HoxA3 is an apical regulator of haemogenic endothelium.

During development, haemogenesis occurs invariably at sites of vasculogenesis. Between embryonic day (E) 9.5 and E10.5 in mice, endothelial cells in the caudal part of the dorsal aorta generate haematopoietic stem cells and are referred to as haemogenic endothelium. The mechanisms by which haematopoiesis is restricted to this domain, and how the morphological transformation from endothelial to haematopoietic is controlled are unknown. We show here that HoxA3, a gene uniquely expressed in the embryonic but not yolk sac vasculature, restrains haematopoietic differentiation of the earliest endothelial progenitors, and induces reversion of the earliest haematopoietic progenitors into CD41-negative endothelial cells. This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1. Through loss-of-function, and gain-of-function epistasis experiments, and the identification of antipodally regulated targets, we show that among these factors, Runx1 is uniquely able to erase the endothelial program set up by HoxA3. These results suggest both why a frank endothelium does not precede haematopoiesis in the yolk sac, and why haematopoietic stem cell generation requires Runx1 expression only in endothelial cells

Radiomics-Based Outcome Prediction for Pancreatic Cancer Following Stereotactic Body Radiotherapy

(1) Background: Radiomics use high-throughput mining of medical imaging data to extract unique information and predict tumor behavior. Currently available clinical prediction models poorly predict treatment outcomes in pancreatic adenocarcinoma. Therefore, we used radiomic features of primary pancreatic tumors to develop outcome prediction models and compared them to traditional clinical models. (2) Methods: We extracted and analyzed radiomic data from pre-radiation contrast-enhanced CTs of 74 pancreatic cancer patients undergoing stereotactic body radiotherapy. A panel of over 800 radiomic features was screened to create overall survival and local-regional recurrence prediction models, which were compared to clinical prediction models and models combining radiomic and clinical information. (3) Results: A 6-feature radiomic signature was identified that achieved better overall survival prediction performance than the clinical model (mean concordance index: 0.66 vs. 0.54 on resampled cross-validation test sets), and the combined model improved the performance slightly further to 0.68. Similarly, a 7-feature radiomic signature better predicted recurrence than the clinical model (mean AUC of 0.78 vs. 0.66). (4) Conclusion: Overall survival and recurrence can be better predicted with models based on radiomic features than with those based on clinical features for pancreatic cancer

Weekly Wellness Program

My capstone project brings to light some reasons why employees do not participate in in-house wellness programs which can worsen the feelings of burnout and isolation at work. A weekly wellness program, consisting of short and fun wellness activities, will help people be resilient physically and mentally

Using historical data and CMMS to track and manage preventative maintenance and emerging costs for fleet vehicles on a university campus

Indiana University Purdue University IndianapolisMaintenance of vehicle fleets can be costly and cumbersome if done inefficiently or incorrectly. This project will look at how computerized maintenance management systems (CMMS) can be used to more efficiently manage the preventative maintenance program for a large fleet of vehicles at a university campus. Preventative maintenance programs can be difficult to implement, even more so when CMMS is being used to track and monitor the programs. It takes collaboration and buy-in between several groups to have this process go smoothly. This project will need to document all vehicular assets within the current vehicle pool and their required preventative maintenance. This data will then be used to create a maintenance program through a CMMS that is expected to decrease corrective maintenance, effectively increasing more efficient and sustainable predicative maintenance. Historical maintenance data will be used to identify failure trends in each of the vehicles that is used during snow removal at the University of Chicago. These trends will then be used to project emerging costs.Facilities Management Technolog

BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery.

Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2-deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2-deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation

Predicting Fault Transients on Underground Residential Distribution Systems - A Project of the Purdue Electric Power Center

This thesis addresses the problem of calculating and utilizing the voltage and current transients that may occur in underground residential distribution (URD) systems. A computational model for such systems is proposed and evaluated by comparisons to experimental results. The propagation characteristics of standard URD cables are complex but central to the computational model. The specific objective of this study was to determine whether a relatively simple approximation for the cable propagation constant is accurate enough that, when incorporated into the computational model for the transients resulting from a fault in the system, the resulting fault transient can be utilized to locate the fault. The conclusion is that over a frequency range of approximately 0.1 to 10 MHz, the computational model does provide a useful description of the transients. The approximation for the cable propagation constant does seem to provide adequate information about the variation with frequency of the phase constant and the attenuation constant when plausible ad hoc values of the parameters are included. The computational model is simple and quick to evaluate. It is based on standard lattice diagram analysis of the multiple reflections in the system. The model provides an approximation to the impulse response of the system, when the impulse is applied at various positions in the system

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

The Grave affair and other Gothic romances

LD2668 .R4 SPCH 1988 R89Master of ArtsCommunication Studie

Registered nurses\u27 lived experiences of peer-to-peer incivility in the workplace

This qualitative study explored registered nurses lived experiences of peer-to-peer incivility in the workplace and to the effect of incivility on patient safety and nursing job satisfaction and retention. Study findings, inform required actions to elevate the work atmosphere from uncivil to a healthy workplace for nurses