Embryonic Signaling Pathways and Rhabdomyosarcoma: Contributions to Cancer Development and Opportunities for Therapeutic Targeting

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence, accounting for approximately 7% of childhood cancers. Current therapies include nonspecific cytotoxic chemotherapy regimens, radiation therapy, and surgery; however, these multimodality strategies are unsuccessful in the majority of patients with high-risk disease. It is generally believed that these tumors represent arrested or aberrant skeletal muscle development, and, accordingly, developmental signaling pathways critical to myogenesis such as Notch, WNT, and Hedgehog may represent new therapeutic targets. In this paper, we summarize the current preclinical studies linking these embryonic pathways to rhabdomyosarcoma tumorigenesis and provide support for the investigation of targeted therapies in this embryonic cancer

The Grizzly, November 10, 2016

Ursinus Picks New Dean / VPAA after Months-Long Search • Innovation and Discovery Center Breaks New Ground • Q&A with Anupy Singla • International Perspective: Chinese Teaching Assistant Embraces the Freedom to be Herself in the U.S. • U-Speak Talk to Explore Under-Represented Voices • Women Entrepreneurs Share Stories of Success • Opinions: Offensive Costumes are Micro-aggressions; UC Needs In-Person Activism to Make Progress • Wrestling Looks to Win it All in 2016-2017 • Field Hockey Tops Conference Once Againhttps://digitalcommons.ursinus.edu/grizzlynews/1655/thumbnail.jp

The Grizzly, September 8, 2016

Marcon Under Fire for Controversial Tweets • First-Year Class Smaller Than Usual • Ursinus Offers Gateway to Success • Ursinus\u27 Students Mourn the Loss of Beloved Wawa • History Department Welcomes New Professor • Student Researchers Spend Summer with NASA • Opinions: Ostrum to Marcon: Let\u27s Work Toward Inclusion; Students Happily Embrace Changes to Wismer • Spike! Ursinus Volleyball is Back in Action! • The Bears and the Bisonhttps://digitalcommons.ursinus.edu/grizzlynews/1647/thumbnail.jp

Illumination in symbiotic binary stars: Non-LTE photoionization models. II. Wind case

We describe a non-LTE photoionization code to calculate the wind structure and emergent spectrum of a red giant wind illuminated by the hot component of a symbiotic binary system. We consider spherically symmetric winds with several different velocity and temperature laws and derive predicted line fluxes as a function of the red giant mass loss rate, \mdot. Our models generally match observations of the symbiotic stars EG And and AG Peg for \mdot about 10^{-8} \msunyr to 10^{-7} \msunyr. The optically thick cross- section of the red giant wind as viewed from the hot component is a crucial parameter in these models. Winds with cross-sections of 2--3 red giant radii reproduce the observed fluxes, because the wind density is then high, about 10^9 cm^{-3}. Our models favor winds with acceleration regions that either lie far from the red giant photosphere or extend for 2--3 red giant radii.Comment: 51 pages, LaTeX including three tables, requires 15 Encapsulated Postscript figures, to appear in Ap

Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

Palaeogeographic reconstruction in the transition zone : the role of geophysical forward modelling in ground investigation surveys

Geophysical survey techniques are commonly used as part of studies to reconstruct past geographies in archaeological and palaeoenvironmental landscape investigations onshore and offshore. However, their use across the intertidal zone for constructing contiguous models is far more challenging. In order to enhance the interpretation of the recovered data forward modelling is used here to demonstrate the effective use of a staged approach to site investigation. Examples of data from electrical and electromagnetic techniques have been modelled and tested with ground truth measurements including trial pits, coring and cone penetrometer testing. This combination of forward modelling and testing has proved to be particularly effective at mapping key geological situations of archaeological interest. The approach is demonstrated by reference to varying sub-surface sediment types exemplified by two field examples from the UK coast where typical palaeolandscape features, namely incised channels and deeply buried topographies are encountered. These palaeogeographic features were chosen as they have high potential for association with the evidence of past human activity.PostprintPeer reviewe

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Active site prediction using evolutionary and structural information

Motivation: The identification of catalytic residues is a key step in understanding the function of enzymes. While a variety of computational methods have been developed for this task, accuracies have remained fairly low. The best existing method exploits information from sequence and structure to achieve a precision (the fraction of predicted catalytic residues that are catalytic) of 18.5% at a corresponding recall (the fraction of catalytic residues identified) of 57% on a standard benchmark. Here we present a new method, Discern, which provides a significant improvement over the state-of-the-art through the use of statistical techniques to derive a model with a small set of features that are jointly predictive of enzyme active sites

Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.National Center for Complementary and Alternative Medicine (U.S.) (R01AT005280