1,006 research outputs found
Exploring the Universe with Metal-Poor Stars
The early chemical evolution of the Galaxy and the Universe is vital to our
understanding of a host of astrophysical phenomena. Since the most metal-poor
Galactic stars (with metallicities down to [Fe/H]\sim-5.5) are relics from the
high-redshift Universe, they probe the chemical and dynamical conditions of the
Milky Way and the origin and evolution of the elements through nucleosynthesis.
They also provide constraints on the nature of the first stars, their
associated supernovae and initial mass function, and early star and galaxy
formation. The Milky Way's dwarf satellites contain a large fraction (~30%) of
the known most metal-poor stars that have chemical abundances that closely
resemble those of equivalent halo stars. This suggests that chemical evolution
may be universal, at least at early times, and that it is driven by massive,
energetic SNe. Some of these surviving, ultra-faint systems may show the
signature of just one such PopIII star; they may even be surviving first
galaxies. Early analogs of the surviving dwarfs may thus have played an
important role in the assembly of the old Galactic halo whose formation can now
be studied with stellar chemistry. Following the cosmic evolution of small
halos in simulations of structure formation enables tracing the cosmological
origin of the most metal-poor stars in the halo and dwarf galaxies. Together
with future observations and additional modeling, many of these issues,
including the reionization history of the Milky Way, may be constrained this
way. The chapter concludes with an outlook about upcoming observational
challenges and ways forward is to use metal-poor stars to constrain theoretical
studies.Comment: 34 pages, 11 figures. Book chapter to appear in "The First Galaxies -
Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V.
Bromm, B. Mobasher, T. Wiklin
Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity
While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al
A realtime observatory for laboratory simulation of planetary flows
Motivated by the large-scale circulation of the atmosphere and ocean, we develop a system that uses
observations from a laboratory analog to constrain, in real time, a numerical simulation of the laboratory
flow. This system provides a tool to rapidly prototype new methods for state and parameter
estimation, and facilitates the study of prediction, predictability, and transport of geophysical fluids
where observations or numerical simulations would not independently suffice.
A computer vision system is used to extract measurements of the physical simulation. Observations
are used to constrain the model-state of the MIT General Circulation Model in a probabilistic, ensemble based assimilation approach. Using a combination of parallelism, domain decomposition and an efficient
scheme to select ensembles of model-states, we show that estimates that effectively track the fluid state
can be produced. To the best of our knowledge this is the first such observatory for laboratory
analogs of planetary circulation that functions in real time.National Science Foundation (U.S.) (CNS-0540259)National Science Foundation (U.S.) (grant CNS-0540248
Human Wavelength Discrimination of Monochromatic Light Explained by Optimal Wavelength Decoding of Light of Unknown Intensity
We show that human ability to discriminate the wavelength of monochromatic light
can be understood as maximum likelihood decoding of the cone absorptions, with a
signal processing efficiency that is independent of the wavelength. This work is
built on the framework of ideal observer analysis of visual discrimination used
in many previous works. A distinctive aspect of our work is that we highlight a
perceptual confound that observers should confuse a change in input light
wavelength with a change in input intensity. Hence a simple ideal observer model
which assumes that an observer has a full knowledge of input intensity should
over-estimate human ability in discriminating wavelengths of two inputs of
unequal intensity. This confound also makes it difficult to consistently measure
human ability in wavelength discrimination by asking observers to distinguish
two input colors while matching their brightness. We argue that the best
experimental method for reliable measurement of discrimination thresholds is the
one of Pokorny and Smith, in which observers only need to distinguish two
inputs, regardless of whether they differ in hue or brightness. We
mathematically formulate wavelength discrimination under this
wavelength-intensity confound and show a good agreement between our theoretical
prediction and the behavioral data. Our analysis explains why the discrimination
threshold varies with the input wavelength, and shows how sensitively the
threshold depends on the relative densities of the three types of cones in the
retina (and in particular predict discriminations in dichromats). Our
mathematical formulation and solution can be applied to general problems of
sensory discrimination when there is a perceptual confound from other sensory
feature dimensions
Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?
Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure
MDM2 Promoter SNP344T>A (rs1196333) Status Does Not Affect Cancer Risk
The MDM2 proto-oncogene plays a key role in central cellular processes like growth control and apoptosis, and the gene locus is frequently amplified in sarcomas. Two polymorphisms located in the MDM2 promoter P2 have been shown to affect cancer risk. One of these polymorphisms (SNP309T>G; rs2279744) facilitates Sp1 transcription factor binding to the promoter and is associated with increased cancer risk. In contrast, SNP285G>C (rs117039649), located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk. Thus, fine tuning of MDM2 expression has proven to be of significant importance with respect to tumorigenesis. We assessed the potential functional effects of a third MDM2 promoter P2 polymorphism (SNP344T>A; rs1196333) located on the SNP309T allele. While in silico analyses indicated SNP344A to modulate TFAP2A, SPIB and AP1 transcription factor binding, we found no effect of SNP344 status on MDM2 expression levels. Assessing the frequency of SNP344A in healthy Caucasians (n = 2,954) and patients suffering from ovarian (n = 1,927), breast (n = 1,271), endometrial (n = 895) or prostatic cancer (n = 641), we detected no significant difference in the distribution of this polymorphism between any of these cancer forms and healthy controls (6.1% in healthy controls, and 4.9%, 5.0%, 5.4% and 7.2% in the cancer groups, respectively). In conclusion, our findings provide no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk
Timing of crystallization of the lunar magma ocean constrained by the oldest zircon
The Moon is thought to have formed through the consolidationof debris from the collision of a Mars-sized body with the Earthmore than 4,500 million years ago. The primitive Moon wascovered with a thick layer of melt known as the lunar magmaocean1, the crystallization of which resulted in the Moon?ssurface as it is observed today. There is considerable debate,however, over the precise timing and duration of the processof magma ocean crystallization. Here we date a zircon fromlunar breccias to an age of 4,4176 million years. This dateprovides a precise younger age limit for the solidification ofthe lunar magma ocean. We propose a model that suggestsan exponential rate of lunar crystallization, based on acombination of this oldest known lunar zircon and the age of theMoon-forming giant impact. We conclude that the formationof the Moon?s anorthositic crust followed the solidification of80?85% of the original melt, within about 100 million years ofthe collision. The existence of younger zircons2 is indicative ofthe continued solidification of a small percentage of melt for anextra 200?400 million years
Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature
<p>Abstract</p> <p>Background</p> <p>Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease.</p> <p>Case presentation</p> <p>A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non-bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up.</p> <p>Conclusion</p> <p>This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.</p
Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease
Parkinson's disease (PD) is a neurodegenerative disorder marked by the selective degeneration of dopaminergic neurons in the nigrostriatal pathway. Several lines of evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested that alterations in sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, we used a toxin-induced mouse model of PD and measured levels of nine sterol intermediates. We found that lanosterol is significantly (∼50%) and specifically reduced in the nigrostriatal regions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, indicative of altered lanosterol metabolism during PD pathogenesis. Remarkably, exogenous addition of lanosterol rescued dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in culture. Furthermore, we observed a marked redistribution of lanosterol synthase from the endoplasmic reticulum to mitochondria in dopaminergic neurons exposed to MPP+, suggesting that lanosterol might exert its survival effect by regulating mitochondrial function. Consistent with this model, we find that lanosterol induces mild depolarization of mitochondria and promotes autophagy. Collectively, our results highlight a novel sterol-based neuroprotective mechanism with direct relevance to PD
Rituximab retherapy in patients with relapsed aggressive B cell and mantle cell lymphoma
Neither effective salvage regimens nor the outcome and response to retherapy with rituximab containing chemotherapy have been defined for rituximab pre-treated patients with relapsing aggressive lymphoma. We report here a single-centre retrospective outcome analysis of second-line immunochemotherapy with rituximab. In 28 patients with relapsed or refractory diffuse large B cell lymphomas, first-line immunochemotherapy had induced objective responses in 18 patients. Nine of 28 patients responded to rituximab containing salvage therapy, leading to a median overall survival of 243 days after start of second immunochemotherapy. Long-term disease free survivors (1,260 and 949 days) were restricted to the group of twelve patients that had received allogeneic stem cell transplantation as consolidation therapy. In 21 patients with relapsed mantle cell lymphomas (MCL), 19 patients had reached remissions with first-line therapy. Of those, 16 patients experienced responses to salvage therapy with a median overall survival of 226 days. Noteworthy, none of patients with initial non-responding disease reached a remission with second immunochemotherapy. Seven patients with MCL stayed free from progression after high-dose therapy with autologous or allogeneic stem cell transplantation in two and five cases, respectively. In summary, responses to repeated immunotherapy with rituximab were observed in approximately one third and two thirds of initially responding patients with aggressive B cell lymphoma and mantle cell lymphoma, respectively, but not in primarily refractory disease. Lasting remissions were achieved only by high-dose chemotherapy with stem cell transplantation
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