A tracking code for injection and acceleration studies in synchrotrons

CAPTURE-SPC is a Monte-Carlo-based tracking program that simulates the injection and acceleration processes in proton synchrotrons. The time evolution of a distribution of charged particles is implemented by a symplectic, second-order-accurate integration algorithm. The recurrence relations follow a time-stepping leap--frog method. The time-step can be varied optionally to reduce computer time. Space-charge forces are calculated by binning the phase-projected particle distribution. The statistical fluctuations introduced by the binning process are reduced by presmoothing the data by the cloud-in-cell method and by filtering. Both the bin size and amount of filtering can be varied during the acceleration cycle so that the bunch fine structure is retained while the short wavelength noise is attenuated. The initial coordinates of each macro particle together with its time of injection are retained throughout the calculations. This information is useful in determining low-loss injection schemes

Redox-sensitive DNA Binding by Homodimeric Methanosarcina Acetivorans MsvR is Modulated by Cysteine Residues

Background: Methanoarchaea are among the strictest known anaerobes, yet they can survive exposure to oxygen. The mechanisms by which they sense and respond to oxidizing conditions are unknown. MsvR is a transcription regulatory protein unique to the methanoarchaea. Initially identified and characterized in the methanogen Methanothermobacter thermautotrophicus (Mth), MthMsvR displays differential DNA binding under either oxidizing or reducing conditions. Since MthMsvR regulates a potential oxidative stress operon in M. thermautotrophicus, it was hypothesized that the MsvR family of proteins were redox-sensitive transcription regulators. Results: An MsvR homologue from the methanogen Methanosarcina acetivorans, MaMsvR, was overexpressed and purified. The two MsvR proteins bound the same DNA sequence motif found upstream of all known MsvR encoding genes, but unlike MthMsvR, MaMsvR did not bind the promoters of select genes involved in the oxidative stress response. Unlike MthMsvR that bound DNA under both non-reducing and reducing conditions, MaMsvR bound DNA only under reducing conditions. MaMsvR appeared as a dimer in gel filtration chromatography analysis and site-directed mutagenesis suggested that conserved cysteine residues within the V4R domain were involved in conformational rearrangements that impact DNA binding. Conclusions: Results presented herein suggest that homodimeric MaMsvR acts as a transcriptional repressor by binding Ma PmsvR under non-reducing conditions. Changing redox conditions promote conformational changes that abrogate binding to Ma PmsvR which likely leads to de-repression

Longitudinal tracking studies for a high intensity proton synchrotron

Results from longitudinal tracking studies for a high intensity proton synchrotron designed for a 1-MW spallation source are presented. The machine delivers a proton beam of 0.5 mA time-averaged current at a repetition rate of 30 Hz. The accelerator is designed to have radiation levels that allow hands-on-maintenance. However, the high beam intensity causes strong space charge fields whose effects may lead to particle loss and longitudinal instabilities. The space charge fields modify the particle distribution, distort the stable bucket area and reduce the rf linear restoring force. Tracking simulations were conducted to analyze the space charge effects on the dynamics of the injection and acceleration processes and means to circumvent them. The tracking studies led to the establishment of the injected beam parameters and rf voltage program that minimized beam loss and longitudinal instabilities. Similar studies for a 10-GeV synchrotron that uses the 2-GeV synchrotron as its injector are also discussed

Singularity Free (Homogeneous Isotropic) Universe in Graviton-Dilaton Models

We present a class of graviton-dilaton models in which a homogeneous isotropic universe, such as our observed one, evolves with no singularity at any time. Such models may stand on their own as interesting models for singularity free cosmology, and may be studied further accordingly. They may also arise from string theory. We discuss critically a few such possibilities.Comment: 11 pages. Latex file. Revised in response to referees' Comments. Results remain same. To appear in Phys. Rev. Let

Energy Distribution for Non-commutative Radiating Schwarzschild Black Holes

The aim of this article is the calculation of the energy-momentum for a non-commutative radiating Schwarzschild black hole in order to obtain the expressions for energy. We make the calculations with the Einstein and M\oller prescriptions. We show that the expressions for energy in both the prescriptions depend on the mass $M$, $\theta$ parameter and radial coordinate. We make some comparisons between the results. Our results show that the Einstein prescription is a more powerful concept than the M\oller prescription.Comment: 5 pages and 6 figures. Revised version submitted in Int.J.Theor.Phys. after minor revisio

Integrated transcriptomic and proteomic analysis of the global response of Wolbachia to doxycycline-induced stress

The bacterium Wolbachia (order Rickettsiales), representing perhaps the most abundant vertically transmitted microbe worldwide, infects arthropods and filarial nematodes. In arthropods, Wolbachia can induce reproductive alterations and interfere with the transmission of several arthropod-borne pathogens. In addition, Wolbachia is an obligate mutualist of the filarial parasites that cause lymphatic filariasis and onchocerciasis in the tropics. Targeting Wolbachia with tetracycline antibiotics leads to sterilisation and ultimately death of adult filariae. However, several weeks of treatment are required, restricting the implementation of this control strategy. To date, the response of Wolbachia to stress has not been investigated, and almost nothing is known about global regulation of gene expression in this organism. We exposed an arthropod Wolbachia strain to doxycycline in vitro, and analysed differential expression by directional RNA-seq and label-free, quantitative proteomics. We found that Wolbachia responded not only by modulating expression of the translation machinery, but also by upregulating nucleotide synthesis and energy metabolism, while downregulating outer membrane proteins. Moreover, Wolbachia increased the expression of a key component of the twin-arginine translocase (tatA) and a phosphate ABC transporter ATPase (PstB); the latter is associated with decreased susceptibility to antimicrobials in free-living bacteria. Finally, the downregulation of 6S RNA during translational inhibition suggests that this small RNA is involved in growth rate control. Despite its highly reduced genome, Wolbachia shows a surprising ability to regulate gene expression during exposure to a potent stressor. Our findings have general relevance for the chemotherapy of obligate intracellular bacteria and the mechanistic basis of persistence in the Rickettsiales

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells