Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection

AbstractRecent epidemiological studies have found that women infected with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) type 16 or HPV-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. However, it remains unclear if HSV-2 is a cofactor for cervical cancer or if HPV and HSV-2 interact in any way. We have studied the effect of HSV-2 infection on HPV-11 gene expression in an in vitro double-infection assay. HPV transcripts were down-regulated in response to HSV-2 infection. Two HSV-2 vhs mutants failed to reduce HPV-16 E1^E4 transcripts. We also studied the effect of HSV-2 infection on preexisting experimental papillomas in a vaginal epithelial xenograft model. Doubly infected grafts demonstrated papillomatous transformation and the classical cytopathic effect from HSV-2 infection. HPV and HSV DNA signals were mutually exclusive. These studies may have therapeutic applications for HPV infections and related neoplasms

Three electron beams from a laser-plasma wakefield accelerator and the energy apportioning question

Laser-wakefield accelerators are compact devices capable of delivering ultra-short electron bunches with pC-level charge and MeV-GeV energy by exploiting the ultra-high electric fields arising from the interaction of intense laser pulses with plasma. We show experimentally and through numerical simulations that a high-energy electron beam is produced simultaneously with two stable lower-energy beams that are ejected in oblique and counter-propagating directions, typically carrying off 5-10% of the initial laser energy. A MeV, 10s nC oblique beam is ejected in a 30-60 degree hollow cone, which is filled with more energetic electrons determined by the injection dynamics. A nC-level, 100s keV backward-directed beam is mainly produced at the leading edge of the plasma column. We discuss the apportioning of absorbed laser energy amongst the three beams. Knowledge of the distribution of laser energy and electron beam charge, which determine the overall efficiency, is important for various applications of laser-wakefield accelerators, including the development of staged high-energy accelerators

Wide-angle electron beams from laser-wakefield accelerators

Advances in laser technology have driven the development of laser-wakefield accelerators, compact devices that are capable of accelerating electrons to GeV energies over centimetre distances by exploiting the strong electric field gradients arising from the interaction of intense laser pulses with an underdense plasma. A side-effect of this acceleration mechanism is the production of high-charge, low-energy electron beams at wide angles. Here we present an experimental and numerical study of the properties of these wide-angle electron beams, and show that they carry off a significant fraction of the energy transferred from the laser to the plasma. These high-charge, wide-angle beams can also cause damage to laser-wakefield accelerators based on capillaries, as well as become source of unwanted bremsstrahlung radiation

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Effects of environmental pollutants on the reproduction and welfare of ruminants

Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone. Reported effects of exposure include changes in organ weight and gross structure, histology and gene and protein expression but these changes are not reflected in changes in reproductive performance under the conditions tested. These results illustrate the complexity of the effects of endocrine disrupting compounds on the reproductive axis, which make it difficult to extrapolate between, or even within, species. Effects of pollutant exposure on the thyroid gland, immune, cardiovascular and obesogenic systems have not been shown explicitly, in ruminants, but work on other species suggests that these systems can also be perturbed. It is concluded that exposure to a mixture of anthropogenic pollutants has significant effects on a wide variety of physiological systems, including the reproductive system. Although this physiological insult has not yet been shown to lead to a reduction in ruminant gross performance, there are already reports indicating that anthropogenic pollutant exposure can compromise several physiological systems and may pose a significant threat to both reproductive performance and welfare in the longer term. At present, many potential mechanisms of action for individual chemicals have been identified but knowledge of factors affecting the rate of tissue exposure and of the effects of combinations of chemicals on physiological systems is poor. Nevertheless, both are vital for the identification of risks to animal productivity and welfare

Next-to-Leading Order QCD Analysis of Polarized Deep Inelastic Scattering Data

We present a Next-to-Leading order perturbative QCD analysis of world data on the spin dependent structure functions $g_1^p, g_1^n$, and $g_1^d$, including the new experimental information on the $Q^2$ dependence of $g_1^n$. Careful attention is paid to the experimental and theoretical uncertainties. The data constrain the first moments of the polarized valence quark distributions, but only qualitatively constrain the polarized sea quark and gluon distributions. The NLO results are used to determine the $Q^2$ dependence of the ratio $g_1/F_1$ and evolve the experimental data to a constant $Q^2 = 5 GeV^2$. We determine the first moments of the polarized structure functions of the proton and neutron and find agreement with the Bjorken sum rule.Comment: 21 pages, 4 figures; final version to be published in Phys. Lett. B. References updated. Uses elsart.cls version 1996/04/22, 2e-1.4

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Hypoxic Pulmonary Vasoconstriction in Humans:Tale or Myth

Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine