Seasonal performance of air conditioners - an analysis of the DOE test procedures: the thermostat and measurement errors. Report No. 2

Two aspects of the DOE test procedures are analyzed. First, the role of the thermostat in controlling the cycling of conditioning equipment is investigated. The test procedures call for a cycling scheme of 6 minutes on, 24 minutes off for Test D. To justify this cycling scheme as being representative of cycling in the field, it is assumed that the thermostat is the major factor in controlling the cycle rate. This assumption is examined by studying a closed-loop feedback model consisting of a thermostat, a heating/cooling plant and a conditioned space. Important parameters of this model are individually studied to determine their influence on the system. It is found that the switch differential and the anticipator gain are the major parameters in controlling the cycle rate. This confirms the thermostat's dominant role in the cycling of a system. The second aspect of the test procedures concerns transient errors or differences in the measurement of cyclic capacity. In particular, errors due to thermocouple response, thermocouple grid placement, dampers and nonuniform velocity and temperature distributions are considered. Problems in these four areas are mathematically modeled and the basic assumptions are stated. Results from these models help to clarify the problem areas and give an indication of the magnitude of the errors involved. It is found that major disagreement in measured capacity can arise in these four areas and can be mainly attributed to test set-up differences even though such differences are allowable in the test procedures. An understanding of such differences will aid in minimizing many problems in the measurement of cyclic capacity

Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture

OBJECTIVE—Immune-mediated destruction of β-cells resulting in type 1 diabetes involves activation of proinflammatory, islet autoreactive T-cells, a process under the control of dendritic cells of the innate immune system. We tested the hypothesis that type 1 diabetes development is associated with disturbance of blood dendritic cell subsets that could enhance islet-specific autoimmunity

Discourse markers activate their, <i>like</i>, cohort competitors

Speech in everyday conversations is riddled with discourse markers (DMs), such as well, you know, and like. However, in many lab-based studies of speech comprehension, such DMs are typically absent from the carefully articulated and highly controlled speech stimuli. As such, little is known about how these DMs influence online word recognition. The present study specifically investigated the online processing of DM like and how it influences the activation of words in the mental lexicon. We specifically targeted the cohort competitor (CC) effect in the Visual World Paradigm: Upon hearing spoken instructions to “pick up the beaker,” human listeners also typically fixate—next to the target object—referents that overlap phonologically with the target word (cohort competitors such as beetle; CCs). However, several studies have argued that CC effects are constrained by syntactic, semantic, pragmatic, and discourse constraints. Therefore, the present study investigated whether DM like influences online word recognition by activating its cohort competitors (e.g., lightbulb). In an eye-tracking experiment using the Visual World Paradigm, we demonstrate that when participants heard spoken instructions such as “Now press the button for the, like … unicycle,” they showed anticipatory looks to the CC referent (lightbulb)well before hearing the target. This CC effect was sustained for a relatively long period of time, even despite hearing disambiguating information (i.e., the /k/ in like). Analysis of the reaction times also showed that participants were significantly faster to select CC targets (lightbulb) when preceded by DM like. These findings suggest that seemingly trivial DMs, such as like, activate their CCs, impacting online word recognition. Thus, we advocate a more holistic perspective on spoken language comprehension in naturalistic communication, including the processing of DMs

Daily adaptive radiotherapy for patients with prostate cancer using a high field MR-linac: Initial clinical experiences and assessment of delivered doses compared to a C-arm linac.

Introduction:MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT). Methods:Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol. Results:95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates. Conclusions:Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment

A role for core planar polarity proteins in cell contact-mediated orientation of planar cell division across the mammalian embryonic skin

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017. Supplementary information accompanies this paper at doi:10.1038/s41598-017-01971-2.The question of how cell division orientation is determined is fundamentally important for understanding tissue and organ shape in both healthy or disease conditions. Here we provide evidence for cell contact-dependent orientation of planar cell division in the mammalian embryonic skin. We propose a model where the core planar polarity proteins Celsr1 and Frizzled-6 (Fz6) communicate the long axis orientation of interphase basal cells to neighbouring basal mitoses so that they align their horizontal division plane along the same axis. The underlying mechanism requires a direct, cell surface, planar polarised cue, which we posit depends upon variant post-translational forms of Celsr1 protein coupled to Fz6. Our hypothesis has parallels with contact-mediated division orientation in early C. elegans embryos suggesting functional conservation between the adhesion-GPCRs Celsr1 and Latrophilin-1. We propose that linking planar cell division plane with interphase neighbour long axis geometry reinforces axial bias in skin spreading around the mouse embryo body.Peer reviewe

The association between acute and late genitourinary and gastrointestinal toxicities: an analysis of the PACE B study

Simple Summary: Several studies have shown the association between significant short-term and long-term side-effects after prostate radiotherapy using older techniques. Our study, tests whether there is an association between short- and long-term bowel and urinary side-effects with modern prostate radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and intensity modulated radiotherapy (IMRT). We use CTCAE clinical assessments of patient symptoms for radiotherapy side-effects in the PACE-B study to answer this question. We show that patients who develop short-term urinary and bowel side-effects are at higher odds of developing long-term side-effects, after conventional fractionated radiotherapy and SBRT. This association remains even after adjusting for patient, treatment and tumour factors. We show that patients who have significant urinary symptoms before radiotherapy are also at higher odds of developing long-term side-effects. We suggest that patients who experience significant short-term side-effects should be closely monitored and potentially have their symptoms treated earlier. Abstract: Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96–7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69–4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91–7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04–9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity

Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity

A Mi\u27kmaq First Nation cosmology: investigating the practice of contemporary Aboriginal Traditional Medicine in dialogue with counselling – toward an Indigenous therapeutics

This paper explores from a Mi’kmaq and Aboriginal standpoint foundational knowledge in Indigenous therapeutics. Based on an eco-social-psycho-spiritual way of working, the article proposes Indigenous cultural models that open a window to a rich cultural repository of meanings associated with Indigenous cosmology, ontology and epistemology. The three layers of meaning, theory and practice within the symbolic ‘Medicine Lodge’ or ‘Place of The Dreaming’ give rise to ways of working that are deeply integrative and wholistic. These forms of Indigenous theory and practice have much to offer the counselling and complimentary health professions

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells