Design,synthesis and evaluation of novel dehydroabietic acid-dithiocarbamate hybrids as potential multi-targeted compounds for tumor cytotoxicity

In the present study, novel representatives of the important group of biologically-active, dehydroabietic acid-bearing dithiocarbamate moiety, were synthesized and characterized by ¹H NMR, ¹³C NMR, HR-MS. The in vitro antiproliferative activity evaluation (MTT) indicated that these compounds exhibited potent inhibitory activities in various cancer cell lines (HepG-2, MCF-7, HeLa, T-24, MGC-803). Particularly, compound III-b possessed extraordinary cytotoxicity with low micromolar IC₅₀ values ranging from 4.07 to 38.84 µM against tested cancer cell lines, while displayed weak cytotoxicity on two normal cell lines (LO-2 and HEK 293 T). Subsequently, the potential mechanisms of representative compound III-b were elementarily investigated by Transwell experiment, which showed III-b can inhibit cancer cells migration. Annexin-V/PI dual staining showed that the compound can induce HepG-2 cells apoptosis in a dose-dependent manner. Meanwhile this apoptosis may be related to the upregulated protein expression of cleaved-caspase 3, cleaved-caspase 9, Bax and downregulated of Bcl-2 indicated by Western Blot. Later study further confirmed that ROS levels in HepG-2 cells increased significantly with the rise of concentrations. In addition, through the network pharmacology data analyzing, the core targets and signaling pathways of compound III-b for treatment of liver neoplasms were forecasted. Molecular docking model showed that compound III-b had high affinity with hub targets (CASP3, EGFR, HSP90AA1, MAPK1, ERBB2, MDM2), suggesting that compound III-b might target the hub protein to modulate signaling activity. Taken together, these data indicated that dehydroabietic acid structural modification following the “Molecular hybridization” principle is a feasible way to discover the potential multi-targeted antitumor compounds.     

A distributionally robust area under curve maximization model

Area under ROC curve (AUC) is a performance measure for classification models. We propose new distributionally robust AUC models (DR-AUC) that rely on the Kantorovich metric and approximate AUC with the hinge loss function, and derive convex reformulations using duality. The DR-AUC models outperform deterministic AUC and support vector machine models and have superior worst-case out-of-sample performance, thereby showing their robustness. The results are encouraging since the numerical experiments are conducted with small-size training sets conducive to low out-of-sample performance.     

Areas,anti-derivatives,and adding up pieces: Definite integrals in pure mathematics and applied science contexts

Research in mathematics and science education reveals a disconnect for students as they attempt to apply their mathematical knowledge to science and engineering. With this conclusion in mind, this paper investigates a particular calculus topic that is used frequently in science and engineering: the definite integral. The results of this study demonstrate that certain conceptualizations of the definite integral, including the area under a curve and the values of an anti-derivative, are limited in their ability to help students make sense of contextualized integrals. In contrast, the Riemann sum-based “adding up pieces” conception of the definite integral (renamed in this paper as the “multiplicatively-based summation” conception) is helpful and useful in making sense of a variety of applied integral expressions and equations. Implications for curriculum and instruction are discussed.     

On lengths,areas and Lipschitz continuity of polyharmonic mappings

In this paper, we continue our investigation of polyharmonic mappings in the complex plane. First, we establish two Landau type theorems. We also show a three circles type theorem and an area version of the Schwarz lemma. Finally, we study Lipschitz continuity of polyharmonic mappings with respect to the distance ratio metric.     

Approximation of planar BV homeomorphisms by diffeomorphisms

We show that a planar BV homeomorphism can be approximated in the area strict sense, together with its inverse, with smooth or piecewise affine homeomorphisms.     

Folded overlapping variance estimators for simulation

We propose and analyze a new class of estimators for the variance parameter of a steady-state simulation output process. The new estimators are computed by averaging individual estimators from “folded” standardized time series based on overlapping batches composed of consecutive observations. The folding transformation on each batch can be applied more than once to produce an entire set of estimators. We establish the limiting distributions of the proposed estimators as the sample size tends to infinity while the ratio of the sample size to the batch size remains constant. We give analytical and Monte Carlo results showing that, compared to their counterparts computed from nonoverlapping batches, the new estimators have roughly the same bias but smaller variance. In addition, these estimators can be computed with order-of-sample-size work.     

Evaluation of three interventions teaching area measurement as spatial structuring to young children

We evaluated the effects of three instructional interventions designed to support young children’s understanding of area measurement as a structuring process. Replicating microgenetic procedures we used in previous research with older children to ascertain whether we can build these competencies earlier, we also extended the previous focus on correctness to include analyses of children’s use of procedural and conceptual knowledge and examined individual differences in strategy shifts before and after transitions, enabling a more detailed examination of the hypothesized necessity of development through each level of a learning trajectory. The two experimental interventions focused on a dynamic conception of area measurement while also emphasizing unit concepts, such as unit identification, iteration, and composition. The findings confirm and extend earlier results that seeing a complete record of the structure of the 2D array—in the form of a drawing of organized rows and columns—supported children’s spatial structuring and performance.     

On an empty triangle with the maximum area in planar point sets

Let P be a finite set of points in general position in the plane. We evaluate the ratio between the maximum area of an empty triangle of P and the area of the convex hull of P.     

Pre-service elementary teachers’ strategies for tiling and relating area units

It has been established that preservice elementary school teachers (PSTs) often employ procedural methods when solving measurement problems without conceptual understanding or flexibility, but a significant gap exists in the literature identifying why. Through the lens of discrete and continuous interpretations of area, this study extends the research base by describing strategies PSTs use to tile a two-dimensional space with varying size tiles and what these strategies imply about PSTs’ conceptions of area measurement. These strategies and implied conceptions enable further discussion on the multiple purposes of the area model as an illustrative measure for mathematics throughout the elementary school curriculum.     

Up-regulation of Na expression in the area postrema of total sleep deprived rats by TOF-SIMS analysis

Area postrema (AP) is a circumventricular organ plays an important role in sodium homeostasis and cardiovascular regulation. Since sleep deficiency will cause cardiovascular dysfunction, the present study aims to determine whether sodium level would significantly alter in AP following total sleep deprivation (TSD). Sodium level was investigated in vivo by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Clinical manifestation of cardiovascular function was demonstrated by mean arterial pressure (MAP) values. Results indicated that in normal rats, TOF-SIMS spectrum revealed a major peak of sodium ion counting as 5.61 × 10⁵ at m/z 23. The sodium ions were homogeneous distributed in AP without specific localization. However, following TSD, the sodium intensity was relatively increased (6.73 × 10⁵) and the signal for sodium image was strongly expressed throughout AP with definite spatial distribution. MAP of TSD rats is 138 ± 5 mmHg, which is significantly higher than that of normal ones (121 ± 3 mmHg). Regarding AP is an important area for sodium sensation and development of hypernatremic related sympatho-excitation; up-regulation of sodium expression following TSD suggests that high sodium level might over-activate AP, through complex neuronal networks involving in sympathetic regulation, which could lead to the formation of TSD relevant cardiovascular diseases.