Doing it differently: Engaging interview participants with imaginative variation

Imaginative variation was identified by Husserl (1936/1970) as a phenomenological technique for the purpose of elucidating the manner in which phenomena appear to consciousness. Briefly, by engaging in the phenomenological reduction and using imaginative variation, phenomenologists are able to describe the experience of consciousness, having stepped outside of the natural attitude through the epochē. Imaginative variation is a stage aimed at explicating the structures of experience, and is best described as a mental experiment. Features of the experience are imaginatively altered in order to view the phenomenon under investigation from varying perspectives. Husserl argued that this process will reveal the essences of an experience, as only those aspects that are invariant to the experience of the phenomenon will not be able to change through the variation. Often in qualitative research interviews, participants struggle to articulate or verbalise their experiences. The purpose of this article is to detail a radical and novel way of using imaginative variation with interview participants, by asking the participants to engage with imaginative variation, in order to produce a rich and insightful experiential account of a phenomenon. We will discuss how the first author successfully used imaginative variation in this way in her study of the erotic experience of bondage, discipline, dominance & submission, and sadism & masochism (BDSM), before considering the usefulness of this technique when applied to areas of study beyond sexuality

Reproducible Isolation of Lymph Node Stromal Cells Reveals Site-Dependent Differences in Fibroblastic Reticular Cells

Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs) between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture

Tuning a Resonance in the Fock Space: Optimization of Phonon Emission in a Resonant Tunneling Device

Phonon-assisted tunneling in a double barrier resonant tunneling device can be seen as a resonance in the electron-phonon Fock space which is tuned by the applied voltage. We show that the geometrical parameters can induce a symmetry condition in this space that can strongly enhance the emission of longitudinal optical phonons. For devices with thin emitter barriers this is achieved by a wider collector's barrier.Comment: 4 pages, 3 figures. Figure 1 changed, typos correcte

The effect of inelastic processes on tunneling

We study an electron that interacts with phonons or other linear or nonlinear excitations as it resonantly tunnels. The method we use is based on mapping a many-body problem in a large variational space exactly onto a one-body problem. The method is conceptually simpler than previous Green's function approaches, and allows the essentially exact numerical solution of much more general problems. We solve tunneling problems with transverse channels, multiple sites coupled to phonons, and multiple phonon degrees of freedom and excitations.Comment: 12 pages, REVTex, 4 figures in compressed tar .ps forma

Open Ocean: Status and Trends, Summary for Policy Makers

The Open Ocean Assessment provides a baseline review of issues linking human well-being with the status of the open ocean through the themes of governance, climate change, ocean ecosystems, fisheries, pollution, and integrated assessment of the human-ocean nexus. It uses indices and indicators where data exist, in many cases with future projections due to global climate change, complemented by expert scientific assessment of numerous low certainty but potentially high impact issues where global ocean monitoring is inadequate

Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co‐localized with FRCs in human LNs, and murine single‐cell RNA‐sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

<b>Background</b> High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p> <b>Methods</b> We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p> <b>Results</b> 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p> <b>Conclusions</b> Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer.

Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p ≤ 0.001 in BT474; p ≤ 0.01 in SKBR3) and in vivo (p ≤ 0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p ≤ 0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p ≤ 0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p ≤ 0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients