2,522 research outputs found
Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC
PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Deep generative modeling for single-cell transcriptomics.
Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task
Quantum memory for entangled two-mode squeezed states
A quantum memory for light is a key element for the realization of future
quantum information networks. Requirements for a good quantum memory are (i)
versatility (allowing a wide range of inputs) and (ii) true quantum coherence
(preserving quantum information). Here we demonstrate such a quantum memory for
states possessing Einstein-Podolsky-Rosen (EPR) entanglement. These
multi-photon states are two-mode squeezed by 6.0 dB with a variable orientation
of squeezing and displaced by a few vacuum units. This range encompasses
typical input alphabets for a continuous variable quantum information protocol.
The memory consists of two cells, one for each mode, filled with cesium atoms
at room temperature with a memory time of about 1msec. The preservation of
quantum coherence is rigorously proven by showing that the experimental memory
fidelity 0.52(2) significantly exceeds the benchmark of 0.45 for the best
possible classical memory for a range of displacements.Comment: main text 5 pages, supplementary information 3 page
Increased insolation threshold for runaway greenhouse processes on Earth like planets
Because the solar luminosity increases over geological timescales, Earth
climate is expected to warm, increasing water evaporation which, in turn,
enhances the atmospheric greenhouse effect. Above a certain critical
insolation, this destabilizing greenhouse feedback can "runaway" until all the
oceans are evaporated. Through increases in stratospheric humidity, warming may
also cause oceans to escape to space before the runaway greenhouse occurs. The
critical insolation thresholds for these processes, however, remain uncertain
because they have so far been evaluated with unidimensional models that cannot
account for the dynamical and cloud feedback effects that are key stabilizing
features of Earth's climate. Here we use a 3D global climate model to show that
the threshold for the runaway greenhouse is about 375 W/m, significantly
higher than previously thought. Our model is specifically developed to quantify
the climate response of Earth-like planets to increased insolation in hot and
extremely moist atmospheres. In contrast with previous studies, we find that
clouds have a destabilizing feedback on the long term warming. However,
subsident, unsaturated regions created by the Hadley circulation have a
stabilizing effect that is strong enough to defer the runaway greenhouse limit
to higher insolation than inferred from 1D models. Furthermore, because of
wavelength-dependent radiative effects, the stratosphere remains cold and dry
enough to hamper atmospheric water escape, even at large fluxes. This has
strong implications for Venus early water history and extends the size of the
habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013.
Accepted version before journal editing and with Supplementary Informatio
Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918
The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized
The clinical and therapeutic uses of MDM2 and PSMA and their potential interaction in aggressive cancers
Prostate-specific membrane antigen (PSMA) overexpression is observed in the neovasculature of solid tumors, but not in the vasculature of normal tissues. Increased PSMA expression is positively associated with tumor stage and grade, although its function in cancer remains unclear. Mouse double minute 2 (MDM2) is a negative regulator of the p53 tumor suppressor and is reported to regulate VEGF expression and angiogenesis. Both proteins have been considered as biomarkers and therapeutic targets for advanced solid tumors. Our work and a recent microarray-based gene profiling study suggest there could be signaling interplay between MDM2 and PSMA. We herein review the mechanisms underlining the outgrowth of tumors associated with PSMA and MDM2, their potential interaction and how this may be applied to anticancer therapeutics
Household-level predictors of the presence of servants in Northern Orkney, Scotland, 1851–1901
Servants were an important part of the northwestern European household economy in the preindustrial past. This study examines household-level characteristics that are predictive of the presence of rural servants using data from Orkney, Scotland. The number of servants present in a household is related to household composition, landholding size, and the marital status of the household head. In addition, the sex of the particular servant hired reveals that the labor of male and female servants is not fungible. The sex of the servant hired is related to the ratio of male and female household members of working age, the occupation of the head, household composition, and the size of the household\u27s landholding
Coordinated optimization of visual cortical maps (II) Numerical studies
It is an attractive hypothesis that the spatial structure of visual cortical
architecture can be explained by the coordinated optimization of multiple
visual cortical maps representing orientation preference (OP), ocular dominance
(OD), spatial frequency, or direction preference. In part (I) of this study we
defined a class of analytically tractable coordinated optimization models and
solved representative examples in which a spatially complex organization of the
orientation preference map is induced by inter-map interactions. We found that
attractor solutions near symmetry breaking threshold predict a highly ordered
map layout and require a substantial OD bias for OP pinwheel stabilization.
Here we examine in numerical simulations whether such models exhibit
biologically more realistic spatially irregular solutions at a finite distance
from threshold and when transients towards attractor states are considered. We
also examine whether model behavior qualitatively changes when the spatial
periodicities of the two maps are detuned and when considering more than 2
feature dimensions. Our numerical results support the view that neither minimal
energy states nor intermediate transient states of our coordinated optimization
models successfully explain the spatially irregular architecture of the visual
cortex. We discuss several alternative scenarios and additional factors that
may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with
arXiv:1102.335
Anisomycin activates JNK and sensitises DU 145 prostate carcinoma cells to Fas mediated apoptosis
Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic signal. Furthermore, we have shown that inhibition of Fas mediated apoptosis is an early event in DU 145 cells, occurring upstream of Caspase 8 cleavage. It is hoped that identifying the target of JNK will allow novel therapies to be developed for the treatment of hormone refractory prostate cancer. Such therapies are especially important because no single or combined treatment to date has significantly prolonged survival in patients with hormone refractory prostate cancer
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