The XO Project: Searching for Transiting Extra-solar Planet Candidates

The XO project's first objective is to find hot Jupiters transiting bright stars, i.e. V < 12, by precision differential photometry. Two XO cameras have been operating since September 2003 on the 10,000-foot Haleakala summit on Maui. Each XO camera consists of a 200-mm f/1.8 lens coupled to a 1024x1024 pixel, thinned CCD operated by drift scanning. In its first year of routine operation, XO has observed 6.6% of the sky, within six 7 deg-wide strips scanned from 0 deg to +63 deg of declination and centered at RA=0, 4, 8, 12, 16, and 20 hours. Autonomously operating, XO records 1 billion pixels per clear night, calibrates them photometrically and astrometrically, performs aperture photometry, archives the pixel data and transmits the photometric data to STScI for further analysis. From the first year of operation, the resulting database consists of photometry of 100,000 stars at more than 1000 epochs per star with differential photometric precision better than 1% per epoch. Analysis of the light curves of those stars produces transiting-planet candidates requiring detailed follow up, described elsewhere, culminating in spectroscopy to measure radial-velocity variation in order to differentiate genuine planets from the more numerous impostors, primarily eclipsing binary and multiple stars.Comment: 29 pages, 12 figures, accepted by PASP for Aug 2005 issu

XO-2b: Transiting Hot Jupiter in a Metal-rich Common Proper Motion Binary

We report on a V=11.2 early K dwarf, XO-2 (GSC 03413-00005), that hosts a Rp=0.98+0.03/-0.01 Rjup, Mp=0.57+/-0.06 Mjup transiting extrasolar planet, XO-2b, with an orbital period of 2.615857+/-0.000005 days. XO-2 has high metallicity, [Fe/H]=0.45+/-0.02, high proper motion, mu_tot=157 mas/yr, and has a common proper motion stellar companion with 31" separation. The two stars are nearly identical twins, with very similar spectra and apparent magnitudes. Due to the high metallicity, these early K dwarf stars have a mass and radius close to solar, Ms=0.98+/-0.02 Msolar and Rs=0.97+0.02/-0.01 Rsolar. The high proper motion of XO-2 results from an eccentric orbit (Galactic pericenter, Rper<4 kpc) well confined to the Galactic disk (Zmax~100 pc). In addition, the phase space position of XO-2 is near the Hercules dynamical stream, which points to an origin of XO-2 in the metal-rich, inner Thin Disk and subsequent dynamical scattering into the solar neighborhood. We describe an efficient Markov Chain Monte Carlo algorithm for calculating the Bayesian posterior probability of the system parameters from a transit light curve.Comment: 14 pages, 10 Figures, Accepted in ApJ. Negligible changes to XO-2 system properties. Removed Chi^2 light curve analysis section, and simplified MCMC light curve analysis discussio

A Transiting Planet of a Sun-like Star

A planet transits an 11th magnitude, G1V star in the constellation Corona Borealis. We designate the planet XO-1b, and the star, XO-1, also known as GSC 02041-01657. XO-1 lacks a trigonometric distance; we estimate it to be 200+-20 pc. Of the ten stars currently known to host extrasolar transiting planets, the star XO-1 is the most similar to the Sun in its physical characteristics: its radius is 1.0+-0.08 R_Sun, its mass is 1.0+-0.03 M_Sun, V sini < 3 km/s, and its metallicity [Fe/H] is 0.015+-0.04. The orbital period of the planet XO-1b is 3.941534+-0.000027 days, one of the longer ones known. The planetary mass is 0.90+-0.07 M_Jupiter, which is marginally larger than that of other transiting planets with periods between 3 and 4 days. Both the planetary radius and the inclination are functions of the spectroscopically determined stellar radius. If the stellar radius is 1.0+-0.08 R_Sun, then the planetary radius is 1.30+-0.11 R_Jupiter and the inclination of the orbit is 87.7+-1.2 degrees. We have demonstrated a productive international collaboration between professional and amateur astronomers that was important to distinguishing this planet from many other similar candidates.Comment: 31 pages, 9 figures, accepted for part 1 of Ap

Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe

BACKGROUND: Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. OBJECTIVE: To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. METHODS: Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. RESULTS: K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aβ 42 and t-Tau metrics further improved the AUC to 0.93. CONCLUSION: Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease

Expressed sequence tag analysis of adult human optic nerve for NEIBank: Identification of cell type and tissue markers

<p>Abstract</p> <p>Background</p> <p>The optic nerve is a pure white matter central nervous system (CNS) tract with an isolated blood supply, and is widely used in physiological studies of white matter response to various insults. We examined the gene expression profile of human optic nerve (ON) and, through the NEIBANK online resource, to provide a resource of sequenced verified cDNA clones. An un-normalized cDNA library was constructed from pooled human ON tissues and was used in expressed sequence tag (EST) analysis. Location of an abundant oligodendrocyte marker was examined by immunofluorescence. Quantitative real time polymerase chain reaction (qRT-PCR) and Western analysis were used to compare levels of expression for key calcium channel protein genes and protein product in primate and rodent ON.</p> <p>Results</p> <p>Our analyses revealed a profile similar in many respects to other white matter related tissues, but significantly different from previously available ON cDNA libraries. The previous libraries were found to include specific markers for other eye tissues, suggesting contamination. Immune/inflammatory markers were abundant in the new ON library. The oligodendrocyte marker QKI was abundant at the EST level. Immunofluorescence revealed that this protein is a useful oligodendrocyte cell-type marker in rodent and primate ONs. L-type calcium channel EST abundance was found to be particularly low. A qRT-PCR-based comparative mammalian species analysis reveals that L-type calcium channel expression levels are significantly lower in primate than in rodent ON, which may help account for the class-specific difference in responsiveness to calcium channel blocking agents. Several known eye disease genes are abundantly expressed in ON. Many genes associated with normal axonal function, mRNAs associated with axonal transport, inflammation and neuroprotection are observed.</p> <p>Conclusion</p> <p>We conclude that the new cDNA library is a faithful representation of human ON and EST data provide an initial overview of gene expression patterns in this tissue. The data provide clues for tissue-specific and species-specific properties of human ON that will help in design of therapeutic models.</p

Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT0120183

Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective: To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2–5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results: The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion: CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT01201837

Recent developments in multiple sclerosis therapeutics

Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-β, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought

Investigating Tissue Optical Properties and Texture Descriptors of the Retina in Patients with Multiple Sclerosis

PURPOSE: To assess the differences in texture descriptors and optical properties of retinal tissue layers in patients with multiple sclerosis (MS) and to evaluate their usefulness in the detection of neurodegenerative changes using optical coherence tomography (OCT) image segmentation. PATIENTS AND METHODS: 38 patients with MS were examined using Stratus OCT. The raw macular OCT data were exported and processed using OCTRIMA software. The enrolled eyes were divided into two groups, based on the presence of optic neuritis (ON) in the history (MSON+ group, n = 36 and MSON- group, n = 31). Data of 29 eyes of 24 healthy subjects (H) were used as controls. A total of seven intraretinal layers were segmented and thickness as well as optical parameters such as contrast, fractal dimension, layer index and total reflectance were measured. Mixed-model ANOVA analysis was used for statistical comparisons. RESULTS: Significant thinning of the retinal nerve fiber layer (RNFL), ganglion cell/inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, RNFL+GCL+IPL) was observed between study groups in all comparisons. Significant difference was found in contrast in the RNFL, GCL+IPL, GCC, inner nuclear layer (INL) and outer plexiform layer when comparing MSON+ to the other groups. Higher fractal dimension values were observed in GCL+IPL and INL layers when comparing H vs. MSON+ groups. A significant difference was found in layer index in the RNFL, GCL+IPL and GCC layers in all comparisons. A significant difference was observed in total reflectance in the RNFL, GCL+IPL and GCC layers between the three examination groups. CONCLUSION: Texture and optical properties of the retinal tissue undergo pronounced changes in MS even without optic neuritis. Our results may help to further improve the diagnostic efficacy of OCT in MS and neurodegeneration