Helicon Plasma Injector and Ion Cyclotron Acceleration Development in the VASIMR Experiment

In the Variable Specific Impulse Magnetoplasma Rocket (VASIMR) radio frequency (rf) waves both produce the plasma and then accelerate the ions. The plasma production is done by action of helicon waves. These waves are circular polarized waves in the direction of the electron gyromotion. The ion acceleration is performed by ion cyclotron resonant frequency (ICRF) acceleration. The Advanced Space Propulsion Laboratory (ASPL) is actively developing efficient helicon plasma production and ICRF acceleration. The VASIMR experimental device at the ASPL is called VX-10. It is configured to demonstrate the plasma production and acceleration at the 10kW level to support a space flight demonstration design. The VX-10 consists of three electromagnets integrated into a vacuum chamber that produce magnetic fields up to 0.5 Tesla. Magnetic field shaping is achieved by independent magnet current control and placement of the magnets. We have generated both helium and hydrogen high density (>10(exp 18) cu m) discharges with the helicon source. ICRF experiments are underway. This paper describes the VX-10 device, presents recent results and discusses future plans

RNA secondary structure formation: a solvable model of heteropolymer folding

The statistical mechanics of heteropolymer structure formation is studied in the context of RNA secondary structures. A designed RNA sequence biased energetically towards a particular native structure (a hairpin) is used to study the transition between the native and molten phase of the RNA as a function of temperature. The transition is driven by a competition between the energy gained from the polymer's overlap with the native structure and the entropic gain of forming random contacts. A simplified Go-like model is proposed and solved exactly. The predicted critical behavior is verified via exact numerical enumeration of a large ensemble of similarly designed sequences.Comment: 4 pages including 2 figure

Guest charges in an electrolyte: renormalized charge, long- and short-distance behavior of the electric potential and density profile

We complement a recent exact study by L. Samaj on the properties of a guest charge $Q$ immersed in a two-dimensional electrolyte with charges $+1/-1$. In particular, we are interested in the behavior of the density profiles and electric potential created by the charge and the electrolyte, and in the determination of the renormalized charge which is obtained from the long-distance asymptotics of the electric potential. In Samaj's previous work, exact results for arbitrary coulombic coupling $\beta$ were obtained for a system where all the charges are points, provided $\beta Q<2$ and $\beta < 2$. Here, we first focus on the mean field situation which we believe describes correctly the limit $\beta\to 0$ but $\beta Q$ large. In this limit we can study the case when the guest charge is a hard disk and its charge is above the collapse value $\beta Q>2$. We compare our results for the renormalized charge with the exact predictions and we test on a solid ground some conjectures of the previous study. Our study shows that the exact formulas obtained by Samaj for the renormalized charge are not valid for $\beta Q>2$, contrary to a hypothesis put forward by Samaj. We also determine the short-distance asymptotics of the density profiles of the coions and counterions near the guest charge, for arbitrary coulombic coupling. We show that the coion density profile exhibit a change of behavior if the guest charge becomes large enough ($\beta Q\geq 2-\beta$). This is interpreted as a first step of the counterion condensation (for large coulombic coupling), the second step taking place at the usual Manning--Oosawa threshold $\beta Q=2$

Field theory for a reaction-diffusion model of quasispecies dynamics

RNA viruses are known to replicate with extremely high mutation rates. These rates are actually close to the so-called error threshold. This threshold is in fact a critical point beyond which genetic information is lost through a second-order phase transition, which has been dubbed the ``error catastrophe.'' Here we explore this phenomenon using a field theory approximation to the spatially extended Swetina-Schuster quasispecies model [J. Swetina and P. Schuster, Biophys. Chem. {\bf 16}, 329 (1982)], a single-sharp-peak landscape. In analogy with standard absorbing-state phase transitions, we develop a reaction-diffusion model whose discrete rules mimic the Swetina-Schuster model. The field theory representation of the reaction-diffusion system is constructed. The proposed field theory belongs to the same universality class than a conserved reaction-diffusion model previously proposed [F. van Wijland {\em et al.}, Physica A {\bf 251}, 179 (1998)]. From the field theory, we obtain the full set of exponents that characterize the critical behavior at the error threshold. Our results present the error catastrophe from a new point of view and suggest that spatial degrees of freedom can modify several mean field predictions previously considered, leading to the definition of characteristic exponents that could be experimentally measurable.Comment: 13 page

NOBAI: a web server for character coding of geometrical and statistical features in RNA structure

The Numeration of Objects in Biology: Alignment Inferences (NOBAI) web server provides a web interface to the applications in the NOBAI software package. This software codes topological and thermodynamic information related to the secondary structure of RNA molecules as multi-state phylogenetic characters, builds character matrices directly in NEXUS format and provides sequence randomization options. The web server is an effective tool that facilitates the search for evolutionary history embedded in the structure of functional RNA molecules. The NOBAI web server is accessible at ‘http://www.manet.uiuc.edu/nobai/nobai.php’. This web site is free and open to all users and there is no login requirement

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30&nbsp;mg once daily for up to 3&nbsp;years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15&nbsp;mg and 30&nbsp;mg once daily, and one trial also evaluated adalimumab 40&nbsp;mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15&nbsp;mg, pooled upadacitinib 30&nbsp;mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15&nbsp;mg (N = 907) or 30&nbsp;mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30&nbsp;mg. Potentially clinically significant laboratory abnormalities were uncommon. Conclusions: Upadacitinib 15&nbsp;mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. Trial Registration Numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374

Improved Efficiency and Throttling Range of the VX-200 Magnetoplasma Thruster

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140438/1/1.b34801.pd

The pesticidal Cry6Aa toxin from Bacillus thuringiensis is structurally similar to HlyE-family alpha pore-forming toxins

Background The Cry6 family of proteins from Bacillus thuringiensis represents a group of powerful toxins with great potential for use in the control of coleopteran insects and of nematode parasites of importance to agriculture. These proteins are unrelated to other insecticidal toxins at the level of their primary sequences and the structure and function of these proteins has been poorly studied to date. This has inhibited our understanding of these toxins and their mode of action, along with our ability to manipulate the proteins to alter their activity to our advantage. To increase our understanding of their mode of action and to facilitate further development of these proteins we have determined the structure of Cry6Aa in protoxin and trypsin-activated forms and demonstrated a pore-forming mechanism of action. Results The two forms of the toxin were resolved to 2.7 Å and 2.0 Å respectively and showed very similar structures. Cry6Aa shows structural homology to a known class of pore-forming toxins including hemolysin E from Escherichia coli and two Bacillus cereus proteins: the hemolytic toxin HblB and the NheA component of the non-hemolytic toxin (pfam05791). Cry6Aa also shows atypical features compared to other members of this family, including internal repeat sequences and small loop regions within major alpha helices. Trypsin processing was found to result in the loss of some internal sequences while the C-terminal region remains disulfide-linked to the main core of the toxin. Based on the structural similarity of Cry6Aa to other toxins, the mechanism of action of the toxin was probed and its ability to form pores in vivo in Caenorhabditis elegans was demonstrated. A non-toxic mutant was also produced, consistent with the proposed pore-forming mode of action. Conclusions Cry6 proteins are members of the alpha helical pore-forming toxins – a structural class not previously recognized among the Cry toxins of B. thuringiensis and representing a new paradigm for nematocidal and insecticidal proteins. Elucidation of both the structure and the pore-forming mechanism of action of Cry6Aa now opens the way to more detailed analysis of toxin specificity and the development of new toxin variants with novel activities

AUG_hairpin: prediction of a downstream secondary structure influencing the recognition of a translation start site

<p>Abstract</p> <p>Background</p> <p>The translation start site plays an important role in the control of translation efficiency of eukaryotic mRNAs. The recognition of the start AUG codon by eukaryotic ribosomes is considered to depend on its nucleotide context. However, the fraction of eukaryotic mRNAs with the start codon in a suboptimal context is relatively large. It may be expected that mRNA should possess some features providing efficient translation, including the proper recognition of a translation start site. It has been experimentally shown that a downstream hairpin located in certain positions with respect to start codon can compensate in part for the suboptimal AUG context and also increases translation from non-AUG initiation codons. Prediction of such a compensatory hairpin may be useful in the evaluation of eukaryotic mRNA translation properties.</p> <p>Results</p> <p>We evaluated interdependency between the start codon context and mRNA secondary structure at the CDS beginning: it was found that a suboptimal start codon context significantly correlated with higher base pairing probabilities at positions 13 – 17 of CDS of human and mouse mRNAs. It is likely that the downstream hairpins are used to enhance translation of some mammalian mRNAs <it>in vivo</it>. Thus, we have developed a tool, <it>AUG_hairpin</it>, to predict local stem-loop structures located within the defined region at the beginning of mRNA coding part. The implemented algorithm is based on the available published experimental data on the CDS-located stem-loop structures influencing the recognition of upstream start codons.</p> <p>Conclusion</p> <p>An occurrence of a potential secondary structure downstream of start AUG codon in a suboptimal context (or downstream of a potential non-AUG start codon) may provide researchers with a testable assumption on the presence of additional regulatory signal influencing mRNA translation initiation rate and the start codon choice. <it>AUG_hairpin</it>, which has a convenient Web-interface with adjustable parameters, will make such an evaluation easy and efficient.</p

Multipolar Reactive DPD: A Novel Tool for Spatially Resolved Systems Biology

This article reports about a novel extension of dissipative particle dynamics (DPD) that allows the study of the collective dynamics of complex chemical and structural systems in a spatially resolved manner with a combinatorially complex variety of different system constituents. We show that introducing multipolar interactions between particles leads to extended membrane structures emerging in a self-organized manner and exhibiting both the necessary mechanical stability for transport and fluidity so as to provide a two-dimensional self-organizing dynamic reaction environment for kinetic studies in the context of cell biology. We further show that the emergent dynamics of extended membrane bound objects is in accordance with scaling laws imposed by physics.Comment: submitted to CMSB 0