Analytical control test plan and microbiological methods for the water recovery test

Qualitative and quantitative laboratory results are important to the decision-making process. In some cases, they may represent the only basis for deciding between two or more given options or processes. Therefore, it is essential that handling of laboratory samples and analytical operations employed are performed at a deliberate level of conscientious effort. Reporting erroneous results can lead to faulty interpretations and result in misinformed decisions. This document provides analytical control specifications which will govern future test procedures related to all Water Recovery Test (WRT) Phase 3 activities to be conducted at the National Aeronautics and Space Administration/Marshall Space Flight Center (NASA/MSFC). This document addresses the process which will be used to verify analytical data generated throughout the test period, and to identify responsibilities of key personnel and participating laboratories, the chains of communication to be followed, and ensure that approved methodology and procedures are used during WRT activities. This document does not outline specifics, but provides a minimum guideline by which sampling protocols, analysis methodologies, test site operations, and laboratory operations should be developed

Targeting the MDM2-p53 Pathway in Dedifferentiated Liposarcoma

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2-p53 interaction has thus garnered interest as a therapeutic target for DDLPS and other malignancies. MDM2 binds p53 via a hydrophobic protein interaction that is easily accessible with synthetic analogues. Multiple agents have been developed, including Nutlins such as RG7112 and small molecular inhibitors including SAR405838 and HDM201. Preclinical in vitro and animal models have shown promising results with MDM2 inhibition, resulting in robust p53 reactivation and cancer cell death. However, multiple early-phase clinical trials have failed to show a benefit with MDM2 pathway inhibition for DDLPS. Mechanisms of resistance are being elucidated, and novel inhibitors and combination therapies are currently under investigation. This review provides an overview of these strategies for targeting MDM2 in DDLPS

Targeting the Molecular and Immunologic Features of Leiomyosarcoma

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, and DNA damage response pathways that may contribute to resistance against immune-checkpoint blockade monotherapy. The LMS immune microenvironment is highly infiltrated with tumor-associated macrophages and tumor-infiltrating lymphocytes, which may represent promising biomarkers. This review provides an overview of the clinical and pathologic behavior of both soft tissue and uterine LMS and summarizes the genomic and immune characteristics of these tumors and how they may provide opportunities for the development of biomarker-based immune therapies

Collaboration in sensor network research: an in-depth longitudinal analysis of assortative mixing patterns

Many investigations of scientific collaboration are based on statistical analyses of large networks constructed from bibliographic repositories. These investigations often rely on a wealth of bibliographic data, but very little or no other information about the individuals in the network, and thus, fail to illustrate the broader social and academic landscape in which collaboration takes place. In this article, we perform an in-depth longitudinal analysis of a relatively small network of scientific collaboration (N = 291) constructed from the bibliographic record of a research center involved in the development and application of sensor network and wireless technologies. We perform a preliminary analysis of selected structural properties of the network, computing its range, configuration and topology. We then support our preliminary statistical analysis with an in-depth temporal investigation of the assortative mixing of selected node characteristics, unveiling the researchers' propensity to collaborate preferentially with others with a similar academic profile. Our qualitative analysis of mixing patterns offers clues as to the nature of the scientific community being modeled in relation to its organizational, disciplinary, institutional, and international arrangements of collaboration.Comment: Scientometrics (In press

What Difference Does Quantity Make? On the Epistemology of Big Data Biology

publication-status: Acceptedtypes: ArticleIs Big Data science a whole new way of doing research? And what difference does data quantity make to knowledge production strategies and their outputs? I argue that the novelty of Big Data science does not lie in the sheer quantity of data involved, but rather in (1) the prominence and status acquired by data as commodity and recognised output, both within and outside of the scientific community and (2) the methods, infrastructures, technologies, skills and knowledge developed to handle data. These developments generate the impression that data-intensive research is a new mode of doing science, with its own epistemology and norms. To assess this claim, one needs to consider the ways in which data are actually disseminated and used to generate knowledge. Accordingly, this article reviews the development of sophisticated ways to disseminate, integrate and re-use data acquired on model organisms over the last three decades of work in experimental biology. I focus on online databases as prominent infrastructures set up to organise and interpret such data and examine the wealth and diversity of expertise, resources and conceptual scaffolding that such databases draw upon. This illuminates some of the conditions under which Big Data needs to be curated to support processes of discovery across biological subfields, which in turn highlights the difficulties caused by the lack of adequate curation for the vast majority of data in the life sciences. In closing, I reflect on the difference that data quantity is making to contemporary biology, the methodological and epistemic challenges of identifying and analysing data given these developments, and the opportunities and worries associated with Big Data discourse and methods.Economic and Social Research CouncilES/F028180/1Leverhulme TrustRPG-2013-153European Union’s Seventh Framework Programme (FP7/2007-2013ERC grant agreement number 335925

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral bloo

Generations of interdisciplinarity in bioinformatics

Bioinformatics, a specialism propelled into relevance by the Human Genome Project and the subsequent -omic turn in the life science, is an interdisciplinary field of research. Qualitative work on the disciplinary identities of bioinformaticians has revealed the tensions involved in work in this “borderland.” As part of our ongoing work on the emergence of bioinformatics, between 2010 and 2011, we conducted a survey of United Kingdom-based academic bioinformaticians. Building on insights drawn from our fieldwork over the past decade, we present results from this survey relevant to a discussion of disciplinary generation and stabilization. Not only is there evidence of an attitudinal divide between the different disciplinary cultures that make up bioinformatics, but there are distinctions between the forerunners, founders and the followers; as inter/disciplines mature, they face challenges that are both inter-disciplinary and inter-generational in nature

(Dis)entangling Barad: Materialisms and ethics

In the wake of the widespread uptake of and debate surrounding the work of Karen Barad, this article revisits her core conceptual contributions. We offer descriptions, elaborations, problematizations and provocations for those intrigued by or invested in this body of work. We examine Barad’s use of quantum physics, which underpins her conception of the material world. We discuss the political strengths of this position but also note tensions associated with applying quantum physics to phenomena at macro-scales. We identify both frictions and unacknowledged affinities with science and technology studies in Barad’s critique of reflexivity and her concept of diffraction. We flesh out Barad’s overarching position of ‘agential realism’, which contains a revised understanding of scientific apparatuses. Building upon these discussions, we argue that inherent in agential realism is both an ethics of inclusion and an ethics of exclusion. Existing research has, however, frequently emphasized entanglement and inclusion to the detriment of foreclosure and exclusion. Nonetheless, we contend that it is in the potential for an ethics of exclusion that Barad’s work could be of greatest utility within science and technology studies and beyond

Bigger, Faster, Better? Rhetorics and Practices of Large-Scale Research in Contemporary Bioscience

publication-status: Publishedtypes: ArticleEditorial for Special Issu