in nearly null dip band D1 in the transmission spectrum [2 at λ = 530 nm, the intensity of the Hy field is entirely localized at the metallic ridge on the incident interface of the multispectral plasmonic color filter with a 1st order SPP mode. Although only a small portion of the light can leak through the slit of the bottom nanograting into the MIM waveguide layer, it is completely bounded at the inner metallic wall of the MIM waveguide layer. The blank distribution of the Hy field on the transmission interface indicates that there is no light transmission through the multispectral plasmonic color filter. Therefore, the excitation of this SPP bound mode on the incident interface of the multispectral plasmonic color filter eventually reflects the incident light in the backward direction, which reduces the transmission to nearly zero. For the dip transmission band D3 at λ = 1130 nm, Hy fields can pass through the bottom grating by the excitation of SPP into the MIM waveguide layer to form 1st order SPP mode. More importantly, the SPP mode inside the MIM waveguide is comparable in intensity with that on the transmission interface of the multispectral plasmonic color filter but completely opposite in phase, which demonstrates the formation of a typical antisymmetrical SPP bound mode [3. For the dip transmission bands, the plots of the electric displacement distribution manifest that the electric dipoles are only induced on the input slit portion of the multispectral plasmonic color filter, which is helpless for the light transmission. Therefore, the above analyses demonstrate that at each dip transmission band, the SPP bound mode is excited on the bottom nanograting, which causes the reflection and the absorption of the incident light to hinder the light transmission through the multispectral plasmonic color filter, resulting in the near null values of the dip transmission band in the spectrum.To examine the physical mechanisms of the null-zero dip transmission bands, both the magnetic field (color map) and electric displacement (arrow map) distributions are displayed in spectrum ,31. For und mode ,31. In atu = 100 nm and tb = 30 nm, and other parameters are the same as in 1 and P2 on the period Λ can be inferred from Equations (1) and (2). Furthermore, the dip bands associated with antisymmetric SPP bound mode and localized SPP bound mode are varied as a function of the structural period, and subject to the linear red-shift with the increase of Λ. Therefore, the high and accurate tunability for the positions of the peak and dip transmission bands can be easily accessed by adjusting Λ. Note that the transmission efficiency of the peak band P1 reaches the maximum at around Λ = 500 nm and will reduce with increasing or decreasing Λ. The reduction of the transmissivity can be attributed to the nondegenerative energies of the two SPP modes localized on the upper and bottom nanogratings [The influence of the structural parameters, such as the period and the air separation thickness, on the transmission behavior has been also investigated. The spectral transmittance of the multispectral plasmonic color filter as a function of the period is presented in ta is shown in tu = 100 nm, tb = 30 nm, w = 150 nm, td = 50 nm, and Λ = 500 nm. For the peak band P1 associated with the antisymmetric SPP leaky mode, its wavelength is nearly invariant with increasing ta due to the constant period. However, its transmission efficiency drops rapidly to below 25% when ta exceeds the range of 50–150 nm. When ta is larger than 150 nm, the declined transmission can be attributed to no formation of the hybrid antisymmetric SPP leaky mode, because ta exceeds the effective coupling distance (about 150 nm) for the two SPP modes supported by the upper and bottom nanogratings. On the other hand, with ta approaching to zero, the dielectric environments surrounding the two cascaded nanogratings are symmetric due to the disappearance of the air separation, the shrinkage of peak band P1 results from the nondegeneration of the energies of the two SPP modes on the upper and bottom nanogratings [2, the wavelength position is slightly blue-shifted while its transmittance gradually reduces with increasing ta. The blue-shifted phenomenon is ascribed to the reduction of the effective wavelength (or index) of the SPP MIM waveguide mode with the increase of ta [3 in the near infrared regime, its wavelength shifts towards the longer wave with an increase of ta, which is due to the enlargement of the optical path between the two cascading nanogratings. In contrast to the two peak bands in the visible regime, the transmittances still remain above 90% since the air separation of ta = 200 nm is still within the effective coupling distance for the near infrared peak band P3, and the corresponding nonresonant SPP mode is still available to travel the incident light through the multispectral plasmonic color filter. Furthermore, this peak transmission band also would be extinct with continuous increase of ta. The dip transmission bands D1 and D2, associated with the SPP bound resonance modes on the bottom grating are located in the same wavelength position due to the invariable structural parameters of the bottom nanograting.The evolution of the spectral transmittance for the cascaded plasmonic nanograting with the variation of the air separation 2 layer thickness, the misaligned distance between the upper and bottom nanogratings, etc., are cumbersome to achieve. However, our simulation results show that the designed multispectral plasmonic filter can be tolerant of at least 30 nm errors for the slit width, metallic and dielectric layer thicknesses, and an approximately 40 nm error for the misaligned distance without influence on its spectral performance. If the fabrication error exceeds the critical value, it is no longer suitable for high-efficient multispectral filtering.For the practical realization of the proposed multispectral plasmonic color filter, its fabrication dimension is supposed to be finite. Referring to the fabrication method of fully suspended slot waveguide and free-standing plasmonic metal-dielectric-metal filter in literature reports ,32,33, oIn summary, we have theoretically proposed a novel design of a multispectral plasmonic color filter by cascading two ultrathin nanogratings with two heterogeneous dielectric layers, and theoretically investigated the transmission properties by utilizing the FDTD method. Based on a series of MIM waveguides formed between the two cascaded plasmonic nanogratings, SPP waves confined on the two nanogratings can be overlapped into new hybrid modes, realizing multispectral near-unity peak transmission bands and near-null dip transmission bands. The simulated EM field distributions show that the emergence of the hybrid asymmetric SPP leaky mode and the localized MIM waveguide SPP mode are responsible for two near-unity peak transmission bands, respectively, while the SPP bound modes on the bottom nanogratings can make contributions to the nearly zero dip transmission bands. Remarkably, the high contrast ratio between the peak and the dip transmissions essentially relies on the two heterogeneous dielectric layers sandwiched between the two cascaded nanogratings. This multispectral plasmonic color filter can improve the transmission efficiency up to 90% at the peak bands and perfectly suppresses the light transmission at the dip bands. Moreover, the peak bandwidth can be reduced to as narrow as 20 nm in the visible regime, and the high accuracy multispectral image and sensor in the entire visible spectrum can be accessed by purposefully designing the structural parameters. High-accuracy color filtering performance requires that the spectral resolution imaging analysis capability of the proposed multilayer plasmonic structure is far superior to the human eye and commercial RGB-based color and spectral imaging systems in photo/video cameras. Using a colored pixel to build an ultracompact spectral filtering device, our proposed color filter has potential applications in many fields, such as the color display devices , complem


The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19), and adiponectin, Δw(21), were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines—the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes. Type 2 diabetes is a disorder resulting from the abnormal secretion or functioning of the key hormone, insulin, which regulates both the biosynthesis of glucose in the liver, as well as glucose utilization by peripheral muscles and fat tissue . In peopTaking into account the factors mentioned above, the paramount aim of the paper is the quantitative assessment of selected regulatory molecules expression, such as leptin, leptin receptor, and adiponectin in the blood of sick, obese individuals with type 2 diabetes both before treatment, as well as six months after the pharmacological therapy with a long-lasting insulin analogue, insulin detemir. The key element is also the discriminant analysis which allows determining which biochemical or anthropometric variables discriminate the patients best before and after treatment which, at the same time, is the confirmation of the pharmacological therapy efficacy. Moreover, the relationship between the plasma concentration of both adiponectin and leptin receptor and the glycated haemoglobin value and body mass index, with the influence of gender and the time of the treatment application on the values of the examined parameters, has also been assessed.The obtained results indicated that, in the blood plasma of patients suffering from diabetes, both the untreated and the treated, leptin occurs in significantly higher concentrations in relation to the concentration of this protein in the blood plasma of the individuals from the control group. Gender appeared to be an important factor modifying the leptin concentration in the blood plasma in all patients with type 2 diabetes. Significantly higher values were observed in women rather than in men. The applied therapy did not affect the plasma concentration of the studied adipokine both in the whole group and in the group divided by gender a.p < 0.0005), as well those subject to the therapy . Such a dependency was not found between the leptin concentration and the mean value of the glycated haemoglobin in the blood of patients suffering from diabetes.The analysis of the relationship between the leptin concentration and Body Mass Index (BMI) revealed a positive correlation between these parameters in the group of the untreated patients  and in the blood plasma of individuals with diabetes after a six-month therapy . The analysis of the relationship between the concentration of the soluble leptin receptor and BMI indicated a negative correlation between these parameters in the group of the untreated patients , as well as those subject to the therapy . Moreover, a significant dependence between the leptin receptor concentration and the mean value of Glycated hemoglobin (HbA1C) was found .Moreover, the obtained results also indicated a statistically significant difference in the concentration of the soluble leptin receptor between the group of sick individuals with diabetes, who were not subject to the therapy, and the subjects from the control group. The concentration of leptin receptor in individuals with diabetes before treatment was remarkably lower than in healthy individuals. The applied therapy caused in fact a significant increase in the plasma concentration of the analysed molecule. Unlike leptin, the plasma concentration of leptin receptor was varying in the group of men, rather than in women b. In theThe results of the adiponectin plasma concentration determination indicated a significant reduction in the amount of this adipokine in patients with diabetes before treatment compared to the healthy individuals. The applied therapy resulted in an increase of adiponectin concentration in relation to the observed values in the control group. Gender appeared to be an important factor determining the concentration of this adipokine in the control group, as well as in the individuals after application of the insulin therapy c. The cow(1) to w(21) both for the control group —as well as in the group of patients before the drug administration —and after six months of the therapy . Moreover, the mean values for the difference between the values of particular parameters before and after the drug administration were also calculated, i.e., for the parameter w(1):The mean values of the particular measured parameters ranging from The obtained results are presented in w(1) to Δw(21) were analysed. The obtained results are shown in In the next stage of the preliminary data analysis, the correlation between the particular parameters ranging from Δw(1) and Δw(2) (body weight and BMI), Δw(4) and Δw(3) (waist and hips circumference), Δw(5) and Δw(6) (WHR with age and WHR without age), Δw(8) and Δw(10) , Δw(15) and Δw(16) (insulin and HOMA-IR), and a high correlation for Δw(7) and Δw(18) (HbA1C and %B), Δw(12) and Δw(20) (creatinine in urine for leptin), Δw(15) and Δw(18) (insulin and %B), Δw(16) and Δw(17) (HOMA and %S). The obtained values of correlation result mainly from the natural ties between BMI and weight, waist and hips circumference, WHR indices, insulin and HOMA-IR, insulin and function index of the pancreatic islets β cells, as well as HOMA-IR and the insulin sensitivity index. On the basis of these preliminary results a further, discriminant analysis was conducted which allowed the selection of the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir.They confirm almost a complete correlation for the difference of the features Δw(1) to Δw(21). The following three types of the discriminant analysis were applied: linear, fitting a multivariate normal density to each group, with a pooled estimate of covariance; diaglinear, with a diagonal covariance matrix estimate (naive Bayes classifiers); quadratic, fitting multivariate normal densities with covariance estimates stratified by group; diagquadratic, with a diagonal covariance matrix estimate (naive Bayes classifiers); and mahalanobis, using Mahalanobis distances with stratified covariance estimates.Discriminant analysis was conducted for all the parameters from Δ21 − 1) = 10,485,755 classifications were performed. Due to a relatively small number of patients (40) the number of the simultaneously-analysed parameters w was limited to 10 [In total 5*(2ed to 10 . Using dTN + TP)/(FN + FP + TN + TP), where TN represents true negative, TP represents true positive, FN represents false negative, and FP represents false positive. The obtained results of the first ten highest values of accuracy for the linear discriminant analysis for different configuration of Δw parameters are, for example, w − ACC = 81, w for ACC = 81, etc.The following were evaluated: accuracy (ACC) defined as  or w. In this case the values of ACC are at the level of 89% and 88%.Results for the discriminant analysis of the quadratic type are, for example, w(10), Δw(11), Δw(16), and Δw(17).The outcomes of accuracy, for example, for the first-highest value types of discriminatory analysis is: linear ACC = 57%, diaglinear ACC = 55%, quadratic ACC = 59%, diagquadratic ACC = 59%, mahalonobis ACC = 57% for parameters Δw(6), Δw(7), Δw(8), Δw(9), Δw(6), Δw(7), Δw(8), Δw(9), Δw(10), Δw(11), Δw(16), Δw(17), and in some cases Δw(15) and Δw(3). For Δw(6), Δw(7), and Δw(16) selected from the mentioned parameters, a discriminant function was presented for all five considered cases, i.e., linear, diaglinear, quadratic, diagquadratic, and mahalonobis, for the test group , and adiponectin, Δw(21). Among the other analysed biochemical and anthropometric parameters, the applied treatment caused the most significant quantitative changes of glycated haemoglobin Δw(7), insulin, Δw(15), and BMI, Δw(2). w(19), in the function Δw(21), while w(7), w(15), and w(2) were obtained before and after the pharmacological treatment.From the diagnostic point of view, the most important results of the discriminant analysis allowing the selection of the parameters best differentiating the group of patients with type 2 diabetes before the implementation of the insulin therapy, as well as after a six-month period of using insulin, were obtained for the two analysed regulatory molecules such as leptin receptor, ΔObesity, which accompanies type 2 diabetes, is a multifactorial disease entity being characterized by an excessive accumulation of fat tissue in the body . The latThe obtained results indicate that in the blood plasma of diabetics, both before and after treatment, leptin occurs in a significantly higher concentration than in the blood plasma of healthy individuals. Moreover, the applied treatment does not affect the plasma concentration of the protein in question. These results only partially correspond with the results described by Uribarri et al. . The latIn this paper it has also been demonstrated that the leptin concentrations in the blood of women with diabetes were significantly higher than in men. The results are concurrent with the observations of other authors who stated that the plasma leptin concentration in women is two or three times higher than the concentration in the plasma of men with the same BMI as in women, both in the case of healthy individuals, as well as those with obesity . A similMoreover, in the present paper a positive high correlation has been indicated between the leptin concentration in the blood plasma of diabetics, both the untreated and those subject to insulin therapy, and the body mass index of the studied individuals. Similar relationships were described in obese individuals with type 2 diabetes and without diabetes, as well as non-obese with diabetes ,31,32,33The subject of the present study was also the evaluation of the soluble leptin receptor concentration (OB-Re or sOB-R) in sick individuals’ blood. There are five isoforms of this receptor, i.e., OB-Ra, OB-Rb, OB-Rc, Od-Rd, and OB-Re or, more often, sOB-R. The first four are membrane isoforms, while the last one, described as “e” (or sOB-R) is a soluble receptor determined also as secretory, not related with cytoplasm or cell membranes ,40. The The obtained results indicate a lower concentration of this receptor in the blood plasma of the untreated patients with diabetes in relation to healthy individuals. The therapy caused a significant increase in the concentration of the studied molecule to the value of the observed individuals from the control group. The studies seem to reflect a potentially beneficial influence of the applied treatment. The thesis may be confirmed by the results described by Ogawa et al. , who fouIn the analysis of the influence of gender on the plasma concentration of the mentioned receptor in particular study groups, a significant difference was found between women and men only in the case of patients suffering from diabetes after the applied treatment. The concentration of the plasma leptin receptor in women was remarkably lower in women than in men. The tendency of the latter changes is partially compatible with the one described by Ogawa et al. , who conIt should be mentioned that the biological role of the soluble receptor for leptin was not fully explained. However, as it has been mentioned above, the protein delays the leptin clearance from circulation, which increases the biologic availability of the mentioned adipokine and intensifies its action . The obtThe studies conducted in this paper also indicated an average, negative correlation between the concentration of the soluble leptin receptor and the value of the glycated haemoglobin in the blood of people with newly-diagnosed type 2 diabetes. This is compatible with the results obtained by other authors, however, for patients with type 1 diabetes .The aim of the present paper was also the evaluation of the concentration of the other regulatory molecule, adiponectin, in the blood of obese patients with type 2 diabetes. A special property of this cytokine is the ability to “insulin-sensitizing” performed by the binding of this adipokine to its receptors: AdipoR1 and AdipoR2 . This chThe conducted quantitative assessment of adiponectin indicated a significantly lower concentration of this adipocytokine in the blood plasma in individuals suffering from diabetes—before treatment, in relation to its concentration in the healthy individuals’ blood plasma as well as in those subject to insulin therapy. The results are in agreement with the results described by other authors ,26. MoreIn the group of healthy women and those suffering from diabetes subject to therapy, the concentrations of adiponectin were higher than in men, which is compatible with the results of Ogawa et al.  and AleiThe conducted studies revealed a lack of correlation between the plasma concentration of adiponectin and the body mass index in patients with type 2 diabetes. There was also no demonstration of any relationship of the plasma concentration of adiponectin with the level of the metabolic control of diabetes, which corresponded with the results described by Schulz et al.  and ViniThe material in the study was constituted by blood samples collected from 40 obese people, of both sexes, between 44 and 72 years of age, with diagnosed type 2 diabetes. The control material in the study was comprised of blood samples collected from 27 healthy individuals, of both sexes, between 40 and 67 years of age. The study was approved by the Bioethics Committee of the Medical University of Silesia in Katowice (KNW/0022/KB1/147/10). The assessment of the anthropometric parameters and laboratory biochemical examinations in patients diagnosed with type 2 diabetes was performed twice: before the beginning of the treatment and after six months of the therapy with a long-acting human insulin analogue—insulin detemir—administered once a day, in the evening in doses from 0.2 unit/kg b.w. or 10 units/day .The inclusion criteria referred to obese male and female patients of all ethnic groups with recognized type 2 diabetes, treated with metformin; patients who reached the age of 18 years and could decide themselves about participating in the study; patients who were able to understand the aim and possible risk associated with participation in the study after signing the informed consent for the study and expressing their consent. The exclusion criteria: patients with type 1 diabetes; patients with different types of diabetes; female patients with gestational diabetes and diabetes during lactation; patients with autoimmune diseases; patients taking glycocorticosteroids, Adrenocorticotropic hormone (ACTH), and interferons; patients with prior stroke or myocardial infarction; patients with unstable angina; patients with class III and IV class heart failures according to New York Heart Association (NYHA); patients with kidney failure; patients with liver failure. The results of morphological and biochemical blood analyses of healthy subjects enrolled to this study ) fell within the reference range.w(1), based on which the Body Mass Index was calculated, w(2), as well as the measurement of the waist w(3) and hips, w(4), based on which the waist/hips ration (WHR) was calculated. The WHR index considered age, w(5), the average for the population considering age, and the WHR index without any reference to age, w(6). The systolic and diastolic arterial blood pressures were also measured.In each sick individual an interview and physical examination were performed. In the interview the following data of patients were collected: age, sex, and disease duration. The physical examination comprised of the measurement of body weight, w(7), the concentration of total cholesterol, w(8), HDL cholesterol, w(9), Low-density lipoprotein (LDL) cholesterol, w(10), and triacylglycerols, w(11), creatinine, w(12), albumin in urine, w(13), glucose concentration, w(14), and insulin, w(15). Additionally, the value of the HOMA-IR insulin-resistance index was also determined, w(16), insulin sensitivity index (%S), w(17), and the function index of the pancreatic islet β cells (%B), w(18), as well as the leptin receptor concentration in blood plasma, w(19), leptin, w(20), and adiponectin, w(21).A series of laboratory tests was also performed in each patient, which was used to monitor the diabetic patients. The tests included the value of glycated haemoglobin, The concentration assessment in the blood plasma of both healthy individuals and patients suffering from type 2 diabetes involved the following tests based on the enzyme-linked immunosorbent assay (ELISA): the test of DRG Instruments GmbH, Marburg, Germany for leptin; the test of Mediagnost GmbH, Reutlingen, Germany for adiponectin, and the test of BioVendor R and D, Brno, Czech Republic for leptin receptor.www.statsoft.com). The statistical analysis covered testing the significance of the mean value differences of the given characteristic for the control group and the study group with the use of Student’s t-test for independent samples, while in the case of the group of the studied patients before administering the drug and the group of patients after a six-month pharmacotherapy—with the use of Student’s t-test for continuous variables. The same statistical significance level p < 0.05 was accepted for all applied tests and statistical analyses. The correlation strengths of two variables was assessed with the Pearson correlation r coefficient.The obtained results underwent a statistical calculations with the use of the computer program STATISTICA of StatSoft, Inc. (2011) ,  version 10 ; Signal Processing Toolbox: Version 7.1) on a PC running Windows 7 Professional, 64-bit with an Intel Core i7-4960X CPU @ 3.60 GHz .The bioinformatic data analysis was performed in two stages:The first stage included a preliminary data analysis: the calculations of the mean values of differences between particular parameters, standard deviations of the mean and the matrix of correlation between all the measured parameters;The second stage covered the selection of the most significant diagnostic features, proposing a discriminant analysis which allows selecting the variables which best forecast the efficacy of the therapy ,55,56.Summing up, the conducted studies have indicated the participation of adipocytokines—the biologically-active mediators of the systemic metabolism—such as leptin and adiponectin, in the pathomechanisms of disorders underlying obesity which, in turn, leads to the development of insulin resistance and consequently contributes to the occurrence of type 2 diabetes. The conducted discriminant analysis has also demonstrated that the concentration of the soluble leptin receptor and adiponectin best reflect the influence of the applied therapy on the endocrine activity of the fat tissue in the course of type 2 diabetes. The complement of the knowledge concerning the regulatory mechanisms influencing the activity of adipocytokines participating in controlling the feeling of appetite and satiety, as well as energy management, may enable the introduction of new therapeutic strategies based on a targeted and more effective therapy of disorders occurring with energy efficiency disorders, such as obesity or type 2 diabetes.