Nurturing diversity and inclusion in AI in Biomedicine through a virtual summer program for high school students

Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus, students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at the final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There were also nominally significant increases in the students’ knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater diversity in AI. This work can guide AI training programs aspiring to engage and educate students entirely online, and motivate people in AI to strive towards increasing diversity and inclusion in this field.     

Correlations between the benzene character of acenes or helicenes and simple molecular descriptors

Aromatic stabilities of acenes and helicenes, which are responsible for their biological, environmental and cancerous behavior have been modeled using a newly introduced Sadhana (Sd) and A indices. The results are compared with those obtained from PI (Padmakar-Ivan) index. The regression analysis has shown that excellent results are obtained by considering acenes and helicenes as separate classes of isomeric benzenoid hydrocarbons and that A index is better index than both PI and Sd indices.     

Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human coagulation factor xa. Studies on catalytic efficiency and inhibitor binding

The serine protease domain of factor Xa (FXa) contains a sodium as well as a calcium-binding site. Here, we investigated the functional significance of these two cation-binding sites and their thermodynamic links to the S1 site. Kinetic data reveal that Na(+) binds to the substrate bound FXa with K(d) approximately 39 mm in the absence and approximately 9.5 mm in the presence of Ca(2+). Sodium-bound FXa (sodium-Xa) has approximately 18-fold increased catalytic efficiency ( approximately 4.5-fold decrease in K(m) and approximately 4-fold increase in k(cat)) in hydrolyzing S-2222 (benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide), and Ca(2+) further increases this k(cat) approximately 1.4-fold. Ca(2+) binds to the protease domain of substrate bound FXa with K(d) approximately 705 microm in the absence and approximately 175 microm in the presence of Na(+). Ca(2+) binding to the protease domain of FXa (Xa-calcium) has no effect on the K(m) but increases the k(cat) approximately 4-fold in hydrolyzing S-2222, and Na(+) further increases this k(cat) approximately 1.4-fold. In agreement with the K(m) data, sodium-Xa has approximately 5-fold increased affinity in its interaction with p-aminobenzamidine (S1 site probe) and approximately 4-fold increased rate in binding to the two-domain tissue factor pathway inhibitor; Ca(2+) (+/-Na(+)) has no effect on these interactions. Antithrombin binds to Xa-calcium with a approximately 4-fold faster rate, to sodium-Xa with a approximately 24-fold faster rate and to sodium-Xa-calcium with a approximately 28-fold faster rate. Thus, Ca(2+) and Na(+) together increase the catalytic efficiency of FXa approximately 28-fold. Na(+) enhances Ca(2+) binding, and Ca(2+) enhances Na(+) binding. Further, Na(+) enhances S1 site occupancy, and S1 site occupancy enhances Na(+) binding. Therefore, Na(+) site is thermodynamically linked to the S1 site as well as to the protease domain Ca(2+) site, whereas Ca(2+) site is only linked to the Na(+) site. The significance of these findings is that during physiologic coagulation, most of the FXa formed will exist as sodium-Xa-calcium, which has maximum biologic activity.     

Ultra-rare-event detection performance of a custom scanning cytometer on a model preparation of fetal nRBCs

BACKGROUND: The performance of a fully automated scanning cytometer incorporating previously reported high-precision autofocus and accurate image segmentation was evaluated for the detection of "ultra-rare" cells using a model of fetal nucleated red blood cells (fnRBCs) in the maternal circulation. These distinctive scanning cytometry techniques were expected to markedly improve sensitivity and specificity. METHODS: Normal adult blood and fetal red blood cells were stained with fluorescein isothiocyanate-conjugated anti-fetal hemoglobin and 4,6-diamidino-2-phenylindole, a nuclear dye. Adult cells were spiked with fetal cells to create ratios of about 1 fnRBC in 10(7) nucleated cells and deposited in monolayers on slides using centrifugal cytology. Rare-event performance parameters were reviewed, formalized, and applied to test the new instrument using this cell model. RESULTS: Fifteen slides were analyzed to establish performance by comparison with manual detection, and four sets of four slides each were then scanned to explore the limit of detection. Results were an average sensitivity of 91%, an average specificity error of 12.3 false-positives per million cells, and repeatability of 100% at a cell analysis rate of 862 Hz. With addition of a quick interactive step subsequent to scanning, the false-positive rate dropped to a total of only one artifact over the 15 experiments. The instrument succeeded at locating 1 fnRBC in 20 million adult cells, the lowest limit of detection tested. CONCLUSION: This consistently high performance, coupled with the capability of scanning arbitrarily large numbers of cells, validates the considerable potential of precise high-speed autofocus and accurate real-time image segmentation for ultra-rare event detection.     

Regulation of N-myristoyltransferase by novel inhibitor proteins

N-myristoylation ensures the proper function and intracellular trafficking of proteins. Many proteins involved in a wide variety of signaling, including cellular transformation and oncogenesis, are myristoylated. The myristoylation of proteins is catalyzed by the ubiquitously distributed eukaryotic enzyme N-myristoyltransferase (NMT). Previously, we reported that NMT activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that the increase in NMT activity appears at an early stage in colonic carcinogenesis. Furthermore, we observed that NMT expression is elevated in colorectal and gallbladder carcinoma. In our laboratory, an endogenous NMT inhibitor protein (NIP71) was discovered from bovine brain that inhibited NMT activity in rat colonic tumors. Very recently we have demonstrated that the protein NIP71, which is a potential inhibitor of NMT, is homologous to heat-shock cognate protein (HSC70). In addition, we have discovered that enolase is a potent inhibitor of NMT. Further work may elucidate the role of HSC70 and/or enolase in the regulation of NMT, which may lead to the development of a gene-based therapy of colorectal cancer. The interaction of oncoproteomic and oncogenomic data sets through powerful bioinformatics will yield a comprehensive database of protein properties, which will serve as an invaluable tool for cancer researchers to understand the progress of tumorigenesis.     

Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities

Variety of N-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)-2,4(un)substituted acridin-9-amine (4a-o) and 1-[(2,4-(un)substituted acridin-9-yl)-3-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)]isothiourea (5a-h) derivatives have been synthesized by condensation of 4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-imine (3a-g) with 9-chloro-2,4-(un)substituted acridine (1a-c) and 9-isothiocyanato-2,4-(un)substituted acridine (2a-d), respectively. All these compounds were characterized by correct 1H NMR, FT-IR, MS and elemental analyses. These compounds were screened for anti-inflammatory, analgesic and kinase (CDK1, CDK5 and GSK3) inhibition activities. Some compounds exhibited good anti-inflammatory (25-32%) and potent analgesic (50-75%) activities, at 50 mg/kg p.o. A compound, 4o (R1 = H, R2 = OCH3, R3 = CH3, R4 = CH3, R5 = H) exhibited moderate CDK1 (IC50 = 8.5 microM) inhibition activity.     

Compressed representations of macromolecular structures and properties

We introduce a new and unified, compressed volumetric representation for macromolecular structures at varying feature resolutions, as well as for many computed associated properties. Important caveats of this compressed representation are fast random data access and decompression operations. Many computational tasks for manipulating large structures, including those requiring interactivity such as real-time visualization, are greatly enhanced by utilizing this compact representation. The compression scheme is obtained by using a custom designed hierarchical wavelet basis construction. Due to the continuity offered by these wavelets, we retain very good accuracy of molecular surfaces, at very high compression ratios, for macromolecular structures at multiple resolutions.     

Topochemical model for prediction of anti-HIV activity of HEPT analogs

The relationship between the superadjacency topochemical index and the anti-HIV activity of HEPT analogs has been investigated in the present study. The values of superadjacency topochemical index of all the analogs involved in the data set were calculated using an in-house computer program. Resulting data were analyzed and a suitable model was developed after identification of the active range. Subsequently, a computed biological activity was assigned to each of the compounds involved in the dataset, which was then compared with the reported anti-HIV activity. Accuracy of prediction was found to be 88% using the said model. The predictive ability of the model indicates that this model can be used for predicting the anti-HIV activity of the compounds prior to synthesis and may prove to be highly beneficial for providing lead structures for development of potent anti-HIV agents.     

Comparison of marker types and map assumptions using Markov chain Monte Carlo-based linkage analysis of COGA data

We performed multipoint linkage analysis of the electrophysiological trait ECB21 on chromosome 4 in the full pedigrees provided by the Collaborative Study on the Genetics of Alcoholism (COGA). Three Markov chain Monte Carlo (MCMC)-based approaches were applied to the provided and re-estimated genetic maps and to five different marker panels consisting of microsatellite (STRP) and/or SNP markers at various densities. We found evidence of linkage near the GABRB1 STRP using all methods, maps, and marker panels. Difficulties encountered with SNP panels included convergence problems and demanding computations.