refnx is a model‐based neutron and X‐ray reflectometry data analysis package written in Python. It is cross platform and has been tested on Linux, macOS and Windows. Its graphical user interface is ...browser based, through a Jupyter notebook. Model construction is modular, being composed from a series of components that each describe a subset of the interface, parameterized in terms of physically relevant parameters (volume fraction of a polymer, lipid area per molecule etc.). The model and data are used to create an objective, which is used to calculate the residuals, log‐likelihood and log‐prior probabilities of the system. Objectives are combined to perform co‐refinement of multiple data sets and mixed‐area models. Prior knowledge of parameter values is encoded as probability distribution functions or bounds on all parameters in the system. Additional prior probability terms can be defined for sets of components, over and above those available from the parameters alone. Algebraic parameter constraints are available. The software offers a choice of fitting approaches, including least‐squares (global and gradient‐based optimizers) and a Bayesian approach using a Markov‐chain Monte Carlo algorithm to investigate the posterior distribution of the model parameters. The Bayesian approach is useful for examining parameter covariances, model selection and variability in the resulting scattering length density profiles. The package is designed to facilitate reproducible research; its use in Jupyter notebooks, and subsequent distribution of those notebooks as supporting information, permits straightforward reproduction of analyses.
The refnx Python modules for neutron and X‐ray reflectometry data analysis are introduced. A sample analysis illustrates a Bayesian approach using a Markov‐chain Monte Carlo algorithm to understand the confidence in the fit parameters.
Nature provides a wide range of inspiration for building mobile micromachines that can navigate through confined heterogenous environments and perform minimally invasive environmental and biomedical ...operations. For example, microstructures fabricated in the form of bacterial or eukaryotic flagella can act as artificial microswimmers. Due to limitations in their design and material properties, these simple micromachines lack multifunctionality, effective addressability and manoeuvrability in complex environments. Here we develop an origami-inspired rapid prototyping process for building self-folding, magnetically powered micromachines with complex body plans, reconfigurable shape and controllable motility. Selective reprogramming of the mechanical design and magnetic anisotropy of body parts dynamically modulates the swimming characteristics of the micromachines. We find that tail and body morphologies together determine swimming efficiency and, unlike for rigid swimmers, the choice of magnetic field can subtly change the motility of soft microswimmers.
It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer's disease, one of the earliest cognitive deficits in this type of ...dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer's disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer's disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer's disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer's disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer's disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer's disease.
Although a growing literature explores occupational identity, or the overlap between "who we are" and "what we do," this literature has not fully considered how occupational identity may interact ...with technological change. In this paper, we explore this interaction, asking how an occupation's identity shapes and is shaped by its interactions with a new technology. We focus, specifically, on the relationship between librarians and Internet search. Drawing on an analysis of 22 years of articles from library journals, we demonstrate how and why librarians initially discounted Internet search and differentiated themselves from it. We argue that these responses were associated with a "paradox of expertise," by which librarians missed innovation opportunities around one of the most important information technologies in history precisely, and ironically, because of their deep knowledge of non-Internet searching. Later, however, we demonstrate how librarians engaged with this same technology, drawing upon it to redefine their occupational identity. Our findings demonstrate how occupational identity conditions the interpretation of a technology, while also showing how these interpretations can change with ongoing interactions. We also illustrate how occupational identity itself can change in response to new technology. Finally, we elaborate upon why expert insiders may not actually be best positioned to pursue emerging technologies.
Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct ...from those in the initial tumor. To explore this hypothesis, we sequenced the exornes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.
•Anterior thalamic nuclei important for specific classes of temporal discriminations.•Anterior thalamic nuclei required for hippocampal-dependent contextual processes.•Critical role for anterior ...thalamic nuclei in selective attention.•Significance of anterior thalamic – anterior cingulate interactions.
The anterior thalamic nuclei are a vital node within hippocampal-diencephalic-cingulate circuits that support spatial learning and memory. Reflecting this interconnectivity, the overwhelming focus of research into the cognitive functions of the anterior thalamic nuclei has been spatial processing. However, there is increasing evidence that the functions of the anterior thalamic nuclei extend beyond the spatial realm. This work has highlighted how these nuclei are required for certain classes of temporal discrimination as well as their importance for processing other contextual information; revealing parallels with the non-spatial functions of the hippocampal formation. Yet further work has shown how the anterior thalamic nuclei may be important for other forms of non-spatial learning, including a critical role for these nuclei in attentional mechanisms. This evidence signals the need to reconsider the functions of the anterior thalamic within the framework of their wider connections with sites including the anterior cingulate cortex that subserve non-spatial functions.
Background: Next generation sequencing is transforming our understanding of transcriptomes. It can determine the expression level of transcripts with a dynamic range of over six orders of magnitude ...from multiple tissues, developmental stages or conditions. Patterns of gene expression provide insight into functions of genes with unknown annotation. Results: The RNA Seq-Atlas presented here provides a record of high-resolution gene expression in a set of fourteen diverse tissues. Hierarchical clustering of transcriptional profiles for these tissues suggests three clades with similar profiles: aerial, underground and seed tissues. We also investigate the relationship between gene structure and gene expression and find a correlation between gene length and expression. Additionally, we find dramatic tissue-specific gene expression of both the most highly-expressed genes and the genes specific to legumes in seed development and nodule tissues. Analysis of the gene expression profiles of over 2,000 genes with preferential gene expression in seed suggests there are more than 177 genes with functional roles that are involved in the economically important seed filling process. Finally, the Seq-atlas also provides a means of evaluating existing gene model annotations for the Glycine max genome. Conclusions: This RNA-Seq atlas extends the analyses of previous gene expression atlases performed using Affymetrix GeneChip technology and provides an example of new methods to accommodate the increase in transcriptome data obtained from next generation sequencing. Data contained within this RNA-Seq atlas of Glycine max can be explored at http://www.soybase.org/soyseq.
Abstract Background Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, ...8–10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3 + 4 = 7 and 4 + 3 = 7 are often considered the same prognostic group. Objective To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. Design, setting, and participants Between 2005 and 2014, 20 845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. Outcome measurements and statistical analysis Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. Results and limitations In the surgery cohort, we found large differences in recurrence rates between both Gleason 3 + 4 versus 4 + 3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3 + 4, 4 + 3, 8, and 9–10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five–grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. Conclusions The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. Patient summary We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.
The diffusion of scientific knowledge is critical for innovation, entrepreneurship, and economic growth. Yet scientists face a fundamental dilemma when it comes to sharing such knowledge: sharing can ...simultaneously advance and challenge both academic and commercial interests. Although several studies explore the different reasons that scientists may or may not share, along with their overall propensity to do so, we have much less insight into how researchers who confront sharing/secrecy tensions attempt to manage them. In turn, our understanding of the ways in which scientists enable cumulative innovation through sharing, even as they attend to their private interests, remains limited. Based on qualitative analysis of 46 interviews and 58 oral histories with researchers in biotechnology and digital audio, I identify 4 tactics that researchers use to manage sharing/secrecy tensions—leveraging trust, strategic withholding, delaying, and patenting—and I analyze how the use of these tactics is tied to particular sharing practices, organizational environments (e.g., universities versus firms), and scientific fields. I then theorize how these tactics address different dimensions of sharing/secrecy tensions, working together as part of an integrated repertoire. Finally, I tie my findings to broader considerations around sharing, including managerial and policy initiatives aimed at promoting cumulative innovation.
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