Isofrequency pairing of geodesic orbits in Kerr geometry

Abstract ? Bound geodesic orbits around a Kerr black hole can be parametrized by three constants of the motion: the (specific) orbital energy, angular momentum, and Carter constant. Generically, each orbit also has associated with it three frequencies, related to the radial, longitudinal, and (mean) azimuthal motions. Here, we note the curious fact that these two ways of characterizing bound geodesics are not in a one-to-one correspondence. While the former uniquely specifies an orbit up to initial conditions, the latter does not: there is a (strong-field) region of the parameter space in which pairs of physically distinct orbits can have the same three frequencies. In each such isofrequency pair, the two orbits exhibit the same rate of periastron precession and the same rate of Lense-Thirring precession of the orbital plane, and (in a certain sense) they remain “synchronized” in phase.<br/

FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation

Inhibition of spindle microtubule (MT) dynamics has been effectively used in cancer treatment. Although the mechanisms by which MT poisons elicit mitotic arrest are fairly understood, efforts are still needed towards elucidating how cancer cells respond to antimitotic drugs owing to cytotoxicity and resistance side effects. Here, we identified the critical G2/M transcription factor Forkhead box M1 (FOXM1) as a molecular determinant of cell response to antimitotics. We found FOXM1 repression to increase death in mitosis (DiM) due to upregulation of the BCL-2 modifying factor (BMF) gene involved in anoikis, an apoptotic process induced upon cell detachment from the extracellular matrix. FOXM1 binds to a BMF intronic cis-regulatory element that interacts with both the BMF and the neighbor gene BUB1B promoter regions, to oppositely regulate their expression. This mechanism ensures that cells treated with antimitotics repress BMF and avoid DiM when FOXM1 levels are high. In addition, we show that this mechanism is partly disrupted in anoikis/antimitotics-resistant tumor cells, with resistance correlating with lower BMF expression but in a FOXM1-independent manner. These findings provide a stratification biomarker for antimitotic chemotherapy response.This work was supported by: FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020 and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia) in the framework of the project POCI-01-0145-FEDER-031120 (PTDC/BIA-CEL/31120/ 2017); and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/ PORTUGAL 2020 through FEDER. S.V. and F.F. were supported by FCT fellowships SFRH/BD/125017/2016 and PD/BD/105745/2014. E.L. was supported by an FCT Investigator Grant (IF/00916/2014). U.B-D. and G.L. were supported by the Azrieli Faculty Fellowship (to U.D.-D.) and the DoD CDMRP Career Development Award (CA191138 to U.B.-D.). J.B. was supported by an FCT Investigator Grant (CEECIND/03482/2018) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-2015-StG-680156-ZPR)

Web: A Wireless Experiment Box for the Dextre Pointing Package ELC Payload

The Wireless Experiment Box (WEB) was proposed to work with the International Space Station (ISS) External Wireless Communication (EWC) system to support high-definition video from the Dextre Pointing Package (DPP). DPP/WEB was a NASA GSFC proposed ExPRESS Logistics Carrier (ELC) payload designed to flight test an integrated suite of Autonomous Rendezvous and Docking (AR&D) technologies to enable a wide spectrum of future missions across NASA and other US Government agencies. The ISS EWC uses COTS Wireless Access Points (WAPs) to provide high-rate bi-directional communications to ISS. In this paper, we discuss WEB s packaging, operation, antenna development, and performance testing

Transient Thresholding: A Mechanism Enabling Noncooperative Transcriptional Circuitry to Form a Switch

Threshold generation in fate-selection circuits is often achieved through deterministic bistability, which requires cooperativity (i.e., nonlinear activation) and associated hysteresis. However, the Tat positive-feedback loop that controls HIV’s fate decision between replication and proviral latency lacks self-cooperativity and deterministic bistability. Absent cooperativity, it is unclear how HIV can temporarily remain in an off-state long enough for the kinetically slower epigenetic silencing mechanisms to act—expression fluctuations should rapidly trigger active positive feedback and replication, precluding establishment of latency. Here, using flow cytometry and single-cell imaging, we find that the Tat circuit exhibits a transient activation threshold. This threshold largely disappears after ∼40 h—accounting for the lack of deterministic bistability—and promoter activation shortens the lifetime of this transient threshold. Continuous differential equation models do not recapitulate this phenomenon. However, chemical reaction (master equation) models where the transcriptional transactivator and promoter toggle between inactive and active states can recapitulate the phenomenon because they intrinsically create a single-molecule threshold transiently requiring excess molecules in the inactive state to achieve at least one molecule (rather than a continuous fractional value) in the active state. Given the widespread nature of promoter toggling and transcription factor modifications, transient thresholds may be a general feature of inducible promoters

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed

Transfer of negative valence in an episodic memory task

Emotion can color what we perceive and subsequently remember in myriad ways. Indeed, it is well established that emotion enhances some aspects of memory, while impairing others. For example, a number of recent episodic memory studies show that emotion—particularly negative emotion—weakens associative memory, including item-item associations. Other literature shows that emotion biases our later attitudes and preferences. That is, the coincident pairing of a negative stimulus with a neutral one can reduce one's preference for that neutral stimulus upon subsequent encounter—a ‘transfer of valence’ effect. In an effort to connect these two phenomena, here we ask if and under what circumstances they co-occur. Across multiple experiments, we show that negative emotion impairs associative memory for item-item pairings, in accordance with prior work. We also show a transfer of valence effect in this paradigm, such that items paired with negative versus neutral stimuli are subsequently rated as less pleasant. Our data further show that transfer of valence is contingent on episodic memory. These findings highlight the complexity and multifaceted nature of emotional effects on memory

Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.

Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment.This research received financial support from the Safra Foundation (who fund DJN as the Edmond J. Safra Professor of Neuropsychopharmacology) and the Beckley Foundation (it was conducted as part of the Beckley-Imperial research programme). ET is supported by a postdoctoral fellowship of the AXA Research Fund. RCH is supported by an MRC clinical development scheme grant. SDM is supported by a Royal Society of New Zealand Rutherford Discovery Fellowship. KM is supported by a Wellcome Trust Fellowship (WT090199). The researchers would like to thank supporters of the Walacea.com crowd-funding campaign for helping to secure the funds required to complete the study. This report presents independent research carried out at the NIHR/Wellcome Trust Imperial Clinical Research Facility. Authors declare no conflict of interest.This is the author accepted manuscript. The final version is available from Cell Press via http://dx.doi.org/10.1016/j.cub.2016.02.01

Denervación renal en el tratamiento de la hipertensión arterial. Posicionamiento conjunto de la SEH-LELHA y la ACI-SEC

Hypertension is the most prevalent cardiovascular risk factor. Despite pharmacological treatment, a high percentage of patients do not achieve an adequate blood pressure control. Renal sympathetic denervation is a minimally invasive intervention for the management of hypertension involving the interruption of the renal artery sympathetic nervous system using a catheter-based approach. The early studies showed promising results, but the controversial results coming from the SYMPLICITY HTN-3 trial sent this technique into oblivion. Over the last 3 years, new clinical trials have appeared including new devices used in different populations, which definitively proves the effectiveness of renal sympathetic denervation. This joint position statement from the Spanish Society of Hypertension-Spanish League for Combating High Blood Pressure (SEH-LELHA), and the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) reviews the evidence available on the efficacy and safety profile of renal sympathetic denervation for the management of hypertension. Based on the results of clinical trials, recommendations have been established on what patients may be eligible for renal sympathetic denervation and under what circumstances