721 research outputs found

    Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.

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    A long-standing controversy is whether autophagy is a bona fide cause of mammalian cell death. We used a cell-penetrating autophagy-inducing peptide, Tat-Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether high levels of autophagy result in cell death by autophagy. Here we show that Tat-Beclin 1 induces dose-dependent death that is blocked by pharmacological or genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death, termed "autosis," has unique morphological features, including increased autophagosomes/autolysosomes and nuclear convolution at early stages, and focal swelling of the perinuclear space at late stages. We also observed autotic death in cells during stress conditions, including in a subpopulation of nutrient-starved cells in vitro and in hippocampal neurons of neonatal rats subjected to cerebral hypoxia-ischemia in vivo. A chemical screen of ~5,000 known bioactive compounds revealed that cardiac glycosides, antagonists of Na(+),K(+)-ATPase, inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown of the Na(+),K(+)-ATPase α1 subunit blocks peptide and starvation-induced autosis in vitro. Thus, we have identified a unique form of autophagy-dependent cell death, a Food and Drug Administration-approved class of compounds that inhibit such death, and a crucial role for Na(+),K(+)-ATPase in its regulation. These findings have implications for understanding how cells die during certain stress conditions and how such cell death might be prevented

    Dynamic mechanical thermal analysis of aqueous sugar solutions containing fructose, glucose, sucrose, maltose and lactose

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    The glass transition of glucose, fructose, lactose, maltose and sucrose solutions at maximum cryo-concentration was studied by Dynamic Mechanical Thermal Analysis (DMTA), using the disc bending technique. The glass transition temperatures were determined from the peaks in the loss modulus E′′, which corresponds theoretically to the resonance point (Maxwell model) for several input frequencies. The frequency dependence was well described by both an Arrhenius-type model and by the WLF (Williams, Landel and Ferry) equation, yielding glass transition temperatures for an average molecular vibration time of 100 s, which were similar to published midpoint temperatures determined by DSC scans. Some sugar mixtures were studied, yielding results that were well described by the Gordon–Taylor equation, using literature data. The frequency dependence of the viscoelastic ratio was also well approximated by an Arrhenius-type equation, with activation energies similar to those of the glass transition temperature and corresponded well to published values of the endset of glass transition

    Thermostatistics of deformed bosons and fermions

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    Based on the q-deformed oscillator algebra, we study the behavior of the mean occupation number and its analogies with intermediate statistics and we obtain an expression in terms of an infinite continued fraction, thus clarifying successive approximations. In this framework, we study the thermostatistics of q-deformed bosons and fermions and show that thermodynamics can be built on the formalism of q-calculus. The entire structure of thermodynamics is preserved if ordinary derivatives are replaced by the use of an appropriate Jackson derivative and q-integral. Moreover, we derive the most important thermodynamic functions and we study the q-boson and q-fermion ideal gas in the thermodynamic limit.Comment: 14 pages, 2 figure

    Origins of the Ambient Solar Wind: Implications for Space Weather

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    The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

    Particles-vortex interactions and flow visualization in He4

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    Recent experiments have demonstrated a remarkable progress in implementing and use of the Particle Image Velocimetry (PIV) and particle tracking techniques for the study of turbulence in He4. However, an interpretation of the experimental data in the superfluid phase requires understanding how the motion of tracer particles is affected by the two components, the viscous normal fluid and the inviscid superfluid. Of a particular importance is the problem of particle interactions with quantized vortex lines which may not only strongly affect the particle motion, but, under certain conditions, may even trap particles on quantized vortex cores. The article reviews recent theoretical, numerical, and experimental results in this rapidly developing area of research, putting critically together recent results, and solving apparent inconsistencies. Also discussed is a closely related technique of detection of quantized vortices negative ion bubbles in He4.Comment: To appear in the J Low Temperature Physic

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    The effect of questioning on concept learning within a hypertext system

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    Abstract Two studies report upon the effect of asking learners to answer questions when learning in a hypertext environment, even when no immediate feedback is given to learners about the appropriateness of their responses. Such questions may be useful as a means to induce responses that can be used to monitor learning, but here the hypothesis was investigated that their inclusion would also improve learning directly. In the first study, 80 student teachers answered embedded multiple-choice questions that encouraged analysis of examples. Concept learning achieved using this environment was significantly reduced when compared with an environment requiring no such responses. In the second study, a cohort of 68 students were asked to summarise the information illustrated by the examples. Here, learning was significantly improved as compared with the no-response condition

    Review Section : Nature/Nurture Revisited I

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    Biologically oriented approaches to the study of human conflict have thus far been limited largely to the study of aggression. A sample of the literature on this topic is reviewed, drawing upon four major approaches: comparative psychology, ethology (including some popularized accounts), evolutionary-based theories, and several areas of human physiology. More sophisticated relationships between so-called "innate" and "acquired" determinants of behavior are discussed, along with the proper relevance of animal behavior studies for human behavior. Unless contained in a comprehensive theory which includes social and psychological variables, biolog ically oriented theories (although often valid within their domain) offer at best severely limited and at worst highly misleading explanations of complex social conflicts. The review concludes with a list of several positive contributions of these biological approaches and suggests that social scientists must become more knowledgeable about them.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68270/2/10.1177_002200277401800206.pd

    Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

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    Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .)
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