2,430 research outputs found
In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells
Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation
Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Older Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes: Comparable Outcomes With Unrelated Umbilical Cord Blood and HLA-Identical Sibling Donors
Carbon nanotubes : from molecular to macroscopic sensors
The components that contribute to Raman spectral shifts of single-wall carbon nanotubes (SWNT’s) embedded in polymer systems have been identified. The temperature dependence of the Raman shift can be separated into the temperature dependence of the nanotubes, the cohesive energy density of the polymer, and the buildup of thermal strain. Discounting all components apart from the thermal strain from the Raman shift-temperature data, it is shown that the mechanical response of single-wall carbon nanotubes in tension and compression are identical. The stress-strain response of SWNT’s can explain recent experimental data for carbon nanotube-composite systems
Smallest small-world network
Efficiency in passage times is an important issue in designing networks, such
as transportation or computer networks. The small-world networks have
structures that yield high efficiency, while keeping the network highly
clustered. We show that among all networks with the small-world structure, the
most efficient ones have a single ``center'', from which all shortcuts are
connected to uniformly distributed nodes over the network. The networks with
several centers and a connected subnetwork of shortcuts are shown to be
``almost'' as efficient. Genetic-algorithm simulations further support our
results.Comment: 5 pages, 6 figures, REVTeX
Master equation approach to the conjugate pairing rule of Lyapunov spectra for many-particle thermostatted systems
The master equation approach to Lyapunov spectra for many-particle systems is
applied to non-equilibrium thermostatted systems to discuss the conjugate
pairing rule. We consider iso-kinetic thermostatted systems with a shear flow
sustained by an external restriction, in which particle interactions are
expressed as a Gaussian white randomness. Positive Lyapunov exponents are
calculated by using the Fokker-Planck equation to describe the tangent vector
dynamics. We introduce another Fokker-Planck equation to describe the
time-reversed tangent vector dynamics, which allows us to calculate the
negative Lyapunov exponents. Using the Lyapunov exponents provided by these two
Fokker-Planck equations we show the conjugate pairing rule is satisfied for
thermostatted systems with a shear flow in the thermodynamic limit. We also
give an explicit form to connect the Lyapunov exponents with the
time-correlation of the interaction matrix in a thermostatted system with a
color field.Comment: 10 page
Combined FUS+ basophilic inclusion body disease and atypical tauopathy presenting with an ALS/MND-plus phenotype
AIMS: Amyotrophic lateral sclerosis / motor neurone disease (ALS/MND) is characterised by the presence of inclusions containing TDP-43 within motor neurones. In rare cases, ALS/MND may be associated with inclusions containing other proteins, such as fused in sarcoma (FUS), whilst motor system pathology may rarely be a feature of other neurodegenerative disorders. We here have investigated the association of FUS and tau pathology. METHODS: We report a case with an ALS/MND-plus clinical syndrome which pathologically demonstrated both FUS pathology and an atypical tauopathy. RESULTS: Clinical motor involvement was predominantly upper motor neurone, and was accompanied by extrapyramidal features and sensory involvement, but with only minimal cognitive impairment. The presentation was sporadic and gene mutation screening was negative. Post-mortem study demonstrated inclusions positive for FUS, including basophilic inclusion bodies. This was associated with 4R-tauopathy, largely as non-fibrillary diffuse phospho-tau in neurones, with granulovacuolar degeneration in a more restricted distribution. Double-staining revealed that neurones contained both types of protein pathology. CONCLUSION: FUS-positive basophilic inclusion body disease is a rare cause of ALS/MND, but in this case was associated with an unusual atypical tauopathy. The coexistence of two such rare neuropathologies raises the question of a pathogenic interaction
Hierarchical Organization in Complex Networks
Many real networks in nature and society share two generic properties: they
are scale-free and they display a high degree of clustering. We show that these
two features are the consequence of a hierarchical organization, implying that
small groups of nodes organize in a hierarchical manner into increasingly large
groups, while maintaining a scale-free topology. In hierarchical networks the
degree of clustering characterizing the different groups follows a strict
scaling law, which can be used to identify the presence of a hierarchical
organization in real networks. We find that several real networks, such as the
World Wide Web, actor network, the Internet at the domain level and the
semantic web obey this scaling law, indicating that hierarchy is a fundamental
characteristic of many complex systems
Variability in aerobic methane oxidation over the past 1.2 Myrs recorded in microbial biomarker signatures from Congo fan sediments
Methane (CH4) is a strong greenhouse gas known to have perturbed global climate in the past, especially when released in large quantities over short time periods from continental or marine sources. It is therefore crucial to understand and, if possible, quantify the individual and combined response of these variable methane sources to natural climate variability. However, past changes in the stability of greenhouse gas reservoirs remain uncertain and poorly constrained by geological evidence. Here, we present a record from the Congo fan of a highly specific bacteriohopanepolyol (BHP) biomarker for aerobic methane oxidation (AMO), 35-aminobacteriohopane-30,31,32,33,34-pentol (aminopentol), that identifies discrete periods of increased AMO as far back as 1.2 Ma. Fluctuations in the concentration of aminopentol, and other 35-aminoBHPs, follow a pattern that correlates with late Quaternary glacial-interglacial climate cycles, with highest concentrations during warm periods. We discuss possible sources of aminopentol, and the methane consumed by the precursor methanotrophs, within the context of the Congo River setting, including supply of methane oxidation markers from terrestrial watersheds and/or marine sources (gas hydrate and/or deep subsurface gas reservoir). Compound-specific carbon isotope values of −30‰ to −40‰ for BHPs in ODP 1075 and strong similarities between the BHP signature of the core and surface sediments from the Congo estuary and floodplain wetlands from the interior of the Congo River Basin, support a methanotrophic and likely terrigenous origin of the 35-aminoBHPs found in the fan sediments. This new evidence supports a causal connection between marine sediment BHP records of tropical deep sea fans and wetland settings in the feeding river catchments, and thus tropical continental hydrology. Further research is needed to better constrain the different sources and pathways of methane emission. However, this study identifies the large potential of aminoBHPs, in particular aminopentol, to trace and, once better calibrated and understood, quantify past methane sources and fluxes from terrestrial and potentially also marine sources
A Topological Glass
We propose and study a model with glassy behavior. The state space of the
model is given by all triangulations of a sphere with nodes, half of which
are red and half are blue. Red nodes want to have 5 neighbors while blue ones
want 7. Energies of nodes with different numbers of neighbors are supposed to
be positive. The dynamics is that of flipping the diagonal of two adjacent
triangles, with a temperature dependent probability. We show that this system
has an approach to a steady state which is exponentially slow, and show that
the stationary state is unordered. We also study the local energy landscape and
show that it has the hierarchical structure known from spin glasses. Finally,
we show that the evolution can be described as that of a rarefied gas with
spontaneous generation of particles and annihilating collisions
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