Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer's Disease: From Early to Advanced Pathological Stages.

In addition to cognitive decline, individuals affected by Alzheimer's disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD.

Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.

Geomorphology of the Imhotep region on comet 67P/Churyumov-Gerasimenko from OSIRIS observations

Context. Since August 2014, the OSIRIS Narrow Angle Camera (NAC) onboard the Rosetta spacecraft has acquired high spatial resolution images of the nucleus of comet 67P/Churyumov-Gerasimenko, down to the decimeter scale. This paper focuses on the Imhotep region, located on the largest lobe of the nucleus, near the equator. Aims. We map, inventory, and describe the geomorphology of the Imhotep region. We propose and discuss some processes to explain the formation and ongoing evolution of this region. Methods. We used OSIRIS NAC images, gravitational heights and slopes, and digital terrain models to map and measure the morphologies of Imhotep. Results. The Imhotep region presents a wide variety of terrains and morphologies: smooth and rocky terrains, bright areas, linear features, roundish features, and boulders. Gravity processes such as mass wasting and collapse play a significant role in the geomorphological evolution of this region. Cometary processes initiate erosion and are responsible for the formation of degassing conduits that are revealed by elevated roundish features on the surface. We also propose a scenario for the formation and evolution of the Imhotep region; this implies the presence of large primordial voids inside the nucleus, resulting from its formation process.

Spectrophotometric properties of the nucleus of comet 67P/Churyumov-Gerasimenko from the OSIRIS instrument onboard the ROSETTA spacecraft

Context. The Rosetta mission of the European Space Agency has been orbiting the comet 67P/Churyumov-Gerasimenko (67P) since August 2014 and is now in its escort phase. A large complement of scientific experiments designed to complete the most detailed study of a comet ever attempted are onboard Rosetta. Aims. We present results for the photometric and spectrophotometric properties of the nucleus of 67P derived from the OSIRIS imaging system, which consists of a Wide Angle Camera (WAC) and a Narrow Angle Camera (NAC). The observations presented here were performed during July and the beginning of August 2014, during the approach phase, when OSIRIS was mapping the surface of the comet with several filters at different phase angles (1.3 degrees-54 degrees). The resolution reached up to 2.1 m/px. Methods. The OSIRIS images were processed with the OSIRIS standard pipeline, then converted into I/F. radiance factors and corrected for the illumination conditions at each pixel using the Lommel-Seeliger disk law. Color cubes of the surface were produced by stacking registered and illumination-corrected images. Furthermore, photometric analysis was performed both on disk-averaged photometry in several filters and on disk-resolved images acquired with the NAC orange filter, centered at 649 ran, using Hapke modeling. Results. The disk-averaged phase function of the nucleus of 67P shows a strong opposition surge with a G parameter value of -0.13 +/- 0.01 in the HG system formalism and an absolute magnitude H-v(1, 1, 0) = 15.74 +/- 0.02 mag. The integrated spectrophotometry in 20 filters covering the 250-1000 nm wavelength range shows a red spectral behavior, without clear absorption bands except for a potential absorption centered at similar to 290 rim that is possibly due to SO2 ice. The nucleus shows strong phase reddening, with disk-averaged spectral slopes increasing from 11%/( 100 nm) to 16%/(100 nm) in the 1.3 degrees-54 degrees phase angle range. The geometric albedo of the comet is 6.5 +/- 0.2% at 649 nm, with local variations of up to similar to 16% in the Hapi region. From the disk-resolved images we computed the spectral slope together with local spectrophotometry and identified three distinct groups of regions (blue, moderately red, and red). The Hapi region is the brightest, the bluest in term of spectral slope, and the most active surface on the comet. Local spectrophotometry shows an enhancement of the flux in the 700-750 nm that is associated with coma emissions.

Gravitational slopes, geomorphology, and material strengths of the nucleus of comet 67P/Churyumov-Gerasimenko from OSIRIS observations

Aims. We study the link between gravitational slopes and the surface morphology on the nucleus of comet 67P/Churyumov-Gerasimenko and provide constraints on the mechanical properties of the cometary material (tensile, shear, and compressive strengths). Methods. We computed the gravitational slopes for five regions on the nucleus that are representative of the different morphologies observed on the surface (Imhotep, Ash, Seth, Hathor, and Agilkia), using two shape models computed from OSIRIS images by the stereo-photoclinometry (SPC) and stereo-photogrammetry (SPG) techniques. We estimated the tensile, shear, and compressive strengths using different surface morphologies (overhangs, collapsed structures, boulders, cliffs, and Philae's footprint) and mechanical considerations. Results. The different regions show a similar general pattern in terms of the relation between gravitational slopes and terrain morphology: i) low-slope terrains (0-20 degrees) are covered by a fine material and contain a few large (>10 m) and isolated boulders; ii) intermediate-slope terrains (20-45 degrees) are mainly fallen consolidated materials and debris fields, with numerous intermediate-size boulders from <1m to 10m for the majority of them; and iii) high-slope terrains (45-90 degrees) are cliffs that expose a consolidated material and do not show boulders or fine materials. The best range for the tensile strength of overhangs is 3-15 Pa (upper limit of 150 Pa), 4-30 Pa for the shear strength of fine surface materials and boulders, and 30-150 Pa for the compressive strength of overhangs (upper limit of 1500 Pa). The strength-to-gravity ratio is similar for 67P and weak rocks on Earth. As a result of the low compressive strength, the interior of the nucleus may have been compressed sufficiently to initiate diagenesis, which could have contributed to the formation of layers. Our value for the tensile strength is comparable to that of dust aggregates formed by gravitational instability and tends to favor a formation of comets by the accrection of pebbles at low velocities.

Temporal morphological changes in the Imhotep region of comet 67P/Churyumov-Gerasimenko

Aims. We report on the first major temporal morphological changes observed on the surface of the nucleus of comet 67P/Churyumov-Gerasimenko in the smooth terrains of the Imhotep region. Methods. We used images of the OSIRIS cameras onboard Rosetta to follow the temporal changes from 24 May 2015 to 11 July 2015. Results. The morphological changes observed on the surface are visible in the form of roundish features that are growing in size from a given location in a preferential direction at a rate of 5.6-8.1 x 10(-5) m s(-1) during the observational period. The location where the changes started and the contours of the expanding features are bluer than the surroundings, which suggests that ices (H2O and/or CO2) are exposed on the surface. However, sublimation of ices alone is not sufficient to explain the observed expanding features. No significant variations in the dust activity pattern are observed during the period of changes.

Large-scale dust jets in the coma of 67P/Churyumov-Gerasimenko as seen by the OSIRIS instrument onboard Rosetta

Context. During the most recent perihelion passage in 2009 of comet 67P/Churyumov-Gerasimenko (67P), ground-based observations showed an anisotropic dust coma where jet-like features were detected at similar to 1.3 AU from the Sun. The current perihelion passage is exceptional as the Rosetta spacecraft is monitoring the nucleus activity since March 2014, when a clear dust coma was already surrounding the nucleus at 4.3 AU from the Sun. Subsequently, the OSIRIS camera also witnessed an outburst in activity between April 27 and 30, and since mid-July, the dust coma at rh similar to 3.7-3.6 AU preperihelion is clearly non-isotropic, pointing to the existence of dust jet-like features. Aims. We aim to ascertain on the nucleus surface the origin of the dust jet-like features detected as early as in mid-July 2014. This will help to establish how the localized comet nucleus activity compares with that seen in previous apparitions and will also help following its evolution as the comet approaches its perihelion, at which phase most of the jets were detected from ground-based observations. Determining these areas also allows locating them in regions on the nucleus with spectroscopic or geomorphological distinct characteristics. Methods. Three series of dust images of comet 67P obtained with the Wide Angle Camera (WAC) of the OSIRIS instrument onboard the Rosetta spacecraft were processed with different enhancement techniques. This was made to clearly show the existence of jet-like features in the dust coma, whose appearance toward the observer changed as a result of the rotation of the comet nucleus and of the changing observing geometry from the spacecraft. The position angles of these features in the coma together with information on the observing geometry, nucleus shape, and rotation, allowed us to determine the most likely locations on the nucleus surface where the jets originate from. Results. Geometrical tracing of jet sources indicates that the activity of the nucleus of 67P gave rise during July and August 2014 to large-scale jet-like features from the Hapi, Hathor, Anuket, and Aten regions, confirming that active regions may be present on the nucleus localized at 60. northern latitude as deduced from previous comet apparitions. There are also hints that large-scale jets observed from the ground are possibly composed, at their place of origin on the nucleus surface, of numerous small-scale features.

Two independent and primitive envelopes of the bilobate nucleus of comet 67P

The factors shaping cometary nuclei are still largely unknown, but could be the result of concurrent effects of evolutionary(1,2) and primordial processes(3,4). The peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of the fusion of two objects that were once separate or the result of a localized excavation by outgassing at the interface between the two lobes(5). Here we report that the comet's major lobe is enveloped by a nearly continuous set of strata, up to 650 metres thick, which are independent of an analogous stratified envelope on the minor lobe. Gravity vectors computed for the two lobes separately are closer to perpendicular to the strata than those calculated for the entire nucleus and adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov-Gerasimenko is an accreted body of two distinct objects with 'onion-like' stratification, which formed before they merged. We conclude that gentle, low-velocity collisions occurred between two fully formed kilometre-sized cometesimals in the early stages of the Solar System. The notable structural similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate that the early-forming cometesimals experienced similar primordial stratified accretion, even though they formed independently.

The SCITEAS experiment: Optical characterizations of sublimating icy planetary analogues

We have designed and built a laboratory facility to investigate the spectro-photometric and morphologic properties of different types of ice-bearing planetary surface analogs and follow their evolution upon exposure to a low pressure and low temperature environment. The results obtained with this experiment are used to verify and improve our interpretations of current optical remote-sensing datasets. They also provide valuable information for the development and operation of future optical instruments. The Simulation Chamber for Imaging the Temporal Evolution of Analogue Samples (SCITEAS) is a small thermal vacuum chamber equipped with a variety of ports and feedthroughs that permit both in-situ and remote characterizations as well as interacting with the sample. A large quartz window located directly above the sample is used to observe its surface from outside with a set of visible and near-infrared cameras. The sample holder can be easily and quickly inserted and removed from the chamber and is compatible with the other measurement facilities of the Laboratory for Outflow Studies of Sublimating Materials (LOSSy) at the University of Bern. We report here on the results of two of the first experiments performed in the SCITEAS chamber. In the first experiment, fine-grained water ice mixed with dark organic and mineral matter was left to sublime in vacuum and at low temperature, simulating the evolution of the surface of a comet nucleus approaching the Sun. We observed and characterized the formation and evolution of a crust of refractory organic and mineral matter at the surface of the sample and linked the evolution of its structure and texture to its spectro-photometric properties. In the second experiment, a frozen soil was prepared by freezing a mixture of smectite mineral and water. The sample was then left to sublime for 6 h to simulate the loss of volatiles from icy soil at high latitudes on Mars. Colour images were produced using the definitions of the filters foreseen for the CaSSIS imager of the Exomars/TGO mission in order to prepare future science operations.

Redistribution of particles across the nucleus of comet 67P/Churyumov-Gerasimenko

Context. We present an investigation of the surface properties of areas on the nucleus of comet 67P/Churyumov-Gerasimenko. Aims. We aim to show that transport of material from one part of the cometary nucleus to another is a significant mechanism that influences the appearance of the nucleus and the surface thermal properties. Methods. We used data from the OSIRIS imaging system onboard the Rosetta spacecraft to identify surface features on the nucleus that can be produced by various transport mechanisms. We used simple calculations based on previous works to establish the plausibility of dust transport from one part of the nucleus to another. Results. We show by observation and modeling that "airfall" as a consequence of non-escaping large particles emitted from the neck region of the nucleus is a plausible explanation for the smooth thin deposits in the northern hemisphere of the nucleus. The consequences are also discussed. We also present observations of aeolian ripples and ventifacts. We show by numerical modeling that a type of saltation is plausible even under the rarified gas densities seen at the surface of the nucleus. However, interparticle cohesive forces present difficulties for this model, and an alternative mechanism for the initiation of reptation and creep may result from the airfall mechanism. The requirements on gas density and other parameters of this alternative make it a more attractive explanation for the observations. The uncertainties and implications are discussed.

The morphological diversity of comet 67P/Churyumov-Gerasimenko

Images of comet 67P/Churyumov-Gerasimenko acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) imaging system onboard the European Space Agency's Rosetta spacecraft at scales of better than 0.8 meter per pixel show a wide variety of different structures and textures. The data show the importance of airfall, surface dust transport, mass wasting, and insolation weathering for cometary surface evolution, and they offer some support for subsurface fluidization models and mass loss through the ejection of large chunks of material.

VIS-NIR reflectance of water ice/regolith analogue mixtures and implications for the detectability of ice mixed within planetary regoliths

Permanently shadowed regions at the poles of the Moon and Mercury have been pointed out as candidates for hosting water ice at their surface. We have measured in the laboratory the visible and near infrared spectral range (VIS-NIR) bidirectional reflectance of intimate mixtures of water ice and the JSC-1AF lunar simulant for different ice concentrations, particle sizes, and measurement geometries. The nonlinearity between the measured reflectance and the amount of ice in the mixture can be reproduced to some extent by the mixing formulas of standard reflectance models, in particular, those of Hapke and Hiroi, which are tested here. Estimating ice concentrations from reflectance data without knowledge of the mixing coefficientsstrongly dependent on the size/shape of the grainscan result in large errors. According to our results, it is possible that considerable amounts of water ice might be intimately mixed in the regolith of the Moon and Mercury without producing noticeable photometric signatures.

A Noachian source region for the "Black Beauty" meteorite, and a source lithology for Mars surface hydrated dust?

The Martian surface is covered by a fine-layer of oxidized dust responsible for its red color in the visible spectral range (Bibring et al., 2006; Morris et al., 2006). In the near infrared, the strongest spectral feature is located between 2.6 and 3.6 mu m and is ubiquitously observed on the planet (Jouglet et al., 2007; Milliken et al., 2007). Although this absorption has been studied for many decades, its exact attribution and its geological and climatic implications remain debated. We present new lines of evidence from laboratory experiments, orbital and landed missions data, and characterization of the unique Martian meteorite NWA 7533, all converging toward the prominent role of hydroxylated ferric minerals. Martian breccias (so-called "Black Beauty" meteorite NWA7034 and its paired stones NWA7533 and NWA 7455) are unique pieces of the Martian surface that display abundant evidence of aqueous alteration that occurred on their parent planet (Agee et al., 2013). These dark stones are also unique in the fact that they arose from a near surface level in the Noachian southern hemisphere (Humayun et al., 2013). We used IR spectroscopy, Fe-XANES and petrography to identify the mineral hosts of hydrogen in NWA 7533 and compare them with observations of the Martian surface and results of laboratory experiments. The spectrum of NWA 7533 does not show mafic mineral absorptions, making its definite identification difficult through NIR remote sensing mapping. However, its spectra are virtually consistent with a large fraction of the Martian highlands. Abundant NWA 7034/7533 (and paired samples) lithologies might abound on Mars and might play a role in the dust production mechanism. (C) 2015 Elsevier B.V. All rights reserved.

Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa.

BACKGROUND Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.