Tunnel Spectroscopy of a Proximity Josephson Junction

We present tunnel spectroscopy experiments on the proximity effect in lateral superconductor-normal metal-superconductor (SNS) Josephson junctions. Our weak link is embedded into a superconducting (S) ring allowing phase biasing of the Josephson junction by an external magnetic field. We explore the temperature and phase dependence of both the induced mini-gap and the modification of the density of states in the normal (N) metal. Our results agree with a model based on the quasiclassical theory in the diffusive limit. The device presents an advanced version of the superconducting quantum interference proximity transistor (SQUIPT), now reaching flux sensitivities of 3 nA$/\Phi_0$ where $\Phi_0$ is the flux quantum.Comment: 5 pages, 4 figure

Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma

Summary Background Incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. Objectives To study the role of complement classical pathway components C1q, C1r and C1s in the progression of cSCC. Methods The mRNA levels of C1Q subunits, C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes (NHEKs), cSCC tumors in vivo and normal skin were analyzed with quantitative RT-PCR. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analyzed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. Results Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared to normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumors in vivo compared to normal skin. Abundant expression of C1r and C1s by tumor cells was detected in invasive sporadic cSCCs and recessive dystrophic epidermolysis bullosa-associated cSCCs, whereas the expression of C1r and C1s was lower in cSCC in situ, actinic keratosis, and normal skin. Knockdown of C1r and C1s expression in cSCC cells inhibited activation of ERK1/2 and Akt, promoted apoptosis of cSCC cells and significantly suppressed growth and vascularization of human cSCC xenograft tumors in vivo. Conclusions These results provide evidence for the role of tumor cell-derived C1r and C1s in the progression of cSCC and identify them as biomarkers and putative therapeutic targets in cSCC. This article is protected by copyright. All rights reserved.Peer reviewe

Association of breathing sound spectra with glottal dimensions in exercise-induced vocal cord dysfunction

The objective of this study was to evaluate associations between the breathing sound spectra and glottal dimensions in exercise-induced vocal cord dysfunction (EIVCD) during a bicycle ergometry test. Nineteen subjects (mean age 21.8 years and range 13-39 years) with suspected EIVCD were studied. Vocal folds were continuously imaged with videolaryngoscopy and breathing sounds were recorded during the bicycle exercise test. Twelve subjects showed paradoxical movement of the vocal folds during inspiration by the end of the exercise. In seven subjects, no abnormal reactions in vocal folds were found; they served as control subjects. The glottal quotient (interarytenoid distance divided by the anteroposterior glottal distance) was calculated. From the same time period, the tracheal-vocal tract resonance peaks of the breathing sound spectra were analyzed, and stridor sounds were detected and measured. Subjects with EIVCD showed significantly higher resonance peaks during the inspiratory phase compared to the expiratory phase (p <0.014). The glottal quotient decreased significantly in the EIVCD group (p <0.001), but not in the control group. 8 out of 12 EIVCD patients (67%) showed stridor sounds, while none of the controls did. There was a significant inverse correlation between the frequencies of the breathing sound resonance peaks and the glottal quotient. The findings indicate that the typical EIVCD reaction of a paradoxical approximation of the vocal folds during inspiration, measured here as a decrease in the glottal quotient, is significantly associated with an increase in inspiratory resonance peaks. The findings are applicable in the documentation of EIVCD findings using videolaryngoscopy, in addition to giving clinicians tools for EIVCD recognition. However, the study is limited by the small number of subjects.Peer reviewe

Visual interaction with dimensionality reduction: a structured literature analysis

Dimensionality Reduction (DR) is a core building block in visualizing multidimensional data. For DR techniques to be useful in exploratory data analysis, they need to be adapted to human needs and domain-specific problems, ideally, interactively, and on-the-fly. Many visual analytics systems have already demonstrated the benefits of tightly integrating DR with interactive visualizations. Nevertheless, a general, structured understanding of this integration is missing. To address this, we systematically studied the visual analytics and visualization literature to investigate how analysts interact with automatic DR techniques. The results reveal seven common interaction scenarios that are amenable to interactive control such as specifying algorithmic constraints, selecting relevant features, or choosing among several DR algorithms. We investigate specific implementations of visual analysis systems integrating DR, and analyze ways that other machine learning methods have been combined with DR. Summarizing the results in a “human in the loop” process model provides a general lens for the evaluation of visual interactive DR systems. We apply the proposed model to study and classify several systems previously described in the literature, and to derive future research opportunities

Brownian refrigeration by hybrid tunnel junctions

Voltage fluctuations generated in a hot resistor can cause extraction of heat from a colder normal metal electrode of a hybrid tunnel junction between a normal metal and a superconductor. We extend the analysis presented in [Phys. Rev. Lett. 98, 210604 (2007)] of this heat rectifying system, bearing resemblance to a Maxwell's demon. Explicit analytic calculations show that the entropy of the total system is always increasing. We then consider a single electron transistor configuration with two hybrid junctions in series, and show how the cooling is influenced by charging effects. We analyze also the cooling effect from nonequilibrium fluctuations instead of thermal noise, focusing on the shot noise generated in another tunnel junction. We conclude by discussing limitations for an experimental observation of the effect.Comment: 16 pages, 16 figure

Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, and the prognosis of patients with metastatic disease is poor. There is an emerging need to identify molecular markers for predicting aggressive behaviour of cSCC. Here, we have examined the role of tight junction (TJ) components in the progression of cSCC. The expression pattern of mRNAs for TJ components was determined with RNA sequencing and oligonucleotide array-based expression analysis from cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK, n=5). The expression of CLDN11 was specifically elevated in primary cSCC cell lines (n=5), but low or absent in metastatic cSCC cell lines (n=3) and NHEKs. Claudin-11 was detected in cell-cell contacts of primary cSCC cells in culture by indirect immunofluorescence analysis. Analysis of a large panel of tissue samples from sporadic UV-induced cSCC (n=65), cSCC in situ (n=56), actinic keratoses (n=31), seborrhoeic keratoses (n=7) and normal skin (n=16) by immunohistochemistry showed specific staining for claudin-11 in intercellular junctions of keratinizing tumor cells in well and moderately differentiated cSCCs, whereas no staining for claudin-11 was detected in poorly differentiated tumors. The expression of claudin-11 in cSCC cells was dependent on the activity of p38 delta MAPK and knock-down of claudin-11 enhanced cSCC cell invasion. These findings provide evidence for the role of claudin-11 in regulation of cSCC invasion and suggest loss of claudin-11 expression in tumor cells as a biomarker for advanced stage of cSCC

Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma

Background The incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. Objectives To study the role of the complement classical pathway components C1q, C1r and C1s in the progression of cSCC. Methods The mRNA levels of C1Q subunits and C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes, cSCC tumours in vivo and normal skin were analysed with quantitative real-time polymerase chain reaction. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analysed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. Results Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared with normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumours in vivo compared with normal skin. Abundant expression of C1r and C1s by tumour cells was detected in invasive sporadic cSCCs and recessive dystrophic epidermolysis bullosa-associated cSCCs, whereas the expression of C1r and C1s was lower in cSCC in situ, actinic keratosis and normal skin. Knockdown of C1r and C1s expression in cSCC cells inhibited activation of extracellular signal-related kinase 1/2 and Akt, promoted apoptosis of cSCC cells and significantly suppressed growth and vascularization of human cSCC xenograft tumours in vivo. Conclusions These results provide evidence for the role of tumour-cell-derived C1r and C1s in the progression of cSCC and identify them as biomarkers and putative therapeutic targets in cSCC.</p

Harnessing ward-level administrative data and expert knowledge to improve staffing decisions: A multi-method case study

© 2019 John Wiley & Sons Ltd Aim: The aim of this study was to investigate the impact of changes to bed configuration and patient mix on nurses’ workload in a single ward. Design: Multi-method case study. Method: The study was undertaken in an acute 28-bed ward in a tertiary referral public hospital in Queensland, Australia. Ward-level administrative data were obtained for a 2-year period, 12 months before bed configuration changes in October 2015 and 12 months after. These data included patient activity (bed occupancy, transfers, length of stay and casemix) and nurse staffing (budgeted and actual staffing levels, employment status and skillmix). Semi-structured interviews were conducted with ward nurses (N = 17) to explore the impact of the bed configuration changes on their workload. Results: Administrative data showed that the bed configuration changes resulted in more complex and dependent patients, increased patient transfers and greater variability in casemix. The interview data found these changes to patient complexity and activity intensified workloads, which were further increased by staffing decisions that resulted in greater reliance on temporary staff. Conclusion: Hospitals already possess the data and expert knowledge needed to improve staffing and bed management decisions without the need for additional, costly workload systems. Impact: Determining appropriate nurse staffing in light of the complexities and variation of patient needs at the ward level remains a challenge. This study identified increases in patient complexity, dependency, variability and churn that increased workload. Staffing grew but hidden factors associated with temporary staffing and skillmix further intensified nurses’ workload. Harnessing existing data and the expertise and experience of nursing unit managers (NUMs) would help staff wards more efficiently and effectively, providing reasonable workloads and appropriate skillmix that can enhance the safety and quality of patient care. To facilitate this, NUMs need access to accurate, timely, data and authority in staffing and bed management decisions