92 research outputs found
Invariant manifolds and orbit control in the solar sail three-body problem
In this paper we consider issues regarding the control and orbit transfer of solar sails in the circular restricted Earth-Sun system. Fixed points for solar sails in this system have the linear dynamical properties of saddles crossed with centers; thus the fixed points are dynamically unstable and control is required. A natural mechanism of control presents itself: variations in the sail's orientation. We describe an optimal controller to control the sail onto fixed points and periodic orbits about fixed points. We find this controller to be very robust, and define sets of initial data using spherical coordinates to get a sense of the domain of controllability; we also perform a series of tests for control onto periodic orbits. We then present some mission strategies involving transfer form the Earth to fixed points and onto periodic orbits, and controlled heteroclinic transfers between fixed points on opposite sides of the Earth. Finally we present some novel methods to finding periodic orbits in circumstances where traditional methods break down, based on considerations of the Center Manifold theorem
Pol II Docking and Pausing at Growth and Stress Genes in C. elegans
Fluctuations in nutrient availability profoundly impact gene expression. Previous work revealed postrecruitment regulation of RNA polymerase II (Pol II) during starvation and recovery in Caenorhabditis elegans, suggesting that promoter-proximal pausing promotes rapid response to feeding. To test this hypothesis, we measured Pol II elongation genome wide by two complementary approaches and analyzed elongation in conjunction with Pol II binding and expression. We confirmed bona fide pausing during starvation and also discovered Pol II docking. Pausing occurs at active stress-response genes that become downregulated in response to feeding. In contrast, âdockedâ Pol II accumulates without initiating upstream of inactive growth genes that become rapidly upregulated upon feeding. Beyond differences in function and expression, these two sets of genes have different core promoter motifs, suggesting alternative transcriptional machinery. Our work suggests that growth and stress genes are both regulated postrecruitment during starvation but at initiation and elongation, respectively, coordinating gene expression with nutrient availability
Defining NELF-E RNA binding in HIV-1 and promoter-proximal pause regions
The four-subunit Negative Elongation Factor (NELF) is a major regulator of RNA Polymerase II (Pol II) pausing. The subunit NELF-E contains a conserved RNA Recognition Motif (RRM) and is proposed to facilitate Poll II pausing through its association with nascent transcribed RNA. However, conflicting ideas have emerged for the function of its RNA binding activity. Here, we use in vitro selection strategies and quantitative biochemistry to identify and characterize the consensus NELF-E binding element (NBE) that is required for sequence specific RNA recognition (NBE: CUGAGGA(U) for Drosophila). An NBE-like element is present within the loop region of the transactivation-response element (TAR) of HIV-1 RNA, a known regulatory target of human NELF-E. The NBE is required for high affinity binding, as opposed to the lower stem of TAR, as previously claimed. We also identify a non-conserved region within the RRM that contributes to the RNA recognition of Drosophila NELF-E. To understand the broader functional relevance of NBEs, we analyzed promoter-proximal regions genome-wide in Drosophila and show that the NBE is enriched +20 to +30 nucleotides downstream of the transcription start site. Consistent with the role of NELF in pausing, we observe a significant increase in NBEs among paused genes compared to non-paused genes. In addition to these observations, SELEX with nuclear run-on RNA enrich for NBE-like sequences. Together, these results describe the RNA binding behavior of NELF-E and supports a biological role for NELF-E in promoter-proximal pausing of both HIV-1 and cellular genes
Recommended from our members
Methadone Initiation in the Emergency Department for Opioid Use Disorder
Introduction: Overdose deaths from high-potency synthetic opioids, including fentanyl and its analogs, continue to rise along with emergency department (ED) visits for complications of opioid use disorder (OUD). Fentanyl accumulates in adipose tissue; although rare, this increases the risk of precipitated withdrawal in patients upon buprenorphine initiation. Many EDs have implemented medication for opioid use disorder (MOUD) programs using buprenorphine. However, few offer methadone, a proven therapy without the risk of precipitated withdrawal associated with buprenorphine initiation. We describe the addition of an ED-initiated methadone treatment pathway and compared its 72-hour follow-up outpatient treatment engagement rates to our existing ED-initiated buprenorphine MOUD program.
Methods: We expanded our ED MOUD program with a methadone treatment pathway. From February 20âSeptember 19, 2023, we screened 20,504 ED arrivals; 5.1% had signs of OUD. We enrolled 61 patients: 28 in the methadone; and 33 in the buprenorphine pathways. For patients who screened positive for opioid use, shared decision-making was employed to determine whether buprenorphine or methadone therapy was more appropriate. Patients in the methadone pathway received their ďŹrst dose of up to 30 milligrams (mg) of methadone in the ED. Two additional methadone doses of up to 40 mg were dispensed at the time of the ED visit and held in the department, allowing patients to return each day for observed dosing until intake at an opioid treatment program (OTP). We compared 72-hour rates of outpatient follow-up treatment engagement at the OTP (for those on methadone) or at the addiction treatment center (ATC) (for those on buprenorphine) for the two treatment pathways.
Results: Of the 28 patients enrolled in the methadone pathway, 12 (43%) successfully engaged in follow-up treatment at the OTP. Of the 33 patients enrolled in the buprenorphine pathway, 15 (45%) successfully engaged in follow-up treatment at the ATC (relative risk 1.06; 95% conďŹdence interval 0.60â1.87).
Conclusion: Methadone initiation in the ED to treat patients with OUD resulted in similar 72-hour follow-up outpatient treatment engagement rates compared to ED-buprenorphine initiation, providing another viable option for MOUD
Real-time imaging of density ducts between the plasmasphere and ionosphere
Ionization of the Earth's atmosphere by sunlight forms a complex, multilayered plasma environment within the Earth's magnetosphere, the innermost layers being the ionosphere and plasmasphere. The plasmasphere is believed to be embedded with cylindrical density structures (ducts) aligned along the Earth's magnetic field, but direct evidence for these remains scarce. Here we report the first direct wide-angle observation of an extensive array of field-aligned ducts bridging the upper ionosphere and inner plasmasphere, using a novel ground-based imaging technique. We establish their heights and motions by feature tracking and parallax analysis. The structures are strikingly organized, appearing as regularly spaced, alternating tubes of overdensities and underdensities strongly aligned with the Earth's magnetic field. These findings represent the first direct visual evidence for the existence of such structures
Comparison of predictive estimates of highâlatitude electrodynamics with observations of globalâscale Birkeland currents
Two of the geomagnetic storms for the Space Weather Prediction Center Geospace Environment Modeling challenge occurred after data were first acquired by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). We compare Birkeland currents from AMPERE with predictions from four models for the 4â5 April 2010 and 5â6 August 2011 storms. The four models are the Weimer (2005b) fieldâaligned current statistical model, the LyonâFedderâMobarry magnetohydrodynamic (MHD) simulation, the Open Global Geospace Circulation Model MHD simulation, and the Space Weather Modeling Framework MHD simulation. The MHD simulations were run as described in Pulkkinen et al. (2013) and the results obtained from the Community Coordinated Modeling Center. The total radial Birkeland current, ITotal, and the distribution of radial current density, Jr, for all models are compared with AMPERE results. While the total currents are well correlated, the quantitative agreement varies considerably. The Jr distributions reveal discrepancies between the models and observations related to the latitude distribution, morphologies, and lack of nightside current systems in the models. The results motivate enhancing the simulations first by increasing the simulation resolution and then by examining the relative merits of implementing more sophisticated ionospheric conductance models, including ionospheric outflows or other omitted physical processes. Some aspects of the system, including substorm timing and location, may remain challenging to simulate, implying a continuing need for realâtime specification.Key PointsPresents the first comparison between observed fieldâaligned currents and models previously evaluated for space weather operational useThe model and observed integrated currents are well correlated, but the ratio between them ranges from 1/3 to 3The 2âD current densities are weakly correlated with observations implying significant areas for improvements in the modelsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136469/1/swe20415_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136469/2/swe20415.pd
Real-time imaging of density ducts between the plasmasphere and ionosphere
Ionization of the Earth's atmosphere by sunlight forms a complex, multilayered plasma environment within the Earth's magnetosphere, the innermost layers being the ionosphere and plasmasphere. The plasmasphere is believed to be embedded with cylindrical density structures (ducts) aligned along the Earth's magnetic field, but direct evidence for these remains scarce. Here we report the first direct wide-angle observation of an extensive array of field-aligned ducts bridging the upper ionosphere and inner plasmasphere, using a novel ground-based imaging technique. We establish their heights and motions by feature tracking and parallax analysis. The structures are strikingly organized, appearing as regularly spaced, alternating tubes of overdensities and underdensities strongly aligned with the Earth's magnetic field. These findings represent the first direct visual evidence for the existence of such structures
- âŚ