Origin of Hysteresis in a Proximity Josephson Junction

We investigate hysteresis in the transport properties of Superconductor - Normal metal - Superconductor (S-N-S) junctions at low temperatures by measuring directly the electron temperature in the normal metal. Our results demonstrate unambiguously that the hysteresis results from an increase of the normal metal electron temperature once the junction switches to the resistive state. In our geometry, the electron temperature increase is governed by the thermal resistance of the superconducting electrodes of the junction

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

Low-temperature characterization of Nb-Cu-Nb weak links with Ar ion-cleaned interfaces

We characterize niobium-based lateral Superconductor (S) - Normal metal (N) - Superconductor weak links through low-temperature switching current measurements and tunnel spectroscopy. We fabricate the SNS devices in two separate lithography and deposition steps, combined with strong argon ion cleaning before the normal metal deposition in the last step. Our SNS weak link consists of high-quality sputtered Nb electrodes that are contacted with evaporated Cu. The two-step fabrication flow enables great flexibility in the choice of materials and pattern design. A comparison of the temperature-dependent equilibrium critical supercurrent with theoretical predictions indicates that the quality of the Nb-Cu interface is similar to that of evaporated Al-Cu weak links. Aiming at increased sensitivity, range of operation temperatures, and thermal isolation, we investigate how these SNS structures can be combined with shadow-evaporated aluminum tunnel junctions for sensor applications that utilize the superconducting proximity effect. To this end, we demonstrate a hybrid magnetic flux sensor based on a Nb-Cu-Nb SNS junction, where the phase-dependent normal metal density of states is probed with an Al tunnel junction.Comment: 5 pages, 3 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

Intentstreams: Smart parallel search streams for branching exploratory search

The user's understanding of information needs and the information available in the data collection can evolve during an exploratory search session. Search systems tailored for well-defined narrow search tasks may be suboptimal for exploratory search where the user can sequentially refine the expressions of her information needs and explore alternative search directions. A major challenge for exploratory search systems design is how to support such behavior and expose the user to relevant yet novel information that can be difficult to discover by using conventional query formulation techniques. We introduce IntentStreams, a system for exploratory search that provides interactive query refinement mechanisms and parallel visualization of search streams. The system models each search stream via an intent model allowing rapid user feedback. The user interface allows swift initiation of alternative and parallel search streams by direct manipulation that does not require typing. A study with 13 participants shows that IntentStreams provides better support for branching behavior compared to a conventional search system

Grit blasted aggregates of hydroxyl apatite functionalized calcium carbonate in occluding dentinal tubules

ObjectivesThis study aimed to investigate the effects of using hydroxyl apatite functionalized calcium carbonate (FCC) particles on occluding dentinal tubules.MethodsDentine specimens extracted from eighteen human molars with exposed dentinal tubules were divided into three groups (n = 6/group): a) Cut surface with smear layer; b) EDTA (smear layer removed with 17% EDTA for 1 min); and c) Grit blasted functionalized calcium carbonate (FCC) with and air pressure of 280 kPa. Microscopic dentinal tubule occlusion, tubule diameter and tubule area were evaluated using scanning electron microscopy (SEM) before and after grit blasting. Biomineralization of specimens was carried out in a simulated body fluid (SBF). Elemental analysis of occluding materials was carried out using energy-dispersive X-ray spectroscopy (EDX). X-ray diffraction (XRD) analysis was performed to demonstrate the crystal structure of the biomineralized layer on dentine.ResultsFCC particles showed penetration into the dentinal tubules by breakage of their original particle shape and size. EDTA treated surface had higher number and larger size tubules than those with smear layer or grit blasted (p ConclusionsGrit blasted FCC particles initially occluded effectively the opened dentinal tubules and biomineralization occurred in tubules primarily occluded by the FCC particles. However, in the optimal in vitro conditions in SBF, no difference between biomineralization was found between the grit blasted surface and the control surface.Clinical significanceSeveral materials and methods have been established for treatment of dentinal hypersensitivity although a golden standard treatment has not been discovered. Grit blasted functionalized calcium carbonate has a potential to occlude and remineralize exposed dentinal tubules. This could offer a more biological approach on treatment of dentin hypersensitivity.<br /

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

c-Src/Cav1-dependent activation of the EGFR by Dsg2.

The desmosomal cadherin, desmoglein 2 (Dsg2), is deregulated in a variety of human cancers including those of the skin. When ectopically expressed in the epidermis of transgenic mice, Dsg2 activates multiple mitogenic signaling pathways and increases susceptibility to tumorigenesis. However, the molecular mechanism responsible for Dsg2-mediated cellular signaling is poorly understood. Here we show overexpression as well as co-localization of Dsg2 and EGFR in cutaneous SCCs in vivo. Using HaCaT keratinocytes, knockdown of Dsg2 decreases EGFR expression and abrogates the activation of EGFR, c-Src and Stat3, but not Erk1/2 or Akt, in response to EGF ligand stimulation. To determine whether Dsg2 mediates signaling through lipid microdomains, sucrose density fractionation illustrated that Dsg2 is recruited to and displaces Cav1, EGFR and c-Src from light density lipid raft fractions. STED imaging confirmed that the presence of Dsg2 disperses Cav1 from the cell-cell borders. Perturbation of lipid rafts with the cholesterol-chelating agent MβCD also shifts Cav1, c-Src and EGFR out of the rafts and activates signaling pathways. Functionally, overexpression of Dsg2 in human SCC A431 cells enhances EGFR activation and increases cell proliferation and migration through a c-Src and EGFR dependent manner. In summary, our data suggest that Dsg2 stimulates cell growth and migration by positively regulating EGFR level and signaling through a c-Src and Cav1-dependent mechanism using lipid rafts as signal modulatory platforms