86 research outputs found
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
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
The role of networks to overcome large-scale challenges in tomography : the non-clinical tomography users research network
Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives
Expression of a bacterial catalase in a strictly anaerobic methanogen significantly increases tolerance to hydrogen peroxide but not oxygen
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Effects of construction and alignment errors on the orbit functions of the advanced photon source storage ring
The orbit functions for the Advanced Photon Source Storage Ring have been studied using the simulation code RACETRACK. Non-linear elements are substituted into the storage ring lattice to simulate the effects of construction and alignment errors in the quadrupole, dipole, and sextupole magnets. The effects of these errors on the orbit distortion, dispersion, and beta functions are then graphically analyzed to show the rms spread of the functions across several machines. The studies show that the most significant error is displacement of the quadrupole magnets. Further studies using a 3 bump correction routine show that these errors can be corrected to acceptable levels. 1 ref., 10 figs., 1 tab
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Effects of errors on the dynamic aperture of the Advanced Photon Source storage ring
The individual tolerance limits for alignment errors and magnet fabrication errors in the 7-GeV Advanced Photon Source storage ring are determined by computer-simulated tracking. Limits are established for dipole strength and roll errors, quadrupole strength and alignment errors, sextupole strength and alignment errors, as well as higher order multipole strengths in dipole and quadrupole magnets. The effects of girder misalignments on the dynamic aperture are also studied. Computer simulations are obtained with the tracking program RACETRACK, with errors introduced from a user-defined Gaussian distribution, truncated at {plus minus}5 standard deviation units. For each error, the average and rms spread of the stable amplitudes are determined for ten distinct machines, defined as ten different seeds to the random distribution, and for five distinct initial directions of the tracking particle. 4 refs., 4 figs., 1 tab
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A new generation of superconducting solenoids for heavy-ion linac application.
The beam dynamics of superconducting (SC) heavy-ion linacs operating in the velocity range below 0.4c require a compact accelerating-focusing lattice. The use of SC solenoids together with SC RF resonators within a common cryostat can solve the real-estate problem. The solenoids must have low fringe fields to avoid magnetic flux capture in the SC RF resonators. Also, incorporating dipole steering coils together with the SC solenoids in one magnet assembly can increase the compactness of the linac lattice. R&D work has been carried out to determine the feasibility of combining the three elements of high solenoid field, low fringe field, and integral dipole field, into one compact package. A 9-Tesla magnet has been initially designed and will be prototyped, with the goal of eventually developing 14-Tesla solenoids of similar design. The most important design issues are: (1) to minimize stray field in the RF cavity region using SC bucking coils and (2) to achieve adequate mechanical stability of the transverse dipole windings in the presence of forces produced by the solenoid/bucking coil assembly. The assembly, including terminals, switches, and protection circuit, are designed to fit inside a 25-cm diameter helium reservoir. The results of the preliminary design of the solenoid, including numerical simulations of the beam dynamics, are reported
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