Genesis of ancestral haplotypes: RNA modifications and reverse transcription–mediated polymorphisms

Understanding the genesis of the block haplotype structure of the genome is a major challenge. With the completion of the sequencing of the Human Genome and the initiation of the HapMap project the concept that the chromosomes of the mammalian genome are a mosaic, or patchwork, of conserved extended block haplotype sequences is now accepted by the mainstream genomics research community. Ancestral Haplotypes (AHs) can be viewed as a recombined string of smaller Polymorphic Frozen Blocks (PFBs). How have such variant extended DNA sequence tracts emerged in evolution? Here the relevant literature on the problem is reviewed from various fields of molecular and cell biology particularly molecular immunology and comparative and functional genomics. Based on our synthesis we then advance a testable molecular and cellular model. A critical part of the analysis concerns the origin of the strand biased mutation signatures in the transcribed regions of the human and higher primate genome, A-to-G versus T-to-C (ratio ~1.5 fold) and C-to-T versus G-to-A (≥1.5 fold). A comparison and evaluation of the current state of the fields of immunoglobulin Somatic Hypermutation (SHM) and Transcription-Coupled DNA Repair focused on how mutations in newly synthesized RNA might be copied back to DNA thus accounting for some of the genome-wide strand biases (e.g., the A-to-G vs T-to-C component of the strand biased spectrum). We hypothesize that the genesis of PFBs and extended AHs occurs during mutagenic episodes in evolution (e.g., retroviral infections) and that many of the critical DNA sequence diversifying events occur first at the RNA level, e.g., recombination between RNA strings resulting in tandem and dispersed RNA duplications (retroduplications), RNA mutations via adenosine-to-inosine pre-mRNA editing events as well as error prone RNA synthesis. These are then copied back into DNA by a cellular reverse transcription process (also likely to be error-prone) that we have called "reverse transcription-mediated long DNA conversion." Finally we suggest that all these activities and others can be envisaged as being brought physically under the umbrella of special sites in the nucleus involved in transcription known as "transcription factories."

Playing to learn: Learning to TALK

‘We love the fact she can learn through play, because she is learning but not realising, and she doesn’t feel pressurised to learn’ (Parent of a child with neurodiverse developmental disorders [NDD]). Engaging children with NDD in meaningful learning can be challenging and exacerbated when children are neither motivated nor equipped with skills to facilitate engagement. Communication barriers hinder learning and children with NDD need extra support to develop language skills. This action research promoted communication competence through structured interventions, consolidated through play. Findings confirmed that progression in spontaneous communication and interaction interrelates with creative play. An innovative structured teaching approach, including video-modelling, was devised, Total Augmented Language and Key Skills (TALKS). This research affirms that by changing conditions in learning environments to an integrated teaching model, Connectivity and adopting TALKS, enhances a whole school approach to communication competence for children with NDD

Primordial black holes in braneworld cosmologies: astrophysical constraints

In two recent papers we explored the modifications to primordial black hole physics when one moves to the simplest braneworld model, Randall--Sundrum type II. Both the evaporation law and the cosmological evolution of the population can be modified, and additionally accretion of energy from the background can be dominant over evaporation at high energies. In this paper we present a detailed study of how this impacts upon various astrophysical constraints, analyzing constraints from the present density, from the present high-energy photon background radiation, from distortion of the microwave background spectrum, and from processes affecting light element abundances both during and after nucleosynthesis. Typically, the constraints on the formation rate of primordial black holes weaken as compared to the standard cosmology if black hole accretion is unimportant at high energies, but can be strengthened in the case of efficient accretion.Comment: 17 pages RevTeX4 file with three figures incorporated; final paper in series astro-ph/0205149 and astro-ph/0208299. Minor changes to match version accepted by Physical Review

Leptogenesis and rescattering in supersymmetric models

The observed baryon asymmetry of the Universe can be due to the $B-L$ violating decay of heavy right handed (s)neutrinos. The amount of the asymmetry depends crucially on their number density. If the (s)neutrinos are generated thermally, in supersymmetric models there is limited parameter space leading to enough baryons. For this reason, several alternative mechanisms have been proposed. We discuss the nonperturbative production of sneutrino quanta by a direct coupling to the inflaton. This production dominates over the corresponding creation of neutrinos, and it can easily (i.e. even for a rather small inflaton-sneutrino coupling) lead to a sufficient baryon asymmetry. We then study the amplification of MSSM degrees of freedom, via their coupling to the sneutrinos, during the rescattering phase which follows the nonperturbative production. This process, which mainly influences the (MSSM) $D-$flat directions, is very efficient as long as the sneutrinos quanta are in the relativistic regime. The rapid amplification of the light degrees of freedom may potentially lead to a gravitino problem. We estimate the gravitino production by means of a perturbative calculation, discussing the regime in which we expect it to be reliable.Comment: (20 pages, 6 figures), references added, typos corrected. Final version in revte

Design of adjustable Tuned Mass Dampers using elastomeric O-rings

Tuned mass dampers (TMDs) are widely used in passive vibration control, and have been implemented on many engineering structures. In general, the design of TMDs is unique to each application; the choice of damping material and its in-situ performance are key issues that can affect design and prototyping costs. The present contribution demonstrates that TMDs can be built using ubiquitous and low-cost elastomeric O-rings. It is shown that the damping and stiffness characteristics of the O-ring can be predicted a priori, in order to achieve an initial design that is fit for purpose. Furthermore, it is shown that the nonlinear characteristics of the O-ring enable the device to be easily tuned in-situ, in order to optimise the final system. Finally, the simple configuration of the device makes it well suited to through-mounting or surface-mounting on thin-walled flexible structures such as beams and plates

The New Look pMSSM with Neutralino and Gravitino LSPs

The pMSSM provides a broad perspective on SUSY phenomenology. In this paper we generate two new, very large, sets of pMSSM models with sparticle masses extending up to 4 TeV, where the lightest supersymmetric particle (LSP) is either a neutralino or gravitino. The existence of a gravitino LSP necessitates a detailed study of its cosmological effects and we find that Big Bang Nucleosynthesis places strong constraints on this scenario. Both sets are subjected to a global set of theoretical, observational and experimental constraints resulting in a sample of \sim 225k viable models for each LSP type. The characteristics of these two model sets are briefly compared. We confront the neutralino LSP model set with searches for SUSY at the 7 TeV LHC using both the missing (MET) and non-missing ET ATLAS analyses. In the MET case, we employ Monte Carlo estimates of the ratios of the SM backgrounds at 7 and 8 TeV to rescale the 7 TeV data-driven ATLAS backgrounds to 8 TeV. This allows us to determine the pMSSM parameter space coverage for this collision energy. We find that an integrated luminosity of \sim 5-20 fb^{-1} at 8 TeV would yield a substantial increase in this coverage compared to that at 7 TeV and can probe roughly half of the model set. If the pMSSM is not discovered during the 8 TeV run, then our model set will be essentially void of gluinos and lightest first and second generation squarks that are \lesssim 700-800 GeV, which is much less than the analogous mSUGRA bound. Finally, we demonstrate that non-MET SUSY searches continue to play an important role in exploring the pMSSM parameter space. These two pMSSM model sets can be used as the basis for investigations for years to come.Comment: 54 pages, 22 figures; typos fixed, references adde

Measurement of the tt¯ production cross-section in pp collisions at s√ = 5.02 TeV with the ATLAS detector

The inclusive top-quark pair (tt¯) production cross-section σtt¯ is measured in proton–proton collisions at a centre-of-mass energy s√ = 5.02 TeV, using 257 pb−1 of data collected in 2017 by the ATLAS experiment at the LHC. The tt¯ cross-section is measured in both the dilepton and single-lepton final states of the tt¯ system and then combined. The combination of the two measurements yields σtt¯=67.5±0.9(stat.)±2.3(syst.)±1.1(lumi.)±0.2(beam)pb, where the four uncertainties reflect the limited size of the data sample, experimental and theoretical systematic effects, and imperfect knowledge of both the integrated luminosity and the LHC beam energy, giving a total uncertainty of 3.9%. The result is in agreement with theoretical quantum chromodynamic calculations at next-to-next-to-leading order in the strong coupling constant, including the resummation of next-to-next-to-leading logarithmic soft-gluon terms, and constrains the parton distribution functions of the proton at large Bjorken-x

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model