The regions of the herpes simplex virus type 1 immediate early protein Vmwl75 required for site specific DNA binding closely correspond to those involved in transcriptional regulation

The immediate-early (IE) protein Vmw175 (ICP4) of HSV-1 is required for the transcription of later classes of viral genes and the repression of IE gene expression. We have previously constructed a panel of plasmid-borne insertion and deletion mutants of the gene encoding Vmw175 and assayed their ability to regulate transcription in transient transfection assays. By this approach we have mapped the regions of the Vmw175 amino acid sequence that are required for transcriptional activation and repression of herpes virus promoters. This paper describes the use of nuclear extracts, made from cells transfected with these mutant plasmids, in gel retardation DNA binding assays in order to define the regions of Vmw175 involved in binding to a specific Vmw175 DNA binding site. The results show that amino acid residues 275–495 (a region which is highly conserved between Vmw175 and the varicella-zoster virus “IE” 140K protein) include structures which are critically required for specific DNA binding, transactivation and repression. This raises the interesting paradox that although the specific DNA sequence recognized by Vmw175 is not commonly found in its target promoters, the protein domain required for recognition of this sequence is required for promoter activation

The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain

Herpes simplex virus type 1 expresses five immediateearly (IE) polypeptides. In the absence of functional Vmw175 (the product of IE gene 3) activation of transcription of later classes of viral genes and repression of IE gene expression does not occur. The recognition of specific DNA sequences by Vmw175 requires, as determined by sensitivity to mutation, a part of the protein highly conserved in the corresponding proteins of related herpes viruses. However, mutations in other parts of the protein can also disrupt specific DNA binding. This paper shows that the DNA binding domain of Vmw175 can be liberated as a functional unit by digestion with proteinase K. Analysis of mutant Vmw175 proteinsshowed that the proteinase K resistant domain has an amino terminus between amino acid residues 229 and 292, while its carboxy terminus is between residues 495 and 518. Mutations outside this region which affect DNA binding by the intact protein do not eliminate binding of the proteinase K resistant domain. This implies that direct DNA binding by Vmw175 involves a linear subsection of the polypeptide, and that mutations in other parts of the polypeptide which affect DNA binding of the whole protein do so by indirect means

High level expression and purification of herpes simplex virus type 1 immediate early polypeptide Vmw110

Herpes simplex virus type 1 (HSV-1) encodes five immediate early (IE) polypeptides. This paper reports the construction of a baculovirus vector which expresses large amounts of Vmw110, the product of IE gene 1. The expressed protein has been purified to near homogeneity and has a mobility on SDS polyacrylamide gels identical to that of Vmw110 produced during HSV-1 infection. Characterisation of its properties indicated that it forms dimers and perhaps higher order oligomers in solution and that the purified protein binds to both single stranded and double stranded calf thymus DNA cellulose columns. However, filter binding experiments were unable to detect any stable association of Vmw110 with DNA in solution

Muon Anomalous Magnetic Moment and Lepton Flavor Violation

A non-universal interaction, which involves only the third family leptons induces lepton flavor violating couplings and contributes to the anomalous magnetic moment of muon. In this paper, we study the effects of non-universal interaction on muon (g-2) and rare decay $\tau \to \mu \gamma$ by using an effective lagrangian technique, and a phenomenological $Z^\prime$ model where $Z^\prime$ couples only to the third family lepton. We find that the deviation from the theory can be explained and the induced $\tau \to \mu \gamma$ rate could be very close to the current experimental limit. In the $Z^\prime$ model, $M_{Z^\prime}$ has to be lighter than 2.6 TeV.Comment: references added, the version to appear in PR

Revisiting consistency conditions for quantum states of systems on closed timelike curves: an epistemic perspective

There has been considerable recent interest in the consequences of closed timelike curves (CTCs) for the dynamics of quantum mechanical systems. A vast majority of research into this area makes use of the dynamical equations developed by Deutsch, which were developed from a consistency condition that assumes that mixed quantum states uniquely describe the physical state of a system. We criticise this choice of consistency condition from an epistemic perspective, i.e., a perspective in which the quantum state represents a state of knowledge about a system. We demonstrate that directly applying Deutsch's condition when mixed states are treated as representing an observer's knowledge of a system can conceal time travel paradoxes from the observer, rather than resolving them. To shed further light on the appropriate dynamics for quantum systems traversing CTCs, we make use of a toy epistemic theory with a strictly classical ontology due to Spekkens and show that, in contrast to the results of Deutsch, many of the traditional paradoxical effects of time travel are present.Comment: 10 pages, 6 figures, comments welcome; v2 added references and clarified some points; v3 published versio

Comparison of sequencing methods and data processing pipelines for whole genome sequencing and minority single nucleotide variant (mSNV) analysis during an influenza A/H5N8 outbreak

As high-throughput sequencing technologies are becoming more widely adopted for analysing pathogens in disease outbreaks there needs to be assurance that the different sequencing technologies and approaches to data analysis will yield reliable and comparable results. Conversely, understanding where agreement cannot be achieved provides insight into the limitations of these approaches and also allows efforts to be focused on areas of the process that need improvement. This manuscript describes the next-generation sequencing of three closely related viruses, each analysed using different sequencing strategies, sequencing instruments and data processing pipelines. In order to determine the comparability of consensus sequences and minority (sub-consensus) single nucleotide variant (mSNV) identification, the biological samples, the sequence data from 3 sequencing platforms and the *.bam quality-trimmed alignment files of raw data of 3 influenza A/H5N8 viruses were shared. This analysis demonstrated that variation in the final result could be attributed to all stages in the process, but the most critical were the well-known homopolymer errors introduced by 454 sequencing, and the alignment processes in the different data processing pipelines which affected the consistency of mSNV detection. However, homopolymer errors aside, there was generally a good agreement between consensus sequences that were obtained for all combinations of sequencing platforms and data processing pipelines. Nevertheless, minority variant analysis will need a different level of careful standardization and awareness about the possible limitations, as shown in this study

Quasars and their host galaxies

This review attempts to describe developments in the fields of quasar and quasar host galaxies in the past five. In this time period, the Sloan and 2dF quasar surveys have added several tens of thousands of quasars, with Sloan quasars being found to z>6. Obscured, or partially obscured quasars have begun to be found in significant numbers. Black hole mass estimates for quasars, and our confidence in them, have improved significantly, allowing a start on relating quasar properties such as radio jet power to fundamental parameters of the quasar such as black hole mass and accretion rate. Quasar host galaxy studies have allowed us to find and characterize the host galaxies of quasars to z>2. Despite these developments, many questions remain unresolved, in particular the origin of the close relationship between black hole mass and galaxy bulge mass/velocity dispersion seen in local galaxies.Comment: Review article, to appear in Astrophysics Update

The Mathematical Universe

I explore physics implications of the External Reality Hypothesis (ERH) that there exists an external physical reality completely independent of us humans. I argue that with a sufficiently broad definition of mathematics, it implies the Mathematical Universe Hypothesis (MUH) that our physical world is an abstract mathematical structure. I discuss various implications of the ERH and MUH, ranging from standard physics topics like symmetries, irreducible representations, units, free parameters, randomness and initial conditions to broader issues like consciousness, parallel universes and Godel incompleteness. I hypothesize that only computable and decidable (in Godel's sense) structures exist, which alleviates the cosmological measure problem and help explain why our physical laws appear so simple. I also comment on the intimate relation between mathematical structures, computations, simulations and physical systems.Comment: Replaced to match accepted Found. Phys. version, 31 pages, 5 figs; more details at http://space.mit.edu/home/tegmark/toe.htm

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe