Differential binding of Escherichia coli McrA protein to DNA sequences that contain the dinucleotide m5CpG

The Escherichia coli McrA protein, a putative C5-methylcytosine/C5-hydroxyl methylcytosine-specific nuclease, binds DNA with symmetrically methylated HpaII sequences (Cm5CGG), but its precise recognition sequence remains undefined. To determine McrA’s binding specificity, we cloned and expressed recombinant McrA with a C-terminal StrepII tag (rMcrA-S) to facilitate protein purification and affinity capture of human DNA fragments with m5C residues. Sequence analysis of a subset of these fragments and electrophoretic mobility shift assays with model methylated and unmethylated oligonucleotides suggest that N(Y > R) m5CGR is the canonical binding site for rMcrA-S. In addition to binding HpaII-methylated double-stranded DNA, rMcrA-S binds DNA containing a single, hemimethylated HpaII site; however, it does not bind if A, C, T or U is placed across from the m5C residue, but does if I is opposite the m5C. These results provide the first systematic analysis of McrA’s in vitro binding specificity

Curriculum Guidelines for Undergraduate Programs in Data Science

The Park City Math Institute (PCMI) 2016 Summer Undergraduate Faculty Program met for the purpose of composing guidelines for undergraduate programs in Data Science. The group consisted of 25 undergraduate faculty from a variety of institutions in the U.S., primarily from the disciplines of mathematics, statistics and computer science. These guidelines are meant to provide some structure for institutions planning for or revising a major in Data Science

(6S)-2,4-Di-tert-butyl-6-[(4S,5R)-3-iso­propyl-4-methyl-5-phenyloxazolidin-2-yl]phenol

The title oxazolidine compound, C27H39NO2, was synthesized from N-isopropyl­norephedrine. The dihedral angle between the aromatic rings is 70.33 (5)°. The N atom of the heterocycle is oriented to allow intra­molecular O—H⋯N hydrogen bonding with the hydr­oxy substituent

Curriculum Guidelines for Undergraduate Programs in Data Science

The Park City Math Institute 2016 Summer Undergraduate Faculty Program met for the purpose of composing guidelines for undergraduate programs in data science. The group consisted of 25 undergraduate faculty from a variety of institutions in the United States, primarily from the disciplines of mathematics, statistics, and computer science. These guidelines are meant to provide some structure for institutions planning for or revising a major in data science

Ruled Legendrian knots and Lagrangian surfaces

We first review some basic facts of contact and symplectic topology. Symplectic cobordisms are the objects that bring these two worlds together: they are symplectic manifolds with contact manifolds as their boundary. Lagrangian submanifolds in a symplectic cobordism limit to Legendrian submanifolds on the boundary. When the symplectic manifold is four-dimensional and the contact manifolds are three- dimensional, the Legendrian submanifolds are knots and links. We review certain restrictions on the classical invariants of such Legendrian knots imposed by the relation of Lagrangian cobordism. Then we specialize to Legendrian knots in the 3-sphere as the boundary of Lagrangian surfaces in the 4-ball. Much of the recent research in this area uses tools related to contact homology. In particular, we explore the notion of a ruling of a Legendrian knot. After defining the ruling polynomial, we show several new ways to compute it, including the extension of a skein relation for ungraded rulings to integer graded rulings. We show how certain kinds of ribbon knots always give rise to rulings. Finally, we construct for any ruled Legendrian knot an immersed Lagrangian surface bounded by the kno

Ruled Legendrian knots and Lagrangian surfaces

We first review some basic facts of contact and symplectic topology. Symplectic cobordisms are the objects that bring these two worlds together: they are symplectic manifolds with contact manifolds as their boundary. Lagrangian submanifolds in a symplectic cobordism limit to Legendrian submanifolds on the boundary. When the symplectic manifold is four-dimensional and the contact manifolds are three- dimensional, the Legendrian submanifolds are knots and links. We review certain restrictions on the classical invariants of such Legendrian knots imposed by the relation of Lagrangian cobordism. Then we specialize to Legendrian knots in the 3-sphere as the boundary of Lagrangian surfaces in the 4-ball. Much of the recent research in this area uses tools related to contact homology. In particular, we explore the notion of a ruling of a Legendrian knot. After defining the ruling polynomial, we show several new ways to compute it, including the extension of a skein relation for ungraded rulings to integer graded rulings. We show how certain kinds of ribbon knots always give rise to rulings. Finally, we construct for any ruled Legendrian knot an immersed Lagrangian surface bounded by the kno

Abstract B59: Analysis of High-Grade Serous Ovarian Cancer in a Cohort of Women diagnosed Epithelial Ovarian Cancer at University of Miami/Jackson Memorial Hospital

Abstract Background: High-grade serous ovarian (HGSC) cancer is the most common and aggressive histotype of epithelial ovarian cancer in women, accounting for 75% of epithelial ovarian carcinomas. Most women present at advanced stages III/IV at diagnosis and 5-year survival for patients with advanced stage disease is approximately 20-30%. However, for patients with stage I disease, five-year survival rates exceed 90%. Ovarian cancer risk factors include nulliparity, early age of menarche, late age of menopause, hormone replacement, obesity and strong family history of hereditary breast and ovarian cancer (HBOC). It is estimated that about 1 in 500 Americans have a mutation in BRCA1 or BRCA2. In women with a germline mutation there is a lifetime risk of: 40%-60% (BRCA1) and 11%-27% (BRCA2), of developing ovarian cancer. Recent studies of different immigrant populations in the United States and in their respective countries of origin have identified pockets of women who bare a similarly high genetic burden as the Ashkenazi Jewish population. Women of Bahamian and Trinidadian heritage are estimated to have 27.1% of breast cancer cases due to BRCA founder mutations. The ovarian cancer burden in these isolated high-risk populations is still unclear, but likely to be as high as those women of Ashkenazi descent. South Florida has the highest Caribbean immigrant community in the US and nearly 4 out of 10 immigrants in Florida were born in the Caribbean. We sought to elucidate the patient demographic, pathologic, and outcome within a university health system between the safety net hospital - Jackson Memorial Hospital (JMH) and the Sylvester comprehensive cancer center (SCCC). Methods: We conducted a retrospective chart review study of women diagnosed with epithelial ovarian cancer with the high-grade serous carcinoma histotype at Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital between 2011 and 2015. We collected data including date of diagnosis, age, body mass index (BMI), country of birth, ethnicity, germ-line and somatic genetic tests results, medical insurance, treatment and vital status. SPSS software was used to analyze using independent samples t-tests when parametric and using Wilcoxon-Mann-Whitney tests when non-parametric; and Chi-squared tests for categorical and binary data. Results: 374 patients were diagnosed and treated for high-grade serous ovarian cancer (HGSC). 50.8% were non-Hispanic, 47.9% Hispanic and 1.3% Unknown. 12.% of the patient population was Black with a significantly higher BMI (39.1 vs 27.9, p=0.004). Mean age was 58 (Hispanic white 57.7yrs (17-93), non-Hispanic white 58.5yrs (17-93) and Black (53.7yrs (18-78), p=0.019)) compared to US national average of 63. At least 32.3% of patients were born in the US while, 60% of patients were born in Latin America and the Caribbean. 72.3% of patients born outside the US were diagnosed and treated at JMH (p&amp;lt;0.001). In a subset analysis of 102 patients, 31% had genetic or somatic testing, of these, 2 patients were Black, not of Afro-Caribbean descent. Patients at JMH presented with 8% Stage I vs 74.7% Stage III/IV, compared to 16.3% Stage I vs 73% Stage IV at SCCC. They had more advanced stage V - 42.7% vs 16.3% at SCCC. JMH patients were more likely to be on Medicaid or uninsured (68% vs 14.2%, p&amp;lt;0.001). Median survival was 47.0 months (44.1-49.9) at SCCC compared to 45.0 months (37.6-52.3) for women at JMH (p=0.392). Conclusion: The majority of women sought care at the SCCC when diagnosed with HGSC had a higher likelihood of early stage diagnosis, were insured and born in the USA, there was no difference in outcome between patients treated at JMH versus SCCC. Genetic testing within the Black population was low compared to Hispanic and non-Hispanic white patients. This data indicate that the quality of care received in this university health system is similar at both sites. Further studies are indicated to explore uptake of genetic testing, disparities between safety net systems and comprehensive cancer centers, particularly with the shift toward targeted disease prevention and personalized therapy. Note: This abstract was not presented at the conference. Citation Format: Sophia HL George, Marilyn Huang, Leah Dodds, Raleigh Butler, Sean Oldak, Moraima Batista, Judith Hurley, Joseph Pearson, Erin Kobetz, Brian Slomovitz. Analysis of High-Grade Serous Ovarian Cancer in a Cohort of Women diagnosed Epithelial Ovarian Cancer at University of Miami/Jackson Memorial Hospital. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B59.</jats:p

Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma.

Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples according to neuronal development gene expression programs that could also be delineated by differences in magnetic resonance blood perfusion. Exome sequencing and phylogenetic analysis reveal epigenomic intratumor heterogeneity and suggest that chromosomal structural alterations may precede accumulation of single-nucleotide variants during ependymoma tumorigenesis. In sum, these findings shed light on the oncogenesis and intratumor heterogeneity of ependymoma

Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma.

Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples according to neuronal development gene expression programs that could also be delineated by differences in magnetic resonance blood perfusion. Exome sequencing and phylogenetic analysis reveal epigenomic intratumor heterogeneity and suggest that chromosomal structural alterations may precede accumulation of single-nucleotide variants during ependymoma tumorigenesis. In sum, these findings shed light on the oncogenesis and intratumor heterogeneity of ependymoma

Imaging Hypoxia in Orthotopic Rat Liver Tumors with Iodine 124–labeled Iodoazomycin Galactopyranoside PET1

Autoradiographic analysis of the regions of high iodine 124–labeled iodoazomycin galactopyranoside uptake were shown to correspond to regions of intense pimonidazole and EF5 immunohistochemical staining, demonstrating that this tracer colocalizes with markers known to concentrate in tissue hypoxia