William M. Wooten, PhD, Oral History Interview, July 6, 2017

Major Topics Covered: Personal background and education Professional path and evolution of a unique perspective on organizational development The field of organizational psychology and its relevance to MD Anderson Critical evaluation of how MD Anderson functions as an organization Anecdotes to demonstrate process improvement at many levels of organizational function Commentary on executive leadership Views on MD Anderson presidents and shifts in administrationhttps://openworks.mdanderson.org/mchv_interviewsessions/1175/thumbnail.jp

William M. Wooten, PhD, Oral History Interview, July 12, 2017

Major Topics Covered: Personal background and education Professional path and evolution of a unique perspective on organizational development The field of organizational psychology and its relevance to MD Anderson Critical evaluation of how MD Anderson functions as an organization Anecdotes to demonstrate process improvement at many levels of organizational function Commentary on executive leadership Views on MD Anderson presidents and shifts in administrationhttps://openworks.mdanderson.org/mchv_interviewsessions/1176/thumbnail.jp

Brain deposition of gadobutrol in children—a cross-sectional and longitudinal MRI T1 mapping study

Objectives:Depositions of linear gadolinium-based MRI contrast agents are readily visible in T1-weighted MRIs of certain brain regions in both adults and children. Macrocyclic contrast agents such as gadobutrol have so far escaped detection by qualitative MRI in children. This study aimed to assess whether there is evidence for deposition of gadobutrol in children using quantitative T1 mapping.Methods:This retrospective study included patients, naive to other gadolinium-based contrast agents than gadobutrol, who had received gadobutrol as part of a clinically indicated MRI. For each patient, T1 relaxation times at 3 T were measured using single-shot T1 mapping at two time points. In each of six brain regions, age-adjusted T1 relaxation times were correlated with a number of previous gadobutrol administrations. To combine interindividual, cross-sectional effects with intraindividual, longitudinal effects, both linear mixed model and generalized additive mixed model were applied.Results:One hundred four examinations of 52 children (age median 11.4, IQR 6.3–15, 26 female) with a median of 7 doses of gadobutrol in the history of their neurological or neurooncological disease were included. After correction for age and indeterminate disease-related effects to T1 time, a negative correlation of T1 time with the number of gadobutrol doses administered was observed in both mixed models in the putamen (beta − 1.65, p = .03) and globus pallidus (beta − 1.98, p = .012)Conclusions:The results indicate that in children, gadobutrol is deposited in the globus pallidus and putamen

MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4

MicroRNA-21 (miR-21) is a key regulator of oncogenic processes. It is significantly elevated in the majority of human tumors and functionally linked to cellular proliferation, survival and migration. In this study, we used two experimental-based strategies to search for novel miR-21 targets. On the one hand, we performed a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE) to identify proteins suppressed upon enhanced miR-21 expression in LNCaP human prostate carcinoma cells. The tumor suppressor acidic nuclear phosphoprotein 32 family, member A (ANP32A) (alias pp32 or LANP) emerged as the most strongly downregulated protein. On the other hand, we applied a mathematical approach to select correlated gene sets that are negatively correlated with primary-miR-21 (pri-miR-21) expression in published transcriptome data from 114 B-cell lymphoma cases. Among these candidates, we found tumor suppressor SMARCA4 (alias BRG1) together with the already validated miR-21 target, PDCD4. ANP32A and SMARCA4, which are both involved in chromatin remodeling processes, were confirmed as direct miR-21 targets by immunoblot analysis and reporter gene assays. Furthermore, knock down of ANP32A mimicked the effect of enforced miR-21 expression by enhancing LNCaP cell viability, whereas overexpression of ANP32A in the presence of high miR-21 levels abrogated the miR-21-mediated effect. In A172 glioblastoma cells, enhanced ANP32A expression compensated for the effects of anti-miR-21 treatment on cell viability and apoptosis. In addition, miR-21 expression clearly increased the invasiveness of LNCaP cells, an effect also seen in part upon downregulation of ANP32A. In conclusion, these results suggest that downregulation of ANP32A contributes to the oncogenic function of miR-21

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

A New Fault Location Algorithm for Use with Current Differential Protective Relays of Two-Terminal Line

A new fault location algorithm utilising synchronised measurements of two-end currents and one-end voltage is presented. It has been assumed that such fault location algorithm is incorporated into the current differential relay. In this way, the communication between the line ends of differential relays is utilised. By incorporating the fault location function, an increase of the relay functionality is achieved. The derived fault location formula is compact and covers different fault types – what requires setting the appropriate fault type coefficients. High accuracy of fault location is assured by strict considering of the distributed parameter line model. The solution is obtained with applying iterative calculations based on the Newton- Raphson method. For starting the calculations, the solutions obtained for the lumped line model are utilised. The performed ATP-EMTP evaluation prove the validity of the presented fault location algorithm and its high accuracy

Chapter 03: In Medical School

The next chapter begins as the Interviewer recaps Dr. Bruner\u27s educational track, providing institution names and dates. Dr. Bruner then explains the professional and personal reasons why she left Toledo for a medical school in Ann Arbor, then returned to study at the Medical College of Ohio. She covers her experiences in a unique, year-long student clerkship at the latter institution, and offers a moving anecdote about performing an autopsy on an elderly man who had been stabbed seventy times, an experience (among many) that convinced her she did not want to enter forensic pathology, as she first thought she might.https://openworks.mdanderson.org/mchv_interviewchapters/1510/thumbnail.jp