Children's Oncology Group's 2013 blueprint for research: Stem cell transplantation

The role of SCT in pediatric oncology has continued to evolve with the introduction of new therapeutic agents and immunological insights into cancer. COG has focused its efforts on the study of hematopoietic stem cell transplantation in the treatment of pediatric malignancies in several major multi‐institutional Phase II and Phase III studies. These studies include addressing the impact of allogenicity in ALL (ASCT0431), and establishing autologous stem cell transplant as the standard of care in neuroblastoma. Reducing transplant‐associated toxicity was addressed in the ASCT0521 study, where the TNFα inhibitor etanercept was tested for the treatment of idiopathic pneumonia syndrome. Impact of cell dose was explored in the single versus tandem umbilical cord blood study CTN‐0501, in close collaboration with the BMT‐CTN. Pediatr Blood Cancer 2013; 60: 1044–1047. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97445/1/24437_ftp.pd

Loose Ends for the Exomoon Candidate Host Kepler-1625b

The claim of an exomoon candidate in the Kepler-1625b system has generated substantial discussion regarding possible alternative explanations for the purported signal. In this work we examine in detail these possibilities. First, the effect of more flexible trend models is explored and we show that sufficiently flexible models are capable of attenuating the signal, although this is an expected byproduct of invoking such models. We also explore trend models using X and Y centroid positions and show that there is no data-driven impetus to adopt such models over temporal ones. We quantify the probability that the 500 ppm moon-like dip could be caused by a Neptune-sized transiting planet to be < 0.75%. We show that neither autocorrelation, Gaussian processes nor a Lomb-Scargle periodogram are able to recover a stellar rotation period, demonstrating that K1625 is a quiet star with periodic behavior < 200 ppm. Through injection and recovery tests, we find that the star does not exhibit a tendency to introduce false-positive dip-like features above that of pure Gaussian noise. Finally, we address a recent re-analysis by Kreidberg et al (2019) and show that the difference in conclusions is not from differing systematics models but rather the reduction itself. We show that their reduction exhibits i) slightly higher intra-orbit and post-fit residual scatter, ii) $\simeq$ 900 ppm larger flux offset at the visit change, iii) $\simeq$ 2 times larger Y-centroid variations, and iv) $\simeq$ 3.5 times stronger flux-centroid correlation coefficient than the original analysis. These points could be explained by larger systematics in their reduction, potentially impacting their conclusions.Comment: 21 pages, 4 tables, 11 figures. Accepted for publication in The Astronomical Journal, January 202

CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a genetically heterogeneous subtype of B-cell ALL characterized by chromosomal rearrangements and mutations that result in aberrant cytokine receptor and kinase signaling. In particular, chromosomal rearrangements resulting in the overexpression of cytokine receptor-like factor 2 (CRLF2) occur in 50% of Ph-like ALL cases. CRLF2 overexpression is associated with particularly poor clinical outcomes, though the molecular basis for this is currently unknown. Glucocorticoids (GCs) are integral to the treatment of ALL and GC resistance at diagnosis is an important negative prognostic factor. Given the importance of GCs in ALL therapy and the poor outcomes for patients with CRLF2 overexpression, we hypothesized that the aberrant signal transduction associated with CRLF2 overexpression might mediate intrinsic GC insensitivity. To test this hypothesis, we exposed Ph-like ALL cells from patient-derived xenografts to GCs and found that CRLF2 rearranged (CRLF2R) leukemias uniformly demonstrated reduced GC sensitivity in vitro. Furthermore, targeted inhibition of signal transduction with the MEK inhibitor trametinib and the Akt inhibitor MK2206, but not the JAK inhibitor ruxolitinib, was sufficient to augment GC sensitivity. These data suggest that suboptimal GC responses may in part underlie the poor clinical outcomes for patients with CRLF2 overexpression and provide rationale for combination therapy involving GCs and signal transduction inhibitors as a means of enhancing GC efficacy

A Transiting Jupiter Analog

Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\pm0.02)$ $R_{\mathrm{Jup}}$, a low orbital eccentricity ($0.06_{-0.04}^{+0.10}$) and an equilibrium temperature of $(131\pm3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet ($1071.2323\pm0.0006$ d), paving the way for follow-up of this $K=11.8$ mag target.Comment: 14 pages, 10 figures. Accepted to ApJ. Posteriors available at https://github.com/CoolWorlds/Kepler-167-Posterior

Detecting and Characterizing Exomoons and Exorings (Handbook of Exoplanets, 2nd Edition)

The circumplanetary environments in our Solar System host a stunning array of moon and ring systems. Study of these environs has yielded valuable insights into planetary system formation and evolution, and there is every reason to believe that we will have much to learn from the moons and rings that are likely to exist in exoplanetary systems as well. This has motivated a small but growing number of researchers to investigate questions related to the formation, stability, long-term viability, composition, and observability of these exomoons and exorings. Still, due to a range of significant observational challenges, we remain at a relatively early stage of this work. As a result, we continue to face a number of difficult, unanswered questions, but this also means there are myriad opportunities for fundamental contributions to the field. In this review we will examine a variety of important issues for the astronomical community to consider, with an aim of providing a comprehensive understanding of ongoing efforts to identify and characterize exomoons and exorings, while also increasing interest and engagement. We begin with an overview of what we expect from systems hosting moons and/or rings in terms of their architectures, habitability, and observational signatures. We then highlight the contributions from a variety of works that have been aimed at detecting and characterizing them. We conclude by examining the outlook for finding these objects and discussing a number of ongoing challenges that we will want to overcome in the years ahead.Comment: To be published in: Handbook of Exoplanets, 2nd Edition, Hans Deeg and Juan Antonio Belmonte (Eds. in Chief), Springer International Publishing AG, part of Springer Nature. 41 pages, 4 figure

Paper 6: The Kennesaw State University Mathematics Methods Model

Kennesaw State University’s comprehensive, nine-credit-hour, methods course integrates general and mathematics-specific pedagogical training with a structured four-week field experience prior to student teaching. This course blends essential units on conceptual understanding of mathematics, lesson planning, assessment, classroom management, and diversity with mathematics-specific methods. All topics are aligned with National Council of Teachers of Mathematics standards and Georgia Performance Standards. Throughout the course, students complete a variety of assignments that require them to practice the skills highlighted in class readings and discussions, and they adapt and generalize those skills during their field experiences. Students have numerous opportunities in class and in the field to implement and to reflect upon pedagogical and assessment strategies and to receive feedback from course instructors, from other students, and from collaborating teachers. This intense course has many benefits and challenges for both the instructors and the students, but it is one of the most highly anticipated courses of secondary mathematics education majors at Kennesaw State University. With strong support of department administrators and the entire mathematics education faculty, this methods class has been quite successful in preparing the seniors for their student teaching experiences