TOWARD ENRICHED VHTS FOR CDK2 INHIBITORS: MOLECULAR DYNAMICS, PHARMACOPHORE MODELLING, AND DOCKING

Cyclin-Dependent Kinases-2 (CDK2) are members of the serine/threonine protein kinases family. They play an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidence indicates that excessive expression of CDK2s should cause abnormal cell cycle regulation. Therefore, since a long time, CDK2s have been considered potential therapeutic targets for cancer therapy. In this work, we collected one-hundred and forty-nine complexes of inhibitors bound in the CDK2-ATP pocket submitting to short MD simulations (10ns) and free energy calculation by means of MM-GBSA. The calculate 06G values have been compared with experimental data (Ki, Kd, and IC50). Information collected on short MD simulations of protein-ligand complexes has been used to perform molecular modeling approaches that incorporates \ufb02exibility into structure-based pharmacophore modeling (Common Hits Approach, CHA,1 and Molecular dYnamics SHAred PharmacophorE, MYSHAPE2 approach) and constraints docking, to enrich the hits list of virtual screening. Short simulations proved to be exhaustive to examine the crucial ligand-protein interactions within the complexes

Moving beyond the socialization hypothesis: The effects of maternal smoking during pregnancy on the development of self-control

Purpose Gottfredson and Hirschi, in A General Theory of Crime, argue that the primary source of self-control is parental socialization. Specifically, parents who fail to supervise their children, to recognize their child's deviant behavior, and to punish such behavior are more likely to raise children with lower levels of self-control. Recent empirical research, however, has broadened the explanatory factors to include sources within schools, neighborhoods, and individual factors as significant contributors to the development of self-control. This study proposes that maternal smoking during pregnancy places additional limits on the development of self-control.Methods Using a subsample of the National Longitudinal Study of Youth (N = 542), we provide a comprehensive investigation of the variety of sources of self-control to include both individual and environmental covariates.Results Results indicate that maternal smoking during pregnancy significantly impacts the development of self-control net of parental, neighborhood, and school socialization. We also found that individual sources of self-control significantly vary across race and neighborhood context.Conclusions The sources of self-control are more complex than socialization from parents, schools, and within neighborhoods occurring in childhood and adolescence.

Treatment of Recurrent Primary Cutaneous Mucinous Carcinoma of the Eyelid with Modified Wide Local Excision

Primary cutaneous mucinous carcinoma (PCMC) is a rare, low-grade malignant neoplasm of the sweat gland, whose history has been controversial regarding eccrine versus apocrine origin. This case report describes a 53-year-old male who presented to the University of Florida, Gainesville, ophthalmology clinic and was referred to the oculoplastics service with a painless, subcentimeter mass on the lateral right upper eyelid including the canthus, consistent with recurrent primary cutaneous mucinous carcinoma of the eyelid. Four years prior, the patient had undergone excisional biopsy of the lesion in a clinic, which revealed residual tumor, but the patient deferred further surgery at the time. The patient underwent surgical excision of the mass with reconstruction without operative complications and with negative surgical margins. PCMC is difficult to diagnose clinically due to its rarity and requires a histopathological examination for confirmation of the diagnosis. This report presents the first case in the literature of primary cutaneous mucinous carcinoma in a patient with human immunodeficiency virus (HIV). With this case report, we aim to raise awareness of primary cutaneous mucinous carcinoma as a potential part of the differential diagnosis for malignant eyelid lesions, including those present in patients with HIV

Space‐Borne Cloud‐Native Satellite‐Derived Bathymetry (SDB) Models Using ICESat‐2 And Sentinel‐2

Shallow nearshore coastal waters provide a wealth of societal, economic, and ecosystem services, yet their topographic structure is poorly mapped due to a reliance upon expensive and time intensive methods. Space-borne bathymetric mapping has helped address these issues, but has remained largely dependent upon in situ measurements. Here we fuse ICESat-2 lidar data with Sentinel-2 optical imagery, within the Google Earth Engine cloud platform, to create openly available spatially continuous high-resolution bathymetric maps at regional-to-national scales in Florida, Crete and Bermuda. ICESat-2 bathymetric classified photons are used to train three Satellite Derived Bathymetry (SDB) methods, including Lyzenga, Stumpf, and Support Vector Regression algorithms. For each study site the Lyzenga algorithm yielded the lowest RMSE (approx. 10%–15%) when compared with validation data. We demonstrate a means of using ICESat-2 for both model calibration and validation, thus cementing a pathway for fully space-borne estimates of nearshore bathymetry in shallow, clear water environments