Wheeler-DeWitt Quantization of Gravity Models of Unified Dark Energy and Dark Matter

First, we describe the construction of a new type of gravity-matter models based on the formalism of non-Riemannian space-time volume forms - alternative generally covariant integration measure densities (volume elements) defined in terms of auxiliary antisymmetric tensor gauge fields. Here gravity couples in a non-conventional way to two distinct scalar fields providing a unified Lagrangian action principle description of: (i) the evolution of both "early" and "late" Universe - by the "inflaton" scalar field; (ii) dark energy and dark matter as a unified manifestation of a single material entity - the "darkon" scalar field. A physically very interesting phenomenon occurs when including in addition interactions with the electro-weak model bosonic sector - we obtain a gravity-assisted dynamical generation of electro-weak spontaneous gauge symmetry breaking in the post-inflationary "late" Universe, while the Higgs-like scalar remains massless in the "early" Universe. Next, we proceed to the Wheeler-DeWitt minisuperspace quantization of the above models. The "darkon" field plays here the role of cosmological "time". In particular, we show the absence of cosmological space-time singularities.Comment: 15 pages, to be published in the Proceedings of QTS10 - 10th International Symposium "Quantum Theory and Symmetries" (Varna, 2017), Springer Proceedings in Mathematics and Statistics, V. Dobrev (ed.). arXiv admin note: text overlap with arXiv:1609.0691

Web-Based Digital Portfolios and Counselor Supervision

Web-based digital portfolios provide a promising tool for counselor supervisors looking for effective ways to evaluate counselor candidates while maximizing the associated learning process. This paper describes a project involving the use of web-based portfolios that were created by counselor candidates. The project illustrates the benefits of the web-based portfolio for both the counselor supervisor and for the counselors in training

Lead optimisation of dehydroemetine for repositioned use in malaria

Drug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of the multi-drug resistant strain K1 of Plasmodium falciparum (IC50: 47 nM ± 2.1 nM). Dehydroemetine, a synthetic analogue of emetine dihydrochloride has been reported to have less cardiotoxic effects than emetine. The structures of two diastereomers of dehydroemetine were modelled on the published emetine binding site on cryo-EM structure 3J7A (Pf 80S ribosome in complex with emetine) and it was found that (-)-R,S-dehydroemetine mimicked the bound pose of emetine more closely than (-)-S,S-dehydroisoemetine. (-)-R,S-dehydroemetine (IC50 71.03 ± 6.1 nM) was also found to be highly potent against the multi-drug resistant K1 strain of P. falciparum in comparison with (-)-S,S-dehydroisoemetine (IC50 2.07 ± 0.26 μM), which loses its potency due to the change of configuration at C-1′. In addition to its effect on the asexual erythrocytic stages of P. falciparum, the compounds exhibited gametocidal properties with no cross-resistance against any of the multi-drug resistant strains tested. Drug interaction studies showed (-)-R,S-dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride, and (-)-R,S-dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed activity on the mitochondrial membrane potential indicating a possible multi-modal mechanism of action. [Abstract copyright: Copyright © 2020 Panwar et al.

Only connect: addressing the emotional needs of Scotland's children and young people

A report on the SNAP (Scottish Needs Assessment Programme) Child and Adolescent Mental Health Phase Two survey. It describes a survey of a wide range of professionals working with children and young people in Scotland, and deals with professional perspectives on emotional, behavioural and psychological problems. Conclusions and recommendations are presented

Deep Halpha imagery of the Eridanus shells

A deep \ha image of interlocking filamentary arcs of nebulosity has been obtained with a wide-field ($\approx$ 30\degree diameter) narrow-band filter camera combined with a CCD as a detector. The resultant mosaic of images, extending to a galactic latitude of 65$^{o}$, has been corrected for field distortions and had galactic coordinates superimposed on it to permit accurate correlations with the most recent H{\sc i} (21 cm), X-ray (0.75 kev) and FIR (IRAS 100 $\mu$m) maps. Furthermore, an upper limit of 0.13 arcsec/yr to the expansion proper motion of the primary 25\degree long nebulous arc has been obtained by comparing a recent \ha image obtained with the San Pedro Martir telescope of its filamentary edge with that on a POSS E plate obtained in 1951. It is concluded that these filamentary arcs are the superimposed images of separate shells (driven by supernova explosions and/or stellar winds) rather than the edges of a single `superbubble' stretching from Barnard's Arc (and the Orion Nebula) to these high galactic latitudes. The proper motion measurement argues against the primary \ha emitting arc being associated with the giant radio loop (Loop 2) except in extraordinary circumstances.Comment: 9 pages, 5 figures, accepted for MNRAS publicatio

Deep Sequencing Analysis of RNAs from Citrus Plants Grown in a Citrus Sudden Death-Affected Area Reveals Diverse Known and Putative Novel Viruses.

Citrus sudden death (CSD) has caused the death of approximately four million orange trees in a very important citrus region in Brazil. Although its etiology is still not completely clear, symptoms and distribution of affected plants indicate a viral disease. In a search for viruses associated with CSD, we have performed a comparative high-throughput sequencing analysis of the transcriptome and small RNAs from CSD-symptomatic and -asymptomatic plants using the Illumina platform. The data revealed mixed infections that included Citrus tristeza virus (CTV) as the most predominant virus, followed by the Citrus sudden death-associated virus (CSDaV), Citrus endogenous pararetrovirus (CitPRV) and two putative novel viruses tentatively named Citrus jingmen-like virus (CJLV), and Citrus virga-like virus (CVLV). The deep sequencing analyses were sensitive enough to differentiate two genotypes of both viruses previously associated with CSD-affected plants: CTV and CSDaV. Our data also showed a putative association of the CSD-symptomatic plants with a specific CSDaV genotype and a likely association with CitPRV as well, whereas the two putative novel viruses showed to be more associated with CSD-asymptomatic plants. This is the first high-throughput sequencing-based study of the viral sequences present in CSD-affected citrus plants, and generated valuable information for further CSD studies

Effects of increasing the affinity of CarD for RNA polymerase on Mycobacterium tuberculosis growth, rRNA transcription, and virulence

CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis. In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro. Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription

Jets and the shaping of the giant bipolar envelope of the planetary nebula KjPn 8

A hydrodynamic model involving cooling gas in the stagnation region of a collimated outflow is proposed for the formation of the giant parsec-scale bipolar envelope that surrounds the planetary nebula KjPn 8. Analytical calculations and numerical simulations are presented to evaluate the model. The envelope is considered to consist mainly of environmental gas swept-up by shocks driven by an episodic, collimated, bipolar outflow. In this model, which we call the ``free stagnation knot'' mechanism, the swept-up ambient gas located in the stagnation region of the bow-shock cools to produce a high density knot. This knot moves along with the bow-shock. When the central outflow ceases, pressurization of the interior of the envelope stops and its expansion slows down. The stagnation knot, however, has sufficient momentum to propagate freely further along the axis, producing a distinct nose at the end of the lobe. The model is found to successfully reproduce the peculiar shape and global kinematics of the giant bipolar envelope of KjPn 8.Comment: 20 pages + 8 figures (in 1 tar-file 0.67 Mb