An investigation of the structure and kinematics of the spiral galaxy NGC 6503

The spiral galaxy NGC 6503 exhibits a regular kinematical structure except for a remarkable drop of the stellar velocity dispersion values in the central region. To investigate the dynamics of the disc a theoretical framework has been described. This includes a mass decomposition of the galaxy into a family of disc/halo realizations compatible with the observed photometry and rotation curve. For this family stellar velocity dispersion values and stability parameters were calculated, showing that the more massive discs, although having larger dispersions, are less stable. However, a reliable theoretical description of the inner regions where the drop occurs cannot be given. That is why we have resorted to numerical calculations. Pure stellar 3d simulations have been performed for the family of decompositions. A clear result is that disc/dark halo mass ratios approaching those of the maximum disc limit generate a large bar structure. This is incompatible with the observed morphology of NGC 6503. For the larger radii the stellar kinematics resulting from the simulations essentially agrees with that predicted by the theory, but the central velocity dispersion drop could not be reproduced. A close inspection reveals that the central nuclear region is very small and bright. Therefore, tentatively, this nucleus was considered as an isothermal sphere and a core fitting procedure was applied. For an adopted equal mass-to-light ratio of disc and nucleus, a velocity dispersion of 21.5 km/s is predicted, in excellent agreement with the observed central value. The observed dispersion drop can thus be explained by a separate kinematically distinct galactic component.Comment: 14 pages, Latex, use mn.sty style fil

Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer’s disease pathology

Background Alzheimer’s disease (AD) is the most common neurodegenerative disease. In addition to the occurrence of amyloid deposits and widespread tau pathology, AD is associated with a neuroinflammatory response characterized by the activation of microglia and astrocytes. Protein kinase 2 (CK2, former casein kinase II) is involved in a wide variety of cellular processes. Previous studies on CK2 in AD showed controversial results, and the involvement of CK2 in neuroinflammation in AD remains elusive. Methods In this study, we used immunohistochemical and immunofluorescent staining methods to investigate the localization of CK2 in the hippocampus and temporal cortex of patients with AD and non-demented controls. We compared protein levels with Western blotting analysis, and we investigated CK2 activity in human U373 astrocytoma cells and human primary adult astrocytes stimulated with IL-1β or TNF-α. Results We report increased levels of CK2 in the hippocampus and temporal cortex of AD patients compared to non-demented controls. Immunohistochemical analysis shows CK2 immunoreactivity in astrocytes in AD and control cases. In AD, the presence of CK2 immunoreactive astrocytes is increased. CK2 immunopositive astrocytes are associated with amyloid deposits, suggesting an involvement of CK2 in the neuroinflammatory response. In U373 cells and human primary astrocytes, the selective CK2 inhibitor CX-4945 shows a dose-dependent reduction of the IL-1β or TNF-α induced MCP-1 and IL-6 secretion. Conclusions This data suggests that CK2 in astrocytes is involved in the neuroinflammatory response in AD. The reduction in pro-inflammatory cytokine secretion by human astrocytes using the selective CK2 inhibitor CX-4945 indicates that CK2 could be a potential target to modulate neuroinflammation in AD

Characterizing benthic macroinvertebrate and algal biological condition gradient models for California wadeable Streams, USA

The Biological Condition Gradient (BCG) is a conceptual model that describes changes in aquatic communities under increasing levels of anthropogenic stress. The BCG helps decision-makers connect narrative water quality goals (e.g., maintenance of natural structure and function) to quantitative measures of ecological condition by linking index thresholds based on statistical distributions (e.g., percentiles of reference distributions) to expert descriptions of changes in biological condition along disturbance gradients. As a result, the BCG may be more meaningful to managers and the public than indices alone. To develop a BCG model, biological response to stress is divided into 6 levels of condition, represented as changes in biological structure (abundance and diversity of pollution sensitive versus tolerant taxa) and function. We developed benthic macroinvertebrate (BMI) and algal BCG models for California perennial wadeable streams to support interpretation of percentiles of reference-based thresholds for bioassessment indices (i.e., the California Stream Condition Index [CSCI] for BMI and the Algal Stream Condition Index [ASCI] for diatoms and soft-bodied algae). Two panels (one of BMI ecologists and the other of algal ecologists) each calibrated a general BCG model to California wadeable streams by first assigning taxa to specific tolerance and sensitivity attributes, and then independently assigning test samples (264 BMI and 248 algae samples) to BCG Levels 1–6. Consensus on the assignments was developed within each assemblage panel using a modified Delphi method. Panels then developed detailed narratives of changes in BMI and algal taxa that correspond to the 6 BCG levels. Consensus among experts was high, with 81% and 82% expert agreement within 0.5 units of assigned BCG level for BMIs and algae, respectively. According to both BCG models, the 10th percentiles index scores at reference sites corresponded to a BCG Level 3, suggesting that this type of threshold would protect against moderate changes in structure and function while allowing loss of some sensitive taxa. The BCG provides a framework to interpret changes in aquatic biological condition along a gradient of stress. The resulting relationship between index scores and BCG levels and narratives can help decision-makers select thresholds and communicate how these values protect aquatic life use goals

A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

AbstractVirotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer

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Efficacy and safety of on-demand use of 2 treatments designed for different etiologies of female sexual interest/arousal disorder:3 Randomized Clinical Trials

Background In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. Aim To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. Methods 497 women (21–70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). Outcomes The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. Results In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57–2.84, P =.004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44–3.45, P =.012; T: Δ = 1.69, 95% CI = 0.58–2.80, P =.003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17–1.82, P =.019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57–2.46, P =.002; T: Δ = 0.98, 95% CI = 0.17–1.78, P =.018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). Clinical Implications T + S and T + B are promising treatments for women with FSIAD. Strengths and Limitations The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. Conclusions T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201–216