RELATIONSHIPS AMONG COMMUNITIES, IDENTITIES, AND ACADEMIC PERFORMANCE OF AFRICAN AMERICAN ENGINEERING UNDERGRADUATES

A potential barrier to increasing diversity in engineering may be the failure of engineering colleges within predominantly White institutions (PWI's) to understand, acknowledge, and/or accommodate the unique perspectives of its under-represented minority students. Numerous studies have shown us that the success of many under-represented minority students at PWI's may be impacted by lack of community, feelings of isolation from their culture, and disidentification within their field (Foor, Walden, & Trytten, 2007; Seymour & Hewitt, 1997; Shehab et al., 2007; Shehab, Murphy, & Foor, 2011; Walden & Shehab, 2009).This study represents a phenomenological analysis of data collected by the Research Institute for STEM Education (RISE), who conducted a study seeking to identify factors contributing to the success of under-represented and under-served minority engineering students at a predominantly White research institution. Minority undergraduate engineering students participated in face-to-face interviews designed to engage them in reflection and discussion of their experiences as engineering students. The interview data for 19 successful African American undergraduate engineering students were selected from three academic performance groups: excellers, persisters, and strugglers. Their interview data were analyzed to address the question of how community and identity contribute to the academic achievement of successful African American engineering undergraduates of a predominantly White institution.To answer this question, student experiential narratives were interpreted through the lenses of community, Black identity, and engineering identity to better understand how these constructs influence the student academic performances. Results suggest that community, Black identity, engineering identity, and academic performance may moderate each other. Students found community in different places based on their academic grouping. Excellers found community in a wider range of places and were most likely to find community in engineering organizations with majority White membership. Persisters and strugglers were more limited in the places they found community and mostly participated in more ethnocentric organizations. Persisters and Strugglers were more reliant on Black reference groups for community than were excellers, indicating stronger reliance on same race communities. Engineering discursive identity increased as academic performance increased. Surprisingly, several students from each grouping held negative images of engineers which often clashed with their own identities, perhaps suggesting a potential friction between Black and Engineering identities

Toward the Construction of an Efficient Set of Robot Arm Operator Performance Metrics

As part of a larger project to identify and validate relevant quantitative measures of robot arm operator proficiency, fifteen metrics of arm maneuvering and hand controller performance were defined and measured for 3-DOF translational movement tasks. Twelve freshly trained operators provided performance data for seven target-acquisition task scenarios involving a variety of distance combinations along the X, Y, and Z axes. Metrics included indicators of task component times, distance traveled, inefficient (inverse) motion, maximum velocities, amount of multi-axis control, and input control onset times along the three axes. Pairwise correlations of all measures and scatter plots of variables yielding strong intercorrelations were examined to determine the potential underlying causes of the significant relationships. By identifying subsets of metrics with explainable co-dependencies, the overall metric set can be reduced to a limited number of key metrics that serve as effective discriminators of operator performance.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Construction of a Bivalent Thrombin Binding Aptamer and Its Antidote with Improved Properties

Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson–Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often. In this study, we have chemically modified the design of previously described thrombin binding aptamers targeting exosites I, HD1, and exosite II, HD22. The individual aptamers were first modified with an inverted deoxythymidine nucleotide, and then constructed bivalent aptamers by connecting the HD1 and HD22 aptamers either through a triethylene glycol (TEG) linkage or four consecutive deoxythymidines together with an inverted deoxythymidine nucleotide at the 3′-end. The anticoagulation potential, the reversal of coagulation with different antidote sequences, and the nuclease stability of the aptamers were then investigated. The results showed that a bivalent aptamer RNV220 containing an inverted deoxythymidine and a TEG linkage chemistry significantly enhanced the anticoagulation properties in blood plasma and nuclease stability compared to the existing aptamer designs. Furthermore, a bivalent antidote sequence RNV220AD efficiently reversed the anticoagulation effect of RNV220 in blood plasma. Based on our results, we believe that RNV220 could be developed as a potential anticoagulant therapeutic molecule

Construction of a Bivalent Thrombin Binding Aptamer and Its Antidote with Improved Properties

Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson–Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often. In this study, we have chemically modified the design of previously described thrombin binding aptamers targeting exosites I, HD1, and exosite II, HD22. The individual aptamers were first modified with an inverted deoxythymidine nucleotide, and then constructed bivalent aptamers by connecting the HD1 and HD22 aptamers either through a triethylene glycol (TEG) linkage or four consecutive deoxythymidines together with an inverted deoxythymidine nucleotide at the 3′-end. The anticoagulation potential, the reversal of coagulation with different antidote sequences, and the nuclease stability of the aptamers were then investigated. The results showed that a bivalent aptamer RNV220 containing an inverted deoxythymidine and a TEG linkage chemistry significantly enhanced the anticoagulation properties in blood plasma and nuclease stability compared to the existing aptamer designs. Furthermore, a bivalent antidote sequence RNV220AD efficiently reversed the anticoagulation effect of RNV220 in blood plasma. Based on our results, we believe that RNV220 could be developed as a potential anticoagulant therapeutic molecule

Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity

Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis.As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies

Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs

Autophosphorylation of a critical residue in the activation loop of several protein kinases is an essential maturation event required for full enzyme activity. However, the molecular mechanism by which this happens is unknown. We addressed this question for two dual-specificity tyrosine-phosphorylation-regulated protein kinases (DYRKs), as they autophosphorylate their activation loop on an essential tyrosine but phosphorylate their substrates on serine and threonine. Here we demonstrate that autophosphorylation of the critical activation-loop tyrosine is intramolecular and mediated by the nascent kinase passing through a transitory intermediate form. This DYRK intermediate differs in residue and substrate specificity, as well as sensitivity to small-molecule inhibitors, compared with its mature counterpart. The intermediate’s characteristics are lost upon completion of translation, making the critical tyrosine autophosphorylation a “one-off” inceptive event. This mechanism is likely to be shared with other kinases