Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer

A major step in the continental Moho and its geodynamic consequences: The Taranaki-Ruapehu line, New Zealand

Receiver function analysis reveals a 7 km step-like change in crustal thickness across the Taranaki-Ruapehu Line (TR-line) of North Island, New Zealand. The TR-line runs east-west between the active andesite volcanoes of Mt Taranaki and Ruapehu and mark

The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.

Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer

Political Bots and the Manipulation of Public Opinion in Venezuela

Social and political bots have a small but strategic role in Venezuelan political conversations. These automated scripts generate content through social media platforms and then interact with people. In this preliminary study on the use of political bots in Venezuela, we analyze the tweeting, following and retweeting patterns for the accounts of prominent Venezuelan politicians and prominent Venezuelan bots. We find that bots generate a very small proportion of all the traffic about political life in Venezuela. Bots are used to retweet content from Venezuelan politicians but the effect is subtle in that less than 10 percent of all retweets come from bot-related platforms. Nonetheless, we find that the most active bots are those used by Venezuela's radical opposition. Bots are pretending to be political leaders, government agencies and political parties more than citizens. Finally, bots are promoting innocuous political events more than attacking opponents or spreading misinformation.Comment: 8 pages, 3 figure

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this ligand.The authors thank the Niagara University Academic Center for Integrated Science and the Rochester Academy of Science for their financial support. MLI would like to thank the Barbara S. Zimmer Memorial Research Award for financial aid. MLC gratefully acknowledges generous allocations of supercomputing time from the Australian National Computational Infrastructure, support from the Australian Research Council under its Centers of Excellence program, and an ARC Future Fellowship. RP would also like to thank Western New England University, College of Pharmacy for generous financial support

Growth of Pedagogical Practice in an Active Multidisciplinary FLC on Flipped Learning

Faculty Learning Communities (FLCs) have gained a lot of attention in higher education. Research has shown that they support student learning, faculty development, and congenial relations among faculty. This paper will shed light on a successful, multidisciplinary FLC comprised of nine faculty members who engaged in Flipped Classroom pedagogy over a two-year period. Guided by Cox’s (2015) recommendations, the FLC members sought to improve their students’ learning while at the same time enhance their instructional practice. Participation in the FLC led to (1) course redesign, (2) instructional redesign, (3) professional growth, and (4) a sense of community

Creating a Professional Development Plan for a Simulation Consortium

As the United States struggles with health care reform and a nursing education system that inadequately prepares students for practice, dramatic advances in educational technology signal opportunities for both academic and practicing nurses to affect our profession as never before. Simulation technologies provide large and small institutions with the means to educate health care students and novice professionals effectively and efficiently through hands-on experience, but the costs of such a venture can be prohibitive. A simulation consortium offers a venue for different health care and educational institutions with shared goals to pool knowledge, monies, and labor toward health care education throughout a geographic area. This article details one Midwestern U.S. region's work in creating a professional development plan for a new simulation consortium