Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Voltage-gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity and Invasion Via Persistent MAPK Signaling

Functional expression of voltage-gated Na+ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes

Efficacy and safety of blonanserin transdermal patch in patients with schizophrenia: A 6-week randomized, double-blind, placebo-controlled, multicenter study

© 2019 The Authors Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia. Methods: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs). Results: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: −5.6 with blonanserin 40 mg; 95% confidence interval [CI] −9.6, −1.6; adjusted p = 0.007, and − 10.4 with blonanserin 80 mg; 95% CI −14.4, −6.4; adjusted p \u3c 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia. Conclusions: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability

Cognitive networks: brains, internet, and civilizations

In this short essay, we discuss some basic features of cognitive activity at several different space-time scales: from neural networks in the brain to civilizations. One motivation for such comparative study is its heuristic value. Attempts to better understand the functioning of "wetware" involved in cognitive activities of central nervous system by comparing it with a computing device have a long tradition. We suggest that comparison with Internet might be more adequate. We briefly touch upon such subjects as encoding, compression, and Saussurean trichotomy langue/langage/parole in various environments.Comment: 16 page

Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury

Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to \u3e/=99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation

Synthetic Mirnov diagnostic for the validation of experimental observations

A synthetic Mirnov diagnostic has been developed to investigate the capabilities and limitations of an arrangement of Mirnov coils in terms of a mode analysis. Eight test cases have been developed, with different coil arrangements and magnetic field configurations. Three of those cases are experimental configurations of the stellarator Wendelstein 7-X. It is observed that, for a high triangularity of the flux surfaces, the arrangement of the coils plays a significant role in the exact determination of the poloidal mode number. For the mode analysis, torus and magnetic coordinates have been used. In most cases, the reconstruction of the poloidal mode number of a prescribed mode was found to be more accurate in magnetic coordinates. As an application, the signal of an Alfvén eigenmode, which has been calculated with a three-dimensional magnetohydrodynamics code, is compared to experimental observations at Wendelstein 7-X. For the chosen example, the calculated and measured mode spectra agree very well and additional information on the toroidal mode number and localization of the mode has been inferred

Infection of Myxobolus turpisrotundus sp n. in allogynogenetic gibel carp, Carassius auratus gibelio (Bloch), with revision of Myxobolus rotundus (s. l.) Nemeczek reported from C-auratus auratus (L.)

Infection of a Myxobolus species, previously identified as Myxobolus rotundus, was detected in 182 of 7892 (2.31%) allogynogenetic gibel carp, Carassius auratus gibelio, in a closed pond culture system in China. Morphological and molecular data showed that this myxosporean is a different species from M. rotundus parasitizing Abramis brama in Europe and is thus designated as a new species, Myxobolus turpisrotundus. M. rotundus (s.l.) ex C. auratusauratus is a synonym of M. turpisrotundus. Plasmodia of M. turpisrotundus develop in the subepidermal tissues of the body surface resulting in an unaesthetic appearance and causing severe economic losses. Prevalence of infection with the myxosporean plasmodia varied seasonally, increasing in winter and decreasing in spring. Prevalence was positively correlated to host size, but no host sex-specificity was found. No infection was observed in other fish species (grass carp, bighead carp and yellow catfish) reared in the same pond, suggesting that the parasite has a relatively strict host specificity. Plasmodia grew gradually as the parasite developed, and reached up to a maximum 5.6 mm in diameter. Plasmodia ruptured naturally to release the mature spores and host fish completely recovered with no mortality. Release of spores and regeneration of lesions were not correlated with water temperature. Histology showed that plasmodia developed sub-epidermally, and that the wall of the plasmodia was composed of a multiple complex structure, including layers of fibroblasts, a collagenous membrane, melanophores and a layer of cup-like cells of unknown derivation and function. The cup-like cells are in direct contact with pre-sporogonic stages located in the peripheral parts of the large plasmodia. No severe host inflammatory response was seen

Propensity-matched analysis of patient-reported outcomes for neoadjuvant chemotherapy prior to radical cystectomy

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: To evaluate patient-reported outcomes (PROs) for bladder cancer patients undergoing neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) using longitudinal data and propensity-matched scoring analyses. Methods: 155 patients with muscle-invasive bladder cancer scheduled for RC completed the European Organization for Research and Treatment of Cancer questionnaires, EORTC QLQ-C30, EORTC QLQ-BLM30, Fear of Recurrence Scale, Mental Health Inventory and Satisfaction with Life Scale within 4 weeks of surgery. A propensity-matched analysis was performed comparing pre-surgery PROs among 101 patients who completed NAC versus 54 patients who did not receive NAC. We also compared PROs pre- and post-chemotherapy for 16 patients who had data available for both time points. Results: In propensity-matched analysis, NAC-treated patients reported better emotional and sexual function, mental health, urinary function and fewer financial concerns compared to those that did not receive NAC. Longitudinal analysis showed increases in fatigue, nausea and appetite loss following chemotherapy. Conclusion: Propensity-matched analysis did not demonstrate a negative effect of NAC on PRO. Several positive associations of NAC were found in the propensity-matched analysis, possibly due to other confounding differences between the two groups or actual clinical benefit. Longitudinal analysis of a small number of patients found small to modest detrimental effects from NAC similar to toxicities previously reported. Our preliminary findings, along with known survival and toxicity data, should be considered in decision-making for NAC

Structural variation of centromeric endogenous retroviruses in human populations and their impact on cutaneous T-cell lymphoma, Sézary syndrome, and HIV infection

© 2019 The Author(s). Background: Human Endogenous Retroviruses type K HML-2 (HK2) are integrated into 117 or more areas of human chromosomal arms while two newly discovered HK2 proviruses, K111 and K222, spread extensively in pericentromeric regions, are the first retroviruses discovered in these areas of our genome. Methods: We use PCR and sequencing analysis to characterize pericentromeric K111 proviruses in DNA from individuals of diverse ethnicities and patients with different diseases. Results: We found that the 5′ LTR-gag region of K111 proviruses is missing in certain individuals, creating pericentromeric instability. K111 deletion (-/- K111) is seen in about 15% of Caucasian, Asian, and Middle Eastern populations; it is missing in 2.36% of African individuals, suggesting that the -/- K111 genotype originated out of Africa. As we identified the -/-K111 genotype in Cutaneous T-cell lymphoma (CTCL) cell lines, we studied whether the -/-K111 genotype is associated with CTCL. We found a significant increase in the frequency of detection of the -/-K111 genotype in Caucasian patients with severe CTCL and/or Sézary syndrome (n = 35, 37.14%), compared to healthy controls (n = 160, 15.6%) [p = 0.011]. The -/-K111 genotype was also found to vary in HIV-1 infection. Although Caucasian healthy individuals have a similar frequency of detection of the -/- K111 genotype, Caucasian HIV Long-Term Non-Progressors (LTNPs) and/or elite controllers, have significantly higher detection of the -/-K111 genotype (30.55%; n = 36) than patients who rapidly progress to AIDS (8.5%; n = 47) [p = 0.0097]. Conclusion: Our data indicate that pericentromeric instability is associated with more severe CTCL and/or Sézary syndrome in Caucasians, and appears to allow T-cells to survive lysis by HIV infection. These findings also provide new understanding of human evolution, as the -/-K111 genotype appears to have arisen out of Africa and is distributed unevenly throughout the world, possibly affecting the severity of HIV in different geographic areas