A test of general relativity from the three-dimensional orbital geometry of a binary pulsar

Binary pulsars provide an excellent system for testing general relativity because of their intrinsic rotational stability and the precision with which radio observations can be used to determine their orbital dynamics. Measurements of the rate of orbital decay of two pulsars have been shown to be consistent with the emission of gravitational waves as predicted by general relativity, providing the most convincing evidence for the self-consistency of the theory to date. However, independent verification of the orbital geometry in these systems was not possible. Such verification may be obtained by determining the orientation of a binary pulsar system using only classical geometric constraints, permitting an independent prediction of general relativistic effects. Here we report high-precision timing of the nearby binary millisecond pulsar PSR J0437-4715, which establish the three-dimensional structure of its orbit. We see the expected retardation of the pulse signal arising from the curvature of space-time in the vicinity of the companion object (the `Shapiro delay'), and we determine the mass of the pulsar and its white dwarf companion. Such mass determinations contribute to our understanding of the origin and evolution of neutron stars.Comment: 5 pages, 2 figure

Epidemic space

The aim of this article is to highlight the importance of 'spatiality' in understanding the materialization of risk society and cultivation of risk sensibilities. More specifically it provides a cultural analysis of pathogen virulence (as a social phenomenon) by means of tracing and mapping the spatial flows that operate in the uncharted zones between the microphysics of infection and the macrophysics of epidemics. It will be argued that epidemic space consists of three types of forces: the vector, the index and the vortex. It will draw on Latour's Actor Network Theory to argue that epidemic space is geared towards instability when the vortex (of expanding associations and concerns) displaces the index (of finding a single cause)

The what and where of adding channel noise to the Hodgkin-Huxley equations

One of the most celebrated successes in computational biology is the Hodgkin-Huxley framework for modeling electrically active cells. This framework, expressed through a set of differential equations, synthesizes the impact of ionic currents on a cell's voltage -- and the highly nonlinear impact of that voltage back on the currents themselves -- into the rapid push and pull of the action potential. Latter studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic Hodgkin-Huxley equations. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly Matlab simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl

Advances in Pediatric Neurovirology

Viral infections of the pediatric central nervous system (CNS) encompass a broad spectrum of both perinatally and postnatally acquired diseases with potentially devastating effects on the developing brain. In children, viral infections have been associated with chronic encephalopathy, encephalitis, demyelinating disease, tumors, and epilepsy. Older diagnostic techniques of biopsy, viral culture, electron microscopy, gel-based polymerase chain reaction (PCR), and viral titer quantification are being replaced with more rapid, sensitive, and specific real-time and microarray-based PCR technologies. Advances in neuroimaging technologies have provided for earlier recognition of CNS injury without elucidation of specific viral etiology. Although the mainstay therapy of many pediatric neurovirologic diseases, aside from HIV, includes intravenous acyclovir, much work is being done to develop novel antiviral immunotherapies aimed at both treating and preventing pediatric CNS viral disease

Pacific Ocean–wide profile of CYP1A1 expression, stable carbon and nitrogen isotope ratios, and organic contaminant burden in sperm whale skin biopsies

This paper is not subject to U.S. copyright. The definitive version was published in Environmental Health Perspectives 119 (2011): 337-343, doi:10.1289/ehp.0901809.Background: Ocean pollution affects marine organisms and ecosystems as well as humans. The International Oceanographic Commission recommends ocean health monitoring programs to investigate the presence of marine contaminants and the health of threatened species and the use of multiple and early-warning biomarker approaches. Objective: We explored the hypothesis that biomarker and contaminant analyses in skin biopsies of the threatened sperm whale (Physeter macrocephalus) could reveal geographical trends in exposure on an oceanwide scale. Methods: We analyzed cytochrome P450 1A1 (CYP1A1) expression (by immunohistochemistry), stable nitrogen and carbon isotope ratios (as general indicators of trophic position and latitude, respectively), and contaminant burdens in skin biopsies to explore regional trends in the Pacific Ocean. Results: Biomarker analyses revealed significant regional differences within the Pacific Ocean. CYP1A1 expression was highest in whales from the Galapagos, a United Nations Educational, Scientific, and Cultural Organization World Heritage marine reserve, and was lowest in the sampling sites farthest away from continents. We examined the possible influence of the whales’ sex, diet, or range and other parameters on regional variation in CYP1A1 expression, but data were inconclusive. In general, CYP1A1 expression was not significantly correlated with contaminant burdens in blubber. However, small sample sizes precluded detailed chemical analyses, and power to detect significant associations was limited. Conclusions: Our large-scale monitoring study was successful at identifying regional differences in CYP1A1 expression, providing a baseline for this known biomarker of exposure to aryl hydrocarbon receptor agonists. However, we could not identify factors that explained this variation. Future oceanwide CYP1A1 expression profiles in cetacean skin biopsies are warranted and could reveal whether globally distributed chemicals occur at biochemically relevant concentrations on a global basis, which may provide a measure of ocean integrity.Funding was provided by National Institute of Environmental Health Sciences grant P42-ES-0469, Superfund Basic Research Program grant P42ES007381, NOAA Sea Grant NA86RG0075 R/B-162, and the Ocean Alliance

Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma

Background: Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. Objective: This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Innovations in total knee replacement: new trends in operative treatment and changes in peri-operative management

The human knee joint can sustain damage due to injury, or more usually osteoarthritis, to one, two or all three of the knee compartments: the medial femorotibial, the lateral femorotibial and the patellofemoral compartments. When pain associated with this damage is unmanageable using nonsurgical techniques, knee replacement surgery might be the most appropriate course of action. This procedure aims to restore a pain-free, fully functional and durable knee joint. Total knee replacement is a well-established treatment modality, and more recently, partial knee replacement—more commonly known as bi- or unicompartmental knee replacement—has seen resurgence in interest and popularity. Combined with the use of minimally invasive surgery (MIS) techniques, gender-specific prosthetics and computer-assisted navigation systems, orthopaedic surgeons are now able to offer patients knee replacement procedures that are associated with (1) minimal risks during and after surgery by avoiding fat embolism, reducing blood loss and minimising soft tissue disruption; (2) smaller incisions; (3) faster and less painful rehabilitation; (4) reduced hospital stay and faster return to normal activities of daily living; (5) an improved range of motion; (6) less requirement for analgesics; and (7) a durable, well-aligned, highly functional knee. With the ongoing advancements in surgical technique, medical technology and prosthesis design, knee replacement surgery is constantly evolving. This review provides a personal account of the recent innovations that have been made, with a particular emphasis on the potential use of MIS techniques combined with computer-assisted navigation systems to treat younger, more physically active patients with resurfacing partial/total implant knee arthroplasty

Expansion and subfunctionalisation of flavonoid 3',5'-hydroxylases in the grapevine lineage

<p>Abstract</p> <p>Background</p> <p>Flavonoid 3',5'-hydroxylases (F3'5'Hs) and flavonoid 3'-hydroxylases (F3'Hs) competitively control the synthesis of delphinidin and cyanidin, the precursors of blue and red anthocyanins. In most plants, <it>F3'5'H </it>genes are present in low-copy number, but in grapevine they are highly redundant.</p> <p>Results</p> <p>The first increase in <it>F3'5'H </it>copy number occurred in the progenitor of the eudicot clade at the time of the γ triplication. Further proliferation of <it>F3'5'H</it>s has occurred in one of the paleologous loci after the separation of Vitaceae from other eurosids, giving rise to 15 paralogues within 650 kb. Twelve reside in 9 tandem blocks of ~35-55 kb that share 91-99% identity. The second paleologous <it>F3'5'H </it>has been maintained as an orphan gene in grapevines, and lacks orthologues in other plants. Duplicate <it>F3'5'H</it>s have spatially and temporally partitioned expression profiles in grapevine. The orphan <it>F3'5'H </it>copy is highly expressed in vegetative organs. More recent duplicate <it>F3'5'H</it>s are predominately expressed in berry skins. They differ only slightly in the coding region, but are distinguished in the structure of the promoter. Differences in <it>cis</it>-regulatory sequences of promoter regions are paralleled by temporal specialisation of gene transcription during fruit ripening. Variation in anthocyanin profiles consistently reflects changes in the <it>F3'5'H </it>mRNA pool across different cultivars. More <it>F3'5'H </it>copies are expressed at high levels in grapevine varieties with 93-94% of 3'5'-OH anthocyanins. In grapevines depleted in 3'5'-OH anthocyanins (15-45%), fewer <it>F3'5'H </it>copies are transcribed, and at lower levels. Conversely, only two copies of the gene encoding the competing F3'H enzyme are present in the grape genome; one copy is expressed in both vegetative and reproductive organs at comparable levels among cultivars, while the other is transcriptionally silent.</p> <p>Conclusions</p> <p>These results suggest that expansion and subfunctionalisation of <it>F3'5'H</it>s have increased the complexity and diversification of the fruit colour phenotype among red grape varieties.</p

Global Health Governance and the Commercial Sector: A Documentary Analysis of Tobacco Company Strategies to Influence the WHO Framework Convention on Tobacco Control

Heide Weishaar and colleagues did an analysis of internal tobacco industry documents together with other data and describe the industry's strategic response to the proposed World Health Organization Framework Convention on Tobacco Control