A numerical methodology developed for the microarchitecture design of 3D elastic two-phase periodic composites with effective isotropic properties close to the theoretical bounds is here presented ...and analyzed. This methodology is formulated as a topology optimization problem and is implemented using a level-set approach jointly with topological derivative.
The most salient characteristic of this methodology is the imposition of preestablished crystal symmetries to the designed topologies; we integrate a topological optimization formulation with crystal symmetries to design mechanical metamaterials.
The computational homogenization of the composite elastic properties is determined using a Fast Fourier Transform (FFT) technique. Due to the design domains are the primitive cells of Bravais lattices compatible with the space group imposed to the material layout, we have adapted the FFT technique to compute the effective properties in 3D parallelepiped domains.
In this work, to find the topologies satisfying the proposed targets, we test four space groups of the cubic crystal system. Thus, the achievement of composites with effective elasticity tensor having cubic symmetry is guaranteed, and the isotropic response is then enforced by adding only one scalar constraint to the topology optimization problem.
To assess the methodology, the following microarchitectures are designed and reported: two auxetic composites, three pentamode materials, and one maximum stiffness composite. With only one exception, all the remaining topologies display effective elastic properties with Zener coefficients approximating to 1.
•A numerical methodology for microarchitecture design of 3D elastic two-phase periodic composites is presented.•The effect of enforcing different crystal symmetries on the topology synthesis of isotropic composites is evaluated.•The numerical assessments aim at designing composites with effective properties close to the theoretical bounds.•The microstructure designs of auxetic, maximum stiffness and pentamode composites are assessed.•An FFT technique for 3D homogenization in parallelepiped domains is used for the topology optimization problem.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple ...similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e., a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation.
Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has ...used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Circulating tumor cells (CTCs) hold promise for studying advanced prostate cancer. A functional collagen adhesion matrix (CAM) assay was used to enrich CTCs from prostate cancer patients’ ...blood. CAM ingestion and epithelial immuno-staining identified CTCs, which were genotyped using oligonucleotide array comparative genomic hybridization. The highest CTC counts were observed in men with metastatic castration resistant prostate cancer (CRPC) compared to castration sensitive prostate cancer. Copy number profiles for CRPC CTCs were similar to paired solid tumor DNA, and distinct from corresponding DNA from the residual CAM-depleted blood. CAM CTC enrichment may allow cellular and genetic analyses in prostate cancer.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The purpose of this paper is to propose a novel hybrid framework for evaluating and benchmarking trustworthy artificial intelligence (AI) applications in healthcare by using multi-criteria ...decision-making (MCDM) techniques under a new fuzzy environment. To develop such a framework, a new decision matrix has been built, and then integrated with q-ROF2TL-FWZIC (q‐Rung Orthopair Fuzzy 2‐Tuple Linguistic Fuzzy-Weighted Zero-Inconsistency) and q-ROF2TL-CODAS (q‐Rung Orthopair Fuzzy 2‐Tuple Linguistic Combinative Distance-Based Assessment). In this integration, q-ROF2TL-FWZIC is utilized for assigning the weights of evaluation attributes of trustworthy AI, while q-ROF2TL-CODAS is employed for benchmarking trustworthy AI applications. Findings show that the q-ROF2TL-FWZIC method effectively weights the evaluation attributes. The transparency attribute receives the highest importance weight (0.173566825), whereas the human agency and oversight criterion has the lowest weight (0.105741901). The remaining attributes are distributed in between. Moreover, alternative_4 receives the highest rank order (score of 7.370410417), while alternative_13 receives the lowest rank order (score of −4.759794397). To evaluate the validity of the proposed framework, systematic ranking and sensitivity analysis assessments were employed.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present a probabilistic data fusion framework that combines multiple computational approaches for drawing relationships between drugs and targets. The approach has special relevance to identifying ...surprising unintended biological targets of drugs. Comparisons between molecules are made based on 2D topological structural considerations, based on 3D surface characteristics, and based on English descriptions of clinical effects. Similarity computations within each modality were transformed into probability scores. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, clinical effects similarity or their combination. The methods were validated within acurated structural pharmacology database (SPDB) and further tested by blind application to data derived from the ChEMBL database. For prediction of off-target effects, 3D-similarity performed best as a single modality, but combining all methods produced performance gains. Striking examples of structurally surprising off-target predictions are presented.
Touristic innovation is understood as the implementation of new or improved products, processes, organization and marketing practices, that consider the non-lineal behavior and the knowledge ...generation. Although the related literature globally establishes the activities that should be contained in an innovation procedure to obtain new and improved products, there are not definitive guidelines regarding the order that should follow the execution of this activities. The current research fills this gap by presenting a framework for sequencing innovation activities in hotels. Specifically, the framework at first introduces the use of association rules to match the features of the hotel and the set of activities to execute. Afterwards, we propose an extension of the Borda rule for generating the sequence of the activities to execute, guaranteeing a trade-off between the generality and the singularity of such sequence. The paper includes the development of a case study to show the application of the presented framework in a real scenario. Finally, the paper concludes with the brief presentation of a software developed to allow the use of the proposal by the final managers in hotels.
Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has ...used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stomatal conductances of normally oriented and inverted leaves were measured as light levels (photosynthetic photon flux densities) were increased to determine whether abaxial stomata of Vicia faba ...leaves were more sensitive to light than adaxial stomata. Light levels were increased over uniform populations of leaves of plants grown in an environmental chamber. Adaxial stomata of inverted leaves reached maximum water vapor conductances at a light level of 60 micromoles per square meter per second, the same light level at which abaxial stomata of normally oriented leaves reached maximum conductances. Abaxial stomata of inverted leaves reached maximum conductances at a light level of 500 micromoles per square meter per second, the same light level at which adaxial stomata of normally oriented leaves reached maximum conductances. Maximum conductances in both normally oriented and inverted leaves were about 200 millimoles per square meter per second for adaxial stomata and 330 millimoles per square meter per second for abaxial stomata. Regardless of whether leaves were normally oriented or inverted, when light levels were increased to values high enough that upper leaf surfaces reached maximum conductances (about 500 micromoles per square meter per second), light levels incident on lower, shaded leaf surfaces were just sufficient (about 60 micromoles per square meter per second) for stomata of those surfaces to reach maximum conductances. This 'coordinated' stomatal opening on the separate epidermes resulted in total leaf conductances for normally oriented and inverted leaves that were the same at any given light level. We conclude that stomata in abaxial epidermes of intact Vicia leaves are not more sensitive to light than those in adaxial epidermes, and that stomata in leaves of this plant do not respond to light alone. Additional factors in bulk leaf tissue probably produce coordinated stomatal opening on upper and lower leaf epidermes to optimally meet photosynthetic requirements of the whole leaf for CO2.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In an attempt to determine whether low epidermal conductances to water vapor diffusion of senescing leaves were caused by internal changes in guard cells or by factors external to guard cells, ...stomatal behavior was examined in intact senescing and nonsenescing leaves of Nicotiana glauca (Graham), tree tobacco, grown in the field or in an environmental chamber. Conductances of senescing leaves were 5 to 10% of the maximum conductances of nonsenescing leaves of the same plant, yet guard cell duplexes isolated from epidermal peels of senescing leaves developed full turgor in the light in solutions containing KCl, and sodium cobaltinitrite staining showed that K+ accumulated as turgor developed. Ninety-five per cent of the guard cells isolated from senescing leaves concentrated neutral red and excluded trypan blue. Intercellular leaf CO2 concentrations of senescing and nonsenescing leaves of chamber-grown plants were not significantly different (about 240 microliters per liter), but the potassium contents of adaxial and abaxial epidermes of senescing leaves taken from plants grown in the field were less than half those of nonsenescing leaves. We conclude that guard cells do not undergo the orderly senescence process that characteristically takes place in mesophyll tissue during whole-leaf senescence and that the reduced conductances of senescing leaves are produced by factors external to guard cells.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
PDF
