Processing of transcripts of a dimeric tRNA gene in yeast uses the nuclease responsible for maturation of the 3′ termini upon 5 S and 37 S precursor rRNAs

AbstractThe rna82 mutation of Saccharomyces cerevisiae inactivates an RNA processing activity responsible for maturation of 3′-terminal sequences upon 5 S and 37 S ribosomal RNA precursors. This study describes a difference in the processing of transcripts of an S. cerevisiae dimeric tRNA gene (tRNAArg-tRNAAsp) in RNA polymerase III in vitro transcription extracts prepared from rna82 and wild-type cells. The mutant extract accumulated additional processing intermediates containing tRNAArg sequences as compared to the extract from wild-type cells. The structure of these intermediates revealed a defect in removal of the 10 nucleotides left 3′ to the tRNAArg sequence by the RNase P cleavage immediately 5′ to tRNAAsp. This is the first demonstration of a mutational defect affecting maturation of 3′ sequences upon a eukaryotic tRNA precursor

Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase

ERK5 is a mitogen-activated protein (MAP) kinase regulated in human cells by diverse mitogens and stresses but also suspected of mediating the effects of a number of oncogenes. Its expression in the slt2Delta Saccharomyces cerevisiae mutant rescued several of the phenotypes caused by the lack of Slt2p (Mpk1p) cell integrity MAP kinase. ERK5 is able to provide this cell integrity MAP kinase function in yeast, as it is activated by the cell integrity signaling cascade that normally activates Slt2p and, in its active form, able to stimulate at least one key Slt2p target (Rlm1p, the major transcriptional regulator of cell wall genes). In vitro ERK5 kinase activity was abolished by Hsp90 inhibition. ERK5 activity in vivo was also lost in a strain that expresses a mutant Hsp90 chaperone. Therefore, human ERK5 expressed in yeast is an Hsp90 client, despite the widely held belief that the protein kinases of the MAP kinase class are non-Hsp90-dependent activities. Two-hybrid and protein binding studies revealed that strong association of Hsp90 with ERK5 requires the dual phosphorylation of the TEY motif in the MAP kinase activation loop. These phosphorylations, at positions adjacent to the Hsp90-binding surface recently identified for a number of protein kinases, may cause a localized rearrangement of this MAP kinase region that leads to creation of the Hsp90-binding surface. Complementation of the slt2Delta yeast defect by ERK5 expression establishes a new tool with which to screen for novel agonists and antagonists of ERK5 signaling as well as for isolating mutant forms of ERK5

An end-to-end hyperspectral scene simulator with alternate adjacency effect models and its comparison with cameoSim

In this research, we developed a new rendering-based end to end Hyperspectral scene simulator CHIMES (Cranfield Hyperspectral Image Modelling and Evaluation System), which generates nadir images of passively illuminated 3-D outdoor scenes in Visible, Near Infrared (NIR) and Short-Wave Infrared (SWIR) regions, ranging from 360 nm to 2520 nm. MODTRAN TM (MODerate resolution TRANsmission), is used to generate the sky-dome environment map which includes sun and sky radiance along with the polarisation effect of the sky due to Rayleigh scattering. Moreover, we perform path tracing and implement ray interaction with medium and volumetric backscattering at rendering time to model the adjacency effect. We propose two variants of adjacency models, the first one incorporates a single spectral albedo as the averaged background of the scene, this model is called the Background One-Spectra Adjacency Effect Model (BOAEM), which is a CameoSim like model created for performance comparison. The second model calculates background albedo from a pixel’s neighbourhood, whose size depends on the air volume between sensor and target, and differential air density up to sensor altitude. Average background reflectance of all neighbourhood pixel is computed at rendering time for estimating the total upwelled scattered radiance, by volumetric scattering. This model is termed the Texture-Spectra Incorporated Adjacency Effect Model (TIAEM). Moreover, for estimating the underlying atmospheric condition MODTRAN is run with varying aerosol optical thickness and its total ground reflected radiance (TGRR) is compared with TGRR of known in-scene material. The Goodness of fit is evaluated in each iteration, and MODTRAN’s output with the best fit is selected. We perform a tri-modal validation of simulators on a real hyperspectral scene by varying atmospheric condition, terrain surface models and proposed variants of adjacency models. We compared results of our model with Lockheed Martin’s well-established scene simulator CameoSim and acquired Ground Truth (GT) by Hyspex cameras. In clear-sky conditions, both models of CHIMES and CameoSim are in close agreement, however, in searched overcast conditions CHIMES BOAEM is shown to perform better than CameoSim in terms of ℓ1 -norm error of the whole scene with respect to GT. TIAEM produces better radiance shape and covariance of background statistics with respect to Ground Truth (GT), which is key to good target detection performance. We also report that the results of CameoSim have a many-fold higher error for the same scene when the flat surface terrain is replaced with a Digital Elevation Model (DEM) based rugged one

Determining the validity of cumulant expansions for central spin models

For a model with many-to-one connectivity it is widely expected that mean-field theory captures the exact many-particle $N\to\infty$ limit, and that higher-order cumulant expansions of the Heisenberg equations converge to this same limit whilst providing improved approximations at finite $N$. Here we show that this is in fact not always the case. Instead, whether mean-field theory correctly describes the large-$N$ limit depends on how the model parameters scale with $N$, and we show that convergence of cumulant expansions may be non-uniform across even and odd orders. Further, even when a higher-order cumulant expansion does recover the correct limit, the error is not monotonic with $N$ and may exceed that of mean-field theory.Comment: 7 pages, 3 figures plus supplementary materia

Signal to noise ratio of a coded slit hyperspectral sensor

In recent years, a wide range of hyperspectral imaging systems using coded apertures have been proposed. Many implement compressive sensing to achieve faster acquisition of a hyperspectral data cube, but it is also potentially beneficial to use coded aperture imaging in sensors that capture full-rank (non-compressive) measurements. In this paper we analyse the signal-to-noise ratio for such a sensor, which uses a Hadamard code pattern of slits instead of the single slit of a typical pushbroom imaging spectrometer. We show that the coded slit sensor may have performance advantages in situations where the dominant noise sources do not depend on the signal level; but that where Shot noise dominates a conventional single-slit sensor would be more effective. These results may also have implications for the utility of compressive sensing systems

Modelling of a new X-ray backscatter imaging system: simulation investigation

X-ray backscatter imaging is a powerful technique for medical, aerospace, and security applications. Conventionally, a pinhole is commonly used for focusing x-ray, but there is always a desire to enhance the signal-to-noise-ratio (SNR) and optical throughput compared to a single pinhole. The main aim of this paper is to present a new x-ray backscatter imaging system which was inspired by a Twisted Slit collimator system called the Vortex Collimator and compare the optical throughput and the imaging performance with that of the Twisted Slit' collimator1,2 and the Pinhole imaging systems for axial point sources, where the pinhole system was used purely for comparison purposes. All the comparisons were performed through Ray tracing (Trace-Pro) simulation software. This work shows that the Vortex design yields ~4% higher SNR/optical throughput than that of the Twisted Slit collimator, and ~42.5% higher transmittance. Furthermore, the opening of the Vortex Collimator was increased and reduced to observe the performance, resulting in about ~1% transmittance increment when the opening was increased. Also, thicknesses of the Vortex Collimator and Twisted Slit collimator were increased and reduced and found that reducing the thickness seems to increase the system's throughput marginally

OQuPy : a Python package to efficiently simulate non-Markovian open quantum systems with process tensors

Funding: G.E.F. acknowledges the support from EPSRC (Grant No. EP/L015110/1) and from ERC under Grant Agreement No. 101053159 (RAVE). J.B. acknowledges the support from the Laidlaw Foundation (Leadership and Research Program scholarship). E.P.B. acknowledges the support from the Irish Research Council (Grant No. GOIPG/2019/1871). D.G. acknowledges the support from the QuantERA II Program that has received funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 101017733 (“QuSiED”). P.R.E. acknowledges the support from Science Foundation Ireland (Grant No. 21-FFP-10142). E.D.C.L. acknowledges the support from EPSRC (Grant No. EP/T517938/1). R.d.W. acknowledges the support from EPSRC (Grant No. EP/W524505/1). B.W.L. and J.K. acknowledge the support from EPSRC (Grant No. EP/T014032/1).Non-Markovian dynamics arising from the strong coupling of a system to a structured environment is essential in many applications of quantum mechanics and emerging technologies. Deriving an accurate description of general quantum dynamics including memory effects is however a demanding task, prohibitive to standard analytical or direct numerical approaches. We present a major release of our open source software package, OQuPy (Open Quantum System in Python), which provides several recently developed numerical methods that address this challenging task. It utilizes the process tensor approach to open quantum systems in which a single map, the process tensor, captures all possible effects of an environment on the system. The representation of the process tensor in a tensor network form allows an exact yet highly efficient description of non-Markovian open quantum systems (NM-OQS). The OQuPy package provides methods to (1) compute the dynamics and multi-time correlations of quantum systems coupled to single and multiple environments, (2) optimize control protocols for NM-OQS, (3) simulate interacting chains of NM-OQS, and (4) compute the mean-field dynamics of an ensemble of NM-OQS coupled to a common central system. Our aim is to provide an easily accessible and extensible tool for researchers of open quantum systems in fields such as quantum chemistry, quantum sensing, and quantum information.Peer reviewe

The circadian clock protein REVERBα inhibits pulmonary fibrosis development

Pulmonary inflammatory responses lie under circadian control; however, the importance of circadian mechanisms in the underlying fibrotic phenotype is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of amplitude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the little-understood transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinβ1 focal-adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of 2 human cohorts. In the UK Biobank, circadian strain markers (sleep length, chronotype, and shift work) are associated with pulmonary fibrosis, making them risk factors. In a separate cohort, REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, thus suggesting that targeting of REVERBα could be a viable therapeutic approach

UCS protein function is partially restored in the Saccharomyces cerevisiae she4 mutant with expression of the human UNC45-GC, but not UNC45-SM

A dedicated UNC45, Cro1, She4 (UCS) domain-containing protein assists in the Hsp90-mediated folding of the myosin head. Only weak sequence conservation exists between the single UCS protein of simple eukaryotes (She4 in budding yeast) and the two UCS proteins of higher organisms (the general cell and striated muscle UNC45s; UNC45-GC and UNC45-SM, respectively). In vertebrates, UNC45-GC facilitates cytoskeletal functions, whereas the 55% identical UNC45-SM assists assembly of the contractile apparatus of cardiac and skeletal muscles. A Saccharomyces cerevisiae she4Δ mutant, totally lacking any UCS protein, was engineered to express as its sole Hsp90 either the Hsp90α or the Hsp90β isoforms of human cytosolic Hsp90. A transient induction of the human UNC45-GC, but not UNC45-SM, could rescue the defective endocytosis in these she4Δ cells at 39 °C, irrespective of whether they possessed Hsp90α or Hsp90β. UNC45-GC-mediated rescue of the localisation of a Myo5-green fluorescent protein (GFP) fusion to cortical patches at 39 °C was more efficient in the yeast containing Hsp90α, though this may relate to more efficient functioning of Hsp90α as compared to Hsp90β in these strains. Furthermore, inducible expression of UNC45-GC, but not UNC45-SM, could partially rescue survival at a more extreme temperature (45 °C) that normally causes she4Δ mutant yeast cells to lyse. The results indicate that UCS protein function has been most conserved-yeast to man-in the UNC45-GC, not UNC45-SM. This may reflect UNC45-GC being the vertebrate UCS protein that assists formation of the actomyosin complexes needed for cytokinesis, cell morphological change, and organelle trafficking-events also facilitated by the myosins in yeast