Gaseous Dark Matter Detectors

Dark Matter detectors with directional sensitivity have the potential of yielding an unambiguous positive observation of WIMPs as well as discriminating between galactic Dark Matter halo models. In this article, we introduce the motivation for directional detectors, discuss the experimental techniques that make directional detection possible, and review the status of the experimental effort in this field.Comment: 19 pages, review on gaseous directional dark matter detectors submitted to New Journal of Physic

Positron-molecule interactions: resonant attachment, annihilation, and bound states

This article presents an overview of current understanding of the interaction of low-energy positrons with molecules with emphasis on resonances, positron attachment and annihilation. Annihilation rates measured as a function of positron energy reveal the presence of vibrational Feshbach resonances (VFR) for many polyatomic molecules. These resonances lead to strong enhancement of the annihilation rates. They also provide evidence that positrons bind to many molecular species. A quantitative theory of VFR-mediated attachment to small molecules is presented. It is tested successfully for selected molecules (e.g., methyl halides and methanol) where all modes couple to the positron continuum. Combination and overtone resonances are observed and their role is elucidated. In larger molecules, annihilation rates from VFR far exceed those explicable on the basis of single-mode resonances. These enhancements increase rapidly with the number of vibrational degrees of freedom. While the details are as yet unclear, intramolecular vibrational energy redistribution to states that do not couple directly to the positron continuum appears to be responsible for these enhanced annihilation rates. Downshifts of the VFR from the vibrational mode energies have provided binding energies for thirty species. Their dependence upon molecular parameters and their relationship to positron-atom and positron-molecule binding energy calculations are discussed. Feshbach resonances and positron binding to molecules are compared with the analogous electron-molecule (negative ion) cases. The relationship of VFR-mediated annihilation to other phenomena such as Doppler-broadening of the gamma-ray annihilation spectra, annihilation of thermalized positrons in gases, and annihilation-induced fragmentation of molecules is discussed.Comment: 50 pages, 40 figure

Photoelectric Emission from Interstellar Dust: Grain Charging and Gas Heating

We model the photoelectric emission from and charging of interstellar dust and obtain photoelectric gas heating efficiencies as a function of grain size and the relevant ambient conditions. Using realistic grain size distributions, we evaluate the net gas heating rate for various interstellar environments, and find less heating for dense regions characterized by R_V=5.5 than for diffuse regions with R_V=3.1. We provide fitting functions which reproduce our numerical results for photoelectric heating and recombination cooling for a wide range of interstellar conditions. In a separate paper we will examine the implications of these results for the thermal structure of the interstellar medium. Finally, we investigate the potential importance of photoelectric heating in H II regions, including the warm ionized medium. We find that photoelectric heating could be comparable to or exceed heating due to photoionization of H for high ratios of the radiation intensity to the gas density. We also find that photoelectric heating by dust can account for the observed variation of temperature with distance from the galactic midplane in the warm ionized medium.Comment: 50 pages, including 18 figures; corrected title and abstract field

Explaining oscillations and variability in the p53-Mdm2 system

<p>Abstract</p> <p>Background</p> <p>In individual living cells p53 has been found to be expressed in a series of discrete pulses after DNA damage. Its negative regulator Mdm2 also demonstrates oscillatory behaviour. Attempts have been made recently to explain this behaviour by mathematical models but these have not addressed explicit molecular mechanisms. We describe two stochastic mechanistic models of the p53/Mdm2 circuit and show that sustained oscillations result directly from the key biological features, without assuming complicated mathematical functions or requiring more than one feedback loop. Each model examines a different mechanism for providing a negative feedback loop which results in p53 activation after DNA damage. The first model (ARF model) looks at the mechanism of p14^ARFwhich sequesters Mdm2 and leads to stabilisation of p53. The second model (ATM model) examines the mechanism of ATM activation which leads to phosphorylation of both p53 and Mdm2 and increased degradation of Mdm2, which again results in p53 stabilisation. The models can readily be modified as further information becomes available, and linked to other models of cellular ageing.</p> <p>Results</p> <p>The ARF model is robust to changes in its parameters and predicts undamped oscillations after DNA damage so long as the signal persists. It also predicts that if there is a gradual accumulation of DNA damage, such as may occur in ageing, oscillations break out once a threshold level of damage is acquired. The ATM model requires an additional step for p53 synthesis for sustained oscillations to develop. The ATM model shows much more variability in the oscillatory behaviour and this variability is observed over a wide range of parameter values. This may account for the large variability seen in the experimental data which so far has examined ARF negative cells.</p> <p>Conclusion</p> <p>The models predict more regular oscillations if ARF is present and suggest the need for further experiments in ARF positive cells to test these predictions. Our work illustrates the importance of systems biology approaches to understanding the complex role of p53 in both ageing and cancer.</p

Метод лабораторного определения параметров устройства гидроимпульсного воздействия

Дана стаття описує лабораторний метод, що визначає: мету, умови, обсяг і порядок проведення досліджень параметрів пристрою гідроімпульсної дії.This article describes the laboratory method that defines: the purpose, conditions, effort and procedure of the researching the device settings of hydroimpulsive impact

Temporal Dissection of K-rasG12D Mutant In Vitro and In Vivo Using a Regulatable K-rasG12D Mouse Allele

Animal models which allow the temporal regulation of gene activities are valuable for dissecting gene function in tumorigenesis. Here we have constructed a conditional inducible estrogen receptor-K-rasG12D (ER-K-rasG12D) knock-in mice allele that allows us to temporally switch on or off the activity of K-ras oncogenic mutant through tamoxifen administration. In vitro studies using mice embryonic fibroblast (MEF) showed that a dose of tamoxifen at 0.05 µM works optimally for activation of ER-K-rasG12D independent of the gender status. Furthermore, tamoxifen-inducible activation of K-rasG12D promotes cell proliferation, anchor-independent growth, transformation as well as invasion, potentially via activation of downstream MAPK pathway and cell cycle progression. Continuous activation of K-rasG12D in vivo by tamoxifen treatment is sufficient to drive the neoplastic transformation of normal lung epithelial cells in mice. Tamoxifen withdrawal after the tumor formation results in apoptosis and tumor regression in mouse lungs. Taken together, these data have convincingly demonstrated that K-ras mutant is essential for neoplastic transformation and this animal model may provide an ideal platform for further detailed characterization of the role of K-ras oncogenic mutant during different stages of lung tumorigenesis

A p53-Dependent Response Limits Epidermal Stem Cell Functionality and Organismal Size in Mice with Short Telomeres

Telomere maintenance is essential to ensure proper size and function of organs with a high turnover. In particular, a dwarf phenotype as well as phenotypes associated to premature loss of tissue regeneration, including the skin (hair loss, hair graying, decreased wound healing), are found in mice deficient for telomerase, the enzyme responsible for maintaining telomere length. Coincidental with the appearance of these phenotypes, p53 is found activated in several tissues from these mice, where is thought to trigger cellular senescence and/or apoptotic responses. Here, we show that p53 abrogation rescues both the small size phenotype and restitutes the functionality of epidermal stem cells (ESC) of telomerase-deficient mice with dysfunctional telomeres. In particular, p53 ablation restores hair growth, skin renewal and wound healing responses upon mitogenic induction, as well as rescues ESCmobilization defects in vivo and defective ESC clonogenic activity in vitro. This recovery of ESC functions is accompanied by a downregulation of senescence markers and an increased proliferation in the skin and kidney of telomerase-deficient mice with critically short telomeres without changes in apoptosis rates. Together, these findings indicate the existence of a p53-dependent senescence response acting on stem/progenitor cells with dysfunctional telomeres that is actively limiting their contribution to tissue regeneration, thereby impinging on tissue fitness

p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System

The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. promoter, ii) single copy, chromosomally located p53-responsive and control luminescence reporters, iii) enhanced chemical uptake using modified ABC-transporters, iv) small-volume formats for treatment and dual-luciferase assays, and v) opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins