NetSci High: Bringing Agency to Diverse Teens Through the Science of Connected Systems

This paper follows NetSci High, a decade-long initiative to inspire teams of teenage researchers to develop, execute and disseminate original research in network science. The project introduced high school students to the computer-based analysis of networks, and instilled in the participants the habits of mind to deepen inquiry in connected systems and statistics, and to sustain interest in continuing to study and pursue careers in fields involving network analysis. Goals of NetSci High ranged from proximal learning outcomes (e.g., increasing high school student competencies in computing and improving student attitudes toward computing) to highly distal (e.g., preparing students for 21st century science), with an emphasis on doing real-world research into relevant and ambiguous problems through technologically-infused and highly collaborative projects and defending them to a clear (and sometimes potentially intimidating) audience. The cognitive goals of the project covered broad areas including analyzing, synthesizing, and visualizing quantitative data, and understanding modeling and network statistics. Attitudinal outcomes included improving attitudes toward the statistical study of networks, self-efficacy, and a sense of agency for continuing to pursue further involvement in college studies and careers

Intratumoral heterogeneity analysis reveals hidden associations between protein expression losses and patient survival in clear cell renal cell carcinoma.

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups using Fisher\u27s exact tests. Univariate and multivariable analyses were used to correlate biomarker changes and patient survivals. Multivariable analyses were performed by constructing decision trees using the classification and regression trees (CART) methodology. IHC detected widespread ITH in ccRCC tumors. The statistical analysis of the Truncal loss (root loss) found additional correlations between biomarker losses and tumor stages than the traditional Loss in tumor (total) . Losses of SMARCA4 or SMARCA2 significantly improved prognosis for overall survival (OS). Losses of PBRM1, ARID1A or SETD2 had the opposite effect. Thus Truncal Loss analysis revealed hidden links between protein losses and patient survival in ccRCC

NiCE Teacher Workshop: Engaging K-12 Teachers in the Development of Curricular Materials That Utilize Complex Networks Concepts

Our educational systems must prepare students for an increasingly interconnected future, and teachers require equipping with modern tools, such as network science, to achieve this. We held a Networks in Classroom Education (NiCE) workshop for a group of 21 K-12 teachers with various disciplinary backgrounds. The explicit aim of this was to introduce them to concepts in network science, show them how these concepts can be utilized in the classroom, and empower them to develop resources, in the form of lesson plans, for themselves and the wider community. Here we detail the nature of the workshop and present its outcomes - including an innovative set of publicly available lesson plans. We discuss the future for successful integration of network science in K-12 education, and the importance of inspiring and enabling our teachers.Comment: 11 pages, 4 figures, 2 table

Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC. © 2018, Liao et al

Disulfiram-induced cytotoxicity and endo-lysosomal sequestration of zinc in breast cancer cells

Disulfiram, a clinically used alcohol-deterrent has gained prominence as a potential anti-cancer agent due to its impact on copper-dependent processes. Few studies have investigated zinc effects on disulfiram action, despite it having high affinity for this metal. Here we studied the cytotoxic effects of disulfiram in breast cancer cells, and its relationship with both intra and extracellular zinc. MCF-7 and BT474 cancer cell lines gave a striking time-dependent biphasic cytotoxic response between 0.01 and 10 μM disulfiram. Co-incubation of disulfiram with low-level zinc removed this effect, suggesting that availability of extracellular zinc significantly influences disulfiram efficacy. Live-cell confocal microscopy using fluorescent endocytic probes and the zinc dye Fluozin-3 revealed that disulfiram selectively and rapidly increased zinc levels in endo-lysosomes. Disulfiram also caused spatial disorganization of late endosomes and lysosomes, suggesting they are novel targets for this drug. This relationship between disulfiram toxicity and ionophore activity was consolidated via synthesis of a new disulfiram analog and overall we demonstrate a novel mechanism of disulfiram-cytotoxicity with significant clinical implications for future use as a cancer therapeutic

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure