For more than a decade, the CheMin X-ray diffraction instrument on the Mars Science Laboratory rover, Curiosity, has been returning definitive and quantitative mineralogical and mineral–chemistry ...data from ~3.5-billion-year-old (Ga) sediments in Gale crater, Mars. To date, 40 drilled rock samples and three scooped soil samples have been analyzed during the rover’s 30+ km transit. These samples document the mineralogy of over 800 m of flat-lying fluvial, lacustrine, and aeolian sedimentary rocks that comprise the lower strata of the central mound of Gale crater (Aeolis Mons, informally known as Mt. Sharp) and the surrounding plains (Aeolis Palus, informally known as the Bradbury Rise). The principal mineralogy of the sedimentary rocks is of basaltic composition, with evidence of post-depositional diagenetic overprinting. The rocks in many cases preserve much of their primary mineralogy and sedimentary features, suggesting that they were never strongly heated or deformed. Using aeolian soil composition as a proxy for the composition of the deposited and lithified sediment, it appears that, in many cases, the diagenetic changes observed are principally isochemical. Exceptions to this trend include secondary nodules, calcium sulfate veining, and rare Si-rich alteration halos. A surprising and yet poorly understood observation is that nearly all of the ~3.5 Ga sedimentary rocks analyzed to date contain 15–70 wt.% of X-ray amorphous material. Overall, this >800 m section of sedimentary rock explored in lower Mt. Sharp documents a perennial shallow lake environment grading upward into alternating lacustrine/fluvial and aeolian environments, many of which would have been habitable to microbial life.
FTY720 is the first of a new drug class: sphingosine-1-phosphate receptor agonist. Its effect relates to the modulation of lymphocytes trafficking from blood and peripheral tissues to lymph nodes. ...This is the first study to evaluate the efficacy and safety of FTY720 in de novo renal transplantation.
This phase 2a, multicenter, open-label, dose-finding study compared FTY720 (0.25, 0.5, 1.0, or 2.5 mg) with mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids. Patients (n=208) received FTY720 (n=167) or MMF (n=41) for 3 months followed by a 3-month follow-up.
The incidence of biopsy-confirmed acute rejection at month 3 was 23.3%, 34.9%, 17.5%, and 9.8%, respectively, with FTY720 at doses of 0.25, 0.5, 1.0, and 2.5 mg, versus 17.1% with MMF. The incidence for the composite endpoint (biopsy-confirmed acute rejection, graft loss, or death) was lowest with FTY720 at a dose of 2.5 mg at month 3 (14.6%) compared with FTY720 at doses of 0.25 mg (25.6%), 0.5 mg (34.9%), and 1.0 mg (17.5%), and MMF (19.5%). Safety was comparable between FTY720 and MMF group. The main difference in tolerability was a mild and transient reduction in heart rate. A decrease in peripheral lymphocytes occurred in patients receiving FTY720, as expected from the mode of action, and this was reversible after treatment cessation.
FTY720 at 2.5 mg was found to be as effective as MMF in combination with cyclosporine for the prevention of acute rejection after renal transplantation. FTY720 was well tolerated and not associated with the side effects commonly observed with immunosuppressant therapies.
Abstract It is widely accepted that hypoperfusion and changes in capillary morphology are involved in the etiopathogenesis of Alzheimer's disease (AD). This is difficult to reconcile with the ...hyperperfusion observed in young high-risk subjects. Differences in the way cerebral blood flow (CBF) is coupled with the local metabolic needs during different phases of the disease can explain this apparent paradox. This review describes this coupling in terms of a model of cerebral oxygen availability that takes into consideration the heterogeneity of capillary blood flow patterns. The model predicts that moderate increases in heterogeneity requires elevated CBF in order to maintain adequate oxygenation. However, with progressive increases in heterogeneity, the resulting low tissue oxygen tension will require a suppression of CBF in order to maintain tissue metabolism. The observed biphasic nature of CBF responses in preclinical AD and AD is therefore consistent with progressive disturbances of capillary flow patterns. Salient features of the model are discussed in the context of AD pathology along with potential sources of increased capillary flow heterogeneity.
The geographic distribution throughout Europe of each of 32 chloroplast DNA variants belonging to eight white oak species sampled from 2613 populations is presented. Clear-cut geographic patterns ...were revealed by the survey. These distributions, together with the available palynological information, were used to infer colonisation routes out of the glacial period refugia. In western Europe in particular, movements out of the Iberian and the Italian Peninsulas can be clearly identified. Separate refugia are also present in eastern Balkans, whereas further west in this peninsula similarities with Italy were evident. Movements resulting in the exchange of haplotypes between refugia both during the present interglacial and probably also during earlier glacial cycles were therefore inferred. The consequences of these past exchanges is that phylogenetically divergent haplotypes have sometimes followed very similar colonisation routes, limiting somewhat the phylogeographic structure. Cases of geographic disjunction in the present-day distribution of haplotypes are also apparent and could have been induced by the existence of rapid climatic changes at the end of the glacial period (specifically the Younger Dryas cold period), which resulted in range restriction following an early warm period during which oak first expanded from its primary refugia. This cold phase was followed by a new period of expansion at the outset of the Holocene, involving in some cases ‘secondary’ refugia. It is expected that these short climate oscillations would have led to a partial reshuffling of haplotype distribution. Early association between haplotypes and oak species are also suggested by the data, although extensive introgression among species has ultimately largely blurred the pattern. This implies that colonisation routes may have been initially constrained by the ecological characteristics of the species hosting each chloroplast variant. We suggest for instance that two oak species distributed in the north of the Iberian Peninsula (Quercus petraea and Q. pubescens) are recent post-glacial immigrants there. When considered together, conclusions on the location of glacial period refugia and the colonisation routes derived from molecular information and fossil pollen data appear to be both largely compatible and complementary.
A consortium of 16 laboratories have studied chloroplast DNA (cpDNA) variation in European white oaks. A common strategy for molecular screening, based on restriction analysis of four PCR-amplified ...cpDNA fragments, was used to allow comparison among the different laboratories. A total of 2613 oak populations (12,214 individual trees from eight species) were sampled from 37 countries, and analysed with the four fragments. They belong to eight related oak species: Quercus robur, Q. petraea, Q. pubescens, Q. frainetto, Q. faginea, Q. pyrenaica, Q. canariensis and Q. macranthera. During this survey, 45 chloroplast variants were detected and are described together with their phylogenetic relationships, but several of these haplotypes were pooled when there were some risks of confusion across laboratories during the survey, and finally 32 remained that were mapped and used in diversity analyses. A strong phylogeographic structure is apparent from the data, where related haplotypes have broadly similar geographic distributions. In total, six cpDNA lineages are identified, which have distinct geographic distributions, mainly along a longitudinal gradient. Most haplotypes found in northern Europe are also present in the south, whereas the converse is not true, suggesting that the majority of mutations observed were generated prior to postglacial recolonisation, corroborating the conclusions of earlier studies. The description of a new western European lineage constitutes a major finding, compared to earlier phylogenetic treatments. Although the eight oak species studied systematically share cpDNA variants when in sympatry, they partition cpDNA diversity differently, as a consequence of their different ecology and life history attributes. Regional differences in levels of differentiation also exist (either species-specific or general); these seem to be related to the intensity of past and present management of the forests across Europe but also to the level of fragmentation of the range within these regions.
This paper investigates the applicability of currently available analytical, empirical and numerical heat flow models for interpreting thermal response tests (TRT) of quadratic cross section precast ...pile heat exchangers. A 3D finite element model (FEM) is utilised for interpreting five TRTs by inverse modelling. The calibrated estimates of soil and concrete thermal conductivity are consistent with independent laboratory measurements. Due to the computational cost of inverting the 3D model, simpler models are utilised in additional calibrations. Interpretations based on semi-empirical pile G-functions yield soil thermal conductivity estimates statistically similar to those obtained from the 3D FEM inverse modelling, given minimum testing times of 60 h. Reliable estimates of pile thermal resistance can only be obtained from type curves computed with 3D FEM models. This study highlights the potential of applying TRTs for sizing quadratic, precast pile heat exchanger foundations.
•TRTs on precast quadratic energy piles are interpreted using 3D numerical analysis.•Thermal conductivity from inverse analysis closely matches laboratory test results.•Simpler models without concrete capacity or pile length are inappropriate.•Semi-empirical G-functions give acceptable thermal conductivity but not resistance.•Minimum recommended TRT duration for 30 cm square piles is 60 h.
Summary
The pattern of weight loss and regain, termed “weight cycling,” is common in overweight individuals. It is unclear whether the well‐established benefits of weight loss persist following ...weight regain or whether weight cycling is harmful. Human studies of weight cycling have conflicting results reflecting limitations of the observational designs of these studies. By controlling the macronutrient content of diets in animal studies, weight cycling can be studied in a highly controlled manner, thereby overcoming the limitations of human studies. We conducted a systematic review and meta‐analysis of animal studies which assessed the health consequences of weight cycling. Studies were classified into those which compared weight cycling to lifelong obesity and those which compared weight cycling to later onset obesity. There were no differences in health outcomes between weight cycled animals and those with lifelong obesity, highlighting that weight regain reverses health benefits achieved by weight loss. In comparison with animals with later onset obesity, weight cycled animals had higher fasting glucose levels and more impaired glucose tolerance following weight regain. Our review of animal studies suggests that health benefits of diet‐induced weight loss do not persist after weight regain and weight cycling results in adverse metabolic outcomes.
Because of the northern location of Denmark, the length of the day over the year varies from 7 to 17.5 hours. Experimental and clinical results suggest that the development of myopia may be related ...to ambient light exposure. The purpose of current study was to investigate whether axial eye growth, myopia progression, or corneal power change in Danish myopic children varies with the length of the day.
Cross-sectional study.
Two hundred thirty-five children 8 to 14 years of age found to have myopia during screening for a clinical trial (ClinicalTrial.gov identifier, NCT00263471; accessed December 6, 2005). All children found to have any value of spherical equivalent that was myopic (<0 diopters D) at the first of 2 visits were included.
Cycloplegic refraction was measured using an autorefractor, axial eye length, and corneal power using an automatic combined noncontact partial coherence interferometer and keratometer. The accumulated number of daylight hours during the measurement period was calculated for each participant using an astronomical table.
Change over 6 months in axial length, refraction, and corneal power.
Accumulated hours of daylight ranged from 1660 to 2804 hours. Significant correlations were found between hours of daylight and eye elongation (P = 0.00), myopia progression (P = 0.01), and corneal power change (P = 0.00). In children with an average of 2782 ± 19 hours of daylight, axial eye growth was 0.12 ± 0.09 mm, myopia progression was 0.26 ± 0.27 D, and corneal power change was 0.05 ± 0.10 D per 6 months, whereas in children with an average of 1681 ± 24 hours of daylight, axial eye growth was 0.19 ± 0.10 mm, myopia progression was 0.32 ± 0.27 D, and corneal power change was -0.04 ± 0.08 D per 6 months.
Eye elongation and myopia progression seem to decrease in periods with longer days and to increase in periods with shorter days. Children should be encouraged to spend more time outside during daytime to prevent myopia.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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