A Robust Determination of the Time Delay in 0957+561A,B and a Measurement of the Global Value of Hubble's Constant

Photometric monitoring of the gravitational lens system 0957+561A,B in the g and r bands with the Apache Point Observatory (APO) 3.5 m telescope during 1996 shows a sharp g band event in the trailing (B) image light curve at the precise time predicted from the observation of an event during 1995 in the leading (A) image with a delay of 415 days. This success confirms the "short delay," and the lack of any feature at a delay near 540 days rejects the "long delay" for this system, resolving a long-standing controversy. A series of statistical analyses of our light curve data yield a best fit delay of 417 +/- 3 days (95% confidence interval). Recent improvements in the modeling of the lens system (consisting of a galaxy and cluster) allow us to derive a value of the global (at z = 0.36) value of Hubble's constant H_0 using Refsdal's method, a simple and direct distance determination based on securely understood physics and geometry. The result is H_0 = 63 +/- 12 km/s/Mpc (for Omega = 1) where this 95% confidence interval is dominated by remaining lens model uncertainties.Comment: accepted by ApJ, AASTeX 4.0 preprint, 4 PostScript figure

Reduction of fibrillar strain-rate sensitivity in steroid-induced osteoporosis linked to changes in mineralized fibrillar nanostructure

As bone is used in a dynamic mechanical environment, understanding the structural origins of its time-dependent mechanical behaviour – and the alterations in metabolic bone disease – is of interest. However, at the scale of the mineralized fibrillar matrix (nanometre-level), the nature of the strain-rate dependent mechanics is incompletely understood. Here, we investigate the fibrillar- and mineral-deformation behaviour in a murine model of Cushing’s syndrome, used to understand steroid induced osteoporosis, using synchrotron small- and wide-angle scattering/diffraction combined with in situ tensile testing at three strain rates ranging from 10-4 to 10-1 s-1. We find that the effective fibril- and mineral-modulus and fibrillar-reorientation show no significant increase with strain-rate in osteoporotic bone, but increase significantly in normal (wild-type) bone. By applying a fibril-lamellar two-level structural model of bone matrix deformation to fit the results, we obtain indications that altered collagen-mineral interactions at the nanoscale – along with altered fibrillar orientation distributions – may be the underlying reason for this altered strain-rate sensitivity. Our results suggest that an altered strain-rate sensitivity of the bone matrix in osteoporosis may be one of the contributing factors to reduced mechanical competence in such metabolic bone disorders, and that increasing this sensitivity may improve biomechanical performance

A Sharp Event in the Image a Light Curve of the Double Quasar 0957+561 and Prediction of the 1996 Image B Light Curve

CCD photometry of the gravitational lens system 0957+561A,B in the g and r bands was obtained on alternate nights, weather permitting, from December 1994 through May 1995 using the Double Imaging Spectrograph (DIS) on the Apache Point Observatory (APO) 3.5-meter telescope. The remote observing and fast instrument change capabilities of this facility allowed accumulation of light curves sampled frequently and consistently. The Honeycutt ensemble photometry algorithm was applied to the data set and yielded typical relative photometric errors of approximately 0.01 magnitudes. Image A exhibited a sharp drop of about 0.1 magnitudes in late December 1994; no other strong features were recorded in either image. This event displays none of the expected generic features of a microlensing-induced flux variation and is likely to be intrinsic to the quasar; if so, it should also be seen in the B image with the lensing differential time delay. We give the expected 1996 image B light curves based on two values of the time delay and brightness ratio which have been proposed and debated in the literature. Continued monitoring of the system in the first half of 1996 should easily detect the image B event and thus resolve the time-delay controversy.Comment: submitted to ApJ Letters, 15 pages, uuencoded PostScript with figures included; also available through WWW at http://www.astro.princeton.edu/~library/prep.htm

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Perceptions of and practical experience with the National Surveillance Centre in managing medicines availability amongst users within public healthcare facilities in South Africa : findings and implications

The introduction of the National Surveillance Centre (NSC) has improved the efficiency and effectiveness of managing medicines availability within the public healthcare system in South Africa. However, at present, there is limited data regarding the perceptions among users of the NSC and challenges that need addressing. A descriptive quantitative study was performed among all registered active NSC users between August and November 2022. Overall, 114/169 users responded to a custom-developed, self-administered questionnaire (67.5% response rate). Most respondents used the Stock Visibility System (SVS) National Department of Health (NDoH) (66.7% for medicines and 51.8% for personal protective equipment (PPE) or SVS COVID-19 (64.9% for COVID-19 vaccines) or RxSolution (57.0% manual report or 42.1% application programming interface (API)) for reporting medicines, PPE, and COVID-19 vaccines to the NSC and were confident in the accuracy of the reported data. Most respondents focused on both medicines availability and reporting compliance when accessing the NSC, with the integrated medicines availability dashboard and the COVID-19 vaccine dashboard being the most popular. The respondents believed the NSC allowed ease of access to data and improved data quality to better monitor medicines availability and use. Identified areas for improvement included improving internet connectivity, retraining some users, standardising the dashboards, adding more data points and reports, and expanding user adoption by increasing licence limits. Overall, this study found that the NSC in South Africa provides an effective solution for monitoring and improving medicines availability

Variation in the Microbiota of Ixodes Ticks with Regard to Geography, Species, and Sex

Ixodes scapularis is the principal vector of Lyme disease on the East Coast and in the upper Midwest regions of the United States, yet the tick is also present in the Southeast, where Lyme disease is absent or rare. A closely related species, I. affinis, also carries the pathogen in the South but does not seem to transmit it to humans. In order to better understand the geographic diversity of the tick, we analyzed the microbiota of 104 adult I. scapularis and 13 adult I. affinis ticks captured in 19 locations in South Carolina, North Carolina, Virginia, Connecticut, and New York. Initially, ticks from 4 sites were analyzed by 454 pyrosequencing. Subsequently, ticks from these sites plus 15 others were analyzed by sequencing with an Illumina MiSeq machine. By both analyses, the microbiomes of female ticks were significantly less diverse than those of male ticks. The dissimilarity between tick microbiomes increased with distance between sites, and the state in which a tick was collected could be inferred from its microbiota. The genus Rickettsia was prominent in all locations. Borrelia was also present in most locations and was present at especially high levels in one site in western Virginia. In contrast, members of the family Enterobacteriaceae were very common in North Carolina I. scapularis ticks but uncommon in I. scapularis ticks from other sites and in North Carolina I. affinis ticks. These data suggest substantial variations in the Ixodes microbiota in association with geography, species, and sex

Molecular Characterization of Haemaphysalis Species and a Molecular Genetic Key for the Identification of Haemaphysalis of North America

Haemaphysalis longicornis (Acari: Ixodidae), the Asian longhorned tick, is native to East Asia, but has become established in Australia and New Zealand, and more recently in the United States. In North America, there are other native Haemaphysalis species that share similar morphological characteristics and can be difficult to identify if the specimen is damaged. The goal of this study was to develop a cost-effective and rapid molecular diagnostic assay to differentiate between exotic and native Haemaphysalis species to aid in ongoing surveillance of H. longicornis within the United States and help prevent misidentification. We demonstrated that restriction fragment length polymorphisms (RFLPs) targeting the 16S ribosomal RNA and the cytochrome c oxidase subunit I (COI) can be used to differentiate H. longicornis from the other Haemaphysalis species found in North America. Furthermore, we show that this RFLP assay can be applied to Haemaphysalis species endemic to other regions of the world for the rapid identification of damaged specimens. The work presented in this study can serve as the foundation for region specific PCR-RFLP keys for Haemaphysalis and other tick species and can be further applied to other morphometrically challenging taxa

Stellar Population Trends in S0 Galaxies

We present stellar population age and metallicity trends for a sample of 59 S0 galaxies based on optical SDSS and NIR J & H photometry. When combined with optical g and r passband imaging data from the SDSS archive and stellar population models, we obtain radial age and metallicity trends out to at least 5 effective radii for most of the galaxies in our sample. The sample covers a range in stellar mass and light concentration. We find an average central light-weighted age of ~ 4 Gyr and central metallicity [Z/H] ~ 0.2 dex. Almost all galaxies show a negative metallicity gradient from the center out, with an average value of Delta[Z/H]/Delta(log(r/Re)) = -0.6. An age increase, decrease, and minimal change with radius is observed for 58%, 19%, and 23%, respectively, for a mean age gradient of Delta(age)/Delta(log(r/Re)) = 2.3 Gyr dex^{-1}. For 14 out of 59 galaxies, the light-weighted age of the outer region is greater than 10 Gyr. We find that galaxies with both lower mass and lower concentration have younger light-weighted ages and lower light-weighted metallicities. This mass-metallicity relation extends into the outer regions of our S0 galaxies. Our results are consistent with the formation of S0 galaxies through the transformation of spiral galaxy disks. Determining the structural component that makes up the outer region of galaxies with old outksirts is a necessary step to understand the formation history of S0 galaxies.Comment: accepted to MNRA

Gravitational Lensing

Gravitational lensing has developed into one of the most powerful tools for the analysis of the dark universe. This review summarises the theory of gravitational lensing, its main current applications and representative results achieved so far. It has two parts. In the first, starting from the equation of geodesic deviation, the equations of thin and extended gravitational lensing are derived. In the second, gravitational lensing by stars and planets, galaxies, galaxy clusters and large-scale structures is discussed and summarised.Comment: Invited review article to appear in Classical and Quantum Gravity, 85 pages, 15 figure