Feasibility of a chemical poison loop system

Chemical poison loop system for reactivity control of tungsten water moderated rocket reacto

On the possibility of measuring relativistic gravitational effects with a LAGEOS-LAGEOS II-OPTIS-mission

In this paper we wish to preliminary investigate if it would be possible to use the orbital data from the proposed OPTIS mission together with those from the existing geodetic passive SLR LAGEOS and LAGEOS II satellites in order to perform precise measurements of some general relativistic gravitoelectromagnetic effects, with particular emphasis on the Lense-Thirring effect.Comment: Abridged version. 16 pages, no figures, 1 table. First results from the GGM01C Earth gravity model. GRACE data include

Functional Amyloid Formation within Mammalian Tissue

Amyloid is a generally insoluble, fibrous cross-β sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin—a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin) may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property

One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge

On the Possibility of Measuring the Gravitomagnetic Clock Effect in an Earth Space-Based Experiment

In this paper the effect of the post-Newtonian gravitomagnetic force on the mean longitudes $l$ of a pair of counter-rotating Earth artificial satellites following almost identical circular equatorial orbits is investigated. The possibility of measuring it is examined. The observable is the difference of the times required to $l$ in passing from 0 to 2$\pi$ for both senses of motion. Such gravitomagnetic time shift, which is independent of the orbital parameters of the satellites, amounts to 5$\times 10^{-7}$ s for Earth; it is cumulative and should be measured after a sufficiently high number of revolutions. The major limiting factors are the unavoidable imperfect cancellation of the Keplerian periods, which yields a constraint of 10$^{-2}$ cm in knowing the difference between the semimajor axes $a$ of the satellites, and the difference $I$ of the inclinations $i$ of the orbital planes which, for $i\sim 0.01^\circ$, should be less than $0.006^\circ$. A pair of spacecrafts endowed with a sophisticated intersatellite tracking apparatus and drag-free control down to 10$^{-9}$ cm s$^{-2}$ Hz$^{-{1/2}}$ level might allow to meet the stringent requirements posed by such a mission.Comment: LaTex2e, 22 pages, no tables, 1 figure, 38 references. Final version accepted for publication in Classical and Quantum Gravit

Systemic properties of metabolic networks lead to an epistasis-based model for heterosis

The genetic and molecular approaches to heterosis usually do not rely on any model of the genotype–phenotype relationship. From the generalization of Kacser and Burns’ biochemical model for dominance and epistasis to networks with several variable enzymes, we hypothesized that metabolic heterosis could be observed because the response of the flux towards enzyme activities and/or concentrations follows a multi-dimensional hyperbolic-like relationship. To corroborate this, we used the values of systemic parameters accounting for the kinetic behaviour of four enzymes of the upstream part of glycolysis, and simulated genetic variability by varying in silico enzyme concentrations. Then we “crossed” virtual parents to get 1,000 hybrids, and showed that best-parent heterosis was frequently observed. The decomposition of the flux value into genetic effects, with the help of a novel multilocus epistasis index, revealed that antagonistic additive-by-additive epistasis effects play the major role in this framework of the genotype–phenotype relationship. This result is consistent with various observations in quantitative and evolutionary genetics, and provides a model unifying the genetic effects underlying heterosis

Formation and Growth of Oligomers: A Monte Carlo Study of an Amyloid Tau Fragment

Small oligomers formed early in the process of amyloid fibril formation may be the major toxic species in Alzheimer's disease. We investigate the early stages of amyloid aggregation for the tau fragment AcPHF6 (Ac-VQIVYK-NH2) using an implicit solvent all-atom model and extensive Monte Carlo simulations of 12, 24, and 36 chains. A variety of small metastable aggregates form and dissolve until an aggregate of a critical size and conformation arises. However, the stable oligomers, which are β-sheet-rich and feature many hydrophobic contacts, are not always growth-ready. The simulations indicate instead that these supercritical oligomers spend a lengthy period in equilibrium in which considerable reorganization takes place accompanied by exchange of chains with the solution. Growth competence of the stable oligomers correlates with the alignment of the strands in the β-sheets. The larger aggregates seen in our simulations are all composed of two twisted β-sheets, packed against each other with hydrophobic side chains at the sheet–sheet interface. These β-sandwiches show similarities with the proposed steric zipper structure for PHF6 fibrils but have a mixed parallel/antiparallel β-strand organization as opposed to the parallel organization found in experiments on fibrils. Interestingly, we find that the fraction of parallel β-sheet structure increases with aggregate size. We speculate that the reorganization of the β-sheets into parallel ones is an important rate-limiting step in the formation of PHF6 fibrils

Sequencing of Pooled DNA Samples (Pool-Seq) Uncovers Complex Dynamics of Transposable Element Insertions in Drosophila melanogaster

Transposable elements (TEs) are mobile genetic elements that parasitize genomes by semi-autonomously increasing their own copy number within the host genome. While TEs are important for genome evolution, appropriate methods for performing unbiased genome-wide surveys of TE variation in natural populations have been lacking. Here, we describe a novel and cost-effective approach for estimating population frequencies of TE insertions using paired-end Illumina reads from a pooled population sample. Importantly, the method treats insertions present in and absent from the reference genome identically, allowing unbiased TE population frequency estimates. We apply this method to data from a natural Drosophila melanogaster population from Portugal. Consistent with previous reports, we show that low recombining genomic regions harbor more TE insertions and maintain insertions at higher frequencies than do high recombining regions. We conservatively estimate that there are almost twice as many “novel” TE insertion sites as sites known from the reference sequence in our population sample (6,824 novel versus 3,639 reference sites, with on average a 31-fold coverage per insertion site). Different families of transposable elements show large differences in their insertion densities and population frequencies. Our analyses suggest that the history of TE activity significantly contributes to this pattern, with recently active families segregating at lower frequencies than those active in the more distant past. Finally, using our high-resolution TE abundance measurements, we identified 13 candidate positively selected TE insertions based on their high population frequencies and on low Tajima's D values in their neighborhoods