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

Ge Detectors and 0νββ0\nu\beta\beta: The Search for Double Beta Decay with Germanium Detectors: Past, Present and Future

High Purity Germanium Detectors have excellent energy resolution; the best among the technologies used in double beta decay. Since neutrino-less double beta decay hinges on the search for a rare peak upon a background continuum, this strength has enabled the technology to consistently provide leading results. The Ge crystals at the heart of these experiments are very pure; they have no measurable U or Th contamination. The added efforts to reduce the background associated with electronics, cryogenic cooling, and shielding have been very successful, leading to the longevity of productivity. The first experiment published in 1967 by the Milan group of Fiorini, established the benchmark half-life limit $>3\times10^{20}$ yr. More recently, the \MJ\ and GERDA collaborations have developed new detector technologies that optimize the pulse waveform analysis. As a result, the GERDA collaboration refuted the claim of observation with a revolutionary approach to shielding by immersing the detectors directly in radio-pure liquid argon. In 2018, the \MJ\ collaboration, using a classic vacuum cryostat and high-Z shielding, achieved a background level near that of GERDA by developing very pure materials for use nearby the detectors. Together, GERDA and \MJ\ have provided limits approaching $10^{26}$ yr. In this article, we elaborate on the historical use of Ge detectors for double beta decay addressing the strengths and weaknesses. We also summarize the status and future as many \MJ\ and GERDA collaborators have joined with scientists from other efforts to give birth to the LEGEND collaboration. LEGEND will exploit the best features of both experiments to extend the half-life limit beyond $10^{28}$ yr with a ton-scale experiment.Comment: Invited submission to Frontiers in Physic

Radiation pressure detection and density estimate for 2011 MD

We present our astrometric observations of the small near-Earth object 2011~MD ($H \sim 28.0$), obtained after its very close fly-by to Earth in June 2011. Our set of observations extends the observational arc to $73$ days, and together with the published astrometry obtained around the Earth fly-by allows a direct detection of the effect of radiation pressure on the object, with a confidence of $5\sigma$. The detection can be used to put constraints on the density of the object, pointing to either an unexpectedly low value of \rho = (640 \pm 330) \mbox{ kg} / \mbox{m} ^3 ($68\%$ confidence interval) if we assume a typical probability distribution for the unknown albedo, or to an unusually high reflectivity of its surface. This result may have important implications both in terms of impact hazard from small objects and in light of a possible retrieval of this target.Comment: Submitted to ApJ Letter

An evaluation of the Amblyopia and Strabismus Questionnaire using Rasch analysis

noPURPOSE. To evaluate whether the Amblyopia and Strabismus Questionnaire (A&SQ) is a suitable instrument for the assessment of vision-related quality-of life (VR-QoL) in individuals with strabismus and/or amblyopia. METHODS. The A&SQ was completed by 102 individuals, all of whom had amblyopia, strabismus, or both. Rasch analysis was used to evaluate the usefulness of individual questionnaire items (i.e., questions); the response-scale performance; how well the items targeted VR-QoL; whether individual items showed response bias, depending on factors such as whether strabismus was present; and dimensionality. RESULTS. Items relating to concerns about the appearance of the eyes were applicable only to those with strabismus, and many items showed large ceiling effects. The response scale showed disordered responses and underused response options, which improved after the number of response options was reduced from five to three. This change improved the discriminative ability of the questionnaire (person separation index increased from 1.98 to 2.11). Significant bias was found between strabismic and nonstrabismic respondents. Separate Rasch analyses conducted for subjects with and without strabismus indicated that all A&SQ items seemed appropriate for individuals with strabismus (Rasch infit values between 0.60 and 1.40), but several items fitted the model poorly in amblyopes without strabismus. The AS&Q was not found to be unidimensional. CONCLUSIONS. The findings highlight the limitations of the A&SQ instrument in the assessment of VR-QoL in subjects with strabismus and especially in those with amblyopia alone. The results suggest that separate instruments are needed to quantify VR-QoL in amblyopes with and without strabismus

Driving Markov chain Monte Carlo with a dependent random stream

Markov chain Monte Carlo is a widely-used technique for generating a dependent sequence of samples from complex distributions. Conventionally, these methods require a source of independent random variates. Most implementations use pseudo-random numbers instead because generating true independent variates with a physical system is not straightforward. In this paper we show how to modify some commonly used Markov chains to use a dependent stream of random numbers in place of independent uniform variates. The resulting Markov chains have the correct invariant distribution without requiring detailed knowledge of the stream's dependencies or even its marginal distribution. As a side-effect, sometimes far fewer random numbers are required to obtain accurate results.Comment: 16 pages, 4 figure

Universal Dynamical Steps in the Exact Time-Dependent Exchange-Correlation Potential

We show that the exact exchange-correlation potential of time-dependent density-functional theory displays dynamical step structures that have a spatially non-local and time non-local dependence on the density. Using one-dimensional two-electron model systems, we illustrate these steps for a range of non-equilibrium dynamical situations relevant for modeling of photo-chemical/physical processes: field-free evolution of a non-stationary state, resonant local excitation, resonant complete charge-transfer, and evolution under an arbitrary field. Lack of these steps in usual approximations yield inaccurate dynamics, for example predicting faster dynamics and incomplete charge transfer