Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 are orthologs of B_3454, B_3455, B_3457, B_3458, respectively found in \u3cem\u3eEscherichia coli\u3c/em\u3e coding for a Branched Chain Amino Acid ATP Binding Cassette (ABC) Transporter System

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted to have a solute binding protein, which is a component of most ABC transporters. This transport system is found in E. coli K12 MG1655, the predicted orthologs of Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328, livF, livG, livH, and livK respectively, are b3454, b3455, b3457, and b3458, form a livFGHK operon encoding an ABC transporter for branched chain amino acid transport. Mrub_1326 is likely a fused protein of both livG and livM suggesting it may also be orthologous to b3456. This project is part of the Meiothermus ruber genome analysis project, which predicts gene function using the bioinformatics tools collected under the umbrella of the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT)

Spectatorship and the new (critical) sincerity: the case of Forced Entertainment’s Tomorrow’s Parties

This article considers Forced Entertainment’s Tomorrow Parties (2011) as an example of the New Sincerity – an aesthetic mode that has emerged in the wake of postmodernism, particularly visible in contemporary American fiction. The particular contribution here is the trans-disciplinary shift from fiction to theatre studies as the New Sincerity – as theorised by American fiction scholars via Lionel Trilling’s Sincerity and Authenticity (1972) and David Foster Wallace’s essay ‘E Unibus Pluram: Television and U.S. Fiction’ (1993) – is assessed in terms of its applicability to the specificities of theatre performance. A trusting and trusted spectator is central to the operational practice of sincerity in performance. In many ways Tomorrow’s Parties succeeds in interpellating such a spectator; however, it remains a piece performed by an experimental theatre company renowned for engaging in metatheatrical innovation, immersive practice and ironic game playing, all of which haunt this particular postdramatic performance. To account for this troubling of sincerity – and all performance is on one level insincere – the term ‘critical sincerity’ is coined, a term that describes the knowingness that certain theatre pieces – like Tomorrow’s Parties – exhibit of the inherent insincerity of performance, while simultaneously striving for a sincere encounter

Hybrid modeling of biological networks: mixing temporal and qualitative biological properties

<p>Abstract</p> <p>Background</p> <p>Modeling a dynamical biological system is often a difficult task since the a <it>priori </it>unknown parameters of such models are not always directly given by the experiments. Despite the lack of experimental quantitative knowledge, one can see a dynamical biological system as (i) the combined evolution tendencies (increase or decrease) of the biological compound concentrations, and: (ii) the temporal features, such as delays between two concentration peaks (i.e. the times when one of the components completes an increase (resp. decrease) phase and starts a decrease (resp. increase) phase).</p> <p>Results</p> <p>We propose herein a new hybrid modeling framework that follows such biological assumptions. This hybrid approach deals with both a qualitative structure of the system and a quantitative structure. From a theoretical viewpoint, temporal specifications are expressed as equality or inequality constraints between delay parameters, while the qualitative specifications are expressed as an ordered pattern of the concentrations peaks of the components. Using this new hybrid framework, the temporal specifications of a biological system can be obtained from incomplete experimental data. The model may be processed by a hybrid model-checker (e.g. Phaver) which is able to give some new constraints on the delay parameters (e.g. the delay for a given transition is exactly 5 hours after the later peak of a gene product concentration). Furthermore, by using a constraint solver on the previous results, it becomes possible to get the set of parameters settings which are consistent with given specifications. Such a modeling approach is particularly accurate for modeling oscillatory biological behaviors like those observed in the Drosophila circadian cycles. The achieved results concerning the parameters of this oscillatory system formally confirm the several previous studies made by numerical simulations. Moreover, our analysis makes it possible to propose an automatic investigation of the respective impact of per and tim on the circadian cycle.</p> <p>Conclusions</p> <p>A new hybrid technique for an automatic formal analysis of biological systems is developed with a special emphasis on their oscillatory behaviors. It allows the use of incomplete and empirical biological data.</p

Self-control enhancement in children:Ethical and conceptual aspects

Childhood self-control is currently receiving great scientific and public attention because it could predict much of adult’s life success and well-being. Specialized interventions based on findings in social psychology and neuroscience potentially enhance children’s capacity to exercise self-control. This perspective triggers hopes that self-control enhancement allows us to say good-bye for good to potentially unsafe psychopharmacological agents and electronic brain stimulants. This chapter provides an in-depth ethical analysis of pediatric self-control enhancement and points toward a series of serious conceptual and ethical concerns. First, it gives an overview of current psychological as well as neuroscientific research on self-control, and it presents longitudinal studies that emphasize the importance of childhood self-control for adult life success. Second, it critically discusses the concept of self-control presupposed in these approaches and points to crucial limitations. Going beyond an understanding of self-control as a sophisticated means of goal-achievement, i will argue for a comprehensive understanding that takes the inherent normativity of self-controlled behavior seriously. In that context, self-control enhancement appears as not necessarily desirable and occasionally even detrimental. Finally, this chapter questions the notion of childhood implicit in current research and how values typically put on this phase of life could get affected by self-control enhancement. I finish with an exploration of the conditions under which pediatric self-control enhancement is either impermissible, permissible, or maybe obligatory

C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays

Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit these residue differences between the histone substrate binding sites in order to improve affinity for the KDM4-subfamily over KDM5-subfamily enzymes. In particular, residues E169 and V313 (KDM4A numbering) were targeted. Additionally, the conformational restriction of the flexible pyridopyrimidinone C8-substituent was investigated. These approaches yielded potent and cell-penetrant dual KDM4/5-subfamily inhibitors including 19a (KDM4A and KDM5B Ki = 0.004 and 0.007 μM, respectively). Compound cellular profiling in two orthogonal target engagement assays revealed a significant reduction from biochemical to cell-based activity across multiple analogues; this decrease was shown to be consistent with 2OG competition, and suggest that sub-nanomolar biochemical potency will be required with C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one compounds to achieve sub-micromolar target inhibition in cells

Infrared spectra and optical constants of astronomical ices: III. Propane, propylene, and propyne

Infrared (IR) spectra of the hydrocarbon ices C3H8 (propane), C3H6 (propylene, propene), and C3H4 (propyne, methylacetylene) are relevant to the study of the low-temperature chemistry and spectroscopy of objects within and beyond the Solar System, but IR band strengths and absorption coefficients are lacking for these compounds. Here we present new IR spectra of crystalline and non-crystalline forms of C3H8, C3H6, and C3H4. Measurements of ice density and refractive index also are reported, two quantities needed to compute IR absorption coefficients, band strengths, optical constants, and, ultimately, abundances of propane, propylene, and propyne in extraterrestrial environments and in laboratory experiments. Suggestions and interpretations are offered regarding the multiple crystalline forms of propane and propylene observed. Applications and extensions are described

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion