2,510 research outputs found
Dynamical friction and the evolution of satellites in virialized halos: the theory of linear response
The evolution of a small satellite inside a more massive truncated isothermal
spherical halo is studied using both the Theory of Linear Response for
dynamical friction and N-Body simulations. The analytical approach includes the
effects of the gravitational wake, of the tidal deformation and the shift of
the barycenter of the primary, so unifying the local versus global
interpretation of dynamical friction. Sizes, masses, orbital energies and
eccentricities are chosen as expected in hierarchical clustering models. We
find that in general the drag force in self-gravitating backgrounds is weaker
than in uniform media and that the orbital decay is not accompanied by a
significant circularization. We also show that the dynamical friction time
scale is weakly dependent on the initial circularity. We provide a fitting
formula for the decay time that includes the effect of mass and angular
momentum loss. Live satellites with dense cores can survive disruption up to an
Hubble time within the primary, notwithstanding the initial choice of orbital
parameters. Dwarf spheroidal satellites of the Milky Way, like Sagittarius A
and Fornax, have already suffered mass stripping and, with their present
masses, the sinking times exceed 10 Gyr even if they are on very eccentric
orbits.Comment: 27 pages including 9 figures. Accepted for publication in the
Astrophysical Journal. Part 2, issue November 10 1999, Volume 52
Are the dead taking over Facebook? A Big Data approach to the future of death online
We project the future accumulation of profiles belonging to deceased Facebook users. Our analysis suggests that a
minimum of 1.4 billion users will pass away before 2100 if Facebook ceases to attract new users as of 2018. If the
network continues expanding at current rates, however, this number will exceed 4.9 billion. In both cases, a majority of
the profiles will belong to non-Western users. In discussing our findings, we draw on the emerging scholarship on digital
preservation and stress the challenges arising from curating the profiles of the deceased. We argue that an exclusively
commercial approach to data preservation poses important ethical and political risks that demand urgent consideration.
We call for a scalable, sustainable, and dignified curation model that incorporates the interests of multiple stakeholders
Electromagnetically Induced Transparency and Slow Light with Optomechanics
Controlling the interaction between localized optical and mechanical
excitations has recently become possible following advances in micro- and
nano-fabrication techniques. To date, most experimental studies of
optomechanics have focused on measurement and control of the mechanical
subsystem through its interaction with optics, and have led to the experimental
demonstration of dynamical back-action cooling and optical rigidity of the
mechanical system. Conversely, the optical response of these systems is also
modified in the presence of mechanical interactions, leading to strong
nonlinear effects such as Electromagnetically Induced Transparency (EIT) and
parametric normal-mode splitting. In atomic systems, seminal experiments and
proposals to slow and stop the propagation of light, and their applicability to
modern optical networks, and future quantum networks, have thrust EIT to the
forefront of experimental study during the last two decades. In a similar
fashion, here we use the optomechanical nonlinearity to control the velocity of
light via engineered photon-phonon interactions. Our results demonstrate EIT
and tunable optical delays in a nanoscale optomechanical crystal device,
fabricated by simply etching holes into a thin film of silicon (Si). At low
temperature (8.7 K), we show an optically-tunable delay of 50 ns with
near-unity optical transparency, and superluminal light with a 1.4 microseconds
signal advance. These results, while indicating significant progress towards an
integrated quantum optomechanical memory, are also relevant to classical signal
processing applications. Measurements at room temperature and in the analogous
regime of Electromagnetically Induced Absorption (EIA) show the utility of
these chip-scale optomechanical systems for optical buffering, amplification,
and filtering of microwave-over-optical signals.Comment: 15 pages, 9 figure
Flaws in design, analysis and interpretation of Pfizer's antifungal trials of voriconazole and uncritical subsequent quotations
We have previously described how a series of trials sponsored by Pfizer of its antifungal drug, fluconazole, in cancer patients with neutropenia handicapped the control drug, amphotericin B, by flaws in design and analysis. We describe similar problems in two pivotal trials of Pfizer's new antifungal agent, voriconazole, published in a prestigious journal. In a non-inferiority trial, voriconazole was significantly inferior to liposomal amphothericin B, but the authors concluded that voriconazole was a suitable alternative. The second trial used amphothericin B deoxycholate as comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days. Voriconazole was given for 77 days on average, but the comparator for only 10 days, which precludes a meaningful comparison. In a random sample of 50 references to these trials, we found that the unwarranted conclusions were mostly uncritically propagated. It was particularly surprising that relevant criticism raised by the FDA related to the first trial was only quoted once, and that none of the articles noted the obvious flaws in the design of the second trial. We suggest that editors ensure that the abstract reflects fairly on the remainder of the paper, and that journals do not impose any time limit for accepting letters that point out serious weaknesses in a study that have not been noted before
Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study
Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178
Isolation and fine mapping of Rps6: An intermediate host resistance gene in barley to wheat stripe rust
A plant may be considered a nonhost of a pathogen if all known genotypes of a plant species are resistant to all known isolates of a pathogen species. However, if a small number of genotypes are susceptible to some known isolates of a pathogen species this plant maybe considered an intermediate host. Barley (Hordeum vulgare) is an intermediate host for Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust. We wanted to understand the genetic architecture underlying resistance to Pst and to determine whether any overlap exists with resistance to the host pathogen, Puccinia striiformis f. sp. hordei (Psh). We mapped Pst resistance to chromosome 7H and show that host and intermediate host resistance is genetically uncoupled. Therefore, we designate this resistance locus Rps6. We used phenotypic and genotypic selection on F2:3 families to isolate Rps6 and fine mapped the locus to a 0.1 cM region. Anchoring of the Rps6 locus to the barley physical map placed the region on two adjacent fingerprinted contigs. Efforts are now underway to sequence the minimal tiling path and to delimit the physical region harbouring Rps6. This will facilitate additional marker development and permit identification of candidate genes in the region
Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study
This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc
The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation
Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al
Noncardiac genetic predisposition in sudden infant death syndrome.
PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible
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