Exploration of Risk Management Process Usage Levels and Their Relationship to Project Outcomes

Project management processes such as risk management are used in many organizations however; research shows risk management is the least mature of all project management knowledge areas. This is important because poor risk management is one of many challenges on IS/IT projects that can lead to failure. The goal of this paper is to determine if the level of actual risk management process usage is important to successful project outcomes. A research study was conducted which surveyed over 550 project management practitioners about risk management on their own virtual IS/IT project. Survey responses were analyzed and a correlation analysis was conducted to determine if a relationship existed between risk management process usage and project outcome. The results indicated there was a definite relationship and specifically the “high usage” level of risk management processes is important to successful project outcomes while other lower levels are not as important

Enhancing Software Development in the MIS Curriculum using Pair Programming

Management Information Systems (MIS) majors often must perfect their programming skills with one course which can be a daunting task. In an effort to enhance the software development abilities of MIS majors a pair programming lab experiment was conducted in an introductory software development course to determine if that technique would produce benefits for the MIS curriculum. Pair programming experiments are often performed with Computer Science majors but rarely with MIS majors. The researchers’ observations as well as participant’s responses to a survey questionnaire were analyzed after the experiment. The results indicated that pair programming may be beneficial as a pedagogical tool to a MIS students’ ability to create programs using high-level concepts. Additionally, researcher observations revealed pairs worked collaboratively to produce the program while actively communicating and enjoying the process

Differing Impact Levels from Risk Factors on Virtual and Co-Located Software Development Projects

Although software development projects increasingly incorporate virtual team members they still fall prey to risks which produce challenges as do co-located projects. Most research performed on project risk was conducted on projects using traditional co-located team members. This paper reports on the results of a survey of over 150 Information Technology (IT) practitioners. One goal of the survey was to identify differences in the degree of impact between risk factors on virtual software projects and those on co-located software projects. Out of fifty-five surveyed risk factors, seven risk factors showed significant differences in impact on the successful completion of projects in these two types of project environments. Additionally, the results showed a greater impact for each of the seven risk factors on virtual rather than co-located software projects. These results can be useful to practitioners who are managing in a virtual environment and need to correctly identify potential risks

Small-molecule inhibitors of proteins involved in base excision repair potentiate the anti-tumorigenic effect of existing chemotherapeutics and irradiation

There has been a recent upsurge in the development of small-molecule inhibitors specific to DNA repair proteins or proteins peripherally involved in base excision repair and the DNA damage response. These specific, nominally toxic inhibitors are able to potentiate the effect of existing cancer cell treatments in a wide array of cancers. One of the largest obstacles to overcome in the treatment of cancer is incomplete killing with initial cancer treatments, leading to resistant cancer. The progression of our understanding of cancer and normal cell responses to DNA damage has allowed us to develop biomarkers that we can use to help us predict responses of cancers, more specifically target cancer cells and overcome resistance. Initial successes using these small-molecule DNA repair inhibitors in target-validation experiments and in the early stages of clinical trials indicate an important role for these inhibitors, and allow for the possibility of a future in which cancers are potentially treated in a highly specific, individual manner

Using STEM Camps to Improve Female Interest in Technology Careers

Science, technology, engineering, and math (STEM) fields have been traditionally entered by men, often establishing women as underrepresented in many of these fields. This research study focuses on participants at a STEM camp for middle- and high-school girls designed to introduce them to technology. The camp was held 4 times over 3 years, with many of the participants from rural areas, underrepresented by race and economic status. Sixty camp attendees completed pre- and post-camp surveys and are referred to as the intervention group. A control group of 200 middle- and high-school girls who did not attend the camp also took the survey. This paper focuses on a subset of the survey results that sought to determine the impact on camp participants in the areas of technology self-efficacy and technology career interest as it related to management information systems (MIS). Analysis of the data collected found a significant difference in MIS self-efficacy between the intervention group and control group but no significant difference in choices of MIS-related careers. Results also include recommended improvements to STEM camp design

Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain

Ape1 is a molecule with dual functions in DNA repair and redox regulation of transcription factors. In Ape1-deficient mice, embryos do not survive beyond embryonic day 9, indicating that this molecule is required for normal embryo development. Currently, direct evidence of the role of Ape1 in regulating hematopoiesis is lacking. We used the embryonic stem (ES) cell differentiation system and an siRNA approach to knockdown Ape1 gene expression to test the role of Ape1 in hematopoiesis. Hemangioblast development from ES cells was reduced 2- to 3-fold when Ape1 gene expression was knocked down by Ape1-specific siRNA, as was primitive and definitive hematopoiesis. Impaired hematopoiesis was not associated with increased apoptosis in siRNA-treated cells. To begin to explore the mechanism whereby Ape1 regulates hematopoiesis, we found that inhibition of the redox activity of Ape1 with E3330, a specific Ape1 redox inhibitor, but not Ape1 DNA repair activity, which was blocked using the small molecule methoxyamine, affected cytokine-mediated hemangioblast development in vitro. In summary, these data indicate Ape1 is required in normal embryonic hematopoiesis and that the redox function, but not the repair endonuclease activity, of Ape1 is critical in normal embryonic hematopoietic development

Discovery of macrocyclic inhibitors of apurinic/apyrimidinic endonuclease 1

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential base excision repair enzyme that is upregulated in a number of cancers, contributes to resistance of tumors treated with DNA-alkylating or -oxidizing agents, and has recently been identified as an important therapeutic target. In this work, we identified hot spots for binding of small organic molecules experimentally in high resolution crystal structures of APE1 and computationally through the use of FTMAP analysis (http://ftmap.bu.edu/). Guided by these hot spots, a library of drug-like macrocycles was docked and then screened for inhibition of APE1 endonuclease activity. In an iterative process, hot-spot-guided docking, characterization of inhibition of APE1 endonuclease, and cytotoxicity of cancer cells were used to design next generation macrocycles. To assess target selectivity in cells, selected macrocycles were analyzed for modulation of DNA damage. Taken together, our studies suggest that macrocycles represent a promising class of compounds for inhibition of APE1 in cancer cells.This work was supported by grants from the National Institutes of Health (Grant R01CA205166 to M.R.K. and M.M.G. and Grant R01CA167291 to M.R.K.) and by the Earl and Betty Herr Professor in Pediatric Oncology Research, Jeff Gordon Children's Foundation, and the Riley Children's Foundation (M.R.K.). Work at the BU-CMD (J.A.P., L.E.B., R.T.) is supported by the National Institutes of Health, Grant R24 GM111625. D.B. and S.V. were supported by the National Institutes of Health, Grant R35 GM118078. (R35 GM118078 - National Institutes of Health; R01CA205166 - National Institutes of Health; R01CA167291 - National Institutes of Health; R24 GM111625 - National Institutes of Health; Earl and Betty Herr Professor in Pediatric Oncology Research; Jeff Gordon Children's Foundation; Riley Children's Foundation)Accepted manuscriptSupporting documentatio

Ref-1/APE1 as Transcriptional Regulator and Novel Therapeutic Target in Pediatric T-cell Leukemia

The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia. Leukemia patients' transcriptome databases showed increased expression in T-ALL of Ref-1 and other genes of the Ref-1/SET interactome. Validation studies demonstrated that Ref-1 is expressed in high-risk leukemia T-cells, including in patient biopsies. Ref-1 redox function is active in leukemia T-cells, regulating the Ref-1 target NF-kB, and inhibited by the redox-selective Ref-1 inhibitor E3330. Ref-1 expression is not regulated by Notch signaling, but is upregulated by glucocorticoid treatment. E3330 disrupted Ref-1 redox activity in functional studies and resulted in marked inhibition of leukemia cell viability, including T-ALL lines representing different genotypes and risk groups. Potent leukemia cell inhibition was seen in primary cells from ALL patients, relapsed and glucocorticoid-resistant T-ALL cells, and cells from a murine model of Notch-induced leukemia. Ref-1 redox inhibition triggered leukemia cell apoptosis and down-regulation of survival genes regulated by Ref-1 targets. For the first time, this work identifies Ref-1 as a novel molecular effector in T-ALL and demonstrates that Ref-1 redox inhibition results in potent inhibition of leukemia T-cells, including relapsed T-ALL. These data also support E3330 as a specific Ref-1 small molecule inhibitor for leukemia