3,617 research outputs found
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Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.
HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer's disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181 and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181 to characterize HAND
ChainQueen: A Real-Time Differentiable Physical Simulator for Soft Robotics
Physical simulators have been widely used in robot planning and control.
Among them, differentiable simulators are particularly favored, as they can be
incorporated into gradient-based optimization algorithms that are efficient in
solving inverse problems such as optimal control and motion planning.
Simulating deformable objects is, however, more challenging compared to rigid
body dynamics. The underlying physical laws of deformable objects are more
complex, and the resulting systems have orders of magnitude more degrees of
freedom and therefore they are significantly more computationally expensive to
simulate. Computing gradients with respect to physical design or controller
parameters is typically even more computationally challenging. In this paper,
we propose a real-time, differentiable hybrid Lagrangian-Eulerian physical
simulator for deformable objects, ChainQueen, based on the Moving Least Squares
Material Point Method (MLS-MPM). MLS-MPM can simulate deformable objects
including contact and can be seamlessly incorporated into inference, control
and co-design systems. We demonstrate that our simulator achieves high
precision in both forward simulation and backward gradient computation. We have
successfully employed it in a diverse set of control tasks for soft robots,
including problems with nearly 3,000 decision variables.Comment: In submission to ICRA 2019. Supplemental Video:
https://www.youtube.com/watch?v=4IWD4iGIsB4 Project Page:
https://github.com/yuanming-hu/ChainQuee
Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease.
How stage-specific enhancer dynamics modulate gene expression patterns essential for organ development, homeostasis and disease is not well understood. Here, we addressed this question by mapping chromatin occupancy of GATA4--a master cardiac transcription factor--in heart development and disease. We find that GATA4 binds and participates in establishing active chromatin regions by stimulating H3K27ac deposition, which facilitates GATA4-driven gene expression. GATA4 chromatin occupancy changes markedly between fetal and adult heart, with a limited binding sites overlap. Cardiac stress restored GATA4 occupancy to a subset of fetal sites, but many stress-associated GATA4 binding sites localized to loci not occupied by GATA4 during normal heart development. Collectively, our data show that dynamic, context-specific transcription factors occupancy underlies stage-specific events in development, homeostasis and disease
Ribbons on the CBR Sky: A Powerful Test of a Baryon Symmetric Universe
If the Universe consists of domains of matter and antimatter, annihilations
at domain interfaces leave a distinctive imprint on the Cosmic Background
Radiation (CBR) sky. The signature is anisotropies in the form of long, thin
ribbons of width , separated by angle where L is the characteristic domain size, and
y-distortion parameter . Such a pattern could potentially be
detected by the high-resolution CBR anisotropy experiments planned for the next
decade, and such experiments may finally settle the question of whether or not
our Hubble volume is baryon symmetric.Comment: LaTeX, 10 pages, 4 figures in epsf. Revised version corrects a couple
of relevant mistake
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Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration.
Recessive Stargardt disease (STGD1) is an inherited blinding disorder caused by mutations in the Abca4 gene. ABCA4 is a flippase in photoreceptor outer segments (OS) that translocates retinaldehyde conjugated to phosphatidylethanolamine across OS disc membranes. Loss of ABCA4 in Abca4 -/- mice and STGD1 patients causes buildup of lipofuscin in the retinal pigment epithelium (RPE) and degeneration of photoreceptors, leading to blindness. No effective treatment currently exists for STGD1. Here we show by several approaches that ABCA4 is additionally expressed in RPE cells. (i) By in situ hybridization analysis and by RNA-sequencing analysis, we show the Abca4 mRNA is expressed in human and mouse RPE cells. (ii) By quantitative immunoblotting, we show that the level of ABCA4 protein in homogenates of wild-type mouse RPE is about 1% of the level in neural retina homogenates. (iii) ABCA4 immunofluorescence is present in RPE cells of wild-type and Mertk -/- but not Abca4 -/- mouse retina sections, where it colocalizes with endolysosomal proteins. To elucidate the role of ABCA4 in RPE cells, we generated a line of genetically modified mice that express ABCA4 in RPE cells but not in photoreceptors. Mice from this line on the Abca4 -/- background showed partial rescue of photoreceptor degeneration and decreased lipofuscin accumulation compared with nontransgenic Abca4 -/- mice. We propose that ABCA4 functions to recycle retinaldehyde released during proteolysis of rhodopsin in RPE endolysosomes following daily phagocytosis of distal photoreceptor OS. ABCA4 deficiency in the RPE may play a role in the pathogenesis of STGD1
CSF Cytokines in Aging, Multiple Sclerosis, and Dementia
Inflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We collected cerebrospinal fluid (CSF) from 105 healthy control subjects representing a wide age range (23–86), and analyzed levels of cytokines associated innate immunity (TNF-α) and different T-helper subtypes: interferon–gamma induced protein 10 (IP-10) for Th1, interleukin-10 (IL-10) for Th2, and interleukin 8 (IL-8/CXCL8) for Th17. We show that CSF levels of TNF-α, IP-10, and IL-8 all increased linearly with age, but levels of IL-10 demonstrated a U-shaped relationship with age. We further found greater age-related increases in TNF-α, IL-10, and IL-8 relative to increases in IP-10 levels, consistent with a shift from Th1 to other inflammatory phenotypes. Finally, when we analyzed the same four cytokines in people with neurological disorders, we found that MS and AD, but not PD or dementia with Lewy bodies, further accentuated the age-related shift from Th1- to non-Th1-related cytokines. We propose that CSF cytokine levels represent powerful surrogates of brain inflammation and aging, and some, but not all, neurological disorders accelerate the shift away from Th1 phenotypes
Ar39 Detection at the 10\u3csup\u3e-\u3c/sup\u3e16 Isotopic Abundance Level with Atom Trap Trace Analysis
Atom trap trace analysis, a laser-based atom counting method, has been applied to analyze atmospheric Ar39 (half-life=269yr), a cosmogenic isotope with an isotopic abundance of 8×10-16. In addition to the superior selectivity demonstrated in this work, the counting rate and efficiency of atom trap trace analysis have been improved by 2 orders of magnitude over prior results. The significant applications of this new analytical capability lie in radioisotope dating of ice and water samples and in the development of dark matter detectors. © 2011 American Physical Society
Semiclassical effects in black hole interiors
First-order semiclassical perturbations to the Schwarzschild black hole
geometry are studied within the black hole interior. The source of the
perturbations is taken to be the vacuum stress-energy of quantized scalar,
spinor, and vector fields, evaluated using analytic approximations developed by
Page and others (for massless fields) and the DeWitt-Schwinger approximation
(for massive fields). Viewing the interior as an anisotropic collapsing
cosmology, we find that minimally or conformally coupled scalar fields, and
spinor fields, decrease the anisotropy as the singularity is approached, while
vector fields increase the anisotropy. In addition, we find that massless
fields of all spins, and massive vector fields, strengthen the singularity,
while massive scalar and spinor fields tend to slow the growth of curvature.Comment: 29 pages, ReVTeX; 4 ps figure
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