Responsible Collaborations: Scholarship and Cultural Heritage Assets

I recently served as a national consultant on collaborations between libraries and museums. There are not that many articles published about collaborations and cultural heritage collections, although I suspect many unreported activities are being done in the field. From the 2009 program my College Libraries Section (CLS) committee developed when I was CLS chair on town/gown relationships (Our Town, Common Ground) with public and academic librarian panelists to a 2016 article, cultural heritage institutions and collaboration has been a focus of mine. My life and work experiences gave me a broad exposure to a wide variety of cultures, cultural norms, and an appreciation and valuing of diversity, equity, and inclusion

Morphological analysis of cells by means of an elastic metric in the shape space

Shape analysis is of great importance in many fields, such as computer vision, medical imaging, and computational biology. This analysis can be performed considering shapes as closed planar curves in the shape space. This approach has been used for the first time to obtain the morphological classification of erythrocytes in digital images of sickle cell disease considering the shape space S1, which has the property of being isometric to an infinite-dimensional Grassmann manifold of two-dimensional subspaces (Younes et al., 2008), without taking advantage of all the features offered by the elastic metric related to the possibility of stretching and bending of the curves. In this paper, we study this deformation in the shape space, S2, which is based on the representation of closed planar curves by means of the square-root velocity function (SRVF) (Srivastava et al., 2011), using the elastic metric of this space to obtain more efficient geodesics and geodesic lengths between planar curves. Supervised classification with this approach achieved an accuracy of 94.3%, classification using templates achieved 94.2% and unsupervised clustering in three groups achieved 94.7%, considering three classes of erythrocytes: normal, sickle, and with other deformations. These results are better than those previously achieved in the morphological analysis of erythrocytes and the method can be used in different applications related to the treatment of sickle cell disease, even in cases where it is necessary to study the process of evolution of the deformation, something that can not be done in a natural way in the feature space

The Triple Bottom Line: Portable Applications and Best Practices for Sustainability in Academic Libraries

Triple Bottom Line Accounting (TBLA) refers to a method of measuring the economic, environmental, and community service impacts of an organization rather than the traditional practice of measuring just the financial bottom line. This chapter explores TBLA from a historical point-of-view; offers examples in higher education and discusses the implications for academic libraries. It concludes with ideas for the implementation of TBLA in libraries

Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a

SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as a potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first co-crystal structure of G9a with a small molecule inhibitor, was obtained. The co-crystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin remodeling

Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines.

Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is over expressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth and the di-methylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a-10 complex, the first co-crystal structure of G9a with a small molecule inhibitor, was obtained. Based on the structural insights revealed by this co-crystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison Ki = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies