Unification of Radio Galaxies and Their Accretion/Jet Properties

We investigate the relation between black hole mass, M_bh, and jet power, Q_jet, for a sample of BL Lacs and radio quasars. We find that BL Lacs are separated from radio quasars by the FR I/II dividing line in M_bh-Q_jet plane, which strongly supports the unification scheme of FR I/BL Lac and FR II/radio quasar. The Eddington ratio distribution of BL Lacs and radio quasars exhibits a bimodal nature with a rough division at L_bol/L_Edd~0.01, which imply that they may have different accretion modes. We calculate the jet power extracted from advection dominated accretion flow (ADAF), and find that it require dimensionless angular momentum of black hole j~0.9-0.99 to reproduce the dividing line between FR I/II or BL Lac/radio quasar if dimensionless accretion rate mdot=0.01 is adopted, which is required by above bimodal distribution of Eddington ratios. Our results suggest that black holes in radio galaxies are rapidly spinning.Comment: To appear JAA in Jun

Home-Based Monitoring of Pulmonary Function in Patients with Duchenne Muscular Dystroph

BACKGROUND: Loss of pulmonary function is a main cause of early morbidity and mortality in patients with Duchenne muscular dystrophy (DMD). Standard of care guidelines recommend regular assessment of pulmonary function by hospital-based spirometry to detect onset and monitor progression of pulmonary function decline. OBJECTIVE: To assess the feasibility of home-based monitoring of pulmonary function by a hand-held device (HHD) in adolescent and adult patients with DMD over a period of 12 months. METHODS: In the phase III randomized placebo-controlled DELOS trial in 10-18 year old DMD patients, peak expiratory flow (PEF) measurements were collected weekly at home by the patient (assisted by parent/caregiver) using a peak flow meter HHD. Adherence to the use of the HHD was assessed and 12-month changes in PEF as percent of predicted (PEF% p) for the idebenone (N = 31) and the placebo treatment groups (N = 33) from HHD-derived data were compared to results from hospital-based spirometry. RESULTS: A total of 2689 individual HHD assessments were analysed. Overall adherence to the use of the HHD over the course of the 12-month study duration was good (75.9%, SD 21.5%) and PEF% p data obtained at the same day by HHD and standard spirometry correlated well (Spearman's rho 0.80; p < 0.001). Several analysis methods of HHD-derived data for PEF% p consistently demonstrate that idebenone treatment slowed the decline in PEF% p compared to placebo, which supports the statistically significant difference in favour of idebenone for PEF% p measured by standard spirometry. CONCLUSIONS: This study demonstrates that home-based monitoring of pulmonary function in adolescent patients with DMD using a HHD is feasible, provides reliable data compared to hospital-based spirometry and is therefore suitable for use in clinical practice and for clinical trials

Sex Differences in Semantic Processing: Event-Related Brain Potentials Distinguish between Lower and Higher Order Semantic Analysis during Word Reading

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processin

Prognosis of Sentinel Node Staged Patients with Primary Cutaneous Melanoma

Background: This study investigated survival probabilities and prognostic factors in sentinel lymph node biopsy (SLNB) staged patients with cutaneous melanoma (CM) with the aim of defining subgroups of patients who are at higher risk for recurrences and who should be considered for adjuvant clinical trials.\ud \ud Methods: Patients with primary CM who underwent SLNB in the Department of Dermatology, University of Tuebingen, Germany, between 1996 and 2009 were included into this study. Survival probabilities and prognostic factors were evaluated by Kaplan-Meier and multivariate Cox proportional hazard models.\ud \ud Results: 1909 SLNB staged patients were evaluated. Median follow-up time was 44 months. Median tumor thickness was 1.8 mm, ulceration was present in 31.8% of cases. The 5-year Overall Survival (OS) was 90.3% in SLNB negative patients (IB 96.2%, IIA 87.0%, IIB 78.1%, IIC 72.6%). Patients with micrometastases (stage IIIA/B) had a 5-year OS rate of 70.9% which was clearly less favorable than for stages I–II. Multivariate analysis revealed tumor thickness, ulceration, body site, histopathologic subtype and SLNB status as independent significant prognostic factors.\ud \ud Conclusion: Survival rates of patients with primary CM in stages I–II were shown to be much more favorable than previously reported from non sentinel node staged collectives. For future clinical trials, sample size calculations should be adapted using survival probabilities based on sentinel node staging

Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy

Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well‐characterized cohort of 10–18 year‐old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by −0.29 L/sec in patients on placebo (95%CI: −0.51, −0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: −0.22, 0.24; P = 0.950). The between‐group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by −3.0% among patients on placebo (between‐group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD

The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-β to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation of kinase activity. Similarly, the mammalian CK counterpart, MYO7A, binds to and impinges on CASPASE-8, revealing a new regulatory axis affecting receptor interacting protein kinase-1 (RIPK1)>CASPASE-8 signalling. Together, our results expose a conserved role for unconventional myosins in transducing caspase-dependent regulation of kinases, allowing them to take part in specific signalling events

Thermoelectric Signal Enhancement by Reconciling the Spin Seebeck and Anomalous Nernst Effects in Ferromagnet/Non-magnet Multilayers

The utilization of ferromagnetic (FM) materials in thermoelectric devices allows one to have a simpler structure and/or independent control of electric and thermal conductivities, which may further remove obstacles for this technology to be realized. The thermoelectricity in FM/non-magnet (NM) heterostructures using an optical heating source is studied as a function of NM materials and a number of multilayers. It is observed that the overall thermoelectric signal in those structures which is contributed by spin Seebeck effect and anomalous Nernst effect (ANE) is enhanced by a proper selection of NM materials with a spin Hall angle that matches to the sign of the ANE. Moreover, by an increase of the number of multilayer, the thermoelectric voltage is enlarged further and the device resistance is reduced, simultaneously. The experimental observation of the improvement of thermoelectric properties may pave the way for the realization of magnetic-(or spin-) based thermoelectric devicesopen4