Single-Quantum-Dot Heat Valve.

We demonstrate gate control of electronic heat flow in a thermally biased single-quantum-dot junction. Electron temperature maps taken in the immediate vicinity of the junction, as a function of the gate and bias voltages applied to the device, reveal clearly defined Coulomb diamond patterns that indicate a maximum heat transfer at the charge degeneracy point. The nontrivial bias and gate dependence of this heat valve results from the quantum nature of the dot at the heart of device and its strong coupling to leads.

[Fulminant acute kidney injury after cholecystectomy in a 45-year-old female patient]. / Fulminantes akutes Nierenversagen nach Cholezystektomie bei einer 45­jährigen Patientin.

A cholecystectomy was carried out on a 45-year-old female patient with fever, myalgia and right upper abdominal pain because of a suspected cholecystitis. Postoperatively acute kidney injury occurred. A comprehensive medical history taken later revealed a presumed occupational contact to rodents. Serological testing detected a recent infection with Dobrava-Belgrade hantavirus. The kidney function normalized with supportive therapeutic measures. Hantavirus infection should be considered in the differential diagnosis of acute kidney injury combined with fever, myalgia and abdominal pain.

[Injury to the upper limbs and prevention in equestrian sports]. / Verletzungen der oberen Extremität und Prävention im Reitsport.

The upper limb is one of the most frequently injured body regions in equestrian sports, but it is unclear which injuries are involved, and there are no data on the associated accident mechanism. The present study is aimed at evaluating the accident mechanisms, injuries of the upper limbs, and the circumstances of the accident in equestrian sports. We included 218 patients who were all treated between 2006 and 2014 at the level I trauma center at the Medical University in Hannover because of equestrian-related accidents. The most frequent injuries were fractures and bruising in the shoulder area, fingers and hands, and the distal area of the lower arm, which were mostly caused by the horse kicking. To prevent hand injuries it is recommended that gloves are worn; the potential introduction of strengthened materials could protect the bones from severe bumping. Training in falling techniques to prevent serious injury to the upper limb would be useful. In general, primary prevention in equestrian sports should be extended to counteract the increasing neglect of protective equipment.

Thermal Conductance of a Single-Electron Transistor.

We report on combined measurements of heat and charge transport through a single-electron transistor. The device acts as a heat switch actuated by the voltage applied on the gate. The Wiedemann-Franz law for the ratio of heat and charge conductances is found to be systematically violated away from the charge degeneracy points. The observed deviation agrees well with the theoretical expectation. With a large temperature drop between the source and drain, the heat current away from degeneracy deviates from the standard quadratic dependence in the two temperatures.

Charge Puddles in Graphene near the Dirac Point.

The charge carrier density in graphene on a dielectric substrate such as SiO_{2} displays inhomogeneities, the so-called charge puddles. Because of the linear dispersion relation in monolayer graphene, the puddles are predicted to grow near charge neutrality, a markedly distinct property from conventional two-dimensional electron gases. By performing scanning tunneling microscopy and spectroscopy on a mesoscopic graphene device, we directly observe the puddles' growth, both in spatial extent and in amplitude, as the Fermi level approaches the Dirac point. Self-consistent screening theory provides a unified description of both the macroscopic transport properties and the microscopically observed charge disorder.

Single Quantum Level Electron Turnstile.

We report on the realization of a single-electron source, where current is transported through a single-level quantum dot (Q) tunnel coupled to two superconducting leads (S). When driven with an ac gate voltage, the experiment demonstrates electron turnstile operation. Compared to the more conventional superconductor-normal-metal-superconductor turnstile, our superconductor-quantum-dot-superconductor device presents a number of novel properties, including higher immunity to the unavoidable presence of nonequilibrium quasiparticles in superconducting leads. Moreover, we demonstrate its ability to deliver electrons with a very narrow energy distribution.

Reversibility of superconducting nb weak links driven by the proximity effect in a quantum interference device.

We demonstrate the role of the proximity effect in the thermal hysteresis of superconducting constrictions. From the analysis of successive thermal instabilities in the transport characteristics of micron-size superconducting quantum interference devices with a well-controlled geometry, we obtain a complete picture of the different thermal regimes. These determine whether or not the junctions are hysteretic. Below the superconductor critical temperature, the critical current switches from a classical weak-link behavior to one driven by the proximity effect. The associated small amplitude of the critical current makes it robust with respect to the heat generation by phase slips, leading to a nonhysteretic behavior.

[Primary Prevention during Interaction of Teachers and Students--An Interdisciplinary Modular Programme According to Psychic and Psychosomatic Disorders in the Setting of Vocational Schools]. / Primärprävention in der Interaktion zwischen Schülern und Lehrern--Ein interdisziplinäres modulares Programm für psychische und psychosomatische Beeinträchtigungen im Setting Berufsschule.

The aim of the project was the development of a modular primary preventive programme according to psychic and psychosomatic disorders in the setting of vocational schools and the evaluation of the corresponding interventions. Preventive strategies were integrated in the basic and further education of teachers and a concept for their occupational medical care. These strategies with long-term effects were supplemented by interventions to promote health and competence directly in the field.

Occupation-related long-term sensory training enhances roughness discrimination but not tactile acuity.

Extensive use of sensorimotor properties has been shown to lead to use-dependent plasticity in the human motor cortex as well as sensory areas. The sensory consequences of these cortical changes, however, remain widely unclear. We were interested whether job-related long-term haptic training is measurable in terms of changes in haptic perception (active touch exploration) in manual physiotherapists (PT). To that end, the haptic thresholds of PT (students and employed) and registered osteopathic manual therapists (OMT; PT with postgraduate specialization) were measured and compared to age- and sex-matched control groups. Additionally, tactile acuity (passive static touch) was assessed using grating domes. PT and OMT had superior mean haptic thresholds compared to the control group, suggesting an increase in sensitivity through use. An age-related decline in haptic perception capacity occurred only in the control group, suggesting that the job-related training of the manual therapist groups may have slowed their age-related decline. Contrary to our expectation, we found significantly poorer mean haptic threshold results in the PT student group than for the controls. No significant differences or changes in tactile acuity were found for any of the groups (students and professional). The present results demonstrate use-dependent plasticity in manual therapists. Furthermore, the results underline the known effect of a superior discrimination ability of haptic as opposed to tactile perception.

EGFR pathway biomarkers in erlotinib-treated patients with advanced pancreatic cancer: translational results from the randomised, crossover phase 3 trial AIO-PK0104.

BACKGROUND: We aimed to identify molecular epidermal growth factor receptor (EGFR) tissue biomarkers in pancreatic cancer (PC) patients treated with the anti-EGFR agent erlotinib within the phase 3 randomised AIO-PK0104 study. METHODS: AIO-PK0104 was a multicenter trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC; primary study end point was the time-to-treatment failure after first- and second-line therapy (TTF2). Translational analyses were performed for KRAS exon 2 mutations, EGFR expression, PTEN expression, the EGFR intron 1 and exon 13 R497K polymorphism (PM). Biomarker data were correlated with TTF, overall survival (OS) and skin rash. RESULTS: Archival tumour tissue was available from 208 (74%) of the randomised patients. The KRAS mutations were found in 70% (121 out of 173) of patients and exclusively occurred in codon 12. The EGFR overexpression was detected in 89 out of 181 patients (49%) by immunohistochemistry (IHC), and 77 out of 166 patients (46%) had an EGFR gene amplification by fluorescence in-situ hybridisation (FISH); 30 out of 171 patients (18%) had a loss of PTEN expression, which was associated with an inferior TTF1 (first-line therapy; HR 0.61, P=0.02) and TTF2 (HR 0.66, P=0.04). The KRAS wild-type status was associated with improved OS (HR 1.68, P=0.005); no significant OS correlation was found for EGFR-IHC (HR 0.96), EGFR-FISH (HR 1.22), PTEN-IHC (HR 0.77), intron 1 (HR 0.91) or exon 13 R497K PM (HR 0.83). None of the six biomarkers correlated with the occurrence of skin rash. CONCLUSION: The KRAS wild-type was associated with an improved OS in erlotinib-treated PC patients in this phase 3 study; it remains to be defined whether this association is prognostic or predictive.

Niobium-based superconducting nano-device fabrication using all-metal suspended masks.

We report a novel method for the fabrication of superconducting nano-devices based on niobium. The well-known difficulties of lithographic patterning of high-quality niobium are overcome by replacing the usual organic resist mask by a metallic one. The quality of the fabrication procedure is demonstrated by the realization and characterization of long and narrow superconducting lines and niobium-gold-niobium proximity SQUIDs.

New approaches to sexuality education and underlying paradigms.

The issue of sexuality education has been--and still is--contested to varying degrees. While sexuality education in many western European countries has a long tradition going back to the 1950s, in other parts of the world it became more prominent after the onset of the HIV epidemic in the 1980s. At present, the field is characterized by different underlying paradigms often rooted in moral convictions. The dominant approach in the US to sexuality education is mainly influenced by public health concerns--including prevention of HIV and other sexually transmitted infections (STIs), unintended pregnancies, and possibly sexual abuse. This approach may include"abstinence-only" messages, but could also be more open and offer comprehensive information as a means to harm reduction. Another approach, rooted in a European understanding of sexuality education and published in the"Standards for Sexuality Education in Europe" (2010), is based on the human rights of children and adolescents to access information and education and at its core has a positive understanding of sexuality. This article highlights international developments around sexuality education, with a focus on Europe. It also compares differences in approaches and their often implicit underlying paradigms, with the aim of generating more international discussion on the advantages and disadvantages of these different approaches. International organizations need to be aware of the different approaches and need to reflect them in their work.

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

A subKelvin scanning probe microscope for the electronic spectroscopy of an individual nano-device.

We present a combined scanning force and tunneling microscope working in a dilution refrigerator that is optimized for the study of individual electronic nano-devices. This apparatus is equipped with commercial piezo-electric positioners enabling the displacement of a sample below the probe over several hundred microns at very low temperature, without excessive heating. Atomic force microscopy based on a tuning fork resonator probe is used for cryogenic precise alignment of the tip with an individual device. We demonstrate the local tunneling spectroscopy of a hybrid Josephson junction as a function of its current bias.

Probing "cosmological" defects in superfluid 3He-B with a vibrating-wire resonator.

We report on the observation of an anomalously high damping measured by a vibrating-wire resonator (VWR) immersed into superfluid at ultralow temperatures. The observed dissipation is orders of magnitude above that corresponding to friction with the dilute normal fraction and superfluid vortices. A clear pinning behavior is also observed, as well as a strong magnetic field dependence. Our analysis points to the interaction of the VWR with a planar topological defect, analogue to cosmological vacua defects, as proposed by Salomaa and Volovik.

Mechanism of action of galanin on myenteric neurons.

1. Conventional intracellular recording methods were used to investigate the mechanism of action of galanin on electrical behavior of AH/type 2 myenteric neurons in the guinea pig small intestine. 2. The overall action of galanin was inhibitory and consisted of membrane hyperpolarization, decreased input resistance, and suppression of excitability. 3. The action of galanin was on the somatic membrane. There were no effects on spike initiation or propagation velocity in the processes. 4. The reversal potential for the hyperpolarizing action of galanin was near the estimated K+ equilibrium potential and was dependent on the concentration of K+ in the bathing medium. 5. Treatment with tetraethylammonium (TEA) broadened the action-potential and enhanced long-lasting hyperpolarizing after-potentials (AH). Application of galanin or depletion of Ca2+ in the bathing medium offset the effects of TEA on the spike and the AH. Galanin or reduced Ca2+ had the same effect when both TEA and tetrodotoxin (TTX) were present. 6. Simultaneous application of TEA and 4-aminopyridine (4-AP) evoked spontaneous spike discharge with broadened spikes and enhanced AH. This activity was suppressed by galanin. 7. Intrasomatic injection of Cs+ in the presence of TTX appeared to abolish all K+ conductances leaving pure Ca2+ spikes in response to depolarizing current pulse. Galanin abolished these Ca2+ spikes. 8. The results suggest two major mechanisms of action for galanin. One is to open K+ channels, decrease input resistance, and hyperpolarize the membrane toward EK+. The second is blockade of voltage gated Ca2+ channels and suppression of the AH by indirect prevention of opening of Ca2+-dependent K+ channels.

Hodgkin's disease and peripheral T-cell lymphoma: composite lymphoma with evidence of Epstein-Barr virus infection.

This paper reports the case of a patient with a composite lymphoma consisting of nodular sclerosing Hodgkin's disease and peripheral T-cell lymphoma. The Hodgkin and Reed-Sternberg (HRS) cells harboured the Epstein-Barr virus (EBV) and displayed a type II EBV latency (LMP1(+)/EBNA2(-)), whereas the neoplastic T-cells were EBV-negative. Four years later, the patient presented with a relapse of the peripheral T-cell lymphoma. In situ hybridization revealed numerous EBV-carrying lymphocytes, which were shown to be polyclonal B-cells with a latency III pattern of EBV gene expression (LMP1(+)/EBNA2(+)). This observation suggests that impairment of EBV-specific immunity in the micro-environment of T-cell lymphomas may facilitate the outgrowth of EBV-carrying B-lymphocytes and emphasizes the importance of determining the phenotype of EBV-infected cells, particularly when studying T-cell lymphomas. The results further suggest that the HRS cells and neoplastic T-cells were of different clonal origins. The detection of EBV-carrying cell populations admixed with the neoplastic T-cells at primary presentation and at relapse raises the possibility that the growth of the T-cell lymphoma was dependent on the presence of such cells.

Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) ORF54 encodes a functional dUTPase expressed in the lytic replication cycle.

The complete ORF54 of the Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus-8; HHV-8) was cloned and expressed in E. coli. The results show that KSHV/HHV-8 ORF54 encodes a functional dUTPase which specifically hydrolyses dUTP to dUMP. Monoclonal antibodies against the HHV-8 dUTPase detected a protein with the expected molecular mass of 35 kDa in HHV-8-infected BCBL-1 cells. Induction of the lytic replication cycle of HHV-8 by treatment of BCBL-1 cells with the phorbol ester TPA resulted in an increased expression of the protein which was not inhibited by phosphonoacetic acid, indicating that the protein is expressed early in the lytic replication cycle. Moreover, the sporadic expression of the HHV-8 dUTPase in tissue sections of Kaposi's sarcoma was detected by immunohistochemistry.