Engineering stochasticity in gene expression

Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describing the behavior of natural organisms and will be essential for the engineering of synthetic biological systems. Here we describe the design of synthetic constructs, termed ribosome competing RNAs (rcRNAs), as a means to rationally perturb noise in cellular gene expression. We find that noise in gene expression increases in a manner proportional to the ability of an rcRNA to compete for the cellular ribosome pool. We then demonstrate that operons significantly buffer noise between coexpressed genes in a natural cellular background and can even reduce the level of rcRNA enhanced noise. These results demonstrate that synthetic genetic constructs can significantly affect the noise profile of a living cell and, importantly, that operons are a facile genetic strategy for buffering against noise

ADOPTION OF DIGITAL TWIN WITHIN THE DEPARTMENT OF THE NAVY

Digital twins have the potential to support the decision-makers that design, build, operate, and maintain the platforms that the Department of the Navy (DON) relies upon to conduct naval operations. However, the thin body of knowledge on digital twins presents a challenge for the DON as the range of applications and risks associated with onboarding digital twins are still unclear. This thesis conducts a qualitative technology assessment to determine the effects that adopting digital twins has on the DON’s enterprise architecture. Analysis of an enterprise-wide adoption identifies opportunities and risks of digital twins within the context of the DON’s strategy, processes, people, technology, cyber security, and risk management. The business value provided by digital twins is principally dependent upon the aggregate risk value of the physical platform and the fidelity and frequency of the digital twin’s synchronizations.Captain, United States Marine CorpsCaptain, United States Marine CorpsApproved for public release. Distribution is unlimited

A Toy Model of Flying Snake's Glide

We have developed a toy model of flying snake's glide [J.J. Socha, Nature vol. 418 (2002) 603.] by modifying a model for a falling paper. We have found that asymmetric oscillation is a key about why snake can glide. Further investigation for snake's glide will provide us details about how it can glide without a wing.Comment: 6 pages, to be submitted to J. Phys. Soc. Jpn. Revised Version submitted to the abov

Results of two multi-chord stellar occultations by dwarf planet (1) Ceres

We report the results of two multi-chord stellar occultations by the dwarf planet (1) Ceres that were observed from Brazil on 2010 August 17, and from the USA on 2013 October 25. Four positive detections were obtained for the 2010 occultation, and nine for the 2013 occultation. Elliptical models were adjusted to the observed chords to obtain Ceres' size and shape. Two limb fitting solutions were studied for each event. The first one is a nominal solution with an indeterminate polar aspect angle. The second one was constrained by the pole coordinates as given by Drummond et al. Assuming a Maclaurin spheroid, we determine an equatorial diameter of 972 $\pm$ 6 km and an apparent oblateness of 0.08 $\pm$ 0.03 as our best solution. These results are compared to all available size and shape determinations for Ceres made so far, and shall be confirmed by the NASA's Dawn space mission.Comment: 9 pages, 6 figures. Accepted for publication in MNRA

Hachimoji DNA and RNA: A genetic system with eight building blocks

Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

“I’m a Red River local”: rock climbing mobilities and community hospitalities

With individuals continually on the move, mobility fosters constellations of places at which individuals collectively moor and perform community. By focusing on one climbing destination – the Red River Gorge – this paper works across scales to highlight the spatial politics of mobilizing hospitality. In so doing, it summarizes the ways hosting/guesting thresholds dissolve with the growth of particular rock climbing associated infrastructures and moves to examine the ways climbers performances of community result in the (semi-)privatization of public space and attempts at localization. Further, the paper highlights the ways mobility is employed to maintain a political voice from afar, as well as to forge “local” identities with The Red as place with distinct subcultural (in)hospitality practices. Hospitality practices affirm power relations, they communicate who is at “home” and who has the power in a particular space to extend hospitality. The decision to extend hospitality is not simply the difference between an ethical encounter and a conditional one; it takes place in the very performance of identity. Thus, integrating a mobilities perspective into hospitality studies further illuminates the spatial politics that are at play in an ethics of hospitality

Propagating the fear of witchcraft: Pentecostal prophecies in the new prophetic churches in South Africa

Pentecostal prophecy is one of the major themes of the theology and practice of religion among the prophets of New Prophetic Churches in South Africa and a major factor to the growth and expansion of Pentecostalism in Southern Africa. This paper offers a reflection on the role of prophecy in relation to the fear of witchcraft in the region. The contribution is that Pentecostal prophecy is not always in confrontation but sometime propels the fear of witchcraft. Through media analysis, the paper illustrates with some examples of Pentecostal prophecies on witchcraft how Pentecostal prophecy can aid rather than dispel fear of witchcraft. These prophecies raise several challenges to the discernment of Pentecostal prophetic ministry.Christian Spirituality, Church History and Missiolog

Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells.

This document is the Accepted Manuscript version of a published work that appeared in final form in Bioscience Reports. To access the final edited and published work see http://dx.doi.org/10.1042/BSR20202505Drug repurposing is a cost effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts

The role of the genetic counsellor: a systematic review of research evidence

In Europe, genetic counsellors are employed in specialist genetic centres or other specialist units. According to the European Board of Medical Genetics, the genetic counsellor must fulfil a range of roles, including provision of information and facilitation of psychosocial adjustment of the client to their genetic status and situation. To evaluate the extent to which genetic counsellors fulfil their prescribed roles, we conducted a systematic review of the published relevant scientific evidence. We searched five relevant electronic databases (Medline, CINAHL, SocIndex, AMED and PsychInfo) using relevant search terms and handsearched four subject-specific journals for research-based papers published in English between 1 January 2000 and 30 June 2013. Of 419 potential papers identified initially, seven satisfied the inclusion criteria for the review. Themes derived from the thematic analysis of the data were: (i) rationale for genetic counsellors to provide care, (ii) appropriate roles and responsibilities and (iii) the types of conditions included in the genetic counsellor caseload. The findings of this systematic review indicate that where genetic counsellors are utilised in specialist genetic settings, they undertake a significant workload associated with direct patient care and this appears to be acceptable to patients. With the burden on genetic services, there is an argument for the increased use of genetic counsellors in countries where they are under-utilised. In addition, roles undertaken by genetic counsellors in specialist genetic settings could be adapted to integrate genetic counsellors into multi-disciplinary teams in other specialisms