Prelude Mixed-Use Development – Business Plan

The purpose of this paper is to assess the feasibility of Prelude, a land development project that proposes a mix of uses in City Centre, Surrey, BC. Market research needed to focus on both hotel and condominium markets. Additional research was needed to confirm the cost projections of the pro forma. Research was collected in several ways. Some data was mined from municipal websites, other data was gleaned from industry organizations and even further material was harvested from talks with industry experts. Research results largely supported the projections of the pro forma. However, in some cases, the results prompted changes to the financial forecasts. Results also identified certain risks and caused mitigating solutions to be considered. The process resulted in the project being recommended for investment

Examining Student Mentorship Experiences in an Online Doctoral Program

As more students elect to complete their doctoral studies online, faculty need to identify and implement mentorship approaches that are conducive to student understanding of the dissertation process. Faculty to mentee relationships are a prominent aspect of student retention and success in doctoral programs. Due to advances in technology, dissertation chairs have access to tools that allow for real-time feedback and support. Therefore, this study examined student dissertation and faculty mentorship experiences. Participants expressed satisfaction in their doctoral studies and dissertation process. However, students shared challenges associated with balancing multiple commitments, feeling lower levels of writing self-confidence, and understanding the dissertation process and expectations. These findings provide additional support on the importance of developing and maintaining positive online doctoral experiences

The Value of Comparative Animal Research : Krogh’s Principle Facilitates Scientific Discoveries

There are no conflicts of interest to declare. This paper developed from the 2016 Early Career Impact Award from the Federation of Associations in Behavioral & Brain Sciences to TJS. TJS has received funding from The Leverhulme Trust. FJPE is in receipt of funding from the BBSRC (BB/M001555/1). The National Institutes of Health has funded RDF (NS 034950, NS093277, NIMH 087930), AGO (HD079573, IOS-1354760) and AMK (HD081959). BAA is an Arnold O. Beckman postdoctoral fellow.Peer reviewedPostprin

Expression of miR-145 and miR-449 in U87 Glioblastoma Cells

MicroRNAs are known to play a critical oncogenic role in glioblastoma. Several miRNAs have been shown to play roles in growth and cell cycle control in glioblastoma, and have potential as diagnostic markers or as therapeutic targets. miRNA-145 is overexpressed in glioblastoma and is thought to downregulate srGAP1 (SLIT-ROBO Rho GTPase-activating protein1), which promotes an invasive phenotype. This is in contrast to miRNA-145’s proposed tumor-supressive role in many other cancers (1). miRNA-449 is thought to be a tumor suppressor that interrupts the cell cycle and induces apoptosis via suppression of E2F1, CCND1, and GPR158. Therefore it is highly downregulated in many tumor cells (2,3). Both miRNAs-145 and -449 are the topic of continued inquiry in understanding their expression and their molecular targets in glioma cells. Here we attempt to establish the baseline expression of miRNA-145 and miRNA-449 in the U87 cell line using RT-PCR. Weekly passaging of cells was carried out, followed by RNA isolation and RT-PCR. Baseline average concentrations were established for miRNA-145 and miRNA-449 using a set of serial dilutions and a standard curve. Further experimentation will be required to establish a baseline concentration for these miRNAs in healthy glial cells

10 Habits of Successful College Students

Student assignment: As a class, create a group poster that incorporates the following habits discussed in class: organization, study systems, choosing friends carefully, sex and relationships, careers over majors, learning over grades, health and exercise, failing courses, parting, and managing money

Sustainable Sourcing of Global Agricultural Raw Materials: Assessing Gaps in Key Impact and Vulnerability Issues and Indicators.

Understanding how to source agricultural raw materials sustainably is challenging in today's globalized food system given the variety of issues to be considered and the multitude of suggested indicators for representing these issues. Furthermore, stakeholders in the global food system both impact these issues and are themselves vulnerable to these issues, an important duality that is often implied but not explicitly described. The attention given to these issues and conceptual frameworks varies greatly--depending largely on the stakeholder perspective--as does the set of indicators developed to measure them. To better structure these complex relationships and assess any gaps, we collate a comprehensive list of sustainability issues and a database of sustainability indicators to represent them. To assure a breadth of inclusion, the issues are pulled from the following three perspectives: major global sustainability assessments, sustainability communications from global food companies, and conceptual frameworks of sustainable livelihoods from academic publications. These terms are integrated across perspectives using a common vocabulary, classified by their relevance to impacts and vulnerabilities, and categorized into groups by economic, environmental, physical, human, social, and political characteristics. These issues are then associated with over 2,000 sustainability indicators gathered from existing sources. A gap analysis is then performed to determine if particular issues and issue groups are over or underrepresented. This process results in 44 "integrated" issues--24 impact issues and 36 vulnerability issues--that are composed of 318 "component" issues. The gap analysis shows that although every integrated issue is mentioned at least 40% of the time across perspectives, no issue is mentioned more than 70% of the time. A few issues infrequently mentioned across perspectives also have relatively few indicators available to fully represent them. Issues in the impact framework generally have fewer gaps than those in the vulnerability framework

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150

Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53

The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers