Abstract. The spatial extent and temporal behaviour of quasi-periodic (QP) intensity modulations of 0.5-2 kHz ELF-VLF signals were investigated in a comparative study of data collected at the Antarctic stations of South Pole (L=14), Halley (L=4), and Siple (L=4). Frequently, the waveforms of ELF-VLF signals simultaneously received at each site were identical. Although of similar frequency structure, the waveforms of the accompanying Pc3 magnetic pulsations did not show a one-to-one association. Whereas both are dayside phenomena, QP emissions occur over a smaller range of local times, and have a maximum of occurrence later in the day closer to local noon. QP emissions are identified with the periodic modulation of the electron pitch-angle distribution by the propagation of ULF compressional fast-mode waves through a region. However, contrary to previous ideas, rising-tone emissions do not represent the frequency-time signatures of such waves. In addition to generation close to the equatorial plane, we propose an additional high-latitude source of QP emissions. These emissions are associated with regions of minimum B produced by the dayside compression of the magnetosphere close to the magnetopause. Model magnetic field calculations of these minimum-B regions as a function of magnetic local time and invariant latitude are presented.

Parathyroid hormone-related protein (PTHrP) expression in breast cancer is enriched in bone metastases compared to primary tumors. Human MCF7 breast cancer cells “home” to the bones of immune deficient mice following intracardiac inoculation, but do not grow well and stain negatively for Ki67, thus serving as a model of breast cancer dormancy in vivo. We have previously shown that PTHrP overexpression in MCF7 cells overcomes this dormant phenotype, causing them to grow as osteolytic deposits, and that PTHrP-overexpressing MCF7 cells showed significantly lower expression of genes associated with dormancy compared to vector controls. Since early work showed a lack of cyclic AMP (cAMP) response to parathyroid hormone (PTH) in MCF7 cells, and cAMP is activated by PTH/PTHrP receptor (PTHR1) signaling, we hypothesized that the effects of PTHrP on dormancy in MCF7 cells occur through non-canonical (i.e., PTHR1/cAMP-independent) signaling. The data presented here demonstrate the lack of cAMP response in MCF7 cells to full length PTHrP(1–141) and PTH(1–34) in a wide range of doses, while maintaining a response to three known activators of adenylyl cyclase: calcitonin, prostaglandin E2 (PGE2), and forskolin. PTHR1 mRNA was detectable in MCF7 cells and was found in eight other human breast and murine mammary carcinoma cell lines. Although PTHrP overexpression in MCF7 cells changed expression levels of many genes, RNAseq analysis revealed that PTHR1 was unaltered, and only 2/32 previous PTHR1/cAMP responsive genes were significantly upregulated. Instead, PTHrP overexpression in MCF7 cells resulted in significant enrichment of the calcium signaling pathway. We conclude that PTHR1 in MCF7 breast cancer cells is not functionally linked to activation of the cAMP pathway. Gene expression responses to PTHrP overexpression must, therefore, result from autocrine or intracrine actions of PTHrP independent of PTHR1, through signals emanating from other domains within the PTHrP molecule.

Space Weather: A Multi-disciplinary Approach; Leiden, Netherlands, 25–29 September 2017

Background/Aim: SLC7A5 is recognized as the major mediator of melphalan uptake into multiple myeloma (MM) cells; however, its contribution to the inter-patient variability of melphalan efficacy and toxicity is yet to be well elucidated. This study aimed to investigate the impact of a single nucleotide polymorphism (SNP) rs4240803 in SLC7A5 on the gene expression, ex vivo sensitivity to melphalan, and clinical outcomes in MM patients who were undergoing autologous stem cell transplantation with high-dose melphalan. Materials and Methods: Peripheral blood mononuclear cells (PBMC) were collected from 108 MM patients prior to melphalan therapy. Clinical data were also collected from these patients following melphalan therapy. Results: rs4240803 was associated with elevated expression of SLC7A5 mRNA, higher ex vivo sensitivity to melphalan in PBMCs, and positive 90-day response in these patients (p=0.047, 0.10, 0.049, respectively). Conclusion: rs4240803 impacted the expression of SLC7A5, thus contributing to the clinical response of MM patients to melphalan therapy.

Aims Increasing the diversity of the biomedical sciences workforce is a national priority. Having a mentor, and more crucially, a personal network of mentors, improves the likelihood that an individual will pursue an advanced degree and career in the biomedical sciences. The chief mission of the National Research Mentoring Network (NRMN) is to reduce racial and ethnic disparities in the biosciences workforce through the mentoring of historically underrepresented individuals. Methods To address this need, we created MyNRMN, an online mentoring platform that connects mentors and mentees nationwide. The platform enables multiple forms of mentoring and recommends connections to mentees that will help them build their personal networks. Results The MyNRMN online platform has registered more than 13,500 active mentors and mentees across all 50 states and from more than 2100 institutions. Black and Hispanic mentees are highly represented. Discussion MyNRMN has expanded opportunities for mentorship in the biomedical sciences, particularly among those not from a culture or institution that historically supports mentorship. The platform's robust search and recommendation capabilities and graph database technology enable members to grow their personal network of mentors. Conclusion The MyNRMN online platform has proven successful in connecting mentees and mentors nationwide, expanding the pipeline in biomedical science careers to attract a more diverse workforce.