235 research outputs found

    A magnetic wormhole

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    Wormholes are fascinating cosmological objects that can connect two distant regions of the universe. Because of their intriguing nature, constructing a wormhole in a lab seems a formidable task. A theoretical proposal by Greenleaf et al. presented a strategy to build a wormhole for electromagnetic waves. Based on metamaterials, it could allow electromagnetic wave propagation between two points in space through an invisible tunnel. However, an actual realization has not been possible until now. Here we construct and experimentally demonstrate a magnetostatic wormhole. Using magnetic metamaterials and metasurfaces, our wormhole transfers the magnetic field from one point in space to another through a path that is magnetically undetectable. We experimentally show that the magnetic field from a source at one end of the wormhole appears at the other end as an isolated magnetic monopolar field, creating the illusion of a magnetic field propagating through a tunnel outside the 3D space. Practical applications of the results can be envisaged, including medical techniques based on magnetism

    Short tandem repeat profiling: part of an overall strategy for reducing the frequency of cell misidentification

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    The role of cell authentication in biomedical science has received considerable attention, especially within the past decade. This quality control attribute is now beginning to be given the emphasis it deserves by granting agencies and by scientific journals. Short tandem repeat (STR) profiling, one of a few DNA profiling technologies now available, is being proposed for routine identification (authentication) of human cell lines, stem cells, and tissues. The advantage of this technique over methods such as isoenzyme analysis, karyotyping, human leukocyte antigen typing, etc., is that STR profiling can establish identity to the individual level, provided that the appropriate number and types of loci are evaluated. To best employ this technology, a standardized protocol and a data-driven, quality-controlled, and publically searchable database will be necessary. This public STR database (currently under development) will enable investigators to rapidly authenticate human-based cultures to the individual from whom the cells were sourced. Use of similar approaches for non-human animal cells will require developing other suitable loci sets. While implementing STR analysis on a more routine basis should significantly reduce the frequency of cell misidentification, additional technologies may be needed as part of an overall authentication paradigm. For instance, isoenzyme analysis, PCR-based DNA amplification, and sequence-based barcoding methods enable rapid confirmation of a cell line’s species of origin while screening against cross-contaminations, especially when the cells present are not recognized by the species-specific STR method. Karyotyping may also be needed as a supporting tool during establishment of an STR database. Finally, good cell culture practices must always remain a major component of any effort to reduce the frequency of cell misidentification

    A numerical study of dynamic capillary pressure effect for supercritical carbon dioxide-water flow in porous domain

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    This is the accepted version of the following article: DAS, D.B. ... et al., 2014. A numerical study of dynamic capillary pressure effect for supercritical carbon dioxide-water flow in porous domain. AIChE Journal, 60 (12), pp. 4266-4278, which has been published in final form at http://dx.doi.org/10.1002/aic.14577Numerical simulations for core-scale capillary pressure (Pc)–saturation (S) relationships have been conducted for a supercritical carbon dioxide-water system at temperatures between 35°C and 65°C at a domain pressure of 15 MPa as typically expected during geological sequestration of CO2. As the Pc-S relationships depend on both S and time derivative of saturation (∂S / ∂t) yielding what is known as the ‘dynamic capillary pressure effect’ or simply ‘dynamic effect’, this work specifically attempts to determine the significance of these effects for supercritical carbon dioxide-water flow in terms of a coefficient, namely dynamic coefficient (τ). The coefficient establishes the speed at which capillary equilibrium for supercritical CO2-water flow is reached. The simulations in this work involved the solution of the extended version of Darcy’s law which represents the momentum balance for individual fluid phases in the system, the continuity equation for fluid mass balance, as well as additional correlations for determining the capillary pressure as a function of saturation, and the physical properties of the fluids as a function of temperature. The simulations were carried for 3D cylindrical porous domains measuring 10 cm in diameter and 12 cm in height. τ was determined by measuring the slope of a best-fit straight line plotted between (i) the differences in dynamic and equilibrium capillary pressures (Pc,dyn – Pc,equ) against (ii) the time derivative of saturation (dS/dt), both at the same saturation value. The results show rising trends for τ as the saturation values reduce, with noticeable impacts of temperature at 50% saturation of aqueous phase. This means that the time to attain capillary equilibrium for the CO2-water system increases as the saturation decreases. From a practical point view, it implies that the time to capillary equilibrium during geological sequestration of CO2 is an important factor and should be accounted for while simulating the flow processes, e.g., to determine the CO2 storage capacity of a geological aquifer. In this task, one would require both the fundamental understanding of the dynamic capillary pressure effects for supercritical CO2-water flow as well as τ values. These issues are addressed in this article

    Functional Role of Glutamine 28 and Arginine 39 in Double Stranded RNA Cleavage by Human Pancreatic Ribonuclease

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    Human pancreatic ribonuclease (HPR), a member of RNase A superfamily, has a high activity on double stranded (ds) RNA. By virtue of this activity HPR appears to be involved in the host-defense against pathogenic viruses. To delineate the mechanism of dsRNA cleavage by HPR, we have investigated the role of glutamine 28 and arginine 39 of HPR in its activity on dsRNA. A non-basic residue glycine 38, earlier shown to be important for dsRNA cleavage by HPR was also included in the study in the context of glutamine 28 and arginine 39. Nine variants of HPR respectively containing Q28A, Q28L, R39A, G38D, Q28A/R39A, Q28L/R39A, Q28A/G38D, R39A/G38D and Q28A/G38D/R39A mutations were generated and functionally characterized. The far-UV CD-spectral analysis revealed all variants, except R39A, to have structures similar to that of HPR. The catalytic activity of all HPR variants on single stranded RNA substrate was similar to that of HPR, whereas on dsRNA, the catalytic efficiency of all single residue variants, except for the Q28L, was significantly reduced. The dsRNA cleavage activity of R39A/G38D and Q28A/G38D/R39A variants was most drastically reduced to 4% of that of HPR. The variants having reduced dsRNA cleavage activity also had reduction in their dsDNA melting activity and thermal stability. Our results indicate that in HPR both glutamine 28 and arginine 39 are important for the cleavage of dsRNA. Although these residues are not directly involved in catalysis, both arginine 39 and glutamine 28 appear to be facilitating a productive substrate-enzyme interaction during the dsRNA cleavage by HPR

    Network Models of TEM β-Lactamase Mutations Coevolving under Antibiotic Selection Show Modular Structure and Anticipate Evolutionary Trajectories

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    Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here we use the recent evolution of β-lactamase under antibiotic selection as a model for genetic adaptation. We build a network of coevolving residues (possible functional interactions), in which nodes are mutant residue positions and links represent two positions found mutated together in the same sequence. Most often these pairs occur in the setting of more complex mutants. Focusing on extended-spectrum resistant sequences, we use network-theoretical tools to identify triple mutant trajectories of likely special significance for adaptation. We extrapolate evolutionary paths (n = 3) that increase resistance and that are longer than the units used to build the network (n = 2). These paths consist of a limited number of residue positions and are enriched for known triple mutant combinations that increase cefotaxime resistance. We find that the pairs of residues used to build the network frequently decrease resistance compared to their corresponding singlets. This is a surprising result, given that their coevolution suggests a selective advantage. Thus, β-lactamase adaptation is highly epistatic. Our method can identify triplets that increase resistance despite the underlying rugged fitness landscape and has the unique ability to make predictions by placing each mutant residue position in its functional context. Our approach requires only sequence information, sufficient genetic diversity, and discrete selective pressures. Thus, it can be used to analyze recent evolutionary events, where coevolution analysis methods that use phylogeny or statistical coupling are not possible. Improving our ability to assess evolutionary trajectories will help predict the evolution of clinically relevant genes and aid in protein design

    Monitoring frequency influences the analysis of resting behaviour in a forest carnivore

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    Resting sites are key structures for many mammalian species, which can affect reproduction, survival, population density, and even species persistence in human-modified landscapes. As a consequence, an increasing number of studies has estimated patterns of resting site use by mammals, as well as the processes underlying these patterns, though the impact of sampling design on such estimates remain poorly understood. Here we address this issue empirically, based on data from 21 common genets radiotracked during 28 months in Mediterranean forest landscapes. Daily radiotracking data was thinned to simulate every other day and weekly monitoring frequencies, and then used to evaluate the impact of sampling regime on estimates of resting site use. Results showed that lower monitoring frequencies were associated with major underestimates of the average number of resting sites per animal, and of site reuse rates and sharing frequency, though no effect was detected on the percentage use of resting site types. Monitoring frequency also had a major impact on estimates of environmental effects on resting site selection, with decreasing monitoring frequencies resulting in higher model uncertainty and reduced power to identify significant explanatory variables. Our results suggest that variation in monitoring frequency may have had a strong impact on intra- and interspecific differences in resting site use patterns detected in previous studies. Given the errors and uncertainties associated with low monitoring frequencies, we recommend that daily or at least every other day monitoring should be used whenever possible in studies estimating resting site use patterns by mammals

    A Nutrition and Conditioning Intervention for Natural Bodybuilding Contest Preparation: Case Study.

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    Bodybuilding competitions are becoming increasingly popular. Competitors are judged on their aesthetic appearance and usually exhibit a high level of muscularity and symmetry and low levels of body fat. Commonly used techniques to improve physique during the preparation phase before competitions include dehydration, periods of prolonged fasting, severe caloric restriction, excessive cardiovascular exercise and inappropriate use of diuretics and anabolic steroids. In contrast, this case study documents a structured nutrition and conditioning intervention followed by a 21 year-old amateur bodybuilding competitor to improve body composition, resting and exercise fat oxidation, and muscular strength that does not involve use of any of the above mentioned methods. Over a 14-week period, the Athlete was provided with a scientifically designed nutrition and conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not neglect any macronutrient groups; (iii) exercise regularly but not excessively and; (iv) incorporate rest days into his conditioning regime. This strategy resulted in a body mass loss of 11.7 kg’s, corresponding to a 6.7 kg reduction in fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there was a near 3-fold increase in the corresponding exercise intensity that elicited the maximal rate of fat oxidation; 21% V̇ O2max to 60% V̇ O2max. Hamstring concentric peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood-state (BRUMS scale) was not negatively influenced by the intervention and all values relating to the Athlete’s mood-state remained below average over the course of study. This intervention shows that a structured and scientifically supported nutrition strategy can be implemented to improve parameters relevant to bodybuilding competition and importantly the health of competitors, therefore questioning the conventional practices of bodybuilding preparation

    Membrane estrogen receptor-α levels predict estrogen-induced ERK1/2 activation in MCF-7 cells

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    INTRODUCTION: We examined the participation of a membrane form of estrogen receptor (mER)-α in the activation of mitogen-activated protein kinases (extracellular signal-regulated kinase [ERK]1 and ERK2) related to cell growth responses in MCF-7 cells. METHODS: We immunopanned and subsequently separated MCF-7 cells (using fluorescence-activated cell sorting) into mER-α-enriched (mER(high)) and mER-α-depleted (mER(low)) populations. We then measured the expression levels of mER-α on the surface of these separated cell populations by immunocytochemical analysis and by a quantitative 96-well plate immunoassay that distinguished between mER-α and intracellular ER-α. Western analysis was used to determine colocalized estrogen receptor (ER)-α and caveolins in membrane subfractions. The levels of activated ERK1 and ERK2 were determined using a fixed cell-based enzyme-linked immunosorbent assay developed in our laboratory. RESULTS: Immunocytochemical studies revealed punctate ER-α antibody staining of the surface of nonpermeabilized mER(high )cells, whereas the majority of mER(low )cells exhibited little or no staining. Western analysis demonstrated that mER(high )cells expressed caveolin-1 and caveolin-2, and that ER-α was contained in the same gradient-separated membrane fractions. The quantitative immunoassay for ER-α detected a significant difference in mER-α levels between mER(high )and mER(low )cells when cells were grown at a sufficiently low cell density, but equivalent levels of total ER-α (membrane plus intracellular receptors). These two separated cell subpopulations also exhibited different kinetics of ERK1/2 activation with 1 pmol/l 17β-estradiol (E(2)), as well as different patterns of E(2 )dose-dependent responsiveness. The maximal kinase activation was achieved after 10 min versus 6 min in mER(high )versus mER(low )cells, respectively. After a decline in the level of phosphorylated ERKs, a reactivation was seen at 60 min in mER(high )cells but not in mER(low )cells. Both 1A and 2B protein phosphatases participated in dephosphorylation of ERKs, as demonstrated by efficient reversal of ERK1/2 inactivation with okadaic acid and cyclosporin A. CONCLUSION: Our results suggest that the levels of mER-α play a role in the temporal coordination of phosphorylation/dephosphorylation events for the ERKs in breast cancer cells, and that these signaling differences can be correlated to previously demonstrated differences in E(2)-induced cell proliferation outcomes in these cell types
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