The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Development and Exploration of New Automated Tools to Accelerate Research on Tissue and Tumor Model Systems

Drug attrition rates for cancer are much higher than in other therapeutic areas. There is an urgent need for appropriate tumor models that can physiologically replicate the key features of human tissue to find optimal strategies to evaluate novel and effective agents and ultimately develop curative chemotherapies. Historically, 2D or traditional monolayer cancer cell lines, with limited representation of the actual tumors they are derived from, have been utilized for cancer and drug development research, as well as expensive and time-consuming patient-derived xenograft models or mutation-based rodent models. However, the realization of the vision of precision and personalized therapy urgently requires the development of individualized tumor models that are low cost, high throughput and broadly applicable to both research and clinical settings. Organoids, multicellular constructs derived from self-organizing stem cells, are three-dimensional ex vivo tissue models that incorporate many of the physiological and genetic features of the in vivo tissue. Organoids promise to provide realistic research models for developmental and stem cell biology such as characterization of fundamental tumor development mechanisms, drug development and screening, and the study of basic biological processes such as cellular nutrient sensing and hormone secretion. Brain, breast, colon, prostate, lung, liver, and pancreas organoids are just some examples of tissues and tumors currently being studied. In this thesis, I will discuss and report a new solution to advance the use of organoids as a widely practical research technique. To achieve this, chemistry, biology, and engineering principles were used to design and develop a highly reproducible, standardized, miniaturized assay that can be performed in both research and clinical settings, utilizing minimal amounts of reagents in a low-cost automated system permitting screening of thousands of conditions. First, I will discuss the optimization, characterization, and validation of an integrated microfluidic based ex vivo tissue and tumor modeling system that is superior to the currently available approaches in terms of ability to facilitate and accelerate both preclinical and foundational research in a high-throughput fashion with optimal user friendliness and reproducibility. Following, I will reveal a new easy to use and open source, computer vision based platform, called OrganoID, that recognizes, labels, and tracks single organoids in brightfield and phase-contrast microscopy images. OrganoID enables straightforward and accurate analysis of organoid images to accelerate the use of organoids as physiologically relevant models in high-throughput research and compatible with both the new microfluidic culture platform as well as more traditional organoid culture methods

Unexpected plasiticty in the life cycle of Trypanosoma brucei

African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host’s circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia

The Interactive Effects of Antisocial Personality Disorder and Court-Mandated Status on Substance Abuse Treatment Dropout

The present study sought to examine the interactive effects of court-mandated (CM) treatment and antisocial personality disorder (ASPD) on treatment dropout among 236 inner-city male substance users receiving residential substance abuse treatment. Of the 236 participants, 39.4% (n = 93) met criteria for ASPD and 72.5% (n = 171) were mandated to treatment through a pretrial release-to-treatment program. Results indicated a significant interaction between ASPD and CM status, such that patients with ASPD who were voluntarily receiving treatment were significantly more likely to drop out of treatment than each of the other groups. Subsequent discrete time survival analyses to predict days until dropout, using Cox proportional hazards regression, indicated similar findings, with patients with ASPD who were voluntarily receiving treatment completing fewer days of treatment than each of the other groups. These findings suggest the effectiveness of the court system in retaining patients with ASPD, as well as the role of ASPD in predicting treatment dropout for individuals who are in treatment voluntarily. Implications, including the potential value of the early implementation of specialized interventions aimed at improving adherence for patients with ASPD who are receiving treatment voluntarily, are discussed

Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids

The use of organoids in personalized medicine is promising but high throughput platforms are needed. Here the authors develop an automated, high-throughput, microfluidic 3D organoid culture system that allows combinatorial and dynamic drug treatments and real-time analysis of organoids