Cavity QED in superconducting circuits: susceptibility at elevated temperatures

We study the properties of superconducting electrical circuits, realizing cavity QED. In particular we explore the limit of strong coupling, low dissipation, and elevated temperatures relevant for current and future experiments. We concentrate on the cavity susceptibility as it can be directly experimentally addressed, i.e., as the impedance or the reflection coefficient of the cavity. To this end we investigate the dissipative Jaynes-Cummings model in the strong coupling regime at high temperatures. The dynamics is investigated within the Bloch-Redfield formalism. At low temperatures, when only the few lowest levels are occupied the susceptibility can be presented as a sum of contributions from independent level-to-level transitions. This corresponds to the secular (random phase) approximation in the Bloch-Redfield formalism. At temperatures comparable to and higher than the oscillator frequency, many transitions become important and a multiple-peak structure appears. We show that in this regime the secular approximation breaks down, as soon as the peaks start to overlap. In other words, the susceptibility is no longer a sum of contributions from independent transitions. We treat the dynamics of the system numerically by exact diagonalization of the Hamiltonian of the qubit plus up to 200 states of the oscillator. We compare the results obtained with and without the secular approximation and find a qualitative discrepancy already at moderate temperatures.Comment: 7 pages, 6 figure

Multi-scale characterisation of the 3D microstructure of a thermally-shocked bulk metallic glass matrix composite

Bulk metallic glass matrix composites (BMGMCs) are a new class of metal alloys which have significantly increased ductility and impact toughness, resulting from the ductile crystalline phases distributed uniformly within the amorphous matrix. However, the 3D structures and their morphologies of such composite at nano and micrometre scale have never been reported before. We have used high density electric currents to thermally shock a Zr-Ti based BMGMC to different temperatures, and used X-ray microtomography, FIB-SEM nanotomography and neutron diffraction to reveal the morphologies, compositions, volume fractions and thermal stabilities of the nano and microstructures. Understanding of these is essential for optimizing the design of BMGMCs and developing viable manufacturing methods

Dual- and triple-targeting of the HER-family members using combinations of mono- and bispecific antibodies

Epidermal growth factor receptor (EGFR)-targeted cancer treatments with antibodies like Cetuximab are successfully used in the clinic for about 20 years. However, intrinsic, as well as newly developed resistance mechanisms to EGFR-targeted therapies, are the main reason for their failure. Activation of human epidermal growth factor receptor 3 (HER3)-signaling upon EGFR-targeted therapies is frequently observed and has motivated the development of combination therapies that simultaneously block EGFR and HER3. In this study, bispecific and bivalent, or tetravalent, respectively, single-chain diabody (scDb) and scDb-Fc molecules were developed comprising the antigen-binding sites of a humanized version of Cetuximab (hu225) as well as a recently developed anti-HER3 antibody (3-43). In total, eight molecules (two scDb and six scDb-Fc) with varying linkers were engineered. The scDb hu225x3 43 Fc showed the most favorable properties regarding production yield, purity, homogeneity and linker setup. Binding of the scDb-Fc to recombinant receptors, as well as to HER-family receptor expressing cell lines revealed retained binding properties, compared to parental antibodies. Furthermore, the scDb hu225x3 43 Fc showed strong and long-lasting inhibition of downstream signaling by EGF, HRG or combination of both ligands. Proliferation studies on head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), and colorectal cancer (CRC) cell lines revealed either similar, or stronger inhibition, compared to parental antibodies as single or combination treatment, which translated into to long-lasting growth suppression in a s.c. xenograft tumor model. Treatment with the bispecific antibody inhibited in vitro HRG-stimulated oncosphere formation of two TNBC cell lines. In an orthotopic MDA-MB-468 tumor model, superior antitumor effects were observed compared to those obtained by the parental antibodies alone or in combination. Furthermore, this was associated with a reduced number of cells with stem-like properties demonstrating that the bispecific antibody not only efficiently blocks TNBC proliferation but also the survival and expansion of the cancer stem cell population. The high degree of plasticity and compensatory signaling within the HER-family not only leads to compensatory crosstalk by HER3 but also HER2 giving the rational to combine the EGFR- and HER3-targeting scDb-Fc with a HER2-targeting antibody like Trastuzumab. The triple-targeting approach with the scDb-Fc and Trastuzumab was superior in inhibition of HRG-stimulated proliferation of the CRC cell line LIM1215 compared to the combination of IgG hu225, Trastuzumab and IgG 3 43. This was also observed in primary and secondary CRC oncosphere formation assays. Finally, in CRC patient derived organoids (PDOs) grown in HRG-supplemented medium the triple-targeting of EGFR, HER2 and HER3 provided broader efficacy than dual- or mono-targeting of receptors of the HER family. In contrast to Afatinib (anti-EGFR, -HER2, -HER4), the triple-targeted antibody approach showed efficient inhibition in all tested PDOs. Thus, the bispecific scDb-Fc alone or in combination with Trastuzumab represents a superior strategy to deal with primary and acquired resistances compared to targeting a single receptor with different antibodies or any combination of antibodies targeting two receptors of the HER-family

Funktionskapazität und psychosomatische Komorbiditäten bei Patienten mit chronischen Schmerzen - Evaluation einer Schmerzsprechstunde

Im Rahmen der Studie wurden 241 Patienten, die im Zeitraum von Februar 2006 bis Mai 2009 die Psychosomatische Schmerzambulanz in Tübingen besuchten, Fragebögen vorgelegt. Neben den Fragebögen wurde ein klinisch-diagnostisches Interview durch einen erfahrenen Therapeuten (Arzt oder Psychologe) durchgeführt. Der einzelne Patient erhält jeweils einen Fragebogen zu deskriptiven Fragestellungen, den PHQ-D zur Diagnose der häufigsten psychischen Erkrankungen, den FFBH-R zur alltagsnahen Diagnostik von Funktionsbeeinträchtigung von Rückenschmerzen, den SF-36 zur Beurteilung des allgemeinen Gesundheitsstatus und den PSQ zur Stressbeurteilung. Die Stichprobe beinhaltet Patienten von 17 bis 84 Jahre (mittleres Alter 46,2 J). Der Großteil der Patienten (54,6%) ist verheiratet und lebt mit dem Partner zusammen. Die größte Subgruppe stellen Patienten mit Haupt- und Realschulabschluss (kumulativ 54%), außerdem Angestellte, dar. Hauptzuweiser der Patienten sind die Allgemeinmediziner. 75% der Patienten zeigen eine somatoforme Schmerzstörung, 13,9% leiden an einer Angststörung. Die Patienten geben im Mittel eine subjektive Schmerzstärke von 6,79 auf der visuellen Analogskala an, 81,45 % der Patienten an verschiedenen Lokalisationen. Bei 50,5% der Patienten mit mehrfachen Arztbesuchen in den letzten vier Wochen liegt ein großes Inanspruchnahmeverhalten medizinischer Leistungen vor. Es konnte gezeigt werden, dass Patienten mit weiblichem Geschlecht, Verwitwete, Patienten mit geringerer Funktionskapazität im FFBH-R und höherem Schweregrad einer Depression jeweils höhere Werte auf der visuellen Analogskala zeigen. Gerade die Funktionskapazität zeigte sich als großer Einflussfaktor auf das Schmerzerleben, am ehesten in Form eines Markers der erlebten Lebensqualität. Als erklärende Faktoren für die Varianz der Funktionskapazität konnten das Alter und die Depressivität gezeigt werden. Diese erklären 14% der Varianz der Funktionskapazität im gerechneten Regressionsmodell. Das Alter stellt einen unbeeinflussbaren Faktor dar. Die Depression allerdings einen einfach zu diagnostizierenden und außerdem durch Zuführung einer adäquaten Therapie, gut behandelbaren Faktor. Die Diagnose und vor allem die Behandlung der Komorbidität Depression zur Vermeidung einer Chronifizierung der Schmerzerkrankung stellt eine Hauptforderung und Quintessenz der vorliegenden Arbeit dar.

Liver transplantation in primary biliary cirrhosis: Risk assessment and 11-year follow-up

Background/Aims: Liver transplantation (LTx) is the only established treatment in patients with end-stage primary biliary cirrhosis (PBC). Although short-term survival after LTx in this group of patients is usually good, few data exist on the long-term survival. The optimal timing of transplantation is difficult. Thus, the aims of this study were to assess the long-term survival of patients with PBC after LTx and to identify potential predictive factors for a positive outcome. Methods: Survival of 28 patients with PBC who underwent LTx between 1985 and July 1999 in a single center was studied by Kaplan-Meier analysis and was compared to predicted survival without LTx using established prognostic models for PBC, the Mayo and European risk scores. Potential prognostic parameters obtained before LTx were tested for correlation to survival. Rates of bone fractures as markers of hepatic osteodystrophy were compared before and after LTx. Results: Median follow-up after LTx was 90 months with a maximum of 140 months. Actuarial survival of patients with PBC was 89% after 1, 5, and 10 years and was significantly better than estimated survival without LTx after 1-7 years as calculated by the Mayo and European risk scores. Of several parameters tested, only serum bilirubin and the prognostic scores, but no other liver function tests obtained immediately prior to transplantation were significantly correlated with survival after LTx. The duration of intensive care after LTx was not associated with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of patients of whom the vast majority were osteopenic before LTx as determined by osteodensitometry. Conclusion: Longterm survival of a well-defined group of patients with PBC was excellent after LTx and was inversely correlated with preoperative serum bilirubin levels as well as Mayo and European risk scores. Copyright (C) 2000 S. Karger AG. Basel

Mode use in long-distance travel

JTLU, vol. 8, no. 2, pp. 87-105This paper focuses on mode use in long-distance travel. Long-distance travel is responsible for more than 50 percent of climate impact. Nevertheless, it is usually excluded from analyses that examine travel behavior. Whereas studies on daily travel prove that the rural population covers longer distances in daily travel, recent studies (e.g., Holz-Rau, Scheiner, and Sicks 2014; Brand and Preston 2010) show a different picture in long-distance travel. Here, the urban population undertakes more long-distance trips, especially by air. The aim of this paper is to analyze the mode use in long-distance travel in different spatial settings by using multivariate regression models. The (underlying) data derive from a nationwide survey with a sample size of 60,713 respondents, Mobility in Germany 2008 (MiD). A broad range of sociodemographic and socioeconomic characteristics are thereby included as control variables. The results show that even when household income, car accessibility, and education level are considered, the urban population undertakes more long-distance trips, in particular by train and by air. These differences are found in business as well as in private travel

Supramolecular aggregation control in polyoxometalates covalently functionalized with oligoaromatic groups

CLICK-chemistry has become a universal route to covalently link organic molecules functionalized with azides and alkynes, respectively. Here, we report how CLICK-chemistry can be used to attach oligoaromatic organic moieties to Dawson-type polyoxometalates. In step one, the lacunary Dawson anion [α2-P2W17O61]6− is functionalized with phosphonate anchors featuring peripheral azide groups. In step two, this organic-inorganic hybrid undergoes microwave-assisted CLICK coupling. We demonstrate the versatility of this route to access a series of Dawson anions covalently functionalized with oligoaromatic groups. The supramolecular chemistry and aggregation of these systems in solution is explored, and we report distinct changes in charge-transfer behavior depending on the size of the oligoaromatic π-system

Identification of factors influencing insertion characteristics of cochlear implant electrode carriers

Insertion studies in artificial cochlea models (aCM) are used for the analysis of insertion characteristics of different cochlear implant electrode carrier (EC) designs by measuring insertion forces. These forces are summed forces due to the measuring position which is directly underneath the aCM. The current hypothesis is that they include dynamic friction forces during the insertion process and the forces needed to bend an initially straight EC into the curved form of the aCM. For the purposes of the present study, straight EC substitutes with a constant diameter of 0.7 mm and 20.5 mm intracochlear length were fabricated out of silicone in two versions with different stiffness by varying the number of embedded wires. The EC substitutes were inserted into three different models made of polytetrafluoroethylene (PTFE), each model showing only one constant radius. Three different insertion speeds were used (0.11 / 0.4 / 1.6 mm/s) with an automated insertion test bench. For each parameter combination (curvature, speed, stiffness) twelve insertions were conducted. Measurements included six full insertions and six paused insertions. Paused insertions include a ten second paused time interval without further insertion movement each five millimetres. Measurements showed that dynamic and static components of the measured summed forces can be identified. Dynamic force components increase with increased insertion speeds and also with increased stiffness of the EC substitutes. Both force components decrease with larger radius of the PTFE model. After the insertion, the EC substitutes showed a curved shape, which indicates a plastic deformation of the embedded wires due to the insertion into the curved models. The results can be used for further research on an analytical model to predict the insertions forces of a specific combination of selected parameters as insertion speed and type of EC, combined with given factors such as cochlear geometry